Note: Descriptions are shown in the official language in which they were submitted.
1227~39
This invention relates to an antibacterial-containing oral composition
which promotes oral hygiene, controls plaque formation gingivitis and
periodontitis, by the topical application to the oral cavity, of a mouth rinse
or dentifrice containing an effective amount of the anti gingivitis agent, 1-
imidazoyl-l- ~p-chlorophenoxy)3-3-dimethyl 2-butanone known under a common
name as Climbazole by Bayer).
Periodontitis, or pyorrhea, is a disease affecting the supporting
tissues of the teeth including the gingiva, the membrane lining the sockets in
which the teeth lie, and the bones surrounding the teeth. The disease may
initially be associated with conditions of constant irritation of the gingiva
by dental plaque, food impaction, poor dental restorations, traumatic occlusion,
or chemical irritants.
The gums may be seriously harmed by deposits of dental plaque, a
combination of minerals and bacteria found in the mouth. The bacteria
associated with plaque can secrete enzymes and endotoxins which can irritate
the gums and cause an inflammatory gingivitis. As the gums become increasingly
irritated by this process they have a tendency to bleed, lose their toughness
and resiliency, and separate from the teeth, leaving periodontal pockets in
which debris, secretions, more bacteria and toxins further accumulate. It is
also possible for food to accumulate in these pockets, thereby providing noun-
ishment for increased growth of bacteria and production of endotoxins and desk
tructive enzymes. The pus that forms in this process is capable of destroying
gum and bone tissue. Bacteria are generally found to ye present during the
active stages of periodontal disease. Such organisms as anaerobic gram Vega-
lives are usually present, and are found in the purulent discharge as well as
in the involved tissue, and may be absorbed into the general system through the
isles
lymphatic or venous blood stream.
The progression of the pyrrhic process usually begins with gingivitis,
initiating at the margins of the gums, in which the gingiva become more tender
and sensitive, and appear flabby, inflamed and swollen. Periodontal pockets
become apparent, and infection takes place in these pockets. Effective control
and prevention of gingivitis accordingly constitutes a desideratum for the
prevention of further periodontal diseases.
A multitude of materials have been previously proposed and employed
for controlling oral diseases and malfunctions such as plaque, calculus, tartar,
caries, halitosis, and periodontal diseases such as gingivitis and pyorrhea,
but none have been entirely satisfactory. For example, oral compositions
containing anti-inflammatory agents which reduce the symptoms of swelling,
bleeding and inflammation associated with gingivitis, by preventing tartar
formation and/or countering oral calculus, include an imidazole such as vista-
dine or histamine as disclosed in United States Patent No. 3,497,591; a
dichloro-2-quanidino benzimidazole, as disclosed in United States Patent No.
3,523,154; carragheen:in as disclosed in United States Patent No. 4,029,760; a
mixture of tranexamic acid and folio acid, as disclosed in United States
Patent No. 4,272,512; and tannin acid, as disclosed in United States Patent No.
4,273,758. All of aforesaid agents are non-antimicrobial.
United States Patent No. 3,577,520 also discloses a dentifrice come
position containing 5,5-diaryl-2,4-imidazolidinediones in the treatment of
pyorrhea, by repairing the lesions of p~rlodontitis.
United States Patent No. 3,911,133 discloses an antibacterial compost-
lion effective against both gram positive and gram negative bacteria, comprising
an imidazole derivative, which is a bis(imidazolium qua ternary salt), useful in
1227~9
mouthwashes, toothpastes and dental gels as a method of inhibiting the
formation of dental plaque or in the prevention of gingivitis.
United States Patent No. 4,243,670 discloses imidazolium derivatives
having strong antimicrobial activity against dermatophytes, yeasts, molds
buffs fungi and gram positive cocci; and useful as an additive to oral
hygiene products such as toothpastes and mouthwashes, to avoid microbial
caused infections of the mucus of the mouth and as a prophylactic against
infection.
It is also known in the art, that certain gram negative organisms
such as Bacteriodes asaccharolyticus or Bacteriodes gingivalis are associated
with adult periodontitis. By eliminating these and other gram negative
anaerobes from the plaque accumulated on the gingival tissues, effective
control and prevention of periodontal disease can be achieved.
