CA2075287A1 - Enzyme containing denture cleanser - Google Patents
Enzyme containing denture cleanserInfo
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- CA2075287A1 CA2075287A1 CA 2075287 CA2075287A CA2075287A1 CA 2075287 A1 CA2075287 A1 CA 2075287A1 CA 2075287 CA2075287 CA 2075287 CA 2075287 A CA2075287 A CA 2075287A CA 2075287 A1 CA2075287 A1 CA 2075287A1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
- A61Q11/02—Preparations for deodorising, bleaching or disinfecting dentures
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
- A61K8/44—Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
- A61K8/66—Enzymes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
- A61K2800/51—Chelating agents
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Birds (AREA)
- Epidemiology (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Cosmetics (AREA)
Abstract
Enzyme containing denture cleanser composition effective in plaque, calculus and stain removal utilizing proteolytic enzymes, and EDTA.
Description
-- 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
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
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 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.
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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.
:
SUB~T'TUTE SIJ-ET
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 SUBSTITUTE SHEET
. 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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SUBSTITUTE SHEET
~,7 ~? ~7 - 20 - PCT/US9l/0 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 :
SUBSTITUTE SHEET
~ Wo92/10165 ~ 7 - 21 - PCT/US91/0~ 7 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.
:
3~
SUBSTITUTE SHEET
; 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 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.
:
SUB~T'TUTE SIJ-ET
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 SUBSTITUTE SHEET
. 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
:
SUBSTITUTE SHEET
~,7 ~? ~7 - 20 - PCT/US9l/0 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 :
SUBSTITUTE SHEET
~ Wo92/10165 ~ 7 - 21 - PCT/US91/0~ 7 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.
:
3~
SUBSTITUTE SHEET
Claims (60)
1. A denture cleanser composition 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 deposits and calculus deposits.
Wherein the concomitant disruption of proteinaceous material and removal of calcium deposits and calculus deposits results in the removal of calculus plaque and stains.
(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 deposits and calculus deposits.
Wherein the concomitant disruption of proteinaceous material and removal of calcium deposits and calculus deposits results in the removal of calculus plaque and stains.
2. The composition of Claim 1 further comprising a bleaching component which does not react with halides to form an enzyme deactivating composition.
3. The composition of Claim l further comprising an effervescense producing composition.
4. The composition of Claim 2 wherein the bleaching component is a perborate.
5. The composition of Claim 4 wherien said perborate is selected from the group consisting of alkali metal and alkaline earth metal perborate and mixtures thereof.
6. The composition of Claim 3 wherein said effervescense producing composition is anhydrous sodium perborate.
7. The composition of Claim 4 wherein said perborate is sodium perborate monohydrate.
8. The composition of Claim l further comprising a bleaching agent and an effervescence producing composition.
9. The composition of Claim 8 wherein the bleaching agent is sodium perborate monohydrate and the effervescense producing composition is anhydrous sodium perborate.
10. The composition of Claim 9 wherein the weight ratio of sodium perborate monohydrate to sodium perborate anhydrous is from about 5:3 to about 3:5.
11. The composition of Claim 4 wherein the perborate is present in an amount of about 12% to about 55% by weight of the composition.
12. The composition of Claim 4 wherein the perborate is present in an amount of about 25% to about 55% by weight of the composition.
13. The composition of Claim 1 wherein the sequestering agent is selected from the group consisting of phosphonic acid derivatives, carboxylic acid derivatives and mixtures thereof.
14. The composition of Claim 13 wherein the carboxylic acid derivative is selected from the group consisting of amino carboxylate, hydroxycarboxylate and mixtures thereof.
15. The composition of Claim 1 wherein the sequestering agent is ethylenediaminetetraacetic acid.
16. The composition of Claim 1 wherein the sequestering agent is isoserine diacetate.
17. The composition of Claim 1 wherein the sequestering agent is present in an amount of about 8% to about 99.5%
by weight.
by weight.
18. The composition of Claim 1 wherein the sequestering agent is present in an amount of about 15% to about 80%
by weight.
by weight.
19. The composition of Claim 1 wherein the proteolytic enzyme is selected from the group consisting of Alcalase, Savinase, Esperase, Maxatase, Maxacal, Kuzusase, BPN, BPN', Mylezyme and mixtures thereof.
20. The composition of Claim 1 wherein the proteolytic enzyme is esperase.
21. The composition of Claim 1 wherein the enzyme is milezyme.
22. The composition of Claim 1 wherein the enzyme is present in an amount of about 0.5% to about 15% by weight.
23. The composition of Claim 1 wherein the enzyme is present in an amount of about 1% to about 7% by weight.
24. The composition of Claim 1 wherein the proteolytic enzyme is active over a pH range of about 7 to about 11.
25. The composition of Claim 1 wherein the proteolytic enzyme is a neutral or alkaline proteolytic enzyme.
WO 92/10165 - 24 - PCT/US91/08???
