NZ190612A

NZ190612A - Oral compositions containing a magnesium polycarboxylate complex

Info

Publication number: NZ190612A
Application number: NZ19061279A
Authority: NZ
Inventors: A Gaffar; M C S Gaffar
Original assignee: Colgate Palmolive Co
Priority date: 1979-05-31
Filing date: 1979-05-31
Publication date: 1984-04-27

Description

<div id="description" class="application article clearfix"> New Zealand Paient Spedficaiion for Paient Number 1 90612 1 906 1 2 Priority Daisys): Corrtp'.aio Specification Fsied: \~ffl Class: Km J Ilk j-Q.te- No: .....'#>7. g,? /T]5 ? m« Patents Form No. 5 PATENTS ACT 195 3 COMPLETE SPECIFICATION An oral composition We, COLGATE-PALMOLIVE COMPANY, a corporation organized under the laws of the State of Delaware, United States of America, of 300 Park Avenue, New York, New York 10022, United States of America do hereby declare the invention for which //we pray that a Patent may be granted to »e/us, and the method by which it is to be performed, to be particularly described in and by the following tatement: 1 (followed by page la) / i 19D6 1 2 This invention relates to novel oral formulations comprising a combination of a magnesium compound with maleic acid copolymer or a sulfoacrylic acid oligomer, or a tricarboxy-oxa-butanol or pentanol as an effective agent against calculus | formation. t Description of the Prior Art The prior art is replete with oral compositions containing magnesium salts such as magnesium oxide, hydroxide, carbonate, silicate or phosphate to prevent decalcification of tooth enamel as disclosed in U.S. Patent No. 2,216,821 by Lang; magnesium chloride as a desensitizer of sensitive teeth in U.S. Patent No. 3»689,636 to Svajda; and magnesium amino-alkylene phosphonate as a dental polishing agent in U.S. Patent No. 3> - 61*2,979. The prior art also discloses many anticalculus agents, most of which are particular phosphonic acid compounds and- their , pharmaceutical^ acceptable salts wnich include the alkaline la 1 906 12 earth metals such as magnesium. The anticalculus activity is attributed to the phosphonic acid compounds per se as shown by U.S. Patent Nos. 3»U88j!|19 and 3»670,l54» wherein ai*e disclosed polyphosphonates containing two to nine phosphonic radicals; the Francis patents, Nos. 3»553»31l+> 3»553»3l5» 3»5QU»H6, 3,683,080 and 3,737,522 also disclosing the polypho§B]a§&$teis > a tri-phosphonated amine disclosed in U.S. Patent Ho. 3*639,569; and pyrolidine-diphosphonates disclosed in U.S. Patent No. 3,960,888. These phosphonates have replaced the calcium chelating agents heretofore, used as a means of preventing, retarding and removing calculus formation, since chelating agents tend to damage the tooth enamel. Examples of sequestering agents capable of removing soft tartar and other calcium deposits from teeth without any adverse side effects is disclosed in the Globus patents No. 3»U52,0l(.9 and 3,558,769, namely the magnesium polyalkanolamino ethylene diamine tetraacetate:glucono citrate complex. Although the polyphosphonates represent an improvement over the chelating agents as effective anticalculus agents, said phosphonates have been found to adversely affect the post eruptive maturation of dental enamel as shown in the Widder Patent No. 3,678,15i*» wherein is disclosed the addition of a water soluble fluoride compound to counteract said adverse effect, The use of a cyclohexane-hexacarboxylic acid and water soluble salts thereof including the magnesium salt in the therapeutic treatment of tartar is disclosed in U.S. Patent No. 3,920,837. An ammoniui^apoly aery lie acid salt or an ammonii®b« 1 polyacrylic acid polymer complex have also been used in denti- -2- 190612 frice formulations for its demineralization inhibiting and mineralization promoting effects on dental effects on dental enamel. Also known is the use of a water soluble sodium salt of a linear anionic polymer as an anti-calculus agent, as set forth in U.S. Patent No. 3,429,963 to Shedlovsky. This patent discloses that the hydrolyzed copolymers and/or polymers prevent the deposition of calculus by means of their calcium sequestration properties. Patent No. 3,956,480 further discloses a combination of a cationic germicide and an