Accordingly, it has been shown by Listgarton et at in the J.
Periodont. Rest 14: 65-75 (1979), that metronidazole,
CH2CH20H
given systemically causes the elimination of said gram negative anaerobes from
the plaque. This was substantiated by lleijl and Lund in the J. Clinical
Period ontology 6, 197-209 (1979~, wherein is shown that metronidazole is
effective in reducing plaque and gingivitis scores in dogs; and by Lucia et
at in the J. of Clinical Period ontology, 8: 29-44 (1981), wherein it is shown
that metronidazole is effective in reducing the anaerobic B. asaccharolyticus
~7~3~
count in plaque removed from periodontal pockets, concomitantly,
with a substantial reduction in pocket depth and considerable gain
in apparent attachment. However, metronidazole, sold under the
trade mark of Flagella, is carcinogenic (Physician Reference Hand-
book p.1761) and connote be used indiscriminately.
It has now been found that another derivative of imidazole
is effective against said gram negative anaerobic organisms, which
is nonmutagenic, non-carcinogenic and can be topically applied to
the oral cavity in the treatment of gingivitis, namely, l-imidazoyl-
lo l-(p-chlorophenoxy)3-3-dimethyl 2-butanone.
The imidazoyl kittens such as l-imidazoyl-1-(4 sheller-
phenoxy)-3,3-dimethyl 2-butanone, are disclosed in United States
Patent Nos. 3,812,142 and 3,903,287 as an anti-mycotic agent, use-
fur in pharmaceutical compositions including pastes, gels, creams,
aqueous and non aqueous suspensions. Its action against pathogenic
protozoa, gram positive and negative bacteria such as Staphylococci
and Escherichia golf is also noted therein. British Patent No.
1,502,144 and its German counterpart, Patent No. 2,430,039, disclose
hair or skin treating compositions, effective against Pityrosporum
ovate, containing the imidazoyl kitten antimycotic agents dispersed
in a dermatologically acceptable carrier which contains a detergent-
active compound. These compositions are in -the form of creams,
aerosols, powders and liquids. German Patent No. 2,600,800
discloses the l-imidazoyl-l-(4-chlorophenoxy)-3,3-dimethyl 2-
butanone in a fungicidal composition, either in dry form, as a
dispersion in water, water-in-oil or oil-in-water emulsion or a
-- 4
~2~7139
spray, useful for protecting plaster coatings, dispersion dyes,
wallpaper, tiled surfaces, paints, glues, boatmen, furniture,
leather, shower curtains, textiles, carpets, wood and paper,
against a long list of pathogenic fungi, molds and bacteria.
However, there is
pa -
3~3
no Malaysian of Bacteroids asaccharolyticus or gingivalis, the particular
anaerobic gram negative organisms found in gingivitis. German Patent No.
2,700,806 also discloses a mixture of the imidazoyl kitten fungicide and a
qua ternary ammonium bactericide useful for protecting materials such as
paints, glues, bitumen, cellulose paper, textiles, leather and wood.
Although the prior art discloses the specified imidazoyl kitten as
an antimycotic agent, and its use in pharmaceutical formulations, particularly
in hair and skin treating compositions, there is no disclosure of its use in
dental preparations nor its effectiveness against the specific gram negative
anaerobic organisms associated with gingivitis and periodontitis.
It has now been found that the water insoluble imidazoyl kitten, 1-
imidazoyl-l-(p-chlorophenoxy)3-3-dimethyl 2-butanone, is selectively effect
live against the specific anaerobic gram negative organisms associated with
gingivitis, when topically applied to the affected gingiva.
The present invention provides an oral formulation containing the
aforesaid water insoluble imidazoyl kitten as the anti gingivitis agent soul-
bilized in an oral vehicle.
The formulation may be in the form of a mouth rinse or dentifrice
effective in the control and treatment of plague, gingivitis and periodontitis.
Preferably the invention provides an oral composition comprising the
aforesaid anti gingivitis agent solubilized in an aqueous vehicle comprising a
non ionic compound, the antibacterial-colltaining oral composition being usual
in the prevention and treatment of gingivitis in animals.