WO 92/10165 - 24 - PCT/US91/08???
26. The composition of Claim 3 wherein said effervescence-producing composition is 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 bicarborate sodium carbonate and potassium carbonate.
27. The composition of Claim 3 wherein said effervescence-producing composition is sodium perborate anhydrous.
28. The composition of Claim 3 wherein the effervescence-producing compositicn is present in an amount from about 15 to about 60% by weight of the total composition.
29. The composition of Claim 3 wherein the effervescence-producing composition is present in an amount of about 15% to about 30% by weight of the total composition.
30. The composition of Claim 1 wherein the proteolytic enzyme is present in a granular encapsulated form.
31. A method for cleansing dentures, said method comprising placing a water-soluble denture cleanser composition and denture to be cleaned in an amount of water sufficient to completely cover said denture for a sufficient time to dissolve the composition and to effect the desired cleaning, wherein said composition removes plaque and calculus deposits on said dentures which composition comprises:
(a) an effective amount of a proteolytic enzyme to disrupt the proteinaceous material in plaque, and (b) and effective amount of a sequestering agent to rmeove calcium deposits and calculus deposits.
Wherein the concomitant disruption of proteinaceous material and removal of calcium deposits and calculus deposits results in the removal of calculus and plaque.
(a) an effective amount of a proteolytic enzyme to disrupt the proteinaceous material in plaque, and (b) and effective amount of a sequestering agent to rmeove calcium deposits and calculus deposits.
Wherein the concomitant disruption of proteinaceous material and removal of calcium deposits and calculus deposits results in the removal of calculus and plaque.
32. The method of Claim 31 further comprising a bleaching component which does not react with halides to form an enzyme deactivating composition.
WO 92/10165 - 25 - PCT/US91/0????
WO 92/10165 - 25 - PCT/US91/0????
33. The method of Claim 31 further comprising an effervescense producing composition.
34. The method of Claim 32 wherein the bleaching component is a perborate.
35. The method of Claim 34 wherien said perborate is selected from the group consisting of alkali metal and alkaline earth metal perborate and mixtures thereof.
36. The method of Claim 31 wherein said effervescense producing composition is anhydrous sodium perborate.
37. The method of Claim 34 wherein said perborate is sodium perborate monohydrate.
38. The method of Claim 31 further comprising a bleaching agent and an effervescense producing composition.
39. The method of Claim 38 wherein the bleaching agent is sodium perborate monohydrate and the effervescense producing composition is anhydrous sodium perborate.
40. The method of Claim 39 wherein the weight ratio of sodium perborate monohydrate to anhydrous sodium perborate is from about 5:3 to about 3:5.
41. The method of Claim 39 wherein the perborate is present in an amount of about 12% to about 55% by weight of the composition.
42. The method of Claim 39 wherein the perborate is present in an amount of about 25% to about 55% by weight of the composition.
43. The method of Claim 31 wherein the sequestering agent is selected from the group consisting of phosphonic acid derivatives, carboxylic acid derivatives and mixtures thereof.
44. The method of Claim 43 wherein the carboxylic acid is selected from the group consisting of amino carboxylate, hydroxycarboxylate and mixtures thereof.
45. The method of Claim 31 wherein the sequestering agent is ethylenediaminetetraacetic acid.
46. The method of Claim 31 wherein the sequestering agent is isoserine diacetic Tri Sodium Salt. (ISDA Na3)
47. The method of Claim 3l wherein the sequestering agent is present in an amount of about 8% to about 99.5% by weight.
WO 92/10165 - 26 - PCT/US91/08??7
WO 92/10165 - 26 - PCT/US91/08??7
48. The method of Claim 31 wherein the sequestering agent is present in an amount of about 15% to about 80% by weight.
49. The method of Claim 31 wherein the proteolytic enzyme is selected from the group consisting of Alcalase, Savinase, Esperase, Maxatase, Maxacal, Kuzusase, BPN, BPN1, Mylezyme and mixtures thereof.
50. The method of Claim 31 wherein the proteolytic enzyme is esperase.
51. The method of Claim 31 wherein the proteolytic enzyme is milezyme.
52. The method of Claim 31 wherein the enzyme is present in an amount of about 0.5% about 15% by weight.
53. The method cf Claim 31 wherein the enzyme is present in an amount of about 1% to about 7% by weight.
54. The method of Claim 31 wherein the proteolytic enzyme is active over a pH range of about 7 to about 12.
55. The method of Claim 31 wherein the proteolytic enzyme is a neutral or alkaline proteolytic enzyme.
56. The method of Claim 33 wherein said effervescence-producing composition is 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.
