Note: Descriptions are shown in the official language in which they were submitted.
1339410
ANTICALCULUS ORAL COMPOSITION
This invention relates to oral compositions containing
an anticalculus agent and is a divisional application of applica-
tion No. 518,040, filed on September 12th, 1986.
Calculus is a hard, mineralized formation which forms
on the teeth. Regular brushing aids in preventing a rapid
buildup of these deposits, but even regular brushing is not
sufficient to remove all of the calculus deposits which adhere
to the teeth. Calculus is formed on the teeth when crystals of
calcium phosphates begin to be deposited in the pellicle and
extracellular matrix of the dentalplaque and become sufficiently
closely packed together for the aggregates to become resistant to
deformation. There is no complete agreement on the route by
which calcium and orthophosphate ultimately become the crystalline
material called hydroxyapatite (HAP). It is generally agreed,
however, that at higher saturations, that is, above the critical
saturation limit, the precursor to crystalline HAP is an
amorphous or microcrystalline calcium phosphate. "Amorphous
calcium phosphate" although related to hydroxyapatite differs from
it in atomic structure, particle morphology, and stoichiometry.
The X-ray diffraction pattern of amorphous calcium phosphate
shows broad peaks typical of amorphous materials, which lack the
long-range atomic order characteristic of all crystalline
materials, including HAP. It is apparent therefore that agents
which effectively interfere with crystalline growth of HAP will
be effective as anticalculus agents. A suggested mechanism by
which the anticalculus agents of this invention inhibit calculus
- 1339410
formation probably involves an increase of the activation energy
barrier thus inhibiting the transformation of precursor amorphous
calcium phosphate to HAP.
Studies have shown that there is a good correlation
between the ability of a compound to prevent HAP crystalline
growth ln vitro and its ability to prevent calcification in vivo,
provided of course that such compound is stable in and inert to
saliva and its components.
It is well known in the art that water soluble
hexametaphosphates, tripolyphosphates and pyrophosphates and the
like are effective calcium and magnesium ion suppressors,
inhibitors, sequestrants and/or chelating agents, and are
effective inhibitors of HAP formation in vitro. U. S. Patent No.
4,515,772 issued May 7, 1985 to Parran et al discloses and claims
oral anticalculus compositions containing a fluoride ion source
and soluble dialkali metal pyrophosphates alone or admixed with
tetraalkali metal pyrophosphates. Although this patent fails to
disclose experimental evidence of effective and acceptable anti-
calculus results in vivo, it refers to prior art indicating that
"pyrophosphate would be inhibited by pyrophosphatase in vivo",
i.e. by this enzyme in saliva. The voluminous number of
acknowledged prior art and "References Cited" in this patent
indicate the many uses and functions of these polyphosphates
hitherto proposed in oral compositions.
However, as in part admitted in the aforesaid patent
disclosure and as shown hereinafter, these linear molecularly
dehydrated polyphosphates (i.e. hexametaphosphates, tripoly-
1339~10
phosphates, pyrophosphates, etc.) in common, when introduced intothe oral cavity and/or saliva are significantly hydrolyzed by
salivary enzymes (phosphatases) to orthophosphates which are
ineffective as inhibitors of HAP formation.
It is an aim of this invention to provide an improved
anticalculus oral composition which will not be subject to one
or more of the above problems and disadvantages.
The invention also seeks to provide an oral composition
which inhibits the transformation of amorphous calcium phosphate
to HAP crystal structure normally associated with calculus.
This invention also seeks the provision of an improved
method for inhibiting the formation of calculus.
Advantages of the invention will appear as the
description proceeds.
In accordance with certain of its aspects, the invention
of the parent application relates to an oral composition contain-
ing in an orally acceptable vehicle an effective anticalculus
amount of one or a mixture of water soluble linear molecularly
dehydrated polyphosphate salts as essential anticalculus agent,
and as combination inhibitor against enzymatic hydrolysis of said
salt or salts in saliva, an amount of a fluoride ion source
sufficient to supply about 25-2,000 ppm of fluoride ions and
about 0.05-3% of a water soluble alkali metal or ammonium
synthetic anionic linear polymeric polycarboxylate having a
molecular weight of about 1,000 to about 1,000,000, preferably
about 30,000 - 500,000.
