Note: Descriptions are shown in the official language in which they were submitted.
1 339066
Description
DISINFECTING COMPOSITIONS AND METHODS THEREFOR
This is a divisional application of Application Serial
No. 563,942.
Technical Field
This invention relates generally to compositions for
disinfecting substrates as well as to processes for preparing and
using such compositions. Further, this invention relates to
disinfecting compositions useful as oral hygiene compositions
such as a mouthwash, toothpaste, lozenge, chewing gum, or the
like.
Background of the Invention
The term "disinfectant" is used in this specification
to broadly include any substance or composition that disinfects,
sanitizes, deodorizes, sterilizes, or kills germs.
The use of chlorine compounds in various types of
disinfectant compositions is well known. Chlorine compounds
suggested for use in this regard include, for example, sodium
hypochlorite, used in World War I was a wound irrigant, and
chlorinated phenols, such as m-chlorophenol. These compounds
have increased bactericidal activity and reduced toxicity, in
some instances, when compared to non-chlorinated phenols. Thus,
m-chlorophenol has a phenol coefficient of 5.8 (S. aureus) to 7.4
(B. typhosus). Other chlorine compounds having some form of
disinfectant utility include, for example, chlorine gas itself,
chlorine dioxide, chloramine T, calcium hypochlorite (a standard
swimming pool disinfectant), chloropicrin (a larvicide),
chloroform (a fumigant), chlorodane (an insecticide), and
chloromycetin (an antibiotic).
Chlorine dioxide in particular has been found to
be an especially effective disinfectant. This compound is
quite versatile and has long been used as a bleaching
agent, such as in the oxidizing of the natural colorant
*
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present in cotton, wood pulp and other cellulosic fibrous
material. In such uses, chlorine dioxide, though perform- t
ing an oxidizing function, is nevertheless noninjurious
with respect to the fibrous material.
Particularly useful disinfecting compositions
which employ chlorine-containing compounds are disclosed in
U.S. Patent Nos. 4,330,531 and 4,585,482. These composi-
tions comprise chlorite salts, such as sodium chlorite, in
combination with weak organic acids, such as lactic acid,
to provide particularly effective disinfectant compositions.
These compositions are useful in topically treating skin
diseases such as acne and in toothpastes.
One particularly preva]ent disease is mastitis in
dairy herds. Mastitis is a highly infectious disease which
affects the bovine udder. l'he losses in dairy production
resulting from this disease are staggering. For example,
in the United States alone, these losses are estimated to
be in the hundreds of millions of dollars. Mastitis not
only reduces the production of higher yielding animals, but
also shortens their productive life.
It is well known that mastitis is transmitted
from animal to animal. It has also been established that
the only route of transmission of the disease is through
the teat orifice. Conditions which are help primarily
responsible for the high incidence of mastitis include poor
udder hygiene and physical damage to the teats. Dairymen
and veterinarians have long sought a conditioning and
protective composition which is economical and also
provides facility of use. A composition which would
improve the normal condition of the udder and teats and
would also aid in preventing or effectively reducing the
incidence of mastitis would serve to substantially increase
both the production and productive life of a dairy herd.
Infectious mastitis is caused by microorganisms.
Prior art treatments, such as the use of sulfanilimide,
have been only partially effective in controlling the
disease because such treatments are useful against only one
1 339066
type of microorganism which causes mastitis but are not
useful against other types. Since the infection is usually
of a mixed character, it fol~ows that the ef~ectiveness of
drugs such as sulfanilimide is limited for all practical
purposes.
It has also been suggested to use penicillin for
the treatment of mastitis. The use of this compound is not
desirable, however, in view of the high cost and extraordi-
nary conditions necessary for the preservation and use of
penicillin
It has been proposed in U.S. Patent No. 3,222,252
to treat mastitis with a preparation which comprises a
- blend of edible, semidrying oils and drying oils together
with a fatty acid ester, skin emollient, film-forming agent.
It is said that the presence of a drying oil in the prepara-
tion is essential to provide the desired ~ilm-forming
property. But for the most part, these film-forming-based
treatments of mastitis have been unsuccessful. The use of
iodine and peroxide in conjunction with latex emulsion
films has led to other problems, including milk contamina-
tion and skin irritation.
While chlorine-liberating compounds have
germicidal and deodorant properties, their characteristic
taste and odor make them unpleasant for use in oral hygiene
compositions such as mouthwashes. Other oral hygiene
compositions, some commercially avai]able, while pleasant
tasting, are ineffective to reduce dental plaque as well as
control gingivitis and periodontitis.
The search has continued for new and improved
oral hygiene compositions which are both pleasant tasting
and effective in reducing dental plaque as well as control
gingivitis and periodontitis. This invention was made as a
result of that search.
The use of compositions comprising metal chlorite
and a weak organic acid, such as lactic acid, is disclosed
in U.S. Patent No. 4,330,531. A chlorine dioxide releasing
compound offers to substantially alleviate the problems
4 1 339066
associated with the prevention of mastitis. For this,
application, the use of a gelling agent to generate a viscous
topical gel is essential. The viscosity is needed for proper
adhesion to the skin surface for an extended length of time.