anionic polymer as an effective inhibitor of calculus formation. Patent No. 3,934,002 discloses a wide assortment of anti-calculus agents defined in prior art patents together with a bis-biguanide in a non-staining oral composition. However, there is no suggestion in these patents, nor in any of the known prior art, that the combination of a magnesium salt with the specific group of the aforedefined polycarboxylates is unusually effective in preventing and controlling calculus, over a protracted period of time, without adversely affecting the tooth enamel. -3- 2 1 NOV 1980 1 906 1 2 Another object of instant invention is to provide-an oral composition effective in inhibiting calcijltta^formation over a protracted period of time^^^^'^ Still another^etrject of this invention is to provide an oral comgpa-ilflon effective in inhibiting plaque, calculus, capfrea and periodontal disease. Background of the Invention It is well known in the art that the mineralization of dental deposits and the subsequent formation of calculus (hydroxyapatite deposit) occurs via a homogenous nucleation (an increase in Ca ions or orthophosphate ions) and/or via heterogeneous nucleation (specific salivary and bacterial pro- A p teins). However, in either case, salivary Gas* is added to the salivary orthophosphate leading to hydroxyapatite (HAP) formation, The formation of HAP in vitro occurs in two distinct steps: 1. When Ca is added to orthophosphate at constant pH (7.f|, by pH stat), there is rapid consumption of base as a function of time, that is, l-i| minutes. 2. Then the base consumption diminishes for about 15-20 minutes after which the second uptake of base occurs. A delay in the time of the second rapid consumption of base, or a total absence of a second rapid consumption suggests an interference with the crystal growth of HAP. Accordingly, compounds which interfere with crystal growth of HAP are effective anti-calculus agents. It is also known that the magnesium ion, Mg* 2 reduces ' i the overall rate of crystallization by stabilizing the precursor (amorphous deposit) formed initially with Ca and orthophosphate, -U- 1 906 1 a as disclosed in "Growth of Calcium Phosphates on Hydroxyapatite Crystals: The Effect of Magnesium, Arch. Oral Biol, 20:803, 1975. The amorphous deposits are readily removable while the crystalline phase is difficult to remove. However, the resid-ence time of externally introduced Mg ion in the oral cavity is low. Saliva also has an extremely low Mg^ content (J. Periodontal Res. 9:211-221, 197^). It has now been found that the efficacy of the magnesium ions can be improved by combining magnesium with a polycar-boxylate selected from the group consisting of the maleic acid copolymers, the sulfoacrylic oligomers and the tricarboxy-oxa-butanol or pentanol to form a complex therewith. Since there are at least two carboxyl groups per mole of polycarboxyl-containing compound (e.g. two carboxyl groups per mole of maleic acid), one carboxyl is available to react with Mg (2/3 ionized) and there are enough free COO" to react with the tooth enamel. Description of the Invention It has also been found, that the particular group of polycarboxy compounds used herein are substantive to tooth enamel. Accordingly, an effective method of inhibiting calculus formation entails the use of an oral composition comprising a magnesium polycarboxylate complex formed by combining magnesium compounds with said polycarboxyl containing compounds. The positively charged magnesium ions can react with the free carboxyl groups of the polycarboxylate to form magnesium polycarboxylate complexes. In the mouth, the magnesium combinations or complex adsorbs onto the oral surfaces such as the teeth and oral mucosa, thereby forming a reservoir of magnesium ions ' 'Mr "Ms? -5- ' • >*4- ' 190612 capable of being gradually released with time into the oral environment. Thus, the magnesium polycarboxylate complex of instant invention, will have greater substantivity to the +2 tooth enamel than the magnesium ion per se, and provide Mg ions from this complex for a longer period of time. Accordingly, it has now been found that calculus formation can be inhibited without adversely affecting the tooth