-- 3
1339410
The present invention provides an oral composition
containing in an orally acceptable vehicle, approximately by
weight, one or a mixture of water soluble alkali metal or ammonium
tripolyphosphate salts as anticalculus agent or agents and, as
inhibitor against enzymatic hydrolysis of said agents in saliva,
an amount of a fluoride ion source sufficient to supply 25 ppm to
2,000 ppm of fluoride ion, the composition having a pH of about
4.5 to about 9.
Compounds providing a source of fluoride ion have been
profusely disclosed in the prior art as anti-caries agents.
Synthetic anionic linear polymeric polycarboxylates and their
complexes with various cationic germicides, zinc and magnesium
have been previously disclosed as anticalculus agents per se in,
for example United States Patent No. 3,429,963 to Shedlovsky and
instant assignee, United States Patent No. 4,152,420 to Gaffar and
instant assignee, United States Patent No. 3,956,480 to Dichter
et al and
- 3a -
r r -
A
1339410
instant assignee, U. S. Patent No. 4,138,477 to Gaffar andinstant assignee, and U. S. Patent No. 4,183,914 to Gaffar
et al. None of these patents however nor any other known
prior art, discloses use of such polycarboxylates alone for
inhibiting salivary hydrolysis of said linear polyphosphates,
much less in combination with a compound providing a source
of fluoride ion. It is to be understood that the synthetic
anionic linear polymeric polycarboxylates disclosed in these
patents are operative in the compositions and methods of this
invention.
The linear molecularly dehydrated polyphosphate
salts operative herein as anticalculus agents are well known,
being generally employed in the form of their wholly or
partially neutralized water soluble alkali metal (e. g.
potassium and preferably sodium) or ammonium salts, and any
mixtures thereof. Representative examples include sodium
hexametaphosphate, sodium tripolyphosphate, disodium diacid,
trisodium monoacid and tetrasodium pyrophosphates and the like.
Linear polyphosphates correspond to (NaPO3)n where n is about
2 to about 125. They are generally employed in the instant
oral compositions in approximate weight amounts of 0.1 to 7%,
preferably 0.1 to 6%, more preferably 2 to 6%. When n is at
least 3 in (NaPO3)n, said polyphosphates are glassy in
character.
The synthetic anionic linear polymeric polycarboxyl-
ates operative herein are likewise well known, preferably
being employed in the form of their partially or preferably
fully neutralized water soluble alkali metal (e. g. potassium
1339~10
and preferably sodium) or ammonium salts. Preferred are 1:4
to 4:1 copolymers of maleic anhydride or acid with another
polymerizable ethylenically unsaturated monomer, preferably
methyl vinyl ether (methoxyethylene) having a molecular weight
(M. W.) of about
-4a-
X
1339~10
30,000 to about 1,000,000. These copolymers are available for
example as Gantrez AN 139 ~M.W. 500,000), A.N. 119 (I~.W.
250,000) and preferably S-97 Pharmaceutical Grade (M.W.
70,000), of GAF Corporation. The terms "synthetic" and
~linear" are intended to exclude known thickening or gelling
agents comprising carboxymethylcellulose and other derivatives
of cellulose and natural gums, as well as the Carbopols, of
reduced solubility due to cross-linkages.
Other operative polymeric polycarboxylates include those
disclosed in U.S. Patent No. 3,956,180 referred to above, such
as the 1:1 copolymers of maleic anhydride with ethyl acrylate,
hydroxyethyl methacrylate, N-vinyl-2-pyrollidone, or ethylene,
the latter being available for example as Monsanto EMA No.
1103, M.W. 10,000, and EMA Grade 61, an 1:1 copolymers of
- acrylic acid with methyl or hydroxyethyl methacrylate, methyl
or ethyl acrylate, isobutyl vinyl ether or N-vinyl-2-
pyrrolidone.