Past attempts to create a useful viscous topical gel
containing chlorine dioxide releasing compounds have been less
than completely successful. Of the gelling agents tried, none
combined the properties needed for substantial effectiveness.
Carbohydrate-based gels lose their viscosity at higher pH's as
the alkaline chlorites break down the long polymer chains.
Inorganic thickeners, such as bentonite clays, participate in the
reaction between the acid and chlorite, and tend to form stringy,
unsuitable gels.
The search has continued for a viscous topical gel
composition capable of embodying alkaline chlorites for the
treatment and prevention of skin disease, infection and
irritation on humans and other ~n;m~ls. This invention was made
as a result of that search.
Obiects and Summary of the Invention
Accordingly, it is a general object of the present
invention to avoid or substantially alleviate the above-
identified problems of the prior art.
Another object of the present invention is to provide
improved oral hygiene compositions useful in reducing dental
plaque.
A further object of the present invention is to provide
oral hygiene compositions which are pleasant tasting yet
effective to reduce dental plaque and control gingivitis and
periodontitis.
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An additional object of this invention is to provide,
a method for producing these oral hygiene compositions.
Yet another object of this invention is to provide a
method for disinfecting the mouth comprising treating the mouth
with these oral hygiene compositions.
Other objects and advantages of the present invention
will become apparent from the following summary of the invention
and description of its preferred embodiments.
The present invention provides, in one aspect, a
disinfectant oral hygiene composition for reducing dental plaque.
This composition comprises: (a) a flavouring agent acceptable
for oral hygiene compositions, (b) an aqueous solution containing
a suitable amount of an acid, and (c) an amount of a metal
chlorite such that the chlorite ion concentration in the form of
chlorous acid is no more than about 15 percent by weight of the
total amount of chlorite ion concentration. The composition
contains substantially no lactic acid.
In another aspect, the present invention provides a
process for producing these disinfectant oral hygiene
compositions. This process comprises admixing (a) a flavouring
agent acceptable for oral hygiene compositions, (b) from about
0.03 to about 0.3 percent by weight of a chlorine dioxide
liberating compound based upon the total weight of the
composition, and (c) a suitable amount of an organic acid having
a pK of from about 2.8 to about 4.2. The composition contains
substantially no lactic acid.
In yet another aspect, the present invention provides
a disinfectant oral hygiene composition for reducing dental
plaque and controlling gingivitis and periodontitis, which
composition comprises: (a) a flavouring agent acceptable for
oral hygiene compositions, (b) from about 0.03 to about 0.3
1 339066
percent by weight of a chlorine dioxide liberating compound based,
upon the total weight of the composition, and (c) a suitable
amount of an organic acid having a pK of from about 2.8 to about
4.2. The composition contains substantially no lactic acid.
In a further aspect, the present invention provides a
composition comprising an aqueous solution or gel containing a
suitable amount of a protic acid with an amount of a metal
chlorite such that the chlorite metal ion concentration in the
form of chlorous acid is no more than about 15 percent by weight
of the total amount of chlorite ion concentration, the
composition containing substantially no lactic acid.
There is also provided a disinfectant oral hygiene
composition for reducing dental plaque which comprises a
flavouring agent acceptable for oral hygiene compositions, an
aqueous solution containing a compound which contains at least
two vicinal hydroxy groups, a suitable amount of a protic acid,
and an amount of metal chlorite such that the chlorite ion
concentration in the form of a chlorous acid is no more than
about 15 percent by weight of the total amount of chlorite ion
concentration. The composition contains substantially no lactic
acid.
1 339~66
The disinfecting compositions of this invention disinfect by means of a
chlorous acid generating, composition. The composition comprises a flavoring agent,
suitable amount of a carboxylic acid, and a suitable amount of a metal chlorite. The
chlorite ion concentration in the form of chlorous acid is no more than about 15
5 percent by weight of the total amount of chlorite ion concentration.
The oral hygiene formulations of this invention contain low concentrations
of chlorous acid generating compounds which are extremely effective as oral
disinfectants. These compositions provide effective mouthwashes, toothpastes and
other oral disinfecting compositions without the strong characteristic unpleasant taste
10 of chlorine.
DETAILED DESCRIPTION OF THE INVENTION
The composition of this invention is formed by combining one gel which
comprises a dilute aqueous solution of metal chlorite with another gel which comprises
a dilute aqueous solution containing a weak organic acid. The gel containing the metal
15 chlorite also contains the polysulfonic acid salt. The concentrations of chlorite and
acid are relatively low.
This composition provides a metastable chlorous acid composition formed
from small amounts of chlorite and acid. This composition is capable of generating
chlorine dioxide over a long period of time at continuing levels of effectiveness.
'~,
~l,,
1 339066
-8-
As chlorine dioxide forms, more of the chlorite converts to chlorous acid by interacting
with hydrogen ions further generated by ionization of the organic acid.
