CA1196286A - Peroxydiphosphate toothpaste composition - Google Patents

Abstract

PEROXYDIPIIOSPHATE TOOTHPASTE COMPOSITION

ABSTRACT OF THE DISCLOSURE
A toothpaste composition containing a peroxydiphosphate salt and optionally a fluorine-providing anticaries agent as substantially the sole oral chemically active agents, in combination with specially selected polish-ing material, thickeners, and humectants.

Description

This inventlon relates to stabilized toothpaste compositions and especially to such compositions containing a pero~ydiphosphate salt (PDP) preferably the tetrapotassium salt (KPDP), and optionally fluorine-providing anticaries agent as substantially the sole oral chemically ac-tive agents.
It is known in the ar-t that hydrogen peroxide and other peroxygen-containing agents are effective against caries, dental plaque, gingivitIs, periodontitis, mouth odor and tooth stains. In fact, the essential active PDP employed herein has been previously disclosed as an effective anti-odor agent in an oral composition. Thus, U.S. 4,041,149 is~ued August g, 1977 to Maria Gaffar, Abdul Gaffar (applicant herein) and John Hauschild discloses the effectiveness of such oral compositions, the PDP
being activated by the salivary phosphatases to generate hydrogen peroxide and/or active or nascent oxygen which deodori~es the oral cavity.
Other oral compositions have been prepared in which a PDP salt is employed as an additive to inhibit the stains normal-ly produced by the essential oral chemically active agent in the 2Q compositions. More particularly, U.S. 4,273,759 issued June 16/
1981 to Abdul Gaffar and ~aria C. Ga~far discloses oral composi-tions containing PDP salts to inhibit stains normally produced by cationic nitrogen-containing antibacterial antiplaque agents and Canadian Patent No. 1,14B,476 granted June 21, 1983 by Abdul Gaffar discloses oral compositions containing PDP salts to inhibit stains normally produced by a trane~amic acid anti~ingivitis agent.
It is also known however that most peroxy compounds such as hydrogen peroxide and metal peroxides such as magnesium peroxide are unstable in storage, continuously losing the ability to release active or nascent oxygen over relatively short periods Of time~ - 2 -", ~;

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~specially in the presence Or various other incompatib1e ;norganic alld organic mn-terial.s su.ch as many Or the usual excipients in ora:l compositions, especially toothpaste (including den-ta]. cream) composi-tions. Thus, in French Patent 2325304 (75 2~4O2) published ~pril 22 1~77, this problem is recognized ana solved by a rela-tively lifricult an(t costly mel1ns invo:lving pre~cn-ting thc peroxi~ .c~
component such as magnesium peroxide from con-tacting an acidic materia.l reac-tive therewith, as by coating said componen-t and acidic ma-terial wi-th suitable excipients, prior to and until the momen-t of use in the oral cavity.
PDP salts are regarded as substantially more stable than hydrogen peroxide and magnesium peroxide. In said U.S. 4,04l,1~
it is disclosed that a 10% aqueous solution of the preferred KPDP
shows no active oxygen loss after ~ months at 25 C. and a loss of 3% after 6 months at 50C. It was accordingly concluded, and so indicated in the patent, that "this stability permits long shelf-life of oral compositions containing said peroxydiphosphate compound" .
The aforesaid conclusion has however been found to be ror the most part un~ustified. Extensi~e experiments with ora.]
compositions containing KPDP in combination with a variety of common excipients such as polishing material (dental abrasives), humectants, thickeners, f`lavors and the like have established hL-therto unkn~wn incompatibilities resulting in unduly short storage stnbility or shelf-life, premature loss of active oxygen, impair-ment o~ the desired functions of the several components of`-the compositions and/or unacceptable chemical and/or physical and/or cosmetic properties of the compositions and the like.
It is an ob~ect of this invention -to ~rovide ornl 3() compositions which will not be subJect to one or more of the above - - - - - . . ..