The oral composition may be used in a method of improving oral hygiene
by topically applying to the oral cavity the antibacterial-containing composition
comprising aforesaid solubilized imidazoyl kitten.
Objects, advantages and novel features of the invention will be set
-- 5 --
1227~39
2301-1251
forth in part in the description which follows, and in part will
become apparent to those skilled in the art upon examination of
the following or may be learned by practice of the invention. The
objects and advantages of the invention may be realized and
attained by means of the instrumentalities and combinations
particularly pointed out in the appended claims.
According to one aspect of the present invention there
is provided an oral composition, which is a mouthwash having a pi
of about 5 to 7.5, for treating gingivitis and periodontitis
comprising an oral vehicle and an effective amount, which is about
0.1-5% by weight, of the water insoluble anti gingivitis agent,
l-imidazoyl-l-(p-chlorophenoxy)3,3-dimethyl 2-butanone, solubilized
in a non ionic compound containing a hydrophobic radical and about
10-80% by weight of hydrofoil units of polyoxyethylene of suffix-
tent length to effect solubilization, in the weight ratio of 3:1
to 25:1 non ionic; anti gingivitis agent, said agent being selective
elm effective against the gram negative anaerobic microorganisms
Butterheads assaceharolyticus, Bacteriodes gingivalis and mixtures
thereof. Preferably, 0.1-5.0% by weight of said anti gingivitis
agent is solubilized in a non ionic compound containing a hydroph-
obic radical and about lo to 80~ by weight of hydrophilic units
of polyoxyethylene of sufficient length to syllables said imidazoyl
compound in an aqueous medium.
More specifically, such aspect of the present invention
relates to oral compositions comprising about 0.1 to 5% by weight
of said anti gingivitis agent, solubilized in an aqueous oral
vehicle
- 6 -
~2Z~39
comprising a non ionic compound containing a hydrophobic radical
including a higher fatty acid radical containing 10-20 carbons,
polyoxypropylene, hexitan Monroe fatty acid esters, and
fatty acid asides; and the hydrophilic group polyoxyethylene of
sufficient length to effect solubilization. The oral vehicle may
be liquid such as a mouthwash or rinse, solid such as chewing gum,
or tooth powder, pasty or creamy such as a toothpaste or dental
cream. These oral compositions are nontoxic and have a pi of
about 5 to 7.5.
The mouthwash which has a pi of about 5 to 7.5 is an
aqueous-alcohol vehicle containing about 1-5% by weight of a
non ionic surfactant selected from the group consisting of block
polymers of ethylene oxide, mixed polymers of propylene oxide and
ethylene oxide, polyoxyethylene hexitan Monroe fatty acid
esters containing 10-80 moles ethylene oxide per molt and higher
fatty acid moo- and di-ethanolamides and mixtures thereof.
The typical surfactant contains at least 10-80% by
weight of hydrophilic units of polyoxyethylene and the hydrophobic
radical such as polyoxypropylenewhich preferably has a molecular
weight of about 3250, as in the mixed polymers of propylene oxide
and ethylene oxide. The ratio of solubilizer to imidazole come
pound is about 1:1 to 25:1 and preferably about 3:1 to 25:1. At
ratios above 25:1, gelatin occurs.
The toothpaste, which also has a pi of about 5-7.5
comprises a dentally acceptable polishing material, and a liquid
vehicle containing water and about 20-40% by weight of a
~27~39
non ionic humectant including at least one humectant selected
from the group consisting of polyethylene glycol and polypropylene
glycol. Glycerine, sorbitol or minutely maybe substituted for
part of the humectant content provided said anti gingivitis agent
has been solubilized.
The anti gingivitis agent utilized in present invention
is l-imidazolyl-(p-chlorophenoxy) 3,3-dimethyl 2-butanone having
the structural formula:
~3-o-CH-CoC (SHEA
N
u - pa -
~227~39
which is prepared by reacting l-bromo-l-(4-chlorophenoxy)-3,3-dimethyl-2-
butanone with imidazole dissolved in acetonitrile as disclosed in United States
Patent Nos. 3,812,142 and 3,903,287. This imidazoyl kitten is a water
insoluble crystalline powder having a melting point of 94.5-97.8C which may
be obtained from the Bayer Company as Climbazole. Due to the water insolubility
of this imidazole compound, it must first be solubilized in a non ionic compound
prior to the addition of ionic materials in an aqueous medium.
