Note: Descriptions are shown in the official language in which they were submitted.
-- WO92/10165 2~ 7 PCT/US91/08107
ENZYME CONTAINING DENTURE CLEANSER
This invention relates to denture cleanser
; compositions and more particularly to an improved
water-soluble denture cleanser composition containing
enzymatic and chelating cleansing agents.
Dentures may be cleansed either by immersion in a
cleansing solution or by brushing with a cleansing agent
l0 in the manner of natural teeth. The former method is
generally preferred, partly for convenience but primariiy
since brushing tends to mar the smooth surfaces cf
plastic dentures.
Cleansing solutions may be made from preformed
lS liquid solutions but for storage convenience are usually
in solid form in which case the cleansing solutio!l s
prepared at the time of use by dissolving the solid form
in tap water. The solid form cleanser may be in the form
of loose powder or granules or may be in the form of
20 tablets. In addition, denture cleanser tablets usually
also contain one or more active oxygen compounds such as
sodium perborate monohydrate, potassium peroxydisulfate,
potassium monopersulfate, sodium carbonate peroxide,
potassium peroxydiphosphate, diperisophthalic acid,
monoperphthalic acid and the like, which cause the
tablets to evolve micro-bubkles of active or nascent
oxygen as they are dissolved in water and provide an
oxidizing cleansing action including a bleaching effect
on the denture stains. Generally, they also contain a
surfactant to lower the surface tension and to enhance
the cleansing action.
Further, denture cleanser tablets usually also
contain various other relatively inactive ingredients
such as fillers, extenders, binders, indicators or dyes,
flavors and the like. Lubricant systems, such as
magnesium stearate or talc, to facilitate smooth and even
flow of the dry granular materials of the formulations
during tableting operations may also be added.
Improvement in denture cleansers has been primarily
carried out by manipulating the oxidizing system, e.g.,
~;UBSTITUTE SHEET
2~7~
WO92/10165 - 2 - PCT/USgl/C
perborate and persulfate, and pH in order to achieve
improved food stain removal. Hypochlorite generating
formulations are well known to achieve a high level of
; plaque removal and moderate level of ^ood stain removal,
but it is known that they are harmful to denture metals
and generate an odor unacceptable to the consumer.
Food stain does not adhere directly to denture
materials but to biological accretions, such as denture
plaque and calculus. Denture plaque is a complex
glycoproteiin which is believed ~esponsible, in part, for
denture odor. lt is this su~s~a1lce which forms on the
surface cf the dentures ini~iall~. Upon its
disintegration, ~here remains a resicue composed of
l~ hydroxyapetite and other component~ which contain
calcium. It i~ this rQS' due Whicl. hardens to form
calculus which continues to obtain new layers of plaque
if not removed. This layering sequence also aids in
stain retention by preferential stain adsorption.
It is well known that enzymes improve the removal of
plague by its disruption of the proteinaceous material by
catalyzing the hydrolysis of peptide bonds and by
increasing the water solubility of the proteinaceous
material allowing it to be removed during treatment and
subsequent rinses. In addition it is known that
chelating agents are also able to remove to some extent
calcium deposits and the calculus deposits on dentures
and thus may also disrupt the deposits. Formerly,
chelating agents were added to denture cleansers in small
amounts to help reduce (a) the turbidity of the resultant
solution due to hard water content and were essentially
spent in the process or (b) to sequester the heavy metals
which tend to spend the available titratable oxygen in
such systems and thus extend the shelf life of the
product. Such products however even when used at
relatively high levels of either chelating agents or
enzymes fail to remove signi icant amounts of both plaque
and calculus deposits from 'ho denture surface thus
leaving a significant amount of stain on the dentures.
S~BSTITUTE SHE~T
`WO92/10165 _ 3 _ 2~7~7 PCT/US91/08~07
The incorporation and use of enzymes in denture
cleansers is taught by U.S. Patents 4,155,868 and
3,962,107.