i2~

disadvantages and deficiencies. Ano-ther object of this invention is the pro-vision of stable oral compositions containing a PDP salt, and optionally a fluorine-providing anticaries compound, as substantially the only oral chemi-cally active agents. Still another object of this invention is the pro-vi-sion of methods for promoting oral hy~iene employing such composi-tions.
Other objects and advantages will appear as the description proceeds~
In accordance with certain of its aspects, this invention includes the provision of a toothpaste composition comprising:
I an oral vehicle, II as substantially the only oral chemically active agents, A. O to about 2 wt.% of a fluorine-providing anti-caries com-pound and B. about l to about 7 wt.% of a peroxydiphosphate salt III about lO to about 75 wt.% of at least one polishing material selected from the group consisting of silica and hydrated alumina, IV about 0.5 to about lO wt.% of at least one thickener selected from the group consisting of colloidal silica, synthetic hectorite, poly(methyl vinyl ether/maleic anhydride), carboxy-vinyl poiymer, carboxymethyl cellulose, hydroxypropyl methyl cellulose~ hydroxybutyl methyl cellulose, and hydroxyethyl cellulose, and V about 5 to about 75 wt.% of polyethylene glycol as humectant.
The above defined oral chemically active IIA and B components are typically and preferably inorganic. These compositions which comprise mutu-ally compatible components enable the attainment of one or more unexpected improvements such as I

unexpectedly improved stora~e stahility or shelf-life, acceptable chemical and/or physical and/or cosmetic properties, retention of the deslred functions of the individual components, and the like. As employed herein, the term "oral chemically active agent"
refers to anticaries, antiplaque, antigingivitis, antiperiodonti-tis, an~iodor and bleaching agents and the like which act chemically on, with respect to or in relation to the teeth, oral tissues and/or oral en~ironment, in contrast to polishing material (dental abrasives) ~hich act physically on the teeth and inert components which determine the properties of the oral composition per se such as thickeners, humectants, flavors, surfactants r sweeteners, colors, whiteners, brighteners, preservatives, and other conventional excipients. The essential PDP salts employed herein, especially KPDP, fall in the category of each of the aforementioned oral chemically active agents. The oral composi-tions of this invention, for similar reasons, are mutually exclusive of the antibacterial antiplaque compositions of the above mentioned U.S. 4,273,759 and the antigingivitis compositions of the above mentioned Canadian Patent No. 1, 148,476.
Any of the alkali metal, alkaline earth metal, metalor ammonium peroxydiphosphates or their corresponding acid salts that are water-soluble to the extent of about 0.001 weight percent can be used in the compositions of this invention. ~xamples of these a~e tetrapotassium peroxydiphosphate (X4P208), tetralithium peroxydiphosphate (Li4P2O8), tetrasodium peroxydiphosphate (Na4P2O8), tripotassium monosodium peroxydiphosphate (K3~aP2O8), dipotassium disodium peroxydiphosphate (K2Na2P2O82H2O), . . .~,j monopotassium trisodium peroxydiphosphate (KNa3PO8), monopotassium monosodium dihydrogen peroxydiphosphate (KNaH2PO8), trilithium monopotassium peroxydiphosphate (Li3KP2O8), dilithium dipotassium peroxydiphosphate (Li2K2P2O8), monolithium dipotassium diphosphate (LiK3P2O8), trilithium monosdium peroxydiphosphate (Li3NaP2O8), dilithium disodium peroxydiphosphate (Li2Na2P2O8), monolithium trisodium peroxydiphosphate (LiNa3P2O8), monolithium monosodium dihydrogen peroxydiphosphate (LiNaH2P2O8), and monolithium monopotassium dihydrogen peroxydiphosphate (LiKH2Y2O8), in addition to dizinc peroxydiphosphate (Zn2P2O8), tetraammonium peroxydiphosphate dihydrogen peroxydiphosphate (CaH2P2O8), and of group 2 metals such as barium dihydrogen peroxydiphosphate (BaH2P2O8), calcium dihydrogen peroxydiphosphate (CaH2P2O8), and the like.

The preferred tetrapotassium peroxydiphosphate (KPDP) is a stable, odorless, finely divided, free-flowing, white, non-hygroscopic crystalline solid having a molecular weight if 346.35 and an active oxygen content of 4.5%. The potassium peroxydi-phosphate is 47-51% water-soluble at 0°-61°C, but insoluble in common solvents such as acetonitrile, alcohol, others, ketones, dimethyl formamide, dimethyl sulfoxide, and the like, A 2%
aqueous solution has a pH of about 9.6 and a saturated solution thereof a pH of about 10.9.