It has been unexpectedly found that this antibacterial compound added
to oral vehicles is not only effective against the specific anaerobic organisms
involved in periodontal disease, but also reduces the disease significantly
when applied topically, as well as reduces the symptoms of gingivitis ask-
fated with periodontitis. Ike minimum inhibitory concentration (MIX) needed
to kill Bacteroides assaccharolyticus (Forsythe strain), determined according
to the procedure of Walker et at (Antimicrobial and Chemotherapy, Vol. 16,
p. 452-457, 1979), is between 7.8 to 31.2 micrograms per ml. The MIX value
for B. gingivalis is 25 micrograms per ml. The MIX value for B. grizzles
and Fuso-bacterium, other gram negative organisms is greater than 50 for each;
and the MIX value for the gram positive organism Actinomyces viscous is 125
for the aerobic strain and 250 for the anaerobic strain. This is clearly
indicative of the selectivity of the antibacterial activity of the specific
imidazole compound utilized herein as the anti gingivitis agent.
Evaluation of oral compositions against gingivitis, using a 0.3%
Climbazole-containing mouth rinse, median a study on 30 beagle dogs for 10
weeks, clearly shows it superior effectiveness against gingivitis. The prove-
dune used includes tune complete removal of hard and soft dental deposits, after
which the dogs are kept on a soft diet for six weeks to permit the development
~227~39
of gingivitis. The denotations are then treated with the test solutions twice
a day, 5 days a week, for about 15 seconds on each side of the mouth. The
animals are examined and the degree of inflammation of the gingiva is scored
according to a scale of 0 to 3. 0 = No inflammation. 1 = Mild, localized
edema, and redness of gingival margin, no bleeding is elicited upon gentle
finger pressure. 2 = Moderate edema, and redness of gingival margin with
bleeding upon gentle finger pressure. 3 = Severe edema and ulceration of
gingival margin and attached gingiva, and bleeding without gentle finger
pressure. A placebo rinse and 0.5% metronidazole rinse were used as the
lo negative and the positive controls respectfully. The data is summarized in
Table 1.
TABLE 1
Initial
Treatment gingival units 6 weeks 10 weeks
Ratings: 0 1 2 3 0 1 2 3 0 1 2 3
Placebo 9583 8 - - 569 31 - - 528 72
Rinse
0.5% Matron- 13578 9 - - 572 28 - - 576 24
dazzle Rinse
0.3% Climbazole 11589 - - 579 21 - - 578 22
Compared to the placebo, both Metronidazole and Climbazole rinses
significantly reduced the development of the gingival units of 2. However,
a smaller amount (0.3%) of Claimbazole exhibits the same effectiveness against
gingivitis than greater amo~mts (0.5'~) of Metronidazole.
Louvre, although metronidazole is effective against the specific
gram negative micro-organisms involved in periodontal disease when used
systemically, as fully discussed prior art, it does not work as well when
12Z7~39
topically applied. The reason for said poor results is due to the absence in
its structural formula of an appropriate hydrophobic group which is necessary
for penetration into the gingival tissues. On the contrary, Climbazole has a
bulky hydrophobic group, (p-chlorophenoxy) 3-3-dimethyl 2-butanone, which
provides good penetration into the tissues where the destructive process of
periodontitis occurs, enabling this antibacterial to maintain an effective con-
cent ration to reduce the bacterial count of the gram negative anaerobic micro-
organisms associated with this disease. In addition, metronidazole is, due to
its vitro group, mutagenic, whereas Climbazole is not mutagenic in mutagenic
tests, because it lacks the vitro group as can be seen by the structural
formulae below:
Climbazole Metronidazole
SHEA SHEA OH
Of -C-C~H-COC(CH3)3 / N \
_ N NO- I¦ SHEA
The oral composition of this invention may be liquid such as a
mouthwash or rinse. In such a preparation the vehicle is typically a water-
alcohol mixture. Generally, the ratio of water to alcohol is in the range of
from about 1:1 to about 20:1 preferably from 3:1 to 20:1, by weight. The
alcohol content preferably constitutes about 20-~0% by weight of the vehicle.
