Note: Descriptions are shown in the official language in which they were submitted.
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ORAL COMPOSITIONS CONTAINING ZINC CITRATE SALTS
TECHNICAL FIELD
The present invention relates to a method of preventing or controlling colds
and similar maladies, such as flu, through the use of an oral composition
containing
an alkali metal or ammonium zinc citrate applied to the gingival or oral
mucosal
to tissue of the subject susceptible to colds.
BACKGROUND OF THE INVENTION
The common cold, although not usually a serious illness, is a highly
prevalent,
discomforting and annoying infliction. The term "common cold" is applied to
minor
respiratory illnesses caused by a variety of different respiratory viruses.
While
rhinoviruses are the major known cause of common colds, accounting for
approximately 30 percent of colds in adults, viruses in several other groups
are also
important. While immune responses occur, and infection with some respiratory
tract
viruses therefore could be prevented by a vaccine, development of a polytypic
vaccine to cover all possible agents is impractical. Thus, the problem of
controlling
2o acute upper respiratory disease presents complex challenges, and the long-
desired
discovery of a single cure for the common cold is an unrealistic expectation.
With rhinovirus infection, symptoms of nasal discharge, nasal congestion, and
sneezing usually commence on the first day of illness and progress to maximum
severity by the second or third day. The costs of treating colds with over-the-
counter medications in the United States is estimated at an annual cost of
over 1.5
billion dollars. The direct costs of treatment in outpatient clinics is
estimated at
almost four billion dollars. Indirect costs, based on the amount of loss in
wages
because of restricted activity are substantially higher.
At present, only symptomatic treatment is available for the common cold; the
3o majority of these drugs are taken orally. Exemplary prior art oral
compositions for
treatment of nasal and other cold, flu, allergy and sinus symptoms and the
discomfort, pain, fever and general malaise associated therewith generally
contain
an analgesic (aspirin or acetaminophen) and one or more antihistamines, decon-
gestants, cough suppressants, antitussives and expectorants. Other specific
pharmaceutical actives for nasal symptoms (e.g., congestion) generally contain
either oxymetazoline or phenylephrine. These actives are generally delivered
topically to the nasal mucosa via a nasal spray. For individuals with certain
medical
conditions such as heart disease, hypertension, diabetes or thyroid disorders,
oral
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drugs such as decongestants could pose a risk of unfavorable drug interactions
and
may cause an adverse reaction. It would, therefore, be highly desirable to
deliver
relief from specific nasal symptoms via compositions without the need for such
pharmaceutical actives.
It has been discovered that topical application of an alkali metal or ammonium
zinc citrate to the gingival or oral mucosal tissues of a subject susceptible
to colds
and/or flu helps to reduce the incidence of such maladies.
It is therefore an object of the present invention to provide topical oral
compositions which provide treatment to prevent colds and flu.
to SUMMARY OF THE INVENTION
The present invention relates to a method of reducing colds and cold-like
symptoms, such as flu, in subjects susceptible to such maladies by applying a
composition containing an effective amount of an alkali metal or ammonium zinc
citrate to the gingival or oral mucosal tissues.
DETAILED DESCRIPTION OF INVENTION
The compositions of the present invention contain certain essential
components as well as non-essential components.
Alkali Metal on Ammonium Zinc Citrate
The zinc salts found useful in the compositions used in the present method
are described in U.S. Patents 4,289,754, September 15, 1981, and 4,325,939,
April
20, 1982, both incorporated herein by reference in their entirety.
The preferred compound is sodium zinc citrate.
The amount of the zinc compounds used int he composition used in the
method described herein are from about 0.1 % to about 11 %, preferably from
about
0.1 % to about 5%.
Acceptable Carrier
The carrier for the active components) can be any vehicle suitable for use in
the oral cavity. Such carriers include the usual components of mouthwashes,
toothpastes, tooth powders, prophylaxis pastes, lozenges, gums and the like
and are
more fully described hereinafter. Dentifrices and mouthwashes are the
preferred
systems.
' In addition to the active agent(s), the present compositions may contain
antiplaque/gingivitis agent such as quaternary ammonium compounds, water
insoluble agents such as triclosan, teas, as defined herein later, and
stannous salts.