Weak organic acids which may be used in the present invention include
5 salicylic acid as well as citric, malic, tartaric, glycolic, mandelic and other structurally
similar acids as described in Formula I hereinbelow:
FORMULA I
C-OH
R - C - OH
R' and R2 may be the same or different and may be selected from the
10 group consisting of hydrogen, methyl, -CH2COOH, -CH2OH, - CHOHCOOH, -C6H5 and -
CH2C6H5. The pK of the organic acid is from about 2.8 to about 4.2, preferably from
about 3.0 to about 4Ø
Compositions of a metal chlorite and the weak organic acids of Formula
I are disclosed in United States Patent No. 4,986,990.
The gel containing the protic acid also contains a gelling agent or
thickener which is well known to those skilled in this art. Any gelling agent or
thickener which is nontoxic and nonreactive with the other ingredients of the
composition may be used, such as cellulose gels, typically methyl cellulose, or
preferably, hydroxy ethyl cellulose.
B
1 339066
-8a-
Furthermore, that gel may also contain a preservative, such as benzyl alcohol orsodium benzoate. Other additives, such as buffers to adjust the pH of the composition
to become more compatible with the skin, may be used.
The amount of thickener in the protic acid-containing gel may be generally
from about 0.5% to about 5%, typically from 0.8% to about 4%, and preferably from
about 1% to about 3% of the gel, by weight, of the total composition. The amountof preservative in the gel may be generally from about 0.01% to about 0.05%,
typically from about 0.01% to about 0.04%, and preferably from about 0.02% to
about 3%, by weight, of the total composition.
The chlorine dioxide liberating compound or metal chlorite and the protic
acid are present in separate gels, and the amount of the preservative is present in only
that
.~
1 33qo66
gel containing the protic acid. Approximately equal amounts of
the separate gels should be used.
The gel containing metal chlorite is thickened with a
-~lysulfonic acid salt. The amount of polysulfonic acid salt
added will depend on the desired use of the resulting
composition. For a topical cream, toothpaste, or topical gel for
the treatment of facial acne, the amount of the thickener in the
metal chlorite-containing gel may be generally from about 5% to
about 15%, typically from about 5% to about 10%, and preferably
from about 6% to about 8%, by weight, polysulfonic acid salt
based upon the total composition. For a composition particularly
suited to be used as a teat dip for treating cow udders, the
amount of thickener in the metal chlorite-containing gel may be
generally from about 0.5% to about 5%, typically from about 1% to
about 4%, and preferably from about 2% to about 3%, by weight,
solid polysulfonic acid salt based upon the total composition.
These polysulfonic acid salts are polymers of
2-acrylamido-2-methylpropane sulfonate. The preparation of such
polymers is described in U.S. Patent No. 4,128,631, Canadian
Patent No. 864,433, and German OLS No. 2,153,292, laid open May
4, 1972.
The pH of the gel containing the polysulfonic acid is
generally greater than about 8, typically from about 9 to about
12, and preferably from about 10 to about 11.5.
The polymers useful in the present invention are
prepared from:
O
CH2=CH-C-NH-C( CH2 ) -CH2S03H
or a salt thereof. The polymerization reaction may be
accomplished by solution, emulsion, or suspension polymerization
processes. The medium for the polymerization is conveniently
water, an alcohol, or a mixture thereof. The
1 339066
choice of medium is best dictated by the requirements of
the final composition to be formulated.
The polymerization reaction is temperature-, pll-
and catalyst-sensitive. ln addition, it is desirable to
exclude oxygen from the reaction vessel used to form the
polymer, as that material inhibits the polymerization
process. The catalysts which are included to enhance the
rate of polymerization are materials such as ammonium
bisulfite, ferrous sulfate, hydrogen peroxide, sodium
metabisulfite, or other redox catalysts.
The polymer may be varied in molecular weight by
controlling the amount of the cata]yst, the pll, or the rate
of addition of the monomer to the reaction vessel. The
polymerization may be faci]itated by converting the monomer
from its acid form to a salt which is water-soluble.
The salts o~ the polymer preferably contain as
cations, sodium, potassium ammonium, monethanolamine,
diethanolamine, triethanolamine, and 2-amino-2-methyl-1-
propanol as we]l as mixtures thereof. The foregoing list
is merely exemplary of water-soluble salts which may be
used. Also within the scope of the present invention are
water-insoluble salts wherein the final composition is not
adversely affected by precipitation of the polymer. Such
products in which water-insoluble salts of the polymer may
be utilized are toothpastes, or substan~ially nonaqueous
products such as topical creams.
As was previously mentioncd, the molecular weight
of the polymer may be controlled by the pll, the rate of
addition of the monomer, or the judicious use of the cata-
lyst. It has been found desirable to utilize the afore-
described polymers having a molecular weight of from about
1,000,000 to about 5,000,000, more preferably from about
2,500,000 to about 4,500,000, to improve the viscosity and
film-forming characteristics of the composition. That is,
extremely high molecular weight polymers of the type
described may result in a pituitive or stringy consistency
of the end product. It has therefore been found desirable
11 1 339066
to limit the pituitiveness by selecting the preferred mole-
cular weight range. To this end, any common chain transfer
agent, such as mercaptosuccinic acid, may be used to limit
the molecular weight of the polymer.