The total amount of water-alcohol mixture in this type of preparation is
typically in the range of from about 70 to about 98% by weight of the preparation.
The pi of such liquid and ether preparations of the invention is generally in
the range of from about 5 to about 7.5.
- 10 -
7~39
An essential component of the liquid oral preparations
is about 1-5% by weight of a non ionic surfactant containing 10-80
by weight of hydrophilic units of polyoxyethylene and also hydra-
phobic polyoxypropylene or higher fatty acid, fatty ester or fatty
aside, in order to syllables the water insoluble Climbazole in the
aqueous-alcohol vehicle.
Suitable non ionic surfactants include block polymers
of ethylene oxide, mixed propylene oxide-ethylene oxide polymers,
polyoxyethylene hexitan Monroe fatty acid esters having from
10-20 carbon atoms in the higher fatty azalea thereof and 4-100,
preferably 10-80 mows of ethylene oxide per mol. Preferably, the
hexitan is sorbitan, although Montana and other hexitans are also
often useful, the higher fatty azalea will be of 10-16 or 20 carbon
atoms, more preferably of 12-16 or 18 carbon atoms and most
preferably of about 12 carbon atoms, and the number of ethoxies will
be from 15-80, often preferably about 20. Especially useful is an
ICKY. product sold under the trade mark Tweet 20, also known as
Polysorbate 20 which is polyoxyethylene (20) sorbitan monolaurate.
Similarly useful products are sold under similar
identifications, such as Tweets 40, 60, 65 and 80, all of which are
non ionic surface active agents wherein the higher fatty azalea is
palmitoyl, stroll or oilily and the number of the mows of ethyl
tone oxide per mow is about 20. However, of these materials the
polyoxyethylene sorbitan monolaurate is usually favored. Polyp
oxyethylene (80) sorbitan monolaurate may be used in place of said
polysorbate 20.
~27~ 39
Other suitable non ionic surfactants include the moo-
and di-ethanolamides of higher fatty acid having about 10-18 carbon
atoms in the azalea group such as cocomonoethanolamide, cocodiethan-
olamide, Laurie myristic diethanolamide, Laurie monoethanolamide or
combinations thereof.
- ha -
1227~39
Present oral compositions may be substantially pasty in character such
as a toothpaste or dental cream. The vehicle of such pasty oral preparations
contains polishing material. Examples of polishing materials are water insole
ruble sodium metaphosphate, potassium metaphosphate, tricalcium phosphate,
calcium pyrophosphate, magnesium orthophosphate, trimagnesium phosphate,
calcium carbonate, alumina, hydrated alumina, aluminum silicate, zirconium
silicates, silica bentonite, crystalline silica having particle sizes of up to
5 microns, silica gel, complex amorphous alkali metal aluminosilicate, hydrated
alumina, dicalcium phosphate, and mixtures thereof.
When visually clear gels are employed, a polishing agent of colloidal
silica, such as those sold under the trade mark SWILLED as Swilled 72 and Swilled
74 or under the trade mark SANTOCEL as Santocel 100 and alkali metal alumina-
silicate complexes are particularly useful, since they have refractive indices
close to the refractive indices of golfing agent-liquid (including water and/or
humectant) systems commonly used in dentifrices.
The polishing material is generally present in amounts ranging from
about 10 to about 99% by weight of the oral preparation. Preferably, it is
present in amounts ranging from about 10 to about 75% in toothpaste.
In a toothpaste, the liquid vehicle comprises water and humectant
typically in an amount ranging from about 10 to about 90% by weight of the
preparation. An essential component of the toothpaste and dental cream is
about 20-40% by weight of a non ionic humectant including at least one humectantselected from the group consisting of polyethylene glycol and polypropylene
glycol in order to syllables the water insoluble Climbazole in the aqueous
vehicle. Glycerine, sorbitol or minutely may be substituted for part of the
humectant content, provided said imidazole compound is solubilized in the polyp
- 12 -
1~:27~ 9
oxyethylene or polyoxypropylene glycol.