Additional operative polymeric polycarboxylates disclosed
in above referred to U.S. Patent No. 4,138,477 and 4,183,914,
include copolymers of maleic anhydride with styrene,
isobytylene or ethyl vinyl ether, polyacrylic, polyitaconic and
polymaleic acids, and sulfoacrylic oligomers of M.W. as low as
1,000, available as Uniroyal ND-2.
Suitable generally are polymerized olefinically or
ethylenically unsaturated carboxylic acids containing an
activated carbon-to-carbon olefinic double bond and at least
one carboxyl group, that is, an acid containing an olefinic
double bond which readily functions in polymerization because
*Trade-mark
1339410
of its presence in the monomer molecule either in the alpha-
beta position with respect to a carboxyl group or as part of a
terminal methylene grouping. Illustrative of such acids are
acrylic, methacrylic, ethacrylic, alpha-chloroacrylic,
crotonic, beta-acryloxy, propionic, sorbic, alpha-chlorsorbic,
cinnamic, beta-styrilacrylic, muconic, itaconic, citraconic,
mesaconic, glutaconic, aconitic, alpha-phenylacrylic, 2-benzyl
acrylic, 2-cyclohexylacrylic, angelic, umbellic, fumaric,
maleic, acids and anhydrides. Other different olefinic
monomers copolymeri~able with such carboxylic monomers include
vinylacetate, vinyl chloride, dimethyl maleate and the like.
Copolymers contain sufficient carboxylic salt groups for water-
solubility.
The synthetic anionic linear polymeric polycarboxylate
component is mainly a hydrocarbon with optional halogen and O-
containing substituents and linkage as present in for example
ester, ether and OH groups, and is generally employed in the
instant compositions in approximate weight amounts of 0.05 to
3%, preferably 0.05 to 2%, more preferably 0.1 to 2%. Amounts
in the upper portions of these ranges are typically employed in
dentifrice compositions, meaning oral compositions generally
containing a dental abrasive and used in conjunction with
brushing of the teeth, e.g., tooth pastes, gels, creams, and
powders. Amounts in excess of these ranges may be employed for
thickening or gelling purposes.
The source of fluoride ions, or fluorine-providing
compounds, required according to this invention as an essential
component of the described inhibitor combination, are well
known in the art as anti-caries agents and also act as such
agents in the practice of this invention. These compounds may
be slightly soluble in water or may be fully water-soluble.
1339~10
They are characterized by their ability to release fluoride
ions in water and by freedom from undesired reaction with other
compounds of the oral preparation. Among these materials are
inorganic fluoride salts, such as soluble alkali metal,
alkaline earth metal salts, for example, sodium fluoride,
potassium fluoride, ammonium fluoride, calcium fluoride, a
- - copper fluoride such as cuprous fluoride, zinc fluoride, barium
fluoride, sodium fluorosilicate, ammonium fluorosilicate,
sodium fluorozirconate, sodium monofluoro-phosphate, aluminum
mono- and di-fluorophosphate, and fluorinated sodium calcium
pyrophosphate. Alkali metal and tin fluorides, such as sodium
and stannous fluorides, sodium monofluorophosphate (MFP) and
mixtures thereof, are preferred.
The amount of fluorine-providing compound is dependent to
some extent upon the type of compound, its solubility, and the
type of oral preparation, but it must be a nontoxic amount,
generally about 0.005 to about 3.0% in the preparation. In a
-- dentifrice preparation, e.g., gel, cream, toothpaste or
toothpowder, an amount of such compound which releases up to
about 2,000 ppm of F ion by weight of the preparation is
considered satisfactory. Any suitable minimum amount of such
compound may be used, but it is preferable to employ sufficient
compound to release about 300 to about 2,000 ppm more
preferably about 800 to about 1,500 ppm of fluoride ion.
Typically, in the cases of alkali metal fluorides and stannous
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 of about 0.1-3%, more typically about 0.76%.
In oral preparations such as mouthwashes, lozenges and
133941~
chewing gum, the fluorine-providing compound is typically
present in an amount sufficient to release up to about 500 ppm,
preferably about 25 to about 300 ppm by weight of fluoride ion.
