Note: Descriptions are shown in the official language in which they were submitted.
Z7~
This invention relates to oral compositions containing
an anticalculus agent.
Calculus is a hard, mineralized formation which forms
on the teeth~ Regular brushing prevents a rapid build-up of these
deposits; but even regular brushing is not sufficient to remove
all of the calculus deposits which adhere to the teeth. Calculu
is formed on the teeth when crystals of calcium phosphates begin
to be deposited in the pelllc1e and extracellular mat~rix of the
denta~ plaque 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~orthophos-
phate ultimately become the crystalline material called h,droxy~
apatite (~P). It is generally agreed, however, that at higher
saturations, that is, above the critlcal saturation limit, the
,
: ~
precursor to crystalline hydroxyapatite lS an amorphous or
~icrocrystalline calcium phosphate. "Amorphous calcium phosphate"~
although related to hydroxyapatite dIffers from~lt in~atomic
structure, particIe 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~o~ all crystalline materials,
::
includ;ng hydroxyapati~te. It is apparent therefore that agents ~
~ .
: '~
_ .. .. .. . ...... ... .. _. __ . ... _ ... ... __. ... . , ___ . ..
270
which effectively interfere with crystalline growth of hydroxyapatite will be
effective as anticalculus agents, A suggested mechanism by which the anti-
calculus agents of this invention inhibit calculus formation probably
involves an increase of the activation energy barrier ~hus inhibiting the
transformation of precursor amorphous calcium phosphate to hydroxyapatite.
Studies have shown that there is a good correlation between the
ability of a compound to prevent hydroxyapatite crystalline growth in vitro
and its ability to prevent calcification in vivo.
A substantial number of different types of compounds and compositions ~ `
have been developed for use as antibacterial, and antiplaque and anticalculus
agents in oral compositions, including for example such cationic materials ~ `
as the bis-biquanide compounds and quatexnary ammonium compounds, e.g.
benzethonium chloride and cetyl pyridinium chloride, disclosed in United -
States patent application No. 755,895 which has issued as United States Patent
No. 4,110,429 on August 29, 1978. These cationic materials however tend to
stain the teeth with continued use.
It is an object of this invention to provide an improved anti-
calculus oral composition which will have relatively little or no tendency
to stain the teeth.
~o ~ A further object of the invention is to provide an oral composition
which inhibits the transformation of amorphous calcium phosphate to hydroxy- ~;
apatite crystal structure normally~associated with calculus.
: .
, ~.
- 3 -
IL2~70
Another object of this invention is the provision of an
improved method for inhibiting the formation of calculus.
Other objects and advantages will appear as the
description proceeds.
In accordance with certain of its aspects, this inven-
tion relates to an oral composition comprising an oral ~orally
acceptable) vehicle containing in an effective amount as an
anticalculus.agent at least one water soluble oligomer of the
formula:
0 ~1 IR~ . ~3R
L ~ a L ~I b
wherein :
M is a water soluble orally a.cceptable cation;
Rl, R2, R3 and R4 are independently H, methyl or ethyl:
Y is at least one hydrophilic member Of the group
consisting of -COOMl, -CONH2, and -CH20H:
: X is at least one hydrophobic member of the group ~:
B 20 consisting of -CN, -COOR, -COOR50R, -CONHR, -COONHR5COR, ~n6l ooC~
Ml is H or M,
R is Cl_8 alkyl; : ~ F
R5 is Cl_4 alkylene;
a is 0-7~ and
al-b is about 4-l5.