It is noted that the terminal groups on the
polymer have little bearing on the desired properties of
the final composition and are thus not specified. The
terminal groups are most often hydrogens, but may also be
hydroxyl, sulfate, sulfonate, or:
o
~t
-CH2=CI~-C-NE~2
All alcohols, particularly the monhydric
alcohols, may be used as ingredients with the polymer.
Alcohols (Cl-C2~) which are nonirritating to the skin, such
as methanol, ethanol, isopropanol, propyl, lauryl,
myristyl, cetyl, and stearyl, as well as mixtures thereof,
are preferred. Polyols such as glycerine, or ethylene
glycol or propylene glycol may be utilized advantageously
with the polymer. The choice of the alcohol to be utilized
with the particular polymer of the composition o~ the
present invention will ordinarily be dictated by product
aesthetics and the physical form of the composition. For
instance, when liquid compositions are desired, the lower
alcohols are preferably utilized, while cream compositions
within the scope o~ the present invention will normally
require the higher alcohols. Where the compositions of the
present invention contain ingredients other than the
polymer or the alcohol in substantial amounts, the choice
of the particular alcohol becomes less important.
A desirable variable of the present invention is
the incorporation of water with the polymer. A resuLtant
increase in viscosity of the water is noted with no adverse
effects on the stability of the product; that is, water is
a highly suitable carrier which may be used as a vehicle
for contacting the polymer and the substrate. The parti-
cular weight ratios at which the desirable increase in
1 339066
12
- viscosity occurs for mixtures of the polymer and water are
respective~y from about 1:10,000 to about 1:100. ~refer-
ably this ratio is in the range of from about 1:1000 to
about 1:500. Within the aforementioned range, highly
- 5 viscous compositions are obtained with low solids content.
Such compositions are desirable in that they allow eomposi-
tions such as topical creams or gels, acne gels, or teat
dips to be formulated in a thickened state, providing
greater ease of application.
~'he gel containing the protic acid and the gel
containing the metal chlorite are mixed either before appli-
cation to the affected substrate or preferably in situ.
After the gels are mixed, the pl~ of the final composition
is generally less than about 7, typically from about 2 to
about 5, and preferably from about 2.5 to about 4.
In the present invention, the composition is
ordinarily used at a level of about 0.001 gram per square
centimeter to about 0.1 gram per square centimeter of the
affected substrate.
The oral hygiene compositions of this invention
comprise a flavoring agent suitable for use in an oral
hygiene composition, a suitable amount of a carboxylic
- acid, and a suitable amount of a metal chlorite. The
concentrations of chlorite and acid are relatively low and
are such that the amount of chlorite in the form of
chlorous acid is no more than about 15 percent by weight of
the total chlorite ion concentration in solution.
Typically the amount of the chlorite in the form of
chlorous acid is nor more than about 10 percent by weight
of the total chlorite ion concentration in solution.
The percent by weight of chlorite and chlorous
acid may be calculated from the ionization constant of
chlorous acid and the amount of hydrogen ion in solution
produced by the partial ionization of the carboxylic acid.
Thus the hydrogen ion concentration, IH+I, in a solution of
the carboxylic acid, HA, of known molar concentration and
1 339066
-1 3-
whose ionization constant is KA~ may be calculated from the following relationship:
KA = [H+1 [A~]
[HA]
This same relationship may be applied to calculate the relative chlorite and
chlorous acid concentrations where the ionization constant for chlorous acid is 1.1 x
1 o-2. That is:
1 1 X 10-2 = IH ~ ICl02l
where the hydrogen ion concentration, [H+], jS the quantity already
determined by ionization of the known amount of the carboxylic acid, HA. This
calculation is well-known to those skilled in this art.
The oral hygiene compositions of this invention provide a metastable
chlorous acid composition formed from relatively small amounts of chlorite and acid.
This composition is capable of generating chlorine dioxide over a long period of time
at continuing levels of effectiveness. AS chlorine dioxide forms, more of the chlorite
converts to chlorous acid by interacting with hydrogen ions further generated byionization of the carboxylic acid.
The orai hygiene compositions of this invention are therefore different
from many prior art chlorine dioxide generating compositions which consist of
B ~
~ 339066
-14-
relatively high concentrations of chlorite and acid. Prior art chlorine dioxide-containing
compositions were not used as mouthwashes or toothpastes and result in the rapid
conversion of chlorous acid to chlorine dioxide. The rate of chlorine dioxide formation
5 depends on the sum of the square of chlorous acid concentration and the prdduct of
chlorous acid and chlorite concentrations according to the equation:
d[Cl~2] = Kl[HCl02] + k2 [HCl02] [C102]
dt
See Gordon, "The Chemistry of Chlorine Dioxide," Pro~. Inor~. Chem. 15:201 (1972).
10Thus the rate at which chlorine dioxide forms depends exponentially on
the amount of chlorite ion which is converted to chlorous acid and the amount of
chlorite ion present.