The essential PDP salt (or mixture thereof ) is employed in an amount effective for achieving the desired therapeutic, antiordor, bleaching or other function, typically constituting about 1 to about 7 wt. %, preferably about 2 to about 5 wt. %, more preferably about 3 wt. %, of the instant oral compositions.

The fluorine-providing anticaries compounds optionally present in these oral preparations may be slightly soluble in ~196~

water or may be fully water-soluble. They are characterized by their ability to release fluoride ions in water and by substantial freedom from reaction with other compounds of the oral preparation. Among these materials are inorganic fluoride salts, such as soluble alkali metal, alkaline earth metal and heavy metal salts, for example, sodium fluoride, potassium fluo-ride, ammonium fluoride, calcium fluoride, a copper fluoride such as cuprous fluoride, zinc fluoride, a tin fluoride such as stannic fluoride or stannous chlorofluoride, barium fluoride, sodium fluorosilicate, ammonium fluoro-silicate, sodium fluorozirconate, sodium monofluorophosphate, aluminum mono-lQ and di-fluorophosphate, and fluorinated sodium calcium pyrophosphate.
~lkali metal and tin fluorides, such as sodium and stannous fluorides, sodium monofluorophosphate ~MFP) and mixtures thereof, are preferred.
The amount of the fluorine-providing compound is dependent to some extent upon the type of compound, its solubility, and the type of oral pre-paration, but it must be a nontoxic amount. An amount of such compound which releases a maximum of about 1% of fluoride ion by weight of the pre-paration is considered satisfactory. Any suitable minimum amount of such compound may be used, but it is preferable to employ sufficient compound to release about 0.005 to 1%, and preferably about 0.1% of fluoride ion. Typi-cally, especially in the cases of MFP, alkali metal fluorides and stannous fluoride, this component is present in an amount of about 0.01 to about 2%
by weight, based on the weight of the preparation, and preferably in the range o~ about 0.05 to about 1 wt.%, especially about 0.76 wt.%.
To achieve the desired results herein, the component III polishing material should be selected from among silica, preferably hydrated alumina (alpha alumina trihydrate), both of which are per se conventional dental abrasive polishing material with average particle sizes ranging Erom about 0.1 to about 30 microns, preferably abou-t 1.0 to about 15 microns. The following are illustrative of some preEerred polishing material.
The silica polishing material may be in the form of crystalline silica having particle sizes up to 5 microns, a mean particle size of up to about 1.1 microns and a surface area of up to 50,000 cm. /gm., silica gels, Zeodent* (e.g. Zeodent 49, 119) precipitated silica products of J. M. Huber Corporation, complex amorphous alkali metal aluminosilicates, and the like.
The types of silica dental abrasives disclosed in U.S. 3,8~2,307 issued January 21, 1975 may be employed.
When visually clear gels are employed, a polishing agent of silica zerogel or colloidal silica such as those sold under the trademark SYLOID (W. R. Grace and Co. e.g. Syloid 63, ~4, 72 or 74) or under the trademark SANTOCEL as Santocel 100 and alkali metal aluminosilicate complexes are particularly useful, since they have refractive indices close to the refrac-tiv~ indices of gelling agent-liquid (including water and/or humectant) systems commonly used in dentifrices.
~ Iydrated alumina, particularly the hydrated alumina sold by Alcoa as C333, which has an alumina content of 64~9%
by weight, a silica content of 0.008%, a ferric oxide content of 0.003%, and a moisutre content of 0.37%, at 110C., and which has a specific gravity of 2.42 and a particle si~e such that 100% of the particles are less than 50 microns and 84%
of the particles are less than 20 microns, is particularly desirable. Hydrated alumina has been found to be the most * Trade Mark compatible polishing material herein.
The polishing material is generally present in amounts ranging from about 10 to about 75 wt.~, preferably ahout 35 to 65 wt.%, more preferably about 45 to about 55 wt. in these toothpaste compositions.
The thicXener component IV, employed in proportions of about 0.5 to about 10 preEerably about 1 to about 5, wt.%
of the composition should be one or a mixture of the above-named members of the group. A preferred thickener is synthetic hectorite, a synthetic colloidal magnesium alkali metal silicate complex clay available for example as Laponite* (e.g. XLG, XLS, D) marketed by Laporte Industries Limited. I,aponite D analysis shows, approximately by weight, 58.007u SiO2, 25.4CZ MgO, 3.05%
Na20, 0.98% Li20, and some water and trace metals. Its true specific gravity is 2.53 and it has an apparent bulk density (g./ml. at 8% moisture~ of 1Ø
Other thickeners include carboxymethyl cellulosc, hydroxybutyl methyl cellulose, hydroxypropyl ~ethyl cellulose, and preferably hydroxyethyl cellulose (e.g. available as Natrosol).
The poly(methyl vinyl ether/maleic anhydride) tl)icken~
is available for example as Gantrez*AN 139 (GAF Gorporation) and the colloidal silica thickener as a more finely ground Syloid (e.g. 244).
The carboxyvinyl polymer useful as thickener is for¦
example available as Carbopol ~e.g. 934, 940, 941). These pruduct~ of ~ . Coodrich Co. arcdcscribcd ill U. S. 2,798,()~i~