.~
.. . .. , . .... . . .. . ...... .. _ ~ _ , , .
z~ ~
Oligomers of the above formula and methods for their
production are disclosed in United States 3,646,099 and United
States 3,859,260. These oligomers anionic and of relatively
low and accurately regulated degree of polymerization, [in con- -
trast to the conventional free radical redox polymerization con-
ducted with an oxidative initiator such as hydrogen, alkyl, or
acyl peroxides, persulfates or hydroperoxides in relatively
large amounts and a reductive activator such as NaHSO3,
Na2S203, Na2S204 or sodium formaldehyde sulfoxylate in relat-
ively low amounts generally added subsequently to the polymer-
ization medium] are prepared by a reductive polymerization in
which a much larger amount of a bisulfite salt, e.g. NaHS03
~sodium bisulfite, sodium acid sulfite), a reducing agent, is
the initiator charged initially with the monomer, and an oxidi~-
ing agent is added in smaller amounts as the activator dur mg ~ `
the polymeri~ing or oligomerizing process.
Subscript a in formula I represents the number of moles
of hydrophobic groups, and subscript b the number of moles of
hydrophilic groups, in the oligomer;molecule. Th0 proportion
,of X ~i.e. the value of a) must be small enough, or even zero,
to avoid the production of a too large, sticky and hydrophobic
polymer Dolecule, and will of course be dependent for the
most part in any particular instance on the identity of the ~ '
X and Y groups, i.e. the hydrophobic-containing and hydrophilic
, .
,- ' .
: ~
' . ; ',':
;
, ~ .
~Z~7~
containing monomeric reactants. Mixtures of such oligomers may
of course also be employed.
Examples of monomers containing hydrophilic Y groups
are acrylic acid, methacry]ic acid, alpha-ethylacrylic acid,
beta-methylacrylic acid, alpha, beta-dimethylacrylic acid,
orally acceptable salts (Ml) of these acids, for example those
containing such cations as alkali metal (e.g. sodium and potas-
sium), ammonium, Cl_l8 mono-, di-andtri-substituted ammonium
(e.g. alkanol substituted such as mono-, di- and tri-ethanol-
ammonium), etc., acrylamide, methacrylamide, ethacrylamide,
and allyl alcohol and the like.
Examples of monomers containing hydrophobic X groups
are acrylonitrile, methacrylonitrile, ethacrylonltrile, methyl
and ethyl and octyl acrylate and methacrylate, methoxyethyl
acrylate, octoxyethyl methacrylate, ethoxybutyl methacrylate,
propoxymethyl acrylate, ~-ethylacrylamide, N-lsopropylacrylamide,
N-methylacrylamide, N-isooctylmethacrylamide, N-propylethacryl-
amide, vinyl acetate, propionate and octanoate, diacetone
acrylamide and the like.
The oligomerization is carried out ln~water in the
presence of a relatively large amount of the bisulfite reducing
initiator, expressed in mols of monomer/gram formula weight
(gFW) of reducing initiator is about 4 to 15, this ratio
determining the degree of oligomerization.
The reductive initiator is preferably a water soluble
~z~z~
bisulfite salt, (M in formula I), especially alkali metal such as
sodium or potassium, but bisulfite salts containing other orally
acceptable cations of the type referred to above may be employed.
In practice, enough oxidative activator is used to
effect 100% conversion of the monomers to oligomers. The amount
of such activator, expressed as gFW activator/gFW initiator may
range from 0.0001 to 0.1 but usually is from about 0.001 to
0.1. Examples of these oxidative activators are ammonium,
sodium and potassium persulfate, hydrogen peroxide and other
water soluble oxidants commonly employed in the polymerization
art.
Following completion of the oligomerization reaction,
any free carboxylic acid groups in the oligomer molecules may if
desired be partially or completely neutralized, preferably at
least 60%, by treating the aqueous oligomer solution with a
suitable base to convert such groups to their salts with orally
acceptable cations as referred to above. These aqueous oligomer ~
solutions have a highly desirable low viscosity,~and low molecular
weight range depending on the monomer units in the ollgomer.
It will be understood that Formula I above is not intended
to depict the actual structure of the oligomer molecule, the
bracketed units of which formula are randomly distributed in the
molecule with the -S03M group being normally bonded to a terminal _
carbon atom in the oligo~mer chain devoid of X and or ~ substituents.