Generally about 0.005 to about 1.0 wt.% of such compound is
present.
In certain highly preferred forms of the invention the
oral composition may be substantially liquid in cllaracter, such
as a mouthwash or rinse. In such a preparation the vehicle is
typically a water-alcohol mixture desirably including a
humectant as described below. Generally, the weight ratio of
water to alcohol is in the range of from about 1:1 to about
20:1, preferably about 3:1 to 10:1 and more preferably about
4:1 to about 6:1. The total amount of water-alcohol mixture in
this type of preparation is typically in the range of from
about 70% to about 99.9% by weight of the preparation.
The pH of such liquid and other preparations of the
invention is generally in the range of from about 4.5 to about
9 and typically from about 5.5 to 8. The pH is preferably in
the range of from about 6 to about 8Ø It is noteworthy that
the compositions of the invention may be applied orally at a pH
below 5 without substantially decalcifying or otherwise
damaging dental enamel. The pH can be controlled with acid
te.g. citric acid or benzoic acid) or base (e.g. sodium
hydroxide) or buffered tas with sodium citrate, benzoate,
carbonate, or bicarbonate, disodium hydrogen phosphate, sodium
dihydrogen phosphate, ect.).
In certain other desirable forms of this invention, the
oral compositions may be substantially solid or pasty in
character, such as toothpowder, a dental tablet, a toothpaste,
gel or dental cream. The vehicle of such solid or pasty oral
preparations generally contains polishinq material. Examples
1339410
of polishing materials are water-insoluble sodium
metaphosphate, potassium metaphosphate, tricalcium phosphate,
dihydrated calcium phosphate, anhydrous dicalcium phosphate,
calcium pyrophosphate, magnesium orthophosphate, trimagnesium
phosphate, calcium carbonate, aluminum silicate, zirconium
silicate, silica, bentonite, and mixtures thereof. Other
suitable polishing materials include the particulate
thermosetting resins described in U.S. Patent No. 3,070,510 of
December 15, 1962 such as melamine-, phenolic-, and urea-
formaldehydes, and cross-linked polyepoxides and polyesters.
PreEerred polishing materials include crystalline silica having
particle sizes of up to about 5 microns, a mean particle size
of up to about 1.1 microns, and a surface area of up to about
50,000 cm. /gm., silica gel or colloidal silica, and complex
amorphous alkali metal aluminosilicate.
~ ~hen visually clear gels are employed, a polishing agent
of colloidal silica, such as those sold under the trademark
SYLOID as Syloid 72 and Syloid 74 or under the trademark
SANTOCEL as Santocel 100 and alkali metal alumino-silicate
complexes are particularly useful, since they have refractive
indices close to the refractive indices of gelling agent-liquid
~including water and/or humectant) systems commonly used in
dentifrices.
Many of the so-called "water-insoluble" polishing
materials are anionic in character and also include small
amounts oE soluble material. Thus, insoluble sodium
metaphosphate may be formed in any suitable manner as
illustrated
1339410
by Thorpe's Dictionary of Applied Chemistry, Volume 9, 4th
Edition, pp. 510-511. The forms of insoluble sodium meta-
phosphate known as Madrell's salt and Kurrol's salt are
further examples of suitable materials. These metaphosphate
salts exhibit only a minute solubility in water, and therefore
are commonly referred to as insoluble metaphosphates (IMP).
There is present therein a minor amount of soluble phosphate
material as impurities, usually a few percent such as up to
4% by weight. The amount of soluble phosphate material, which
is believed to include a soluble sodium trimetaphosphate in
the case of insoluble metaphosphate/ may be reduced or
eliminated by washing with water if desired. The insoluble
alkali metal metaphosphate is typically employed in powder
form of a particle size such that no more than about 1% of the
material is larger than about 37 microns.
The polishing material is generally present in the
solid or pasty compositions in weight concentrations of about
10% to about 99%. Preferably, it is present in amounts rang-
ing from about 10% to about 75% in toothpaste, and from about
70% to about 99% in toothpowder.