enamel by treating the oral cavity with a combination of a magnesium compound and a polycarboxylate. Said magnesium polycarboxylate complex provides both a means of attachment to the oral cavity as well as a reservoir of magnesium ions which are gradually released over a protracted period of time as an effective means to combat plaque, and calculus. More specifically, this invention relates to an oral composition containing as the essential anticalculus agent, a magnesium polycarboxylate complex of magnesium compound and polycarboxylate compound wherein said polycarboxylate complex contains ionizable carboxyl groups selected from the group consisting of: 1. a copolymer of maleic acid or anhydride and of an olefin having 2 or more carbon atoms per molecule, 2. sulfoacrylic oligomers having an average molecular weight of less than 1000, and 3. a tricarboxy-oxa-butanol or pentanol, wherein bonding between said complex and said magnesium compound comprises ionic bonding and said magnesium compound is dissociable and physiologically acceptable. The polycarboxyl-containing compounds which form a complex with the magnesium are well known in the art. They contain ionizable carboxyl groups and are selected from the group consisting of the copolymers of maleic acid or anhydride and of 2 1 K'OV!?80 1 906 I an olefin having 2 or more carbon atoms per molecule, the sulfoacrylic oligomers and tricarboxy-oxa-butanol or pentanol. They are preferably water soluble per se or the alkali i&eta). or ammonium salts thereof are water soluble, at least to the extent of the concentration in which employed, about 0.1> to 10$, and preferably 0.5-1.5$ of the oral composition. Suitable examples include the copolymers of maleic anhydride or acid with ethylene, styrene, isobutylene, methyl Vinyl ether or ethyl vinyl ether having recurring groups: t i C00M C00Mx wherein M and are individually hydrogen, aod$ttj% potassium or ammonium and may be the same or different, and X is ethylene, styrene, isobutylene, methyl vinyl ether or ethyl vinyl ether. Oligomers generally and their preparation are described in U.S. patent No. 3,859,260. The sulfoacrylic oligomers used herein have an average molecular weight of less than 1000 and can be represented by the following structure: mo3S wherein M is an alkali metal or the ammonium ion, and n is less than 10 and greater than 6. The sulfonate group is not proximate to the carboxylate group. This group of sulfoacrylic oligomers have been found to be active per se in inhibiting hydroxyapatite . n i -C • i H COOH -7- 1 906 1 2 formation in concentrations of 3xl0~^ M or 33 ppm as evidenced by the following results: TABLE I /if; ffe- t (delay in Inhibitor Sulfoacrylic oligomer1 3*10"^ M (ND-2 of mol.^wt. 1000) i-f Concentratlon HAP formation) Ca :Inhibitor 17 minutes MgGl2:ND-2(l:3) H H H n i i lxl0~^ M 23 minutes 1 MO-jS H H i i H r H • i H i q _ c- c - c- c - c - c - c- ' I ' t I I ' 1 H COOH COOH i ' COOHH COOH H ,10*1 kO;l nCIO h ■'.'■■a.. ■ to:. It is additionally evident by the greater t value that the magnesium complex of the sulfoacrylic oligomer is more, effective than the oligomer per se in inhibiting HAP',crystal growth even ' in more dilute concentrations. On the contrary, other polymeric polycarboxylates such as the dimer of acrylic acid, polyacrylic acid polymers of molecular weights of 2000 or higher, and higher molecular weight polycarboxylate polymers including the poljflialeates have been found to be inactive even at greater concentrations (i.e. 8.Ox 10"^ M). In addition, the polyacrylic acid polymers exhibit no substantivity to tooth enamel. The low molecular weight polymaleates represented by the following structure: L H i C i COOH H t -C—- I COOH —l n wherein n is less than 5 have also been found to be active per -8- 1 906 1 2 se as evidenced by the following table wherein the delay in time of the crystal growth of HAP was measured in the preaeixp^ of these polymaleates, TABLE II 'E. "v n 5.0 U.O 3.0 Concentration — i- .1. ■ i .. ! i i i mm 4x10"^ M i+xlO"^ M 1x10 M t (delay time) not active minutes 30 minutes However, it ha3 been found that the magnesium cosiplex of the higher molecular weight polymaleate polymers are active lh