57. The method of Claim 33 wherein said effervescence-producing composition is sodium perborate anhydrous.
58. The method of Claim 33 wherein the effervescence-producing composition is present in an amount from about 15 to about 60% by weight of the total composition.
59. The method of Claim 33 wherein the effervescence-producing composition is present in an amount of about 15% to about 25% by weight.
60. The method of Claim 31 wherein the proteolytic enzyme is present in a granular encapsulated form.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US62288790A | 1990-12-05 | 1990-12-05 | |
| US622,887 | 1996-03-29 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2075287A1 true CA2075287A1 (en) | 1992-06-06 |
Family
ID=24495909
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA 2075287 Abandoned CA2075287A1 (en) | 1990-12-05 | 1991-11-01 | Enzyme containing denture cleanser |
Country Status (4)
| Country | Link |
|---|---|
| EP (1) | EP0514520A1 (en) |
| JP (1) | JPH05503947A (en) |
| CA (1) | CA2075287A1 (en) |
| WO (1) | WO1992010165A1 (en) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5476607A (en) * | 1993-12-01 | 1995-12-19 | Warner-Lambert Company | Perborate:persulfate:protease denture cleanser powder composition |
| US5486304A (en) * | 1993-12-01 | 1996-01-23 | Warner-Lambert Company | Fragrant denture cleanser composition |
| GB2309704B (en) * | 1996-01-30 | 2000-03-15 | Kukident Gmbh | Denture cleansing |
| US6309622B1 (en) * | 1999-03-26 | 2001-10-30 | Protech Professional Products, Inc. | Antimicrobial denture cleansing compositions |
| DE10237317B4 (en) | 2002-08-15 | 2010-04-08 | 3M Espe Ag | Enzyme-containing composition, process for their preparation and their use |
| EP1701691A4 (en) * | 2003-12-22 | 2009-11-04 | Imrex Inc | Methods and compositions for oral hygiene |
| EP1600141B1 (en) | 2004-05-24 | 2013-04-17 | 3M Deutschland GmbH | Collagenolytic active enzyme containing compositions for the treatment of dental caries |
| BRPI0906461A2 (en) * | 2008-02-08 | 2015-07-14 | Colgate Palmolive Co | Oral Care Composition and Method for Applying an Oral Care Composition to the Oral Cavity |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1943441A1 (en) * | 1969-08-27 | 1971-03-04 | Leo Werke Gmbh | Denture cleaner |
| LU59503A1 (en) * | 1969-09-24 | 1970-02-26 | ||
| CA995137A (en) * | 1971-11-11 | 1976-08-17 | Ronald N. Duvall | Dry effervescent denture cleanser containing an enzyme |
| JPS58134014A (en) * | 1982-02-03 | 1983-08-10 | Rooto Seiyaku Kk | Composition for cleaning denture |
| DE3236966A1 (en) * | 1982-10-06 | 1984-04-12 | Helge G. 6380 Bad Homburg Steckmann | Tablet for cleaning dental prosthesis and orthodontic appliances in ultrasonic baths |
| US4518520A (en) * | 1983-04-22 | 1985-05-21 | Warner-Lambert Company | Cleaner having improved dissolution time and clarity and improved of preparation |
| DE3669101D1 (en) * | 1985-11-12 | 1990-04-05 | Douwe Egberts Tabaksfab | MOLDED DETERGENTS. |
| ZA875318B (en) * | 1986-08-28 | 1988-01-25 | Warner-Lambert Company | Enzyme containing denture cleansers and method of use |
| DK501686A (en) * | 1986-10-20 | 1988-04-21 | Otto Melchior Poulsen | ENZYME CONTAINING BACTERICIDIC AGENTS AND DENTALS AND SPECIAL TREATMENTS CONTAINING IT |
| US5108735A (en) * | 1988-09-09 | 1992-04-28 | Sunstar Kabushiki Kaisha | Oral composition |
| US5047163A (en) * | 1990-03-16 | 1991-09-10 | Lever Brothers Company, Division Of Conopco, Inc. | Activation of bleach precursors with sulfonimines |
-
1991
- 1991-11-01 EP EP19920900958 patent/EP0514520A1/en not_active Withdrawn
- 1991-11-01 JP JP50185292A patent/JPH05503947A/en active Pending
- 1991-11-01 CA CA 2075287 patent/CA2075287A1/en not_active Abandoned
- 1991-11-01 WO PCT/US1991/008107 patent/WO1992010165A1/en not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| EP0514520A1 (en) | 1992-11-25 |
| WO1992010165A1 (en) | 1992-06-25 |
| JPH05503947A (en) | 1993-06-24 |
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