*Trade mark ~.~9~

2,923,692 and 2,980,655, being essentialiy colloidally water-soluble acidic carboxylic Dolymers of acrvlic ac;-l cros~sed-linl<ed wiLII al-ollt 0.75 to .lhollt ~ Or a cr(~s.;-LLnklllg a~ent of polyallyl sucrose or polyallyL pell~acrytllriL-l.
`rh~ humectant component V, employod in prol)ortiolls of about 5 to 75, preferably about lO to 45, more preferably about 15 to 35, wt.% of the toothpaste compositions of this invention is polyethylene glycol (e.g. 400,600). This component of relatively low molecular weight (e.g. about 300 to about 1,000~ often also functions as the liquid carrier vehicle, alone or in combination with water and/or ethanol.
Any flavor optionally but preferably employed in the PDP-containing toothpaste compositions of this invention should of course also be compa~ible with the PDP.
Flavor is typically included in the oral compositions of this invention in approximate weight proportions of 0.01 to 3.0%, preferably 0.5 to 2.0%, more preferably 0.75 to 1.0%. Some illustrative examples of compatib]e flavors include pulegol, anethole, isoeugenol, guaiacol, creosol, ~ thymol, menthol, cineol, eu~enol9 clove bud oil, peppermint and spearmint extracts, carvone, methyl paracresol, eucalyptol, safrole, anisol and the like.
The solid and liquid components of the compositions of tiliS invelltion are proportioned in conventional manner to form ~5 a pasty, creamy or gelled mass which may be dispensed or extruded from a pressuri7ed container or from a flexi~le . . .

or collapsible container or tube, e.g. alumina, linecl lead or plastic or the like The compositions may be subsLantially anhydroLIs but generally contain about l to about 25, typically abolJt 5 to about 20, wt.% of water. These compositions preEerably have a pH measured as a 20% aqueous slurry of 7.
to about 10.5 more preferably about 8.5 to about 10.5, especially about 9.5 to 10.5 since the PDP, especially KPDP, appears to be more stable, i.e. with better retention of active oxygen activity, at these more alkaline ranges in tl~e presence of the other components of the compositions. The pH can be controlled by inclusion of the required amounts of acidic substances such as citric or benzoic acid, basic sub-StLlllCeS S~lCh as sodium hydroxide, and/or buffering agents such as sodium citrate, benzoate, bicarbonate or c~rbonate, ~isodium hydrogen phosphate, sodium dihydrogen phosphate, or mixtures thereof. It should be noted that selection of the proper dental abrasive or polishing mLlteria] is importan~
for maintenance of the above described alkaline pH ranges, since most conventional polishing materials cannot be employed in the instant compositions at such pl~ ranges.
For example, when insoluble sodium metaphosphate (IMP) abrasive is employed with the other above-defined componen~s of these compositions and the pll adjusted to 9.7, the composition loses substantial amounts of its available oxygen when aged at 120F and the pH shifts down to about 7.2. In contrast, although compositions of this invention with silica as polishing material show poor stability at an "afi -is" pll Or 7.7 2 51~i the composition is stabilized when the pH is adjusted upwards as indicated above, e.g. to 9.7, and the pH does not shift significantly with aging. Hydrated alumina performs in excellent manner in this respect since its normal pH falls within the above ranges.
The toothpaste compositions of this invention may contain a non-soap synthetic sufficiently water soluble organic anionic or nonionic surfactant in concentrations gener~lly rang-ing from about 0.05 to about 10, preferably about 0.5 to about 5, weight percent, to promote we-tting, detersive and foaming properties.
U.S. Patent No. 4,041,149 discloses such suitable anionic surfactants in col. 4, lines 31-68 and col. 9, lines 1-12.
Pluronic* type nonionic surfactants (polyoxyethylene polyoxy-propylene block polymers) such as Pluronic F108 and F1~7 may also be employed.
Various other conventional toothpaste adjuvants or e~cipients may be included such as whitening or coloring agents, preservatives, silicones, ammoniated material such as urea and ~,o diammonium phosphate, and sweetening agents in amounts ranging from about 0.01 to about 5 wt.~ or more. Suitable sweetening agents include for example sorbitol, xylitol, sodium cyclamate, perillartine, D-tryptophan, dihydrochalcones, and the like, preferably saccharin.
In the practice of this invention r the toothpastes of this invention are applied regularly to the oral cavity, especial ly dental enamel, preferably from about 1 to 3 times daily, for durations of preferably at least about 10 seconds, more prefer-ably at least about 60 seconds, in the usual required amounts employed in brushing the teeth.