inhibiting crystal growth of HAP as evidenced by the results « tabulated below: ; ';C TABLE III ; . Inhibitor Maleic - Vinyl methyl ether copolymer (mol. wt. 250,000) pH 7.1; MgCl2 pH 7.U Mg complex of maleic-vinyl methyl ether copolymer (mol. wt. 250,000) (1:1 mole ratio) Concentration t (minutes) 1x10"^ M 3x10"^ M lxl0"\ M 1.2xl0p+ M 3x10"^" M 1x10"^ M none none 5 18 53 29 Ca^;Inhlbltor 10:1 lj.0:1' 13.3:1 10:1 1+0 ;1 1 906 1 2 Inhibitor Concentration t (minutes) Ca^"; Inhibit or Mg complex of maleic-vinyl methyl 1x10"^- M 26 1*0:1 ether copolymer (mol, wt. 250,000) (1:2 mole ratio) Me complex of maleic-vinyl methyl ether copolymer (mol. wt. 25-0,000) (2:1 mole ratio) MgCl2-4- maleic-vinyl 1x10"^" M 68 i+Osi methyl ether copolymer (mol. wt. 250,000) (1:1). mole ratio) These results additionally show that these magnesium polycarboxylate (maleic copolymer) complexes are more effective in inhibiting crystal growth of HAP than the magnesium ion alone. The tricarboxy-oxa-butanol and pentanol per se have been found to be inactive in inhibiting crystal growth of HAP, whereas the magnesium complex thereof are effective as inhibitors of HAP crystal growth as shown by the following results: TABLE IV | | Inhibitor Concentration t (minutes) Ca ilnhibitor 0TB1 l+xlO"^ M none 10:1 MgCl2:0TB (1:1) lxlO-!+ M 16 1+0:1 MgCl2:0TB (1:1) 2xl0_<+ M 26 20:1 MgCl2:0TB (1:1) 3x10"^ M 68 13.3:1 1 0TB is 3-oxa-2,2,1+ tricarboxybutanol-1, trisodium salt repres- 1 ented by the following structural formula: 1x10"^ M 26 14.0:1 -10- 1 906 12 CO ON a i HOCH2 - G - 0 - CH2COONa COON a Although, citric acid is a tricarboxy acid, it iiis been found to be ineffective to inhibit the growth of HAP crystals. It ex<-' hibita no aubstantivity to tooth enamel and poor diffusion in aqueous medium. The unusual and unexpected effectiveness of the above tricarboxy compounds may be due to, the presence of the hydroxyl group and/or the particular configuration of said compounds. The magnesium compounds that form the magnesium polycarboxylate complex by reaction or interaction with said polycarboxylate may be any dissociable, physiologically acceptable magnesium salt including the water soluble and insoluble, organic and inorganic magnesium salt3. Examples of suitable magnesium compounds that may be employed include: magnesium acetate magnesium isovalerate magnesium acetylacetonate magnesium D-lactate magnesium ammonium sulfate magnesium DL-lactate magnesium benzoate magnesium laurate magnesium bromide magnesium hexafluorosilicate magnesium beryllium orthosilicate magnesium methacrylate magnesium borate magnesium molybdate magnesium butylphthalate magnesium naphthenate magnesium butylxanthate magnesium octoate magnesium caprylate magnesium oleate i magnesium carbonate magnesium orthophosphate -11- 1 90S I 2 magnesium chloroanilate magnesium chlorate magnesium chromate magnesium citrate magnesium cyclohexane butyrate magnesium chloride magnesium gallate magnesium fluoride magnesium alpha-glucoheptonate magnesium gluconate magnesium glycerophosphate magnesium hydroxide magnesium 8-hydroxyquinoline magnesium 12-hydroxy3tearate magnesium iodide magnesium acrylate magnesium oxide magnesium propionate magnesium phenolsulfonate magnesium pyri4Uw-2-thiol-l-'oxide ■■■ ; -v<' •. ■* '. '{ . magnes ium pyrophosphate magnesium reainate magnesium salicylate magnesium sulfate magnesium nitrate magnesium selenlde magnesium stearate magnesium sulfanilate magnesium tartrate magnesium tellurate magnesium tungstate magnesium valerate magnesium vanadate magnesium tribromosalicylan- ilide magnesium ricinoleate The majority of the magnesium salts are water-soluble. Many insoluble magnesium salts are rendered soluble when combined with the polycarboxylate, thereby providing a means of following the interaction or reaction between magnesium and the polycarboxylate. The magnesium compound constitutes about .01-5$ and preferably .025-1$ by weight of the oral composition. Aqueous dispersions-or solutions of magnesium polycar-, boxylate complexes may be produced by adding a magnesium salt -12- 1 906 f 2 in the form of a dilute solution, a paste or in the dry state', > to a dilute solution of polycarboxylate, and. atopping'tfctfi