; Although it has been thought to be desirable to
incorporate enzymes in denture cleanser tablets,
difficulties have arisen because of the inactivating
effect of the enzyme resulting from the active oxygen
when compressed witll the enzyme. U.S. Patent No.
lO 3,962,107 purports to obviate this problem by the
separation of ~he enzyme and active oxygen cleansing
components in separ~te layers of A denture tablet. It is
stated tha. ~he faster dissolving enzv1ne layer permits
enzymatic cleansin~ actl-~ity to ?roceed before
~S dissolution of the active c~yaen la~e~ reaches a level
which would inac~ivate the enzyme. ~n the other hand,
U.S. Patent No. 4,155,868 discloses a single layer tablet
in which an enzyme, active oxygen compounds and an
effervescence producing composition are allegedly
20 incorporated in such a manner that they are retained in a
stable form until the tablet is ready for use. The
patentee states that by careful control of the particle
sizes and the surface treatments of selective components,
the enzyme~ is not detrimentally inactivated during
2~ storage. The patentee further states that they provide
added stability while in the dry tablet, the enzyme may
be granulated or coated.
Both of the aforementioned U.S. Patents fail to
recognize the significant enzyme deactivation partially
attributable to the presence of chloride ions in their
formulations when potassium persulfate is used as the
source of active oxygen. The presence of both
components, even when chlorides are present as minor
impurities in the formulaticn components, results in the
formation of compositions believed to be hypochlorites
which deactivates the enzymes causing the system to
become ineffective.
Thus, while the art :sas proposed storage stable
denture cleanser compositions whicll incorporate enzymes
with active oxygen bleachina components, the art has not
SV~STITUTE SHEET
2C~7~5;~1~37
WO92/10165 ` _ 4 _ PCT/US91/~ ~7
heretofor addressed the problem of deactivation of enzyme
in the cleaning solution formed when the cleanser
composition is added to water. Additionally, the art has
; not provided compositions designed to re~ove calculus
deposits from dentures thereby removin~ embedded stains.
The compositions of this in~ention overcome the p~ior a t
deficiencies by utilizing an effective amount o
chelating agent along with an effective amoullt o~ enzyme
lO to synergistically remove calculus/plaque deposits withi
a short period of time.
Preferred compositions of the present invention
provide for the addition of a bleaching component, whic~
does not react with halides to produce an enzyme
deactivating composition such as a hypohalide, to an
effective amount of a chelatin~ a~er~ alo.l;J iYith .~in
effective amount of enzyme to synergistica~ly remove
calculus/plaque deposits within a short period of time.
It has also been discovered that a water soluble
~0 denture cleanser composition may be prepared which
comprises:
(a) an effective amount of a proteolytic enzyme to
disrupt the proteinaceous material in plaque,
and
2~ tb) an effective amount of a sequestering agent to
remove calcium deposits and calulus deposits,
wherein the concomitant disruption of
proteinaceous material and removal of calcium
deposits and calculus deposits results in the
removal of calculus and plaque.
It has further been discovered that a water soluble
denture cleanser composition may be prepared which
comprises:
(a) an effective amount of a proteolytic enzyme to
disrupt the proteinaceous material in plaque,
and
(b) an effective amount of a sequestering agent to
remove calcium de?osits and calulus deposits,
and
(c) an effervescence producing composition,
SUBST~TU ~_ SHEcT
~7~J;~1~37
~--`WO92/10165 . _ 5 _ PCT/US91/08107
wherein the concomitant disruption of
proteinaceous material and removal of calcium
deposits and calculus deposits results in the
; removal of calculus and plaque.
It has been discovered that a water soluble denture
cleanser composition may be prepared w~ich comprlses:
(a) an effective amount of a proteolytic enzyme to
disrupt the proteinaceous material in plaque,
~0 and
(b) an effective amount of a sequestering agent to
remove calcium deposits and calulus deposits,
and
(c~ an effective amount of a bleaching component
~S which does not react with halide to produce an
enzyme deactivating composition,
wherein the concomitant disruption of
proteinaceous material and removal of calcium
deposits and calculus deposits results in the
removal of calculus and plaque.
A preferred embodiment of the present invention is a
water soluble effervescent denture cleanser composition
which comprises:
(a) an effective amount of a proteolytic enzyme to
2S disrupt the proteinaceous material in plaque,
and
(b) an effective amount of a bleaching component
which does not react with a halide to produce
- an enzyme deactivating composition, and
(c) an effective amount of a sequestering agent to
remove càlcium deposits and calculus deposits,
(d) an effervescense producing composition
wherein the concomitant disruption of proteinaceous
material and removal of calcium deposits and
calculus deposits results in the removal of calculus
and plaque.