In the oligomers preferred for use herein, a is zero, Y is -COOMI,
~ 7
:
-
~L~LZ~L270
Rl-R4 are H, and M and Ml are alkali metal, e.g. sodium, b being
about 10, as derived from acrylic acid. An oligomer of formula
`~ I above in the form of its sodium salt, with a molecular weight
of about 1,000, containing about 10 acrylic acid monomeric units,
is commercially a~ailable under the trade name ND-2 (a product
of UniRoyal).
The concentration of these oligomer anticalculus agents
in oral compositions can range widely, typically upward from
about 0.01% by weight with no upper limit except as dictated
by cost or incompatibility with the vehicle. Generally, concen-
trations of about 0.01% to about 10% and preferably about 0.5%
to 2% by weight are utilized. Oral composltions which in the
ordinary course of usage could be accidentally ingested pre-
ferably contain lower concentrations of these agents. Thus, a
mouthwash in accordance with this invention preferably contains
iess than about 1 weight % of the agent. Dentrifice compositions,
topical solutions and prophylactic pastes, the latter to be
administered professionally, can preferably contain about 0.1 to;;
2 weigh* % of the agent.
The oligomeric anticalculus agents of this in~ention
are antinucleating agents, oral compositions of this invention
containing such agents are effect~ive in reducing formation of
~12~27~
dental calculus without unduly calcifying the dental enamel, and
in contrast to the above-mentioned cationic antibacterial, anti-
plaque and anticalculus agents, such agents and compositions
have little or no tendency to staln the teeth.
In certain highly preferred forms of the invention the
oral composition may be substantially liquid in character,
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 ratio of water to
alcohol is in the range of from about 1:1 to about 17:3, by weight.
The total amount of water alcohol mixture in this type of prepara-
tion 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 i9
noteworthy that the compositions of the invention may be applied
orally at a pH below 5 without~substantially decalcifying dental
:
enamel. The pH can be controlled with acid (e.g. citric acid or
ben~oic aci~l) or base (e.g. sodium hydroxide) or buffered (as with
phosphate buffers). Such~liquid oral preparations may also contain
a surface active agent and/or a fluorine-providing compound.
- In certain other desirable forms of this invention, the
oral composition may be ~substantially solid or pasty in~character,
such as toothpowderr a dental tablet, a toothpaste or dental cream.
~L2~27~
The vehicle of such solid or pasty oral preparations generally
contains polishing material. Examples of polishing materials are
water-insoluble soclium metaphosphate, potassium metaphosphate,
!` tricalcium phosphate, dihydrated calcium phosphate, anhydrous
dicalcium phosphate, calcium pyrophosphate, magnesium orthophosphate,
trimagnesium phosphate, calcium carbonate, alumina, hydrated alumina,
aluminum silicate, zirconium silicate , silica, bentonite, and mix-
tures thereof. Preferred polishing materials include crystalline
silica having particle sizes oE up to 5 microns, a mean particle
size of up to 1.1 microns, and a surface area of up to 50,000
cm /gm~ silica gel, complex amorphorus alkali metal aluminosilicate
and hydrated alumina.
Alumina, particularly the hydrated alumina sold by Alcoa
as C333, which has an alumina content of 64.9% by weight, a silica
content of 0.008%, a ferric oxide content of 0.003%, and a moisture
content of 0.37%, at 110C~, and which has a specific gravity of
2.42 and a particle size such that 100% of the~particles are less
than 50 microns and 84% of the particles are less than 20 microns,
is particularly desirable.
When 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 SA~TOCE~ as
Santocel 100 and alkali metal aluminosilicate complexes are
particularly useful, since they have refractive indices close to
the refractive indices of gelling agent-liquid (including water
10~
~ . .. , _ . . . . . .. .. . , .. . .. .. ... . , . _ .