These types of agents are described in U.S. patent 4,894,220; January 16, 1990
to
Nabi et al, U.S. Patent 4,656,031, April 7, 1987 to Lane et al; and U.S.
Patent
5,004,597, April 2, 1991 to Majeti et al. All incorporated herein by reference
in
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3
their entirety.
The abrasive polishing material contemplated for use in the present invention
can be any material which does not excessively abrade dentin. These include,
for
example, silicas including gels and precipitates, calcium carbonate, dicalcium
orthophosphate dihydrate, calcium pyrophosphate, tricaIcium phosphate, calcium
polymetaphosphate, insoluble sodium polymetaphosphate, hydrated alumina, and
resinous abrasive materials such as particulate condensation products of urea
and
formaldehyde, and other such as disclosed by Cooley et al. in U.S. Patent
3,070,510,
December 25, 1962, incorporated herein by reference. Mixtures of abrasives may
1 o also be used.
Silica dental abrasives, of various types, can provide the unique benefits of
exceptional dental cleaning and polishing performance without unduly abrading
tooth enamel or dentin. Silica abrasive materials are also exceptionally
compatible
with sources of soluble fluoride and polyphosphonates. For these reasons they
are
preferred for use herein.
The silica abrasive polishing materials useful herein, as well as the other
abrasives, generally have an average particle size ranging between about 0.1
to 30
microns, preferably 5 and 15 microns. The silica abrasive can be precipitated
silica
or silica gels such as the silica xerogels described in Pader et al., U.S.
Patent No.
3,538,230, issued March 2, 1970 and DiGiulio, U.S. Patent No. 3,862,307, June
21,
1975, both incorporated herein by reference. Preferred are the silica xerogels
marketed under the tradename "Syloid" by the W. R. Grace & Company, Davison
Chemical Division. Preferred precipitated silica materials include those
marketed
by the J. M. Huber Corporation under the tradename, "Zeodent", particularly
the
silica carrying the designation "Zeodent 119". These silica abrasives are
described
in U.S. Patent No. 4,340,583, July 29, 1982, incorporated herein by reference.
The abrasive in the compositions described herein is present at a level of
from
about 6% to about 70%, preferably from about 1 S% to about 25% when the
dentifrice is a toothpaste. Higher levels, as high as 90%, may be used if the
3o composition is a toothpowder.
The compositions of the present invention may also contain a soluble fluoride
ion source such as sodium, potassium or lithium fluorides, stannous fluoride,
and
sodium monofluorophosphate among many others. The fluoride source should be
suffcient to provide from about 50 to about 3500 ppm fluoride.
Flavoring agents can also be added to dentifrice compositions. Suitable
flavoring agents include, among many others, oil of wintergreen, oil of
peppermint,
oil of spearmint, and oil of clove. Sweetening agents which can be used
include
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4
aspartame, acesulfame, saccharin, dextrose, levulose and sodium cyclamate.
Flavoring and sweetening agents are generally used in dentifrices at levels of
from
about 0.005% to about 2% by weight.
Dentifrice compositions can also contain emulsifying agents. Suitable
emulsifying agents are those which are reasonably stable and foam throughout a
wide pH range, including nonsoap anionic, nonionic, cationic, zwitterionic and
amphoteric organic synthetic detergents. Many of these suitable surfactants
are
disclosed by Gieske et al. in U.S. Patent No. 4,051,234, September 27, 1977,
incorporated herein in its entirety by reference.
to Water is also present in the toothpastes of this invention. Water employed
in
the preparation of commercially suitable toothpastes should preferably be
deionized
and free of organic impurities. Water generally comprises from about I O% to
50%,
preferably from about 20% to 40%, by weight of the toothpaste compositions
herein.
These amounts of water include the free water which is added plus that which
is
~ 5 introduced with other materials such as with sorbitol.
In preparing toothpastes, it is necessary to add some thickening material tb
provide a desirable consistency. Preferred thickening agents are carboxyvinyl
polymers of the type mentioned previously herein, xanthan gum, carrageenan,
hydroxyethyl cellulose and water soluble salts of cellulose ethers such as
sodium
2o carboxymethyl cellulose and sodium carboxymethyl hydroxyethyl cellulose.