In certain embodiments of the invention, the chlorous acid generating
composition comprises an aqueous solution containing generally from about 0.01 to
15about 1, typically from about 0.02 to about 0.5, and preferably from about 0.03 to
about 0.3 percent by weight of metal chlorite and a suitable amount of an organic acid
having a pK of from about 2.8 to about 4.2. The pH of this composition is generally
less than about 7, typically from about 2.2 to about 7Ø
In yet another embodiment of this invention, even lower concentrations
20 of chlorite and acid may be used in the composition. These compositions comprise
an aqueous solution containing generally up to about 0.4, and typically from about
0 0001 to about 0.03 percent by weight of metal chlorite, and a suitable amount of
acid having a pK of from about 2.8 to about 4 2.
B'
1 339066
-14a-
The pH of the composition is generally less than about 7, typically from about 2.2 to
about 7Ø
In certain embodiments of the invention, the carboxylic acid is an alpha-
5 hydroxy carboxylic acid. In preferred embodiments, the alpha-hydroxy carboxylic acid.
has the structure of Formula I herein.
Optionally the compositions of the invention may contain either a suitable
amount of a compound containing vicinal hydroxy groups or an amount of a water-
soluble chloride in a significant molar excess to the chlorite, or both. These optional
10 ingredients may facilitate the
.~
~.
15 1 339066
formation of chlorine dioxide from chlorous acid and are
thus userul in rapidly disinfec~ing compositions where an,
increased rate of chlorine dioxide formation is desired
while maintaining a low concentration o~ chlorite and acid.
~'he metal chlorite useful in the present
composition may more generally be described as a chlorine
dioxide liberating compound. By "chlorine dioxide
liberating compound" is meant any compound which, when
appropriately treated, e~fects the production of chlorine
dioxide as a result of a change in the va]ence state of the
chlorine atom from +3 to +4. While any chlorine dioxide
liberating compound may be used, water-soluble chlorites
are preferred because they are readily available and
inexpensive. Typical water-soluble chlorites include metal
chIorites, such as alkali metal chlorites and alkaline
earth metal chlorites. Sodium chlorite and potassium
chlorite are preferred. Sodium chlorite is particularly
prererred.
The flavoring agents useful in the compositions
of this invention include any flavoring agent or mixture of
flavoring agents acceptable in oral hygiene compositions.
Such flavoring agents are well-known to those skilled in
this art and include l-carvone (mint flavor), peppermint
oil, aspartame, saccharin, wintergreen oil, cinnamon oil,
clove oil, menthol, thymol, euca]yptol, oil of sassafras,
oil of anise, dextrose and levulose, and other flavoring
agents well-known to those skilled in this art.
The term "oral hygiene compositions" is meant to
include any composition which is used in the mou~h in order
to promote oral hygiene. These compositions may be in the
form of a mouthwash, toothpaste, chewing gum, lozenge, or
the like.
These compositions may be in the form of a4ueous
solutions, as in a mouthwash composition, geLs, as in
toothpaste or dentrifice compositions, solids, as in
lozenges, or combined with fillers, as in chewing gum
composition.
1 339066
-16-
The composition of this invention may contain other additives such as
chelating agents (e.g., Na4EDTA), or preservatives (e.g., sodium benzoate). The
identity and amount of the other additives will depend upon the type of oral hygiene
5 composition and its end use. Such additives are well-known to those skilled in the art.
Suitable penetrants, astringents, deodorants, and other therapeutic or preventive
compounds may be added. Dentrifices or toothpaste compositions according to the
invention may also contain humectants, binders sudsing agents, abrasive polishing
materials, and thickening agents.
The amount of chlorine dioxide liberating compound that may be used in
this composition may be generally from about 0.01% to about 1%, typically from
about 0.02% to about 0.05%, and preferably from about 0.03% to about 0.3% by
weight of the total composition (including the application medium).
At chlorite ion levels higher than about 0.5%, the concentration of
15 chlorous acid formed upon admixture of a carboxylic acid may be in excess of that
required for the formation of a metastable chlorous acid solution. These higher
concentrations of chlorous acid would cause the formation of chlorine dioxide, through
the degradation of chlorous acid at too rapid a rate.
Any acid of low toxicity may be used in the compositions of the invention
20 so long as the chlorite ion concentration limits described above and the degree of
conversion to chlorous acid are met. Carbonic acid may be used as the acid, however
preferably carboxylic acids are used. Preferred carboxylic acids include salicylic acid
as well as citric, malic, tartaric, glycolic, mandelic or other structurally similar acids as
described in Formula I hereinabove.
B
1 339066
-16a-
The pK of these carboxylic acids may be generally from about 2.8 to
about 4.2, and preferably from about 3.0 to about 4Ø
The amount of carboxylic acid used in these compositions should be
5 sufficient to lower the pH of the composition to less than about 7, typically from about
2.5
17 1 339066
to about 6, and preferably Irom about 3.0 to about 5Ø
Furthermore, this amount may be generally from about 0.01%
to about 3%, typically from about O.S~ to about 2-~o 1. and
preferably from about 0.1~ to about 1~o by weight of the
total composition (including the application medium).