The invention also contemplates a method for
cleansing dentures which method comprises placing the
water-soluble denture cleanser composition and denture to
be cleaned in an amount of water sufficient to dissolve
SIJBSTITUTE SHEET
WO92/10165 2~7 - ~7 - 6 - PCT/US91/~ 7
the composition and to completely cover the denture for a
sufficient time to effect the desired cleaning. Cleaning
times of up to about 15 minutes and even up to about 5
; minutes have been found suitable to clean dentures with
the formulations of this invention even thou~h such times
are not considered essential to the invention.
In accordance with the present invention there is
provided a water-soluble denture composition comprising
two essential components, a proteolytic enzyme and a
se~uesteri2lg agent. This formulation functions in
cleansing the denture by removal of surface plaque by the
enzyme and concurrent dearadatio1l of proteinaceous
material alon~ t~ith the chelatin e fe~t to remove
lS calcium and calculus deposi~s achieved by the
sequest:^2:l_. The effervescence-producing and bleaching
materials of the preferred composition aid in removing
stains and debris from the object being cleaned as it is
being reacted upon by the other components. Th~
composition once prepared may be used as a powdered
formulation or compressed into tablet form or other
suitable format which is effective upon dissolution in
water to remove denture plaque, calculus and food stains.
In a preferred embodiment, the enzyme is incorporated in
the compositions of the present invention in a granular
encapsulated form. The denture cleanser compositions of
the present invention may be in single layered or
multi-layered tablet form.
In accordance with the present invention, the enzyme
component of the denture composition herein is a
proteolytic enzyme and most preferably a neutral or
alkaline proteolytic enzyme which is capable of acting on
food, food degradation products, mucin and plaque. In
furtherance of the present invention, the proteolytic
enzyme is preferably employed in a granulated,
encapsulated form. The enzymes may be of plant, animal
or microbial origin and even synthetically produced.
Many are available commercia;ly under various tradenames
which are useable in this invention. The enzyme particle
size is not critical for the compositions of this
SUF~ST~TUT;: SHE~T
~W092/1016~ 7 ~7~J~7 PCT/USgl/08107
invention but are preferably able to pass through a lO to
20 mesh sieve (U.S. standard screen) when the composition
is to be tabletted. The enzymes should be active within
; a pH range of about 7.0 to 12.0 and preferably 7 to lO.5.
The proteolytic enzyme, used in the present
invention, can be of vegetable, animal or microorganism
origin. Preferably it is of the latter origin, which
includes yeasts, fungi, molds and bacteria. Particularly
lO preferred are bacterial subtilisin type proteases,
obtained from e.g. particular strains of B. subtilis and
B. lichenlormis. Examples of s~litable commercially
available ~rotease~ are ~lc~lase, S~vinase, Esperase, all
of NOVO Industri A~S; Ma~atase and Maxacal of
~5 Gist-Broca~es; 'l~uzusase o, Showa Denk~; BPN and BPN'
proteases and so on. ~he activity of the proteolytic
enzyme included in the composition, typically ranges from
about 0.1-150 AU/g or its equivalent. Naturally,
mixtures of different proteolytic enzymes may be used.
There are standard measures of enzyme activity such
as the Anson Unit (AU) and the Novo Protease Unit (NPU)
and the Glycine Unit (GU). These measurers of activity
are well known and defined as follows:
-
2~ Unit Definition - Anson Unit (AU!
l Anson Unit = the amount of enzyme* which digests
hemoalobin
at an initial rate such that there is
3~ liberated per minute an amount of
TCA-soluble product which gives the same
color with phenol reagent as one
milliequivalent of tyrosine
* under reaction conditions given in NIAS method AF4/5-GB
Modified Anson-Hemoglobin Method for the Determination of
Proteolytic Activity
SUBSTITUTE SHEET
~7~
W092/10165 - 8 - PCT/US91/~ 7
Unit Definition - Kilo Novo Protease Unit (KNPUl
l Novo Protease Unit (NPU) = the amount of enzyme* which
; hydrolyzes casein at such a rate that the
initial rate of formation of
peptides/minute corresponds to l mic~omole
of glycine/minute
* standard conditions given in NIAS method AF 162~3-6B
Manual DMC Method for the Determination of Proteolytic
Activity formation of peptides from caseln is measured by
color changes resulting from reaction of primary ami~o
groups with trinitrobenzene-sulfonic Qcid to form a
colored compound.