Natural gums such as gum karaya, gum arabic, and gum tragacanth can also be
used.
Colloidal magnesium aluminum silicate or finely divided silica can be used as
part
of the thickening agent to further improve texture. Thickening agents in an
amount
from 0.5% to 5.0% by weight of the total composition can be used.
25 It is also desirable to include some humectant material in a toothpaste to
keep
it from hardening. Suitable humectants include glycerin, sorbitol, xylitol,
and other
edible polyhydric alcohols at a level of from about 5% to about 70%.
Another preferred embodiment of the present invention is a mouthwash
composition. Conventional mouthwash composition components can comprise the
3o carrier for the active agents of the present invention. Mouthwashes
generally
comprise from about 20:1 to about 2:1 of a water/ethyl alcohol solution and
preferably other ingredients such as flavor, sweeteners, humectants and
sudsing
agents such as those mentioned above for dentifrices. The humectants, such as
glycerin and sorbitol give a moist feel to the mouth. Generally, on a weight
basis
35 the mouthwashes of the invention comprise 0% to 60% (preferably 10% to 25%)
ethyl alcohol, 0% to 20% (preferably 5% to 20%) of a humectant, 0% to 2%
(preferably 0.01% to 0.15%) emulsifying agent, 0% to 0.5% (preferably 0.005%
to
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0.06%) sweetening agent such as saccharin, 0% to 0.3% (preferably 0.03% to
0.3%)
flavoring agent, and the balance water.
Suitable lozenge and chewing gum components are disclosed in U.S. Patent
No. 4,083,955, April 11, 1978 to Grabenstetter et al., incorporated herein by
5 reference.
Other optional components useful in the present invention are pyrophosphate
salts such as those described in U.S. 4,515,772, May 7, 1985 to Parran et al.
incorporated herein by reference. Also useful are nonionic antimicrobials such
as
triclosan described in U.S. 4,894,220, January 16, 1990 to Nabi et al. Both
patents
1 o are incorporated herein by reference.
Another agent which can be used in the present compositions is an alkali
metal bicarbonate, such as sodium bicarbonate. These are stable items of
commerce
and can be used together with a peroxide compound in separate compartments
such
as disclosed in U.S. 4,849,213 and U.S. 4,528,180, both to Schaeffer,
incorporated
herein by reference in its entirety.
Other preferred compositions of the subject invention are controlled-release
drug delivery systems for placement in the periodontal pocket. Such systems
include, but are not limited to, the cellulose hollow fibers disclosed in U.S.
Pat. No.
4,175,326, issued to Goodson on Nov. 27, 1979; the ethylcellulose f lms
disclosed
in U.S. Pat. No. 4,568,535 issued to Loesche on Feb. 4, 1986; the absorbable
putty-
like material disclosed in U.S. Pat. No. 4,568,536 issued to Kronenthal,
Maftei and
Levy on Feb. 4, 1986; the biodegradable microspheres and matrix disclosed in
U.S.
Pat. No. 4,685,883 issued to Jernberg on Aug. 11, 1987; the microparticle or
rriicrocapsule suspensions disclosed in U.S. Pat. No. 4,780,320 issued to
Baker on
Oct. 25, 1988; the polymeric devices disclosed in European Patent Applicatin
No.
0;140,766 of Goodson, published May 8, 1985; and the lactidelglycolide
executions
described in U.S. Patent No. 5,198,220, March 30, 1993 to Damani; these
patents
are incorporated herein by reference. Such controlled-release delivery systems
generally include a solid matrix, usually of polymeric material, loaded with
one or
more active agents, the matrix entrapping stannous gluconate. Typically, the
active
agents diffuse from the solid material into the periodontal pocket over time.
Preferred controlled-release drug delivery systems comprise from about
0.001 % to about 50%, more preferably from about 0.01 % to about 25%, more
preferably still from about 0.1 % to about 1 S%, still more preferably from
about 1
to about 10%, of stannous gluconate and a controlled-release carrier.
The pH of the present compositions and/or its pH in the mouth can be any pH
which is safe for the mouth's hard and soft tissues. Such pH's are generally
from
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about 3 to about 10, preferably from about 5 to about 9.