The amount of flavoring agent useful in this
invention may vary widely but is generally from about 0.01
to about 5, typically from about 0.02 to about 2 ~ and
preferably from about 0.05 to about 1 percent by weight
based upon the total weight of the composition.
A suitable amount of a vicinal dihydroxy or
polyhydroxy compound may also be added to the compositions
of the present invention. The use of such compositions
enables one to produce compositions according to the
invention which are more rapidly effective in higher pH
ranges. The use of these vicinal dihydroxy or polyhydroxy
compounds also allows for the use of compositions according
to the invention which contain a much lower acid
concentration than that which is needed if the vicinal
polyhydroxy compound comprising at least two vicinal
hydroxy groups is absent.
Vicinal polyhydroxy compounds which contain at
least two vicinal hydroxy groups are well-known to those
skilled in this art and include dextrose and other sugars,
glycerin, sorbitol, and inositols. In other embodiments,
sugars with vicinal hydroxy groups in the cis configuration
such as galactose, mannose, and ribose may be used.
The use of such vicinal polyhydroxy compounds,
particularly those with cis-vicinal hydroxy groups, in
conjunction with the chlorine dioxide liberating compound
and carboxylic acid results in a synergistic composition.
The vicinal dihydroxy or polyhydroxy compound catalyzes the
formation of chlorine dioxide from chlorous acid. For
example, the rate of formation of the active chlorine
dioxide entity using a composition comprising sodium
chlorite and mandelic acid is substantially enhanced by the
addition of a relatively insubstantial amount of a vicinal
- 1 339066
18
polyhydroxy compound. Thus, the use of as little as 0.1
ribose in the composition substantially enhances the rate~
of formation of the active entity vis-a-vis a composition
containin~ only sodium chlorite and one of the organic
acids discussed hereinabove.
Stated otherwise, a composition containing the
vicinal polyhydroxy compound may be prepared having
substantially the same initial germ-killing efficacy in a
specified time period as a composition which does not
contain the vicinal polyhydroxy compound even though the
composition containing the polyhydroxy compound contains
substantially much less organic acid and sodium chlorite.
Elowever, such activation of the system results in a more
rapid depletion of the chlorite ion in the composition, so
that the germ-k-illing activity at a ]ater time period would-
be less. The vicinal polyhydroxy compounds may also serve
- another purpose in the composition in that it may act as a
sweetener or enhance the solubility of the flavoring-
agents.
lhe amount of vicinal polyhydroxy compound
containing at least two vicinal hydroxy groups may vary
widely, but in the present invention there is employed
generally less than about 20%, typically ~rom about 0.1% to
about 10%, and preferably from about 0.2% to about ~% by
weight of the total composition.
Alternatively, or in addition, the composition
may contain a large excess of chloride ion in the form of
an alkali or an alkaline earth metal salt. The excess may
be from about a 10 to about a 100-fold excess by weight of
chloride ion of total chlorite ion concentration. Large
excesses of chloride ion in acid solutions (below a pH of
about 7) cause the chlorite ion to decompose in an
accelerated manner, via the formation of chlorous acid to
form chlorine dioxide. In a preferred embodiment of the
invention where rapid disinfection is required, the
composition contains both a high excess o~ chloride ion and
1 33qo66
19
a sufficient amount of vicinal polyhydroxy compound
comprising at least two vicinal hydroxy groups.
The chlorine dioxide liberating compound is
generally kept separate from the organic acid prior to use
in order to avoid premature reaction of the ingredients.
l'he flavoring agent may be combined with either the organic
acid or the chlorine dioxide liberating compound, or both,
prior to their admixture.
The oral hygiene compositions of this invention
result in improved bactericidal, fungicidal, virucidal and
taste properties over presently available commercial oral
hygiene compositions and aid in den~al plaque reduction.
The present invention also provides a process for
-- producing d;sinfectant oral hygiene compositions. This
process comprises admixing: (a) a flavoring agent
acceptable for oral hygi~ne compositions, (b) from about
0.03% to about 0.3~ by weight of chlorine dioxide
liberating compound based upon the total weight of the
composition, and (c) a suitable amount of an organic acid
which as a pK of from about 2.8 to about 4.2. The
composition contains substantia~]y no lactic acid.
The present invention also provides a process for
reducing -dental plaque as well as controlling gingivitis
and periodontitis in the mouth. This process comprises
treating the mouth with an oral hygiene composition. The
composition comprises (a) a flavoring agent acceptable for
use in the mouth, (b) from about 0.03 to about 0.3 of a
chlorine dioxide liberating compound based upon the total
weight of the composition, and (c) a suitable amount of an
organic acid having a pK of from about 2.8 to about 4.2.
The composition contains substantially no lactic acid.
The present invention is il]ustrated by the
following examples. Unless otherwise noted, all parts and
3~ percentages in the examples as well as the specification
and claims are by weight.
1 339066
EXAMPrJ~ I
This example illustrates the preparation of a ,
toothpaste composition according to the present invention.
There is prepared a two-part disinfectant
toothpa~te composition according to the invention having a
first base paste or gel and a second ac~ivator paste or
gel.