~2~27~
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 of soluble
material. Thus, insoluble sodlum metaphosphate may be formed in
any suitable manner, as illustrated by Thorpe's Dictionary of Applied
Chmis~ Volume 9, 4th Edition, pp. 510-511. The forms of
insoluble sodium metaphosphate known as Madrell's salt and Kurrol's
salt are further examples of suitable materials. These metaphos-
phate salts exhibit a minute solubility in water, and therefore
are aommonly referred to as insoluble metaphosphates. There is
present therein a minor amount of soluble phosphate material as
impur~ities, usually a few percent such as up to 4/O by weight. The
amoun-t of soluble phosphate material, which is believed to include
a soluble sodium trimetaphosphate in the case of insoluble meta-
phosphate, may be reduced 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 37 microns.
The polishing material is generally present in amounts
ranging from about 20% to about 9~/0 by weight of the oral
preparation. Preferably, it is present in amounts ranging from
about 20% to about 75% in toothpaste, and from about 70% to
about 99/O in toothpowder.
In the preparation of toothpowders, i~ is usually suffi-
Fient to admix mechanically, e.g., by milling, the various solid~
7~ 77~; ~ ,1' r~ ~
:llZ~Z~
ingredients in appropriate quantities and particle sizes.
In pasty oral preparations the above-defined oligomer
should be compatible with the!othér components of the preparation.
Thus, 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, or polyethylene glycol 400 may also be present as
humectants or binders. Particularly advantageous liquid ingredients
comprise mixtures of water, glycerine and sorbitol.
In clear gels where the refractive index is an important
consideration, about 3-30% by weight of water, O to about 80% by
weight of glycerine, and about 20-80% by weight of sorbitol is
preferably employed. A gelling agent, such as natural or synthetic~
gums or gum-like materials, typlcally Irish moss, sodium carboxy-
lS methylcellulose, methyl cellulose, or hydroxyethyl cellulose, may
be employed. Other gelling agents which may be employed include
gum tragacanth, polyvinylpyrrolidone and starch. They are usually
: .
present in toothpaste in an amount up to about 10% by weight,~
preferably in the range of from about 0.5% to about 5%. The
preferred gelling agents are methyI cellulose and hydroxyethyl
cellulose. In a toothpaste or gel, the liquids and solids are
proportioned to form a creamy or gelled mass which is extrudable
from a pressurized container or from a collapsible, e.g., aluminum -
or lead, tube. ~ ,
The solid or pasty oral preparation which typically has
-12
~121~
a pH measurea on a 20% slurry of about 4.5 to 9, generally
about 5.5 to about 8 and preferably about 6 to about 8.0, may
also contain a surface active agent and/or a fluorine providing
compound.
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 la.bel
describ.ing it, in substance, as a mouthrinse or mouthwash and
having directions for its use, and a toothpaste will usually be
in a collapsible tube, typically aluminum or lined lead, or other
squeeze dispenser for metering out the contents, having a label
describing it, in substance, as a toothpaste or dental cream.~
Organic sur-Ea.ce-active agents are used in the compositions
of the present invention to achieve increased prophylactic action,
assist in achieving thorough and complete dlspersion of the anti-
calculus agents throughout the oral cavlty, and render the instant
compositions more cosmetically acceptable. The organic surface-
active material is preferably a.nionic, 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 sa.lts of higher fatty acid monoglyceride monosulfates,
such as the sodium salt of the monosulfated monoglyceride of hydro-
genated coconut oil fatty acids, higher alkyl sulfate,s, such as
sodium lauryl sulfate, alkyl a.ryl sulfonates, such as sodium dodecyl
. . .
-13-
... , . .. . _ _ _ . _ .. ........ . .. . . .