1000 NPU = 1 KNPU
A GU is a glycine unit, which is the amount of
proteolytic enzyme which under standard incubation
conditions produces an amount of terminal NH2-groups
equivalent to l microgramme/ml of glycine.
When utilized in the denture cleanser composition of
this invention the enzymes should be used in amounts of
about 0.5% to about 15% by weight of the total
formulation and preferably 1% to about 7% by weight.
Amounts below these amounts are not effective in removing
sufficient plaque to be economical whereas higher amounts
do not achieve any added benefit other than speed of
cleaning. Typically, the enzymes useful in the present
invention will have an activity of about about 2AU or its
equivalent when expressed in other units.
The chelating or sequestering agents useful in the
present invention are to be used in amounts of about 8%
up to about 99.9% by weight of the total composition.
Sequestering agents useful in the present invention are
carboxylic acid derivatives and phosphonic acid and its
derivatives.
Those carboxylic acid derivatives useful as
chelating or sequestering agents include the
hydroxycarboxylic acids and salts thereof, as well as
SUBSTITUT~ SHEET
,~ WO92/10165 _ 9 _2~7~ 7 PCT/US91/08107
amino carboxylates. For example, the hydroxycarboxylic
acid compounds include gluconic acid and citric acid,
among others known in the art. The amino carboxylates
; include nitriloacetic acid, ethylenediaminetetraacetic
acid (EDTA) and isoserine diacetate and their salts.
Among those specific phosphonic acid derivatives are the
salts of ethane-1- hydroxy-l, l-diphosphonic acid. For
example, aminotriomethylene phosphonic acid),
l-hydroxyethylidene- l,l-diphosphonic acid,
ethylenediamine tetra(methylene phosphonicacid),
ethylenediaminetetra(methylene phosphonicacid),
hexamethylenediaminetetra(methylene-phosphollic acid),
diethylene triamine penta(methylene-phosphonic ac.id),
among others. The alkali metal salts and analoges of the
above phosphonates are also useful. ~i.Y' ures of any or
all of the chelating or sequestering agents is also
contemplated~
The preferred chelating or sequestering agent used
in this invention is EDTA, most preferred is the tetra
sodium salt of ethylenediamine tetraàcetic acid,
dihydrate. Another preferred sequestering agent is
isoserine diacetate trisodium salt. This component is
essential for use in the denture cleanser compositions of
this invention and is employed in an amount of about 8%
up to about 99.5% by weight of _he total composition. A
preferred amount is about 15% to about 80% and a most
preferred amount is 15 to 50% by weight of the total
composition.
The sequestering agent is believed to function in
the inventive compositions by reacting with the calcium
present in the calculus rendering the underlying
proteinous material susceptible to attack by the
proteolytic enzyme. The enzyme in turn attacks plaque
thereby exposing more calculus to attack by the
sequestering agent. This combination reaction results in
the synergistic removal of the plaque and calculus along
with adsorbed stain beyond that which can be achieved by
using these materials separately.
SUBSTITUTE SH~El'
O92/1016~ lO - PCT/US91/~' ~
2~7~J.~1~7
Bleaching or active oxygen components useful in the
present invention are those which do not inactivate
proteolytic enzymes directly and which do not interact
; with halides to produce an enzyme deactivating
composition. Examples of suitable bleaching components
include alkali metal and alkaline earth metal perborates
and percarbonates. Perborates are the preferred
bleaching c~mponen~ and sodium perborate monohydrate is
the most preferred.