In a toothpaste, the liquid vehicle may comprise
water and humectant typically in an amount ranging from about
10% to about 90% by weight of the preparation. Glycerine,
propylene glycol, sorbitol, polypropylene glycol and/or poly-
ethylene glycol (e. g. 400-600) exemplify suitable humectants/-
carriers. Also advantageous are liquid mixtures of water,
glycerine and sorbitol. In clear gels where the refractive
--10--
1339410
index is an important consideration, about 3-30 wt.% of water,
0 to about 80 wt.% of glycerine, and about 20-80 wt.% of
sorbitol is preferably employed.
Toothpastes, creams and gels typically contain a
natural or synthetic thickener or gelling agent in proportions
of about 0.1 to about 10, preferably about 0.5 to about 5 wt.%.
A suitable thickener is synthetic hectorite, a synthetic
colloidal magnesium alkali metal silicate complex clay avail-
able for example as Laponite (e. g. CP, SP 2002, D) marketed
by Laporte Industries Limited. Laponite D analysis shows,
approximately by weight, 58.00% SiO2, 25.40% MgO, 3.05% Na2O,
0.98% Li2O, and some water and trace metals. Its true specific
gravity is 2.53 and it has an apparent bulk density (g./ml. at
8% moisture) of 1Ø
Other suitable thickeners include Irish moss, gum
tragacanth, starch, polyvinylpyrrolidone, hydroxyethylpropyl-
cellulose, hydroxybutyl methyl cellulose, hydroxypropyl methyl
cellulose, hydroxyethyl cellulose (e. g. available as
Natrosol ), sodium carboxymethyl cellulose, and colloidal
silica such as finely ground Syloid (e. g. 244).
It will be understood that, as is conventional, the
oral preparations are to be sold or otherwise distributed in
suitable labelled packages. Thus a jar of mouthrinse will have
a label describing it, in substance, as a mouthrinse or mouth-
wash and having directions for its use' and a toothpaste,
cream or gel will usually be in a collapsible tube, typically
Trade-mark
--11--
X~..
1339110
aluminum, lined lead or plastic, or other squeeze, pump or
pressurized dispenser for metering out the contents, having a
label describing it, in substance, as a toothpaste, gel or
dental cream.
Organic surface-active agents are used in the
compositions of the present invention to achieve increased
prophylactic action, assist in achieving thorough and complete
dispersion of the anticalculus agent throughout the oral cavity,
and render the instant compositions more cosmetically accept-
able. The organic surface-active material is preferably
anionic, nonionic or ampholytic in nature, and it is preferred
to employ as the surface-active agent a detersive material
which imparts to the composition detersive and foaming
properties. Suitable examples of anionic surfactants are
water-soluble salts of higher fatty acid monoglyceride mono-
sulfates, such as the sodium salt of the monosulfated mono-
glyceride of hydrogenated coconut oil fatty acids, higher alkyl
sulfates such as sodium lauryl sulfate, alkyl aryl sulfonates
such as sodium dodecyl benzene sulfonate, higher alkyl sulfo-
acetates, higher fatty acid esters of 1,2-dihydroxy propane
sulfonate, and the substantially saturated higher aliphatic
acyl amides of lower aliphatic amino carboxylic acid compounds,
such as those having 12 to 16 carbons in the fatty acid, alkyl
or acyl radicals, and the like. Examples of the last-mentioned
amides are N-lauroyl sarcosine, and the sodium, potassium, and
ethanolamine salts of N-lauroyl, N-myristoyl, or N-palmitoyl
sarcosine which should be substantially free from soap or
similar higher fatty acid material. The use of these
X ~!
1339410
sarcosinate compounds in the oral compositions of the present
invention is particularly advantageous since these materials
exhibit a prolonged and marked effect in the inhibition of
acid formation in the oral cavity due to carbohydrate break-
down in addition to exerting some reduction in the solubility
of tooth enamel in acid solutions.