~L2~2'7qg
benzene sulfonate, higher alkyi sulfoacetates, higher fatty acid
esters of 1.2 dihydroxy propane sulEonate, 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 a.cid, 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 sarcosinate compounds in dentifrice compositions of the pre-
sent 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 carbohydratebreakdown in addi-
tion to exerting some reduction in the solubility of tooth enamel
in acid solutions.
Examples of water-soluble nonionic surfactants are
condensation products of ethylene oxide with va.rious reactive
hydrogen-containing compounds reactive therewith having long ~:
hydrophobic chains (e.g. aliphatic chains of about 12 to 20
carbon atoms), which condensation products (i'ethoxamers") con~
tain hydrophilic polyoxyethylene moieties, such as condensation
products of poly (ethylene oxide) with fatty acids, atty alcohols,
fatty amides, polyhydric alcohols (e.g. sorbitan monosterate)
IL~ and polypropyleneoxide (i.e. Pluronic materials).
M~K
. ~
--~~
.
~21Z~
In certain forms of this invention a fluorine-providin~
compound is present in the oral preparation. These compounds
may be slightly soluble in water or may be fully water-soluble.
They are characterized by their ability to release fluoride ions
in water and by substantial freedom from reaction with other
compounds of the oral preparation. Among these materials are
inorganic fluorlde salts, such as soluble alkali metal, alkaline
earth metal and heavy metal salts, for example, sodium fluoride,
potassium fluoride, ammonium fluoride, lead fluoride, a copper
fluoride such as cuprous fluoride, zinc fluoride, a tin fluoride
such as stannic fluoride or stannous chlorofluoride, barium fluoride,
sodium fluorsilicate, ammonium fluorosilicate, sodium fluorozir-~
conate, sodium monofluorophosphate, alumLnum mono- and di-fluoro-
phosphate, and fluorinated sodium calcium pyrophosphate. Alkali
metal and tin fluorides, such as sodium and stannous fluorides,
sodium monofluorophosphate and mixtures thereof, are preferred.
The amount of the fluorine-providing compound is depen-
dent to some extent upon the type of compound, its solubility,
and the type of oral preparation, but it must be a nontoxic
amount. In a solid oral preparation, such as toothpaste or tooth-
powder, 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, but it
is preferable to employ sufficient compound to release about
0.005% to 1%, and preferably about 0.1% of fluoride ion.
:
-15-
~L21Z7~
Typically, in the cases of alkali metal fluorides and stannous
fluoride, this component is present in an amount up to about
~/O by weigh-t, based on the weight of the preparation, and pre-
ferably 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~o by weight, more typically about 0~76%~
In a liquid oral preparation such as a mouthwash, the
fluorine-providing compound is typically present in an amount
sufficient to release up to about 0.13%, preferably about 0.0013%
to 0.1% and most preferably about 0.0013% to 0.5%, by weight, of
fluoride ion.
Various other materials may be incorporated in the oral
preparations of this invention such as whitenlng agents, preserv-
atives, silicones, chlorophyll compounds, other anticalculus
agents, antibacterial antiplaque 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 characteristics desired.
Any suitable flavoring or sweetening material may also
be employed. Examples of suitable flavoring or sweetening material
may also be employed. Examples of suitable flavoring constituents
are flavoring oils, e.g., oils of spearmint, peppermint, wintergreen,
sassafras, clove, sage, eucalyptus, marjoram, cinnamon, lemon, and
orange, and methyl salicylate. Suitable sweetening agents include
_ . . . , , . .. , .. _ . _ .. ~ . _ . .. _ ,
~2~27~
sucrose, lactose, maltose, sorbitol, xylitol, sodium cyclamate,
perillartine, and saccharine. Suitably, flavor and sweetening
agents may together comprise from about 0.01% to 5% or more of the
preparation.
In preparing the oral compositions of this invention,
it is preferred but not essential to add the oligomer after the
other ingredients (except perhaps some of the water) are mixed
or contacted with each other to avoid a tendency for said agent
to be precipitated.