* Trade Mark - 12 ~ 3~ ~6 The following exam~les are rurther illusLrativc or thL~
nature of the present invention and are not to be regarded as limitative. All amounts and proportions referre(l to herein and in the appended claims are by weight unless otllerwise indicated.

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In the following examples the stability of the KPDP can be evalu-ated by monitoring active oxygen (A.O.) contents by the following procedure:
KPDP readily hydrolyzes in an acid medium as follows:
P2O8 +2H2O > 2HPO4 +1i22 An excess of ferrous ammoniwn sulfate is added to reduce peroxide:
~ 2( 4)2 22 ll2SO4- > Fe2(so4)3+2(NH4)2so4-~2H
The excess of ferrous ion is back titrated with ceric sul~ate:
2Fe(N~1 ) (SO4)2+2Ce(SO4)2 - ~ Ce2(SO~1)3 Fe2( 4)3 4 2 4 The A.O. is found by difference.
Table I
Example (WT.~) Water, distilled 19.69 17.0 18.0 Laponite XLG 2.4 2.4 2.5 PEG 600 8.7 8.0 7.0 Pluronic F108 4.3 4.0 4.5 Sodium benzoate 0.54 0.5 0.54 Sodium saccharin 0.22 0.2 0.22 Flavor 0.55 0.5 0.55 Water, distilled 7.6 7.0 7.6 KPDP 3.0 3 0 3 0 I-lydrated alumina 53.0 50.0 53.0 Active Oxygen '[`heoretical 0.126 0.126 0.126 [nitial at RT 0.123 0.130 0.122 Aged 7 weeks at lOO F 0.123 0.131 0.130 ,.~

;Z~36 Table IV
Example ~Wt.%) ~ 9 10 llydroxyethyl cellulose l.O 1.0 1.0 PEG 600 20.0 20.0 20.0 Sodium benzoate 0.5 0.5 0.5 Sodium saccharin 0.2 0.2 0.2 ~Iydrated alumina 47.0 47.0 48.0 KPDP 3.0 3.0 3.0 il2o 26.05 26.05 25.6 Flavor 0.75 0.75 0.5 SLS* 1.5 1.5 ---Nonionic Surfactant** ~ 1.2 (p~ 1 0) ~ 1 0) Active Oxygsn Initial at RT 0.136 0.131 0.130 Aged 6 weeks at 120 F 0.134 0.133 Aged 9 weeks at 120 F 0.130 *Sodium lauryl sulfate **Polyethoxylated ~20E.O.) sorbitan monoisostearate The formulations in the above examples exhibit good to excellent active oxygen stability in storage. In contrast, the only toothpaste formu-lation disclosed in U.S. 4,041,14g, namely Example 1, containing incompatible components ~glycerine, precipitated calcium carbonate and dicalcium phosphate dihydrate) exhibits unacceptable active oxygen stability. Some of the above examples show the sequence of addition of underlined individual or grouped components.