-12a-
1339410
Examples of water-soluble nonionic surfactants are condensation
products of ethylene oxide with various reactive hydrogen-
containing compounds reactive therewith having long hydrophobic
chains (e.g. aliphatic chains of about 12 to 20 carbon atoms),
which condensation products ("ethoxamers") contain hydrophillic
polyoxyethylenemoieties, such as condensation products of poly
(ethylene oxide) with fatty acids, fatty alcohols, fatty
amides, polyhydric alcohols (e.g. sorbitan monostearate) and
polypropylenoxide (e.g. Pluronic* materials).
Various other materials may be incorporated in the oral
preparations o~ this invention such as whitening agents,
preservatives, silicones, chlorophyll compounds, other
anticalculus agents, and/or ammoniated material such as urea
diammonium phosphate, and mixtures thereof. These adjuvants,
where present, are incorporated in the preparations in amounts
which do not substantially adversely affect the properties and
charactecistics desired.
- Any suitable flavouring or sweetening material may also be
employed. Examples of suitable flavouring constituents are
flavouring oils, e.g. oil of spearmint, peppermint, winter-
green, sassafras, clove, sage, eucalyptus, marjoram, cinnamon,
lemon, and orange, and methyl salicylate. Suitable sweetening
agents include sucrose, lactose, maltose, sorbitol, xylitol,
sodium cyclamate, perillartine, APM (aspartyl phenyl alanine,
methyl ester), saccharine and the like. Suitably, flavor and
sweetening agents may together comprise from about 0.1~ to 5%
more of the preparation.
In the preferred practice of this invention an oral
composition according to this invention such as a mouthwash or
dentifrice containing the described polyphosphate and inhibitor
*Trade-mark
13
1339~10
comb nation in an amount effective to inhibit calculus on
dental surfaces is preferably applied regularly to dental
- - - enamel, such as every second or third day or preferably from l
to 3 times daily, at a pH of about 4.5 to about 9, generally
about 5.5. to about 8, preferably about 6 to 8, for at least 2
weeks up to 8 weeks or more up to lifetime.
The compositions of this invention can be incorporated in
lozenges, or in chewing gum or other products, e.g. by stirring
into a warm gum base or coating the outer surface of a gum
base, illustrative of which may be mentioned jelutone, rubber
latex, vinylite resins, etc., desirably with conventional
plasticizers or softeners, sugar or other sweeteners or
carbohydrates such as glucose, sorbitol and the like.
~ The following 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 in the appended claims are by weight and
temperatures are in degrees C unless otherwise indicated.
EXAt1PLE A
Effect of Salivary Enzymes on Inhibition of HAP Formation by
HMP~ and TSPP~
~ he in vitro formation of HAP is measured titrimetrically
via a pH stat procedure. Stock solutions of 0.lM Cacl2 and
0.1~1 NaH2PO4 are prepared fresh in carbonate-free deionized
distilled water. To 23 ml CO2-free deionized distilled water
l.0 ml. of the stock phosphate solution and l.0 ml. of an
aqueous solution of lxl0 4M of the anticalculus agent being
tested are added followed by l.0 ml. of the stock calcium
chloride solution which initiates the reaction. The reaction
is conducted at pH 7.4 under a nitrogen atmosphere.
Consumption of 0.lN NaO13 is recorded automatically from which
1339410
the time required for crystal formation is determined. Table A
shows the results of this procedure.
Table A
Time of Crystal Growth Inhibition (Hrs.)
Anticalculus
Agent Water Saliva PyrophosPhatase Alk. Phosphatase
HMP* -12 3 1.0 2.0
TSPP*~ 0.8 0.4 0.3 0.0
*Sodium hexametaphosphate
**Tetrasodium pyrophosphate
Table A shows that in water both agents signficantly delay
HAP formation. However, the effectiveness of these agents is
drastically reduced when incubated with saliva as evidenced by
the shorter delay time. This reduction in efficacy is due to
the enzymatic hydrolysis of P-O-P bonds. Incubation of these
agents with pyrophosphatase and alkaline phosphatase
drastically reduces the delay period and indicates the
susceptibility of the P-O-P bond to hydrolysis by phosphatases.
, . .