For instance, a mouthrinse or m~outhwash may be prepared
by mixing ethanol and water with flavoring oil, surfactant, humectant,
sweetener, color and then the above-defined oligomer, followed
by additional water as desired.
A toothpaste may be prepared by formlng a gel with
humectant, gum or thickener such as hydroxyethyl cellulose,
sweetener and adding thereto polishing agent, flavor, additional
water, and then the above-deEined oligomer. If sodium carboxy- ~
methyl cellu]oseis employed as the gelling agent the procedure of
either U.S. Patent 3,842,168 or U.S~ Patent 3,843,779, modified
~0 by the inclusion of the oliqomer/ is followed~
In the practice of this invention an oral composition
according to this invention such as a mouthwash or toothpaste
containing the defined oligomer in an amount effective to inhibit
calculus on dental surfaces is applied regularly to dçntal enamel,
preferably from about 5 times per week to about 3 times daily, at
.
z~
a pH of about 4.5 to about 9, generally about 5.5 to about 8, pre-
ferably about 6 to 8.
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 in the appended claims are by weight unless
otherwise indicated.
Example A
The procedure of Example 1 of U.S. 3,646~099 is followed,
the initial charge to the reactor being 3.12g NaHS03 (0.03 gFW),
159.8g. water, and 20.74g. acrylic acid (0.288 mol) as the sole
monomer, a correspondingly equivalent amount of the (NH4)2S208
activator being employed. The ratio of mols of monomer to gFW
NaHS03 is 9.6, and the oligomer, fully neutralized with 5N NaOH at
the completion of the reaction, may be represented by the formula
, . ' '
A NaO35 f ~2 fH 1 :
COONa
9.6
In this case, a in formula I above is zero and b is
9.6 (average). A clear solution i9 obtained, this Oligomer
A having a molecular weight oE about 1,000.
-18-
Z7~
Inhibition of Crystal Growth of H~P
This is evaluated by a pH Stat method. 1.0 ml of an
aqueous solution of lX10-4M to lX10 5M~ of the anticalculus
agent being tested and 0.1 M sodium dihydrogen phosphate is placed
in a reaction flask with 22 to 23 ml. of distilled water with con-
tinuous stirring in an atmosphere of nitrogen. To this is added
1 ml. of 0.1M CaC12 and the pH adjusted to 7.4~0.05 (final conc.
of Ca~ and Po43~ -4X10-3M). Consumption of 0.1N NaOH is recorded
automatically by a pH Stat (Radiometer). In this test, the for-
mation of HAP occurs in 2 distinct phases. First rapid base
consumption (1-4 min.) then diminishes until 15-20 minutes when
second rapid uptake takes place. A delay in the time of second
rapid consumption or a total absence of the second rapid consump-
tion indicates an interference with the crystal growth of MAP.
Agents which interfere with HAP crystal growth are effective anti-
calculus agents. When subject-ed to the foregoing procedure, Oli-
gomer A above is found to delay the formation of the second phase
B by more than 12 hours, while Acrysol A-5 polyacrylic acid and
sodium polyacrylic acid have no affect.
It is thus clear that Oligomer A effectively inhibits
the crystal growth of HAP and that the inhibition is not merely
due to the complexation or chelation of calcium from the system
since the ratio of inhibitor to total calcium is 1:40 to 1:80.
In the following examples illustrative of mouthwash
~ ~ral~m~,K -19-
_, . ... , . . .. __ _ .
Z7~
formulations according to the invention
and Pluronlc F108 is a polyalkene oxide block polymer.