A golfing agent, such as natural or synthetic gums or
gum-like materials, typically Irish moss, sodium carboxymethyl-
cellulose, methyl cellulose, hydroxyethyl cellulose, gum tragacanth,
polyvinylpyrrolidone, starch and hydroxypropyl methyl cellulose is
usually present in toothpaste in an amount up to about 1% by weight,
preferably in the range of from about 0.5 to about S%. In a tooth-
paste or gel, the liquids and solids are proportioned to form a
creamy or golfed mass which is extrudable from a pressurized
container or from a collapsible, e.g., aluminum or lead, tube.
The oral compositions of this invention may contain a
non-soap synthetic sufficiently water soluble organic anionic or
non ionic surfactant in concentrations generally ranging from about
l-S weight percent, to promote wetting, detersive and foaming
properties. united States Patent No. 4,041,149 discloses such
suitable anionic surfactants in got. 4, lines 31-38, and such
suitable non ionic surfactants in got. 8, lines 30-68 and got. 9,
lines 1-12.
The antibacterial-containing oral compositions of this
invention may optionally contain a fluorine-providing compound
including inorganic fluoride salts, such as soluble alkali metal,
alkaline earth metal and heavy metal salts, for example, sodium
fluoride, potassium fluoride, ammonium fluoride, calcium fluoride,
a copper fluoride such as cuprous fluoride, zinc fluoride, a tin
fluoride such as stunk fluoride or stuns chlorofluoride,
barium fluoride, sodium fluorosilicate, ammonium fluorosilicate,
- 13 -
122~7~L3~
sodium fluorozirconate~ sodium monofluorophosphate, aluminum
moo- and di-fluorophosphate, and fluorinated sodium calcium
pyrophosphate. Alkali metal and tin fluorides, such as
- aye -
1~7~39
sodium and stuns fluorides, sodium monofluorophosphate and mixtures
thereof, are preferred.
The amount of the fluorine-providing compound is dependent to some
extent upon the type of compound, its volubility, and the type of oral prepare-
lion, but it must be a nontoxic amount. In solid oral preparation, such as
toothpaste or chewing gum, an amount of such compound which releases a maximum
of about 1% by weight of the preparation is considered satisfactory. Any
suitable minimum amount of such compound may be used, built is preferable to
employ sufficient compound to release about 0.005 to 1%, and preferably about
0.1% of fluoride ion. Typically, in the cases of alkali metal fluorides and
stuns fluoride, this component is present in an amount up to about 2% by
weight, based on the weight of the preparation, and preferably in the range of
about 0.05 to 1%. In the case of sodium monofluorophosphate, the compound may
be present in an amount up to 7.6% by weight, more typically about 0.76%.
Various other materials may be incorporated in the oral preparations of
this invention which do not adversely affect the properties of the composition
such as sweetening agents ego., saccharin, sucrose, lactose, maltose, sorbitol,
etc.); flavoring oils (e.g., oils of spearmint, peppermint, winter green, sass-
fray, clove, sage, eucalyptus, marjoram, cinnamon, lemon, orange, etc.), color-
in or whitening agents (e.g., titanium dioxide), preservatives (e.g., sodiumbenzoate) and the like. Minor amounts, up to about 5% in total, and preferably
0.01 to 3% by weight of these materials may be added to the oral composition.
The present oral compositions are readily prepared by simple mixing
methods from readily available components. Louvre, it is essential that the
imidazoyl compound be first mixed with the non ionic component prior to its
addition to the oral vehicle which typically includes water.
- 14 -
1~27139
For instance, a mouth rinse or mouthwash may be prepared by first
solubilizing the imidazole compound by emulsifying in a non ionic surfactant
prior to addition to the aqueous or alcoholic aqueous vehicle. The other
ingredients such as flavor, sweetener, etc. may be added to the aqueous vehicle
either prior to or subsequent to the addition of the solubilized imidazole to
the aqueous vehicle.