METHOD OF MANUFACTURE
The carrier compositions used in the present invention can be made using
methods which are common in the oral products area.
For example, toothpaste compositions may be prepared by mixing part of the
humectant and water together and heating to 66°-71 °C. The
fluoride source, if
present, is then added along with the sweetener, the opacifier and the flavor.
COMPOSITIONS OF USE
The present invention in its method aspect involves applying to the gingival
and/or oral mucosal tissue safe and effective amounts of the compositions.
Generally an amount of at least about 5 grams of a mouthwash and at least
about 0.5
grams of a toothpaste or liquid dentifrice.
A preferred method of the subject invention involves the contact of a
composition of the subject invention with oral cavity soft tissue for at least
about 15
seconds, preferably from about 20 seconds to about 10 minutes, more preferably
from about 30 seconds to about 60 seconds. The method often involves
expectoration of most of the composition following such contact, preferably
followed by rinsing, e.g., with water. The frequency of such contact is
preferably
from about once per week to about five times per day, more preferably from
about
2o thrice per week to about four times per day, more preferably still from
about once
per day to about thrice per day. The period of such treatment typically ranges
from
about one day to a lifetime. Generally, people may recognize that they will be
exposed to a cold's virus and they then can use the products described herein
either
prior to the exposure, following exposure, or at the first signs of a cold.
The compositions used in the present method may also be used by the subject
as a gargle. Additionally, subjects taking large doses of Vitamin C may obtain
an
enhanced colds benefit through the use of compositions described herein.
The following examples further describe and demonstrate preferred
embodiments within the scope of the present invention. The examples are given
3o solely for illustration and are not to be construed as limitations of this
invention as
many variations thereof are possible without departing from the spirit and
scope
thereof.
EXAMPLE I
Toothpastes
Wei hg t % Weight
Water 13.017 12.500
Sorbitol 45.425 44.552
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Glycerin 10.198 10.198
Titanium Dioxide 0.525 0.525
Silica 20.000 20.000
Na Carboxymethyl Cellulose 1.050 1.050
Magnesium Aluminum Silicate 0.408 0.408
Na Alkyl Sulfate (27.9% Solution) 4.000 4.000
Na Zn Citrate
Na Saccharin 0.200 0.200
Flavor 0.851 0.851
I FD&C Blue # 1 ( 1 % Solution) 0.051 0.051
o
Na Monofluoro Phosphate 0.243 -
Na Hydroxide (SO% Solution) 0.500 0.395
pH 4.5 4.5
EXAMPLE II
Mouthrinses
Wei hg_t Weieht
%
Na Zn Citrate
Glycerin 8.000 12.000
Sorbitol (70% Aqueous Solution) _ _
2o Ethanol 10.000 10.000
Polysorbate 80 0.300 0.300
Sodium Saccharin 0.050 0.050
Flavor 0.1 SO 0.150
Sodium Hydroxide 0.020 0.020
Benzoic Acid 0.050 O.OSO
FD&C Blue # 1 ( 1 % Solution) 0.020 0.020
Sodium Monofluoro Phosphate 0.183 -
Water 80.187 77.850
EXAMPLE III
Topical Gels
Weight % Wei htg-%
Na Zn Citrate
Glycerin 91.896 70.000
Sorbitol (70% Solution) - 21.765
3s Sodium Carboxymethyl Cellulose 0.600 0.800
Hydroxyethyl Cellulose _ _
Flavor 1.000 1.000
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Sodium Saccharin 0.200 0.200
Sodium Alkyl Sulfate (27.9%) 2.000 2.000
Sodium Monofluoro Phosphate 0.760 -
EXAMPLE IV
Mouthrinse Tablets
Na Zn Citrate
Flavor 0.1508 0.1508
Sodium Saccharin O.OSOg 0.2008
Mannitol 0.7738 -
to Sodium Carboxymethyl Cellulose 0.0508 -
Sodium Benzoate 0.0308 0.0258
Citric Acid - 0.2008
Sodium Carbonate - O.100g
Sodium Bicarbonate - 0.2008
t 5 Glycine - 0.0508
Sodium Monofluoro Phosphate 0.183
2.2558 2.1448
Dissolve Dissolve
in 97.7458 in 97.8568
2o water water
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