. Example
2 3 4 5
Flavor 0, 22% 00 2~/o 0. 22% 0~ 2~/o
Ethanol 15.0 15.0 15 . 0 15 . O
Pluronic F108 300 3.0 3.0 3.0
Glycerine 10.0 10.0 10.0 10.0
Na Saccharin 0.03 0~03 0.03: 0.03
Oligo~er A 0.1 - 0.2 ~0.5 1.0
Water q.s. to 100 ~ 100 100 100
pH(with NaOH) 7.4 7.4 ::~7.4 : ~ 7.4
Appearance Clear Clear:~ Clear Clear
:; ` ~ : ,
The following examples are illustrative of anticalculus
; toothpastes according to the invention~
Example ~ :
(6) : : (7) ~ ~ ~
Silica 30 ; : 30 ~ :
Glycerine 16 ~ 16 :~
Sorbitol (70/0) 6 6
Pluronic F-108 ~ 3 3
Hydroxyethyl cellulose 1~ 2 l~ 2
Oligomer A 2
Sodium saccharin 0.17 0.17
Flavor :: 0.8 : 0.8
Water q.s. to 100 100
:
-20~- ~
~. ~ , . , , , , , I . ,- . .. . . . .
L27~
Siynificant reductions in calculus are also obtained
according to -the present invention when Oligomer A in the above
examples is replaced by any of the co-oligomers prepared by the
procedures of Examples I-XIII of U.S. 3,646,099 and 3,859,260 suit-
ably adjusted to yield a co-oligomer of formula I above in which
a is 0-7 and a-~b is about 4-15.
Example 8
In this study on 16 beagles, a placebo mouthrinse of
water at a pH of 7.0 and a 1% aqueous solution of Oligomer A as
the test anticalculus mouthrinse are evaluated for effectiveness
against formation of calculus for a 6 week period.
16 beagles are given thorough dental prophylaxis in
order to remove existing soft and hard deposits. Disclosing
solution is used toassure that the teeth are free of such deposits.
The animals are assigned to 2 groups of 8 each. The teeth of one
group is sprayed with the placèbo and the teeth of the other group
is sprayed with the test mouthrlnse twice a day, 5 days a week,
for 6 weeks. At the end of this period, the teeth are scored for
calculus on a scale of 1 to 3, as follows:
Scale Calculus ~ormation
1.0 1/3 of teeth covered with calculus
2.0 2/3 of teeth covered with calculus
3.0 all of teeth covered with calculus
The following results are found:
-21-
, . ~ ..
'7~
Mean Calculus
per tooth _ /O chanqe Siqnificance*
placebo 1.50 - -
Oligomer A
mouthrinse 1~01 -32.6 95%
* data analyzed by the analysis of variance (Student~s t test)
The above results show that a mouthrinse containing
Oligomer A according to the invention is significantly effective
in reducing calculus formation.
Example 9
In this study on 20 rats, a placebo of water at a pH
of 7.0 and an 0.1% aqueous solution of Oligomer A as the test
anticalculus mouth~inse are evaluated ~or effectiveness against
formation o~ calculus for a 30 day period.
Litter matured Osborne Mendel rats are used. They are kept on
Calculogenic Diet 580F supplemented with 0.~/O P ~as Na2~HP04~ Prom
21 days onwards, 100 microliters of the placebo and of the test
mouthrinse are each applied to the molars of a group of 10 ~
such rats daily for a period of 30 days.~ The animals are weighed
at the beginning and at the end of the study to assure that the
: : :
rats remain in otherwise normal condition. At the end of the period,
calculus formation is assessed according to routine procedures and
the following results are found:
Mean --
No. Weight Calculus
Animals Gain (qms) ~ Units Siqnificance
placebo 10 128 ~ 17.9
Oligomer A
mouthrinse 10 131 14.9 at 9~/O level
-22-
. ~ .
- ~:lL2~27~)
The above results establish that a mouthrinse con-
taining Oligomer A according to the invention is significantly
effective in reducing calculus formation.
This inven-tion has been described with respect to
preferred embodiments and it will be understood that modifica-
tions and variations thereof obvious to those skilled in the art
are to be included within the spirit and purview of this application
and the scope of the appended claims.
~~3-
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