. ,~
1339410
Example 1
Stabilization of TSPP, STPP* and HMP to Enzymatic
Hydrolysis in Presence of Inhibitors
Enzymatic hydrolysis is conducted in 100 millimolar
morpholinopropane sulfonic acid - NaOH buffer solution (pH 7.0)
containing 1.3 mg./ml. of the respective polyphosphate.
Inhibitors of this invention are added (except to the control)
to a final concentration of 1,000 ppm fluoride ion (from NaF)
and 0.5% of the sodium salt of hydrolyzed methoxyethylene-
maleic anhydride (1:1) copolymer, M. W. 70,000 (Gantrez S-97
Pharmaceutical Grade). Equal activities of acid, alkaline and
inorganic pyrophosphatase are then added to yield a total
phosphatase activity of 0.3 units/ml. Samples of each test
solution are taken and total orthophosphate available in each
sample measured after 3 hours hydrolysis in 4N HCl at 100~C.
The reaction mixtures are incubated at 37~C. with shaking and
aliquots taken at appropriate times through at least 90
minutes for orthophosphate determination. Table 1 shows the
results expressed as percent orthophosphate released due to
hydrolysis of the polyphosphate.
Table 1
Percent Orthophosphate Percent Relative
Released in 90 min. Protection
Anticalculus Aqent Control With Inhibitors
TSPP 98 58 41
STPP* 100 62 39
HMP 95 40
*Sodium tripolyphosphate
-16-
X~
1339~10
Table I shows that after 90 min. incubation in the
presence of enzyme greater than 95~ of the available
orthophosphate is released from the polyphosphates in the
absence of the inhibitors. With inhibitors, hydrolysis of P-O-
P bonds in pyrophosphate, tripolyphosphate, and
hexametaphosphate is reduced by 41~, 39% and 57%, respectively.
It should be noted that the enzyme activities used in this
study are at least 2-3 fold greater than those normally found
in saliva. These data indicate that the combination of
10 inhibitors of this invention si~nificantly reduces enzymatic
hydrolysis of the linear polyphosphates.
EXAMPLE 2
Dentifrice ComPOSitiOn
Table 2
A. Inqredient Parts
Deionized water 37.578
Glycerine 25.000
Zeo* 49B (Silicon Dioxide) 21.500
HMP (Hexaphos) 6.000
Syloid 244 (synthetic silica) 3.000
Sodium Lauryl Sulfate 1.200
Flavor 1.000
Gantrez (S-97(Pharmaceutical Grade) 1.000
Sodium Hydroxide (50% Solution) 1.000
Xanthan Gum 1.000
Sodium Benzote 0.500
Titanium Dioxide 0.500
Sodium Saccharin 0.300
Sodium Fluoride 0.242
B. Formulation of A above but containing TSPP instead of HMP.
C. Formulation of A above but containing 5 parts of STPP
instead of 6 parts of HMP.
*Trade-mark
13~9410
EXAMPLE 3
Mou thwash
Parts
TSPP 3.0
Ethyl Alcohol 15.0
Gantrez S-97 0.05
Glycerol 10.0
Flavor 0-4
Sodium saccharin 0.03
NaF 0-05
Pluronic F 108* 2.0
Deionized Water to Q.S. 100
*Polyoxyethylenated polyoxypropylene nonionic block polymer
surfactant.
EXAMPLE 4
Lozenqes
Parts
Sugar 75-98
Cornsyrup 1-20
Flavor Oil 0.1-1.0
Tablet lubricant 0.1-5
Polyphosphate 0.1-5
Gantrez polymer 0-05-3
NaF 0.01-0.05
~7ater 0.01-0.2
EXAMPLE 5
Chewinq Gum
Parts
Gum base 10 to 50
Binder 3 to 10
Filler 5 to 80
(sorbitol, mannitol or
combination thereof)
Artificial sweetner 0.1 to 5
Polyphosphate 0.1 to 5
Gantrez polymer 0.1 to 1.0
NaF 0.01-0.05
Flavor 0.1 to 5
This invention has been described with respect to certain
preferred embodiments and it will be understood that
modifications and variations thereof obvious to those skilled
in the art are to be included within the purview of this
application and the scope of the appended claims.
18