The formulations of the two toothpaste parts on a
percent weight to weight basis are as follows:
TOOTHPASTE
BASE % W/W
Poly(sulionic Acid) l16~ aqueous solidsl 45.0
Sodium hydroxide, lN 40.0
Bentonite 2.0
15 Sodium lauryl sulfate 1.0
Titanium dioxide 1.0
Silica, amorphous 0.5
Sodium chlorite l.0
Water q.s
20 ACTIVA'rOR
G]ycerin l0.0
Magnesium a]uminum silicate 5.0
Hydroxyethylcellulose 2.0
Malic acid 1.5
Flavor, wintergreen 0.4
FD&C Blue #1 (0.5% solution) 0.06
Sodium benzoate 0.05
25 sodium saccharine
Water q.s
The p~l of the composition resulting from the
mixture of substantially equal portions of ~he base and
activator gels of the above formulation is about 4.15.
The base gel and the activator gel are preferably
stored separately prior to use, e.g., in a double-compar~-
ment tube. The two g~ls are mixed, preferably just prior
to use, in substantially equal amounts and the mixture is
used in the normal manner as a toothpaste. Alternatively,
substantially equal portions of the gels are placed in the
21 1 339066
mouth and mixed by the brushing action while the subject
brushes his or her teeth.
EXAMPLE II
This example iLlustrates the use of the present
invention as a teat dip for application to cow udders.
~ first gel is prepared by mixing the following
ingredients:
]0 Rheothik~80-ll poly(sulfonic acid)
i]6% aqueous solidsJ l6.00%
NaOH, lN 16.Q0
Naconnol*90F (sodium dodecylbenzene sulfonate~ 1.80~
Sodium chlorite 0.64%
Na~FDTA 0.19%
~ Sil~T-600 (silica) 2.50-~z
15 Water q.s.
A second gel is prepared by mixing the following
ingredients:
20 I.actic acid 2.6~%
Natrosol 250MR 1.00%
Isopropyl alcohol 2.00%
Sodium benzoate o.o~%
Po3oxamer~188 0.40%
FD&C Yellow #5 0 30%
Water q.s.
The two solutions are blended, preferably just
prior to application. The resulting gel is applied to the
cow teat, forming a solid shield around the teat. The film
thus formed, following drying, provides a long-lasting and
continuously acting disinfectant in direct contact with the
skin surface.
EXAME'LE III
l'his example illustrates the preparation of a
topical gel useful for the treatment of infection-based
facial acne.
A first gel is prepared by mixing the following-
ingredients:
~n
22 1 339066
Rheothik 80-ll poly(sulfonic acid)
l16~ aqueous solids~ 45.00Oz
NaOIl, lN 38.00
Naconnol 90F l.80%
Na4E~TA 0.19%
NaClO2 2.50%
Deionized water q.s.
A second gel is prepared by mixing the following
ingredients:
Salieylie aeid 2.00~
Isopropyl alcohol 30.00%
Sodium benzoate o.o~%
Natrosol~250MR 2.10%
P~uronic~-68 0.~0%
Deionized water 65.46%
l'he first and second solutions are mixed,
preferably just prior to use. The resulting gel is applied
to the a~fected region of the skin. A film forms, creating
a long-lasting eover that provides a continuous supply of
disin~ectant to the covered area of skin for a prolonged
period of time.
EXAMI'LE ~V
This example illustrates the properties of
compositions employing hydroxyethyl cellulose as a gelling
ager-t for sodium chlorite in the preparation of a final
composition comprising sodium chlorite and ]act;c acid.
Example I is repeated, but hydroxyethyl cellulose
is used at the 2~ level in place of the polysulfonic acid
salt and excluding ~he sodium hydroxide. This gel is not
storage stable for a commercially acceptable period of time.
l'he cellulose gelling agent depolymerizes and loses
viscosity.
EXAMPLE V
This example illustrates the preparation of a
mouthwash according to the present invention.
23 1 339066
A first solution is prepared by dissolving 0.4
grams of technical grade sodium chlorite, 0.17 grams of
powdered Na4EDTA 4l~2O, 0.5 grams of l-carvone (mint
flavor), and the appropriate amount of a compatible food
grade yellow dye in 500 milliliters of aqueous solution. A
second solution is prepared by dissolving 1.375 grams of
anhydrous citric acid and the appropriate amount of E'D&C
Blue #1 in a batch of 500 milliliters of a ]0 percent by
weight aqueous solution of glycerin.
The two solutions are mixed, preferably just
prior to use, in substantially equal amounts and the
mixture is used in the normal manner as a mouthwash.
EXAMPLE VI
This example also illustrates the preparation of
a mouthwash according to the present invention.
A first aqueous solution o~ 0.25% sodium chlorite
and 0.10% NaOI~ in deionized water is prepared.
A second aqueous activator solution is prepared
of 0.75% malic acid, 10.00% glycerine USP, 0.05% sodium
benzoate, 0.50% Equal (aspartame diluted with dextrose and
corn syrup solids), 0.03% FD~C Blue #1 (0.3% solution), and
0.40% Wintergreen Flavor (BBA),- in deionized water.