The bleaching component whe1l utilized in the denture
cleanser composition is prese1lt in amounts up to about
55~ preferably from about 12,' to about 55% and most
pre~erably from about 25% to about 55% by weight of the
1~ total denture cleanser composition. When used throughout
the specif~catio.l the 'er..~ "bleaclling component" shall
include those compounds known in the art as "active
oxygen" compounds. These compounds reduce stain and
remove calculus and pla~ue.
The effervescence-producing composition may be
selected from a wide range of materials which aid in
cleaning the denture surfaces by causing the active
components to be rapidly dissolved.
The effervescence-producing composition may be
comprised of an acid selected from the group consisting
of citric acid, tartaric acid, gluconic acid and malic
acid and an alkali metal carbonate selected from the
group consisting of sodium bicarbonate, potassium
bicarbonate, sodium carbonate and potassium carbonate.
These formulations are preferably employed when a neutral
proteolytic enzyme is employed since they impart pH
values around 7 to 8.5 when employed in the formulations
of this invention.
In addition the effervescence-producing composition
may be anhydrous sodium perborate. This particular
component is the preferred effervescence-producing
composition when the enzyme employed has a higher pH
activity range, namely an alkaline proteolytic enzyme.
This material exhibits a pH value around 9.5 to lO.5 when
employed in the compositions of this invention.
SlJBSTlTUTE SHE~T
! ~ 92/1016~ '~Z~7 PCT/US91/08107
The effervescence-producing composition should be
employed in amounts up to about 75% by weight of the
total composition and preferably in amounts of about 15%
; to about 25~o by weight. Amounts above 75% do not enable
sufficient active components to be present to remove
ade~uate le~els of plaque and calculus whereas levels
below about 15% do not adequately disperse the components
in solution.
In a preferred embodiment, the bleaching agent is
sodium perborate monohydrate and the
effervescsnce-producing a~ent is anhydrous sodium
perborate. The weight ratio of sodiu~ perborate
monohydrate and anhydrous sodium perborate in a preferred
embodiment is from about 5:3 to about 3:~.
In addition to the ingredieilts set forth above, the
present compositions may contain a variety of additional
ingredients selected on the basis of desired end use.
Thus, for example, the compositions may include detergenb
compounds, such as organic and inorganic detergents,
including non-ionic detergents such as the various
polyoxyethylene esters of aromatic and alaphatic
alcohols, as well as the polyoxyethylene esters of
hydrophobic propylene oxide polymers. These compounds
2S assist in maintaining a foaming action, in the instance
where the cleansing compositions are placed in aqueous
solution.
Also, the compositions may contain other adjuvant
materials, that may be inorganic or organic in structure.
Thus, inorganic water-soluble alkaline builders such as
alkali and alkaline earth metal carbonates, hydroxides,
and mixtures may be added.
The present compositions may optionally contain
additional sequestrants for the purpose of maintaining
solution clarity, in the instance where the compositions
are placed in solution. The additional sequestrants may
also assist in the inhibition of corrosion and tarnish of
articles soaked in solution containing the present
compositions. Useful sequestrants include polyfunctional
SVBSTITUTE SHEET
10165 ~75~7 - 12 - PCT/US91/0. 7
organic acids, such as citric acid, maleic acid and their
corresponding salts.
Other additives such as flavorings, colorants,
; perfumes and the like may be added in various amounts, as
mentioned earlier. For example, the flavorings may
include varieties of mint, oil of clove, ar~i~lci21
vanilla flavoring and others. These materials may be
included and blended in various combinations within the
~0 scope of the present invention. The choice of the
re~uired amounts is likewise within the skill o the art.
In the instance where the present cleansing
compositions are formulated for use as dent~lre c1eanser~,
the colorants useful herein are those known as F.D.~ C. ~
D.& C. dyes and lakes. These materials a-~ ce~i.ied ~y
the Federal Food and Drug Administration as acceptable
for use in food, drug and cosmetic applications, and drug
and cosmetic colorings. The materials acceptable for the
foregoing spectrum of use are preferably water-soluble,
and include indigoid dye, known as F.D.& C. Blue No. 2,
or its Lake which is the disodium salt of
5,5-indigo-tindisulfonic acid. Similarly, the dye known
as F.D.& C. Green No. 1, comprises a triphenylmethane dye
or F.D.