The toothpaste may be prepared by first mixing the imidazole compound
with the humectant which is non ionic, wherein it is solubilized, and then add-
in the thickener such as carboxymethyl cellulose to form a gel, followed by
the addition of polishing agent water and other ingredients. The sequence of
the addition of the various ingredients can be varied, provided the imidazole
compound is first solubilized in the non ionic humectant prior to addition to
the water component.
In the practice of this invention an oral composition according to
this invention such as a mouthwash or toothpaste containing l-imidazoyl-l-
(p-chlorophenoxy) 3-3-dimethyl 2-butanone anti gingivitis agent in an amount
effective to promote oral hygiene, is applied regularly to dental enamel,
preferably from about 1 to about 3 times daily at a pi of about 5 to about 7.5.
The following specific examples are further illustrative of the
nature of the present invention, but it is understood that the invention is not
limited thereto. All amounts and proportions referred to herein and the appended
claims are by weight unless outlawries indicated.
39
EXAMPLE 1
Mouth rinse
Mouth rinse solution:
Alcohol = 25%
Climbazole = 0.3%
Flavor (K-91-3863) = 0.22
*Pluronic F108 = 3.0
Glycerine = 25
Sodium Saccharin = 0.03%
Water to make 100%
*Trade mark for a block polymer of about 80% by weight of
polyoxyethylene and about 20% by weight ofpolyoxypropylene the
polyoxypropylene radical having a molecular weight of 3250,
obtained from BASS Wyandotte Company.
The Climbazole is mixed with Pluronic until homogeneous
and clear, prior to addition to the aqueous-alcoholic vehicle
containing glycerin, flavor and sodium saccharin.
The resultant product is effective in controlling
gingivitis and treating periodontitis, and provides a simple means
of improving oral hygiene, when used on a regular regime of 1 to 3
applications to the oral cavity per day.
The unexpected superior antigingival activity of -this
product is shown in Table 1, wherein the mouth rinse of Example 1
was used as the test solution. This product also possesses anti-
bacterial properties against Bacteroides assaccharolyticus and
B. gingivalis.
16
1227~39
EXAMPLE 2
Dental Paste
Ingredients Percent Go
H20 31.3 156.5
No - Bonniest 0.5 2.5
No - Saccharin 0.2 1.0
Polyethylene glycol 6001 25.0 125
Climbazole 1.0 5.0
Carboxymethyl cellulose 1.5 7.5
Swilled* - 2442 3.0 15.0
Zoo 35.0 175
Sodium laurel sulfate 1.5 7.5
Flavor 1.0 5.0
HASHISH) OH where n is an integer between 10-14, preferably 12.5 Tao
and having a mow weight of 570-630
colloidal silica
sodium aluminosilicate (silica with 1% combined alumina) by Huger Co.
* Trade Mark
The Climbazole is premixed with the polyethylene glycol prior to the
addition of the carboxymethyl cellulose, whereby a gel is formed. To this
gel is added, with agitation, the Swilled, Zoo, sodium laurel sulfate, flavor,
water, bonniest and saccharin. The bonniest and saccharin may be dissolved in
the water prior to mixing with the rest of the ingredients. Similarly, the Zoo,
flavor and sodium laurel sulfate may be premixed prior to addition to the gel.
This product also possesses similarly good antimicrobial and anti-
gingivitis properties.
~227~
Other conventional components may be substituted or
added, as disclosed herein before. For example, hydrated alumina
or water insoluble metaphosphate or dicalcium phosphate dehydrate
and other polishing agents may be substituted for the alkali metal
aluminosilicate (Zoo) or the colloidal silica (Swilled) in total or
in part. Similarly, other non ionic surfactants may be substituted
for the block polymer of propylene oxide and ethylene oxide
(Pluronic) such as the polyoxyethylene hexitan Monroe fatty
acid esters.
It is understood that the foregoing detailed description
is given merely by way of illustration and that variations may be
made therein without departing from the spirit of the invention.
The "Abstract" given above is merely for the convenience of
technical searchers and is not to be given any weight with respect
to the scope of the invention.
- 18 -
,"~,