The two solu-tions are mixed, preferably just
prior to use in substantially equal amounts, -and the
mixt~re is used in the normal manner as a mouthwash.
EXAMPLE VII
This example illustrates the ability o~ a
composition of the present invention to reduce dental
plaque and control gingivitis and periodontitis.
Mouthwash compositions according to the invention
were used in a five day triple-crossover plaque reduction
test. In this test, 18 human subjects were divided into
three groups of six subjects each. The teeth of each
subject were scraped free of plaque immediately prior to
the commencement of each five day period.
1 339066
24
Each group was subjected to three five day
periods of treatment with the following formulations:
(a) placebo, (b) low potency mouthwash formulation, and
(c) high potency mouthwash formulation. The sequence of
the treatments per group were selected in a random fashion.
During the tive day period the subjects rinsed with the
formulation twice daily, i.e., in the morning and afternoon.
The subjects did not brush their teeth or perform any other
oral hygiene procedures. The same treatment procedure was
followed ~or all three of the formulations. Plaque scores
after each five day period were determined by a modified
Quigley-Hein index.
The placebe was formulated so that it had
substantially the same perceived acidity as the other two
formulations. The placebo formulation comprised an aqueous
so]ution of 0.27% citric acid, 0.08% sodium chloride, 0.5%
l-carvone, 0.09~z FD&C Green #3 (5000 ppm solution), 0.03%
ED&C YelLow #5 (5000 ppm solution), and 5.0% glycerin.
The compositions were formulated in two parts, A
and B. Equal volumes of the two parts were mixed
immediately before rinsing. The percent compositions o~
parts A and B of the high potency and ]ow potency
formulations were as follows:
1 339066
INGREDIENT IIIGH POT~NCY LOW POTENCY
Part A
Sodium chlorite (79~) 0.32 0.08
l-Carvone 0.10 0.10
ED&C Green #3
(5000 ppm solution) 0.18 0.18
1 N Sodium hydroxide q.s. q.s.
Part B
Malic acid 0.75 0.275
Sodium benzoate 0.05 0.05
Glycerin 10.00 10.00
FD&C Yellow #5
(5000 ppm solution) q.s. q.s.
The average plaq~le scores of the subjects listed
below show that the mouthwash compositions of this
invention were effective in substantially reducing dental
plaque.
Score (average) ~ Reduction
Placebo 3.82 ---
Low potency 3.35 12.3
lligh potency 2.47 35.3
EXAMPLE VIII
An evaluation was made of the microbiocidal
effectiveness of the High Potency mouthwash (0.32% Sodium
chlorite - Part A; 0.75% Malic acid - Part B) in Example
VII, versus that of 0.2% chlorhexidine digluconate. The
0.2% Chlorhexidine digluconate solution is the recommended
reference standard by which other oral hygiene germicides
should be measured. The procedure employed was based on
26 1 339066
the method in the F~A OTC Oral E3ealth Care Monograph
(Federal Register, Vol. 47, No. 10l, May 25, 1982, pages
22890-22900). The test organisms were:
Candida albicans ATCC 18804 (American Type
Culture Collection, Rockville, Md.)
Actinobacillus actinomycetemcomitans Forsyth
Clinic Isolate #Y4
Streptococcus mutans ATCC 25175
The microorganisms were grown in Brain ~leart
Infusion, and subcultured for two successive days at 37~C.
Two ml of a 50:50 mix of each test organism in sterile
fetal calf serum was added to 8 ml of the mouthwash
formulation, and triplicate aliquots of the inoculated test
formulation were removed at 30 and 60 second for subculture.
C. albicans was grown and subcultured aerobically; all
other organisms, anaerobically. The ~igh Potency test
solutions were neutralized first in fluid thioglycolate
medium, and ~urther neutra]ized in the plate count agar.
The chlorhexidine digluconate control solutions were only
neutralized in the enumeration agar. Results obtained were
as ~ollows:
Average Microbial
Test Log Reduction*
Formulation Organism 30 Sec. Exp. 60 Sec. FJXP.
Iligh Potency C. albicans 3.2 3.0
Actinobacillus 7.5 7.5
Strep. mutans 3.5 4.3
Chlorhexidine C. albicans 3.2 3.3
digluconate,
0.2~ Actinobacillus 6.6 6.3
Strep. mutans 3.0 3.0
*Average of three results.
27 1 339066
The High Potency Formulation shows a
microbiocidal efficacy equal to or greater than of
chlorhexidine digluconate at the 0.2% level.
These microbiocidaL data strongly indicate that
these formu]ations will not onl,y be helpful in reducing
dental plaque formation, but also would inhibit the onset
and severity of gi,ngivitis and other associated oral
disorders such as periodontitis which could lead to
eventual tooth loss.
' The principles, preferred embodiments, and modes
of operation of the invention have been described in the
foregoing specification. I~owever, the invention herein
which is intended to be protected, is not to be construed
as limi~ed to the particular forms disclosed, since these
are to be regarded as illustrative rather than restrictive.
Variations and changes may be made by those skilled in the
art without departing ~rom the spirit of the invention.