2~ & C. Green #3 and is the monosodium salt of 4-[4-N-ethyl-
p-sulfobenzylamino)diphenylmethylene]-~l-(N-ethyl-N-p-
sulfoniumbenzyl)2,5-cyclohexadienimine] or F.D. & C.
Green #3. A full recitation of all F.D. & C. and D. & C.
colorants and their corresponding chemical structures may
be found in the Kirk-Othmer Encyclopedia of Chemical
Technology, 3rd edition, at Volume 6, pages 561-595,
which text is accordingly incorporated herein by
reference. Dyes and colorants will fade at different
3~ rates and may be chosen to provide specific end points.
The foregoing colorants may be blended with each
other in a variety of combinations. It is particularly
desirable that the colorants be chosen so that the
composition when initially dissolved will present a deep
hue. This is important in the instance where the
composition serves as a denture cleanser, as the fading
SUBSTITUTE S~T
;~7S.:~7
WO92/10165 - 13 - PCT/US91/08107
phenonmenon embodied in denture cleansers can be more
easily observed by the end user.
The use of F.D. & C. Blue #l Lake is particularly
; important in that the tablet color is blue without
adversely affecting the color of the solution.
In addition, the inventive denture cleanser
compositions of the present invention include a peroxygen
or active oxygen component~ These materials are
compounds which form hydrogen peroxide or active oxygen
when placed in solution. Typical active oxygen compoun~s
include sodium perborate monohydrate and tetrahydrate,
potassium monopersulfate, sodium car~onate ~ero~ide,
diperisophthalic acid, monoperphthal.c acid, potassium,
~5 peroxydiphosphate, sodium alu1ninum amino- hydroperoxide
and the like. The peroxygen or active oxygen component
is preferably employed in a granular form and in an
amount of from about lO to about 40% weight, preferably
from about 15 to about 25% based on the total
composition.
A further feature of the invention comprises the
preparation of a compacted granulated mixture containing
the anhydrous perborate salt in combination with a
monohydrate perborate salt and optional addition of a
2~ polymeric fluorocarbon. Such mixtures are recited in
Reissue Patent 32,771 and 4,405,486 which is incorporated
herein by reference. In general such formulations
comprise a combination of anhydrous perborate and
monohydrate perborate in the amount of about 50% to about
70% by weight` of the total cleansing compositions,
wherein the combination includes at least 20% by weight
of the total cleansing composition of anhydrous
perborate, said combination having a portion present in a
compacted, granulated mixture with up to about 0.70% by
weight of said combination of a polymeric fluorocarbon.
The instant compositions and tablets described
herein are superior in efficacy to the prior art in
removal of stains, pla~ue and calculus. The efficacy of
these compositions is of course a function of time,
temperature and water volume used and as such comparisons
SUBSTITUTE SHEET
2 ~7~
WO92/]0165 - 14 - PCT/US91/05 7
must be based on an amount of cleansing per a specific
set of values for these factors.
The effervescent, denture cleanser compositions
; prepared as described are employed to clean dentures by
placing them in water with the denture to be cleaned for
a time suf,^icient to effect the desired cleaning. When
the cleanser is in tablet form, the tablets may be from
a~out 2 to about 3.2 grams in total weight, and are
lO usually employed with warm water, preferably about 120ml
initially about 40 to about 50C in an amount sufficient
to comple~ely cover the denture. Tablet weight is not
cri~ical. ~ en so emploved, effective and desired
cleaning may be achieved in about 5 to about 15 minutes
but in more hisllly stainèd dentures, longer periods may
be dasirable. The tablets when thus employed are found
to effectively remove mucin, plaque, calculus, and stains
which are not as readily removed by tablets not
containing enzymes and sequesterants utilized herein:
20 Moreover, this is accomplished without brushing and
usually without the overnight soaking necessary with the
generally available tablets.
The compositions of the invention are prepared by
mixing the components together until a homogenous mixture
is obtained. The composition may then be stored or
compressed into tablets. Prior to packaging or
compression, the optional ingredients may be added and
blended to obtain a uniform mixture. To limit enzyme
inactivation during storage the components may be dried
prior to blending so that they are substantially moisture
free. Drying procedures are well known in the art and do
not constitute a novel aspect of this invention.