I~'X/~MI'I,I~' 1 1 Natrosol 250 ~1~ 1.0 'l (, Goo 20 . o lI y (l r rlt ~ r~ L 5 2 . 0 `;1.; 1.~
50dium benzoate 0.5 Sodium saccharin 0.2

3.0 Deionized water 25.8 (pil at 10.2) The above chemically, physically and cosmetically stable formulation according to this invention and a control form~lation omi-tting the KPDP were evaluated for effectiveness in reducing gingivitis and plaque in a scientifically conducted 12 week test on groups of 10 beagle dogs (5 male and 5 female). The results (average of 10 dogs) were as follows:

CONTROL ~MPLE 11 Gingiva Index Initial 0.85 0.88 Final 0.79 0.47 Plaque Unit Index 1.22 o.96 These results established that the addition of the liPDP
to the control formulati.on significantly reduced both the ginFival index and the plaque index. In contrast.y a simultaneous test using a nonaqueous formulation containing propylene glycol humectant, hydroxypropyl cellulose thickener and Dical abrasi.ve increased the plaque index and a similar test using an aqueous .... .. _ _ .. .. . . . . . . . . .

2~6 neutral formu:Lution containing PEC 600 hurnectZln-t, hydroxyet,llyl ce]lulose thickener and IMP abrasive increased bo-th the gingival and plaque indices.
It has been shown above -that formulations according to tl~c invention coll-tainin~ polyethyl.ene glycol (]'E(,) hulnectnnt are lli,shly sta,ble against loss of available o.xygen. 'I`he criti-cali-ty of combinations o~ required components insllch formulations, and -the mutuality of s-tabilization therein, is established for example by the fact that PEG acts upon and dras-tically reduces the ef`fectiveness of KPDP as a source of availabl.e oxygen in the absence of the other defined components. Thus, aqueous k'Plll' solutions bu~fered to p~l 7 are stable at 120F for 9 weeks, but the addition of varying amoun-ts (3%, 15%, 40%) of PEG to 3%
~PDP solutions (conducted in triplicate~ yield, when age(l 9 weeks at 100F and 120F, the following average results:

% of Available Oxygen 1 wk 3 wk 6 wk 9 wks 6 wks 9wks Initial 120F 120F 120F 120F 100F ]00F
3% PEG 0.126 0.107 .050 0.041 0 0.086 O.()ol 15% PE~I 0.115 0.113 o.o66 0.053 0.023 0.088 o.oG~

40,0 PEG 0.120 0.116 0.091 o.o84 0.029 0.091 0.072 AVERAGE % LOSS
6.7 42.4 50.4 85.2 26.5 41l.g This invention ha.s been disclosed with respect to preferred embodiments, and it will 'be understood that modifications and variations thereof obvious to those skilled in the ar-t are to be included within the spirit and purview of this application and the _.~ . . ~ _ i . . . , . . . . . ~ ~ .. ,

Claims (7)

WE CLAIM:

1. A toothpaste composition comprising:
I an oral vehicle II as substantially the only oral chemically active agents, A. 0 to about 2 wt.% of a fluorine-providing anticaries compound and B. about 1 to about 7 wt.% of a peroxydiphosphate salt, III about 10 to about 75 wt.% of at least one polishing material selected from the group consisting of silica and hydrated alumina, IV about 0.5 to about 10 wt.% of at least one thickener selected from the group consisting of colloidal silica, synthetic hectorite, poly(methyl vinyl ether/maleic anhydride), carboxyvinyl polymer, carboxymethyl cellulose, hydroxypropyl methyl cellulose, hydroxy-butyl methyl cellulose, and hydroxyethyl cellulose, and, V about 5 to about 75 wt.% of polyethylene glycol as humectant.

2. A composition according to claim 1 wherein the polishing material comprises hydrated alumina.

3. A composition according to claim 2 wherein the thickener comprises synthetic hectorite.

4. A composition according to claim 2 wherein the thickener comprises hydroxyethyl cellulose.

5. A composition according to claim 1 wherein the polishing material comprises silica.

6. A composition according to claim 1 wherein said peroxydiphosphate salt is tetrapotassium peroxydiphosphate.

7. A composition according to claim 6 having a pH of 7.8 to about 10.5.