The present invention is further illustrated by the
following examples. All percentages in the examples and
throughout the specification and claims are by total
weight of the final denture cleanser composition unless
otherwise indicated.
SUBST~TUTE SHEET
WO92/1016~ ~`7`'~7 PCT/US91/08107
Examples
With Reference to Table_I
Example A represents a preferred composition of the
; instant invention. Example I represents the prior art
composition whereby the amount of EDTA is low (3.83%), it
contains no en~ymes and the solution p~ is 8.4. Example
II represents a typical composition of the prior art
using enzy;nes in a potassium monopersulfate formula.
Example III represents the prior art whereby the amount
of EDTA is high (39.2%), it contains no enzymes and the
solution pH is lO.3. Example IV represents the use of
only one en~yme (Mile~yme APUG-330) in solution. Example
A which represents the composition of the instant
inven~ion ccntains a larqe amount of the chelating agent,
ethylene diamine tetraacetic acid tetra sodium salt
dihydrate (EDTA), and an effective amount of Enzyme
(Milezyme APUG-330) at a pH of lO.3 and contains an
equivalent amount of titratable oxygen initially to the
prior art levels in I, II, and III.
The preferred composition of the instant invention
Example A was prepared according to the Reissue Patent
#32,771 as follows. Initially, a quantity of anhydrous
sodium perborate, in the form of a fluffy powder, tetra
sodium EDTA dihydrate and sodium perborate monohydrate
was combined in a container with ~ q~antity of
polytetrafluorothylene powder identified as Grade F5A by
Allied Chemical Corp. The polytetrafluoroethylene was
added in the amounts based upon the weight of the
perborate, as indicated with respect to each of the
examples. Blending was performed for about 3 minutes,
after which the mixture was predried for l hour at 90C.
The dried materials which represent almost 94~ of the
formula were added to the other excipients and the
en~yme. The granulation was compressed into a cohesive
tablet having a hardness of 13 to 14 SCU. and the tablets
were not heat cured. ~he tablets showed excellent
stability results including the absence of any ballooning
of the final package at elevated storage conditions
(45C) for 4 months. For comparison purposes, Example
SUBSTITUTE SHEET
2~7-~`7
W092/10l6~ - 16 - PCT/US91/0
III, the prior art composition was also not heat cured.
Reissue Patent #32,771 is incorporated herein by
reference.
; Cleaninq Process
The denture (food stained plaque/calculus matrix)
tiles were immersed in 125 ml. of water a 45C, and one
of the compositions indicated in Table I were addad. A~
the end o 15 minutes, the tiles were dunked in a 200ml
10 volume of tap water 20 times the water replaced with a
fresh 200ml volume and the dunking process repeated
another 20 times and allowed to air dry at (20C) room
temperature. The tiles were visually nspected. The
extent of the calculus and pla~le remo~al was further
determined both by a reflectance method and the S~M
method.
:
SUBSTtTUTE SHEET
.~ ~ 7
` W092/10165 - 17 - PCTtUS91/08107
Tables II and III represent the analysis of the
tiles to determine the percent plaque/tartar removal
using the (SEM) Scaning Electron Microscope method and
S the
Reflectance Method respectively. Table II represents the
percent Ca, P, O, N, and Ti remaining on the surface of
the plaque/tartar coated tiles after treatment with the
test compositions I, II, III, A and IV. Both t:ile virgin
lO tiles and the untreated tartar/plaque coated tiles were
also examined to determine the baseline. As evidenced,
as the Ca, P and O increases the higher the calculus
coating on the surface of the tile. In Table II, the
results of using composition A as the plaque~tartar tiles
~5 gives the lowest Ca, P and O values indicatin~ 'hat (A is
the most efficient in removi1lg the su~face coating of
tartar/plaque.
The Reflectance Method (Table III) determines the
plaque/tartar remaining on the surface after treatment
with the test compositions I, II, III, A and IV. Again
the use of composition A gives the highest %
plague/tartar removal.
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W O 92/10165 2~7~`~7 18 - PCT/US91/0.- 7
TABLE I
In~redients I II III A IV
Sodium Bicarbonate 10.9 10.60
Citric Acid 3.8 3~60
Sodium Cl~bona~e 9.11 8.84
10 Colorant 0.16 0.l45 0.1 0~095
0,Yone 39.0 3i~80
Ethylenediqmine 3.83 3.,l 39.~ 36.6
Tetra~cetic Acid
Tetra Sodium
lS DiHy~r~qte
Flavor ~ FragranceQ.96 0.9~ 0., o~ti~
Magnesium Stearate0.03 0~03 0.025 0~024
Sodium Perborate
Monohydrate 12.39 12.0 36.3 34.6
Anhydrous Sodium
Perborate 2.66 2.58 22.3 21.2
Sodium Benzoate 1.44 1.40
Polytetrafluoro-
ethylene 0.095 0~092 0~6 O~S7
2~ Filler 4~80 4~65
Nilezyne APUG-330 -- 3.1n -- 4~70 100%~
Sodium Tripoly-
phosphate 10~16 9.85
Detergent~* 0~64 0~62 0.~ 0.67
30 % Tartar/Plaque 13~2; 15~79 28~75 55.97 16.11
Removal
* The amount used for the cleaning test all had the equivalent of
100 mg of Enzyme (alcalase)/Treatment.
*~ The detergent is athanol LAL Powder which contains 30% NaCl
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. WO92/1016~ - l9 - PCT/~S91/08107
TABLE II
SEM analysis of the said invention composition
versus prior art products.
;
Before treatment Ca P 0 N Ti
Virgin tile 0.02 0.05~75 1.18 3.27
Tartarjplaque lO.88 4.3515.71 6.41 0.47
lO After treatment
E~ample
I 12.69 4.6115.0l 4.36 0.68
II 7.59 3.0lll.56 5.74 0.42
III 6.16 1.55 10.67 6.59 2.01
13 A ~ A ~C . ~0 6.14 9.75 l.49
IV 5.lO i.o~ 8.45 3.04 0.43
TABLE III
Percent Plaque/Tartar Removal as determined by the
Reflectance Method
Example% Removed
I 13.25
. 2~ II 15~59
III28.75
A 59.97
IV l6.lO
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TABLE IV
Storage Storage Soaking % Plaque
; Example # Period TemP~ Time Removal
A 4 months RT 15 min.36.5%
III 4 months RT 15 min.23.8%
A 4 months 45C 15 min.36.3%
A 0 RT 15 min.36.3%
1~ A 7 days RT 30 m.in. 61.9%
A ~ a~yD ~ o~r~ 7~.~,0
III 1 month RT 30 min.25.5%
III 1 month RT 1~ hour~ 24.1%
1~ In Table IV, Examples A represents the preferred
composition of the instant invention t~hic!~ contains ~ot'~
the EDTA (a chelating agent) and the said enzyme
(Milezyme APUG-330) and III represents a composition
without an enzyme. The objective is to demonstrate that .
the Example A synergistically removes plaque from tiles
which have very little calculus accumulations as
evidenced by an SCM analysis. See Table V where the
calcium level is only 0.03.
TABLE V
Plaque coated Ca P O N Ti
Tile 0.03 0.18 7.72 13.50 0.31
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Based on the results of Table IV, the stability of
the preferred composition A is further evidenced when
tablets are subjected to aging at room temperature and
; accelerated aging by maintaining the temperature at 45C
for 4 months. At the end of this period, the tablets
were tested for % plaque removal to determine the
stability of the enzymes. The 4 month aged tablets were
compared to freshly prepared tablets and the results on
lO Table IV indicate an equal amount of plaque removal. In
addition thereto, Table IV results indicate that when the
tablets are dissolved, the preferred composition (Example
A) continues tc remove pla~ue, that i~, 61.9% after 30
minutes of soaking and 74.3% plaque removal after 16
13 hours Or soakin~. The comparative formulation (Example
III) does not remove more plaque with increased soaking
time and stops cleaning after removing around 25% plaque
in about 15 minutes.
This invention being thus described, it will be
obvious that the same may be varied in many ways. Such
variations are not to be regarded as a departure from the
spirit and scope of the invention and all such
modifications are intended to be included within the
scope of the following claims.
2S
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3~
SUBSTITUTE SHEET