add-ition before the amount of magnesium salt is such as 1^0 fom > 'V a precipitate or gel. With good agitation and oarefuJL addition not to exceed the amount of maximum solubility of the magnesium polycarboxylate complex, a clear solution or dispersion is obtained. This phenomena is clearly indicated in Example 2. The polycarboxylate solution is preferably adjusted to a pH of about 7.0 with ammonium hydroxide or other suitable base prior to the addition of the magnesium salt. The pH of the final magnesium polycarboxylate solution is about 4.5>7.8. For, example a suitable magnesium polycarboxylate complex is formed by adding -i. '' 0.1+% of a magnesium salt solution such as MgGl^ to 100 ml of a 0.1^ solution of a copolymer of methylvinyl ether and maleic anhydride, (adjusted to a pH of 7.0 with ammonium hydroxide) and mixing well. The final solution or dispersion of the magnesium maleic copolymer complex preferably has a pH of about l|..5-7.B. It is believed that the ionized carboxyl groups react or interact with the magnesium ion to form a magnesium copolymer complex. See the article by Crisp et al, J. Dent. Res. March-April 1976, 55. 2, pp. 299-308, particularly pp. 305-307; and by Begala et al, The Journal of Physical Chemistry (1972), J6, 2, pp. 25^-260 dealing with counterion binding by polycarboxylates. The experimental evidence shows that the binding of magnesium to polymers is mostly ionic. Ionic binding leads to either; a) chain bridging salts: 1 '906 12 i CHp » e- ch-c00" i ch0 b) intra chain salts: i ghp i e- ch - i cho h2O ^H2O Mgt2—'"00C h2o h2o I ch t ch i ch coo. ch-coo" c) pendant half salts: chp » ^ ch-coo" i ch-, h2o h2o mgf 2 — oh" I h20 h2o d) chelate (ring) structures with copolymers of vinylmethyl ether and maleic anhydride, since divalent cations like magnesium form a chelate with the ether oxygen and one carboxyl group: ch-c00h I ■« ch-co - Mg Jk-o/ 1 ' I » 1 CHpCH, HO .23 2 ch-cooh -or- ffl3ch2 i ch-cooh t ch-coo HoO 3H-C00"^Mgf^— :h - oS j ch I CK- i ^ i ch .h20 h20 h20 -1)+- t 906 I "mi Accordingly, it is believed that -the magnesium carbpjcy.late complex is ionically bound, but the exact tyjpe pf bin^ing| (Whioh ■ ' ' '-v- may also exist as a mixture of above a~ ' vV"'; r," v; ascertained. 7'/-. . '• Vvv/.-:' ' ■. ''T The following examples are given to illustrate this invention further. In this application all proportions are by weight unless otherwise indicated* * EXAMPLE I 0.2 gm magnesium chloride is dissolved.,in 15 ni|! Wfi't.er and added to a h% aqueous solution of the copolymer, of maleic anhydride and methylvinyl ether with agitation and subsequently \ . . ' : - '. x.. • diluted to 200 ml. A clear solution of the magnesium copolymer complex is obtained. ! , EXAMPLE 2 V'\ a) 100 g of an aqueous magnesium oxide paste containing 0.5% magnesium is prepared and aaded slowly with continuous stirring to 25 ml of a 1$ aqueous solution of methylvinyl ether-maleic anhydride copolymer and subsequently diluted with 75 ml water. The final solution has a pH of 5.5 and is slightly cloudy, The ratio of magnesium to copolymer is 1:2. ■ b) 100 gm of an aqueous^magnesium oxld» paste containing 0.25# magnesium is added to 100 gm of an aquepua solution containing 0.25# methylvinyl ether-maleic anhydride copolymer with continuous agitation. The final solution hasr a pH of 6.5 • •• i and is turbid. The ratio of magnesium to anionic polymer is 2:1. -15- 1 906 12 c) A final solution of magnesium copolymer complex is prepared as above containing 0.25# magnesium and 1.0# maleic copolymer, a ratio of l:l|., which has a pH of >.5 and' 1 s clear. With the addition of about 10 ml. 3N ammonium hydroxide to said clear solution, the pH is adjusted to 6.8 (pH in the oral cavity) and the solution retains its clarity. This example clearly shows that the ratio of magnesium salt to maleic copolymer is dependent on the solubility of the final magnesium copolymer complex formed, maximum solubility being evidenced by a clear solution which is preferable although a slight cloudiness is also acceptable. EXAMPLE 3 A magnesium copolymer complex Is prepared by mixing. 50 ml of 0.05 M aqueous solutions of the following magnesium salts with 50 ml of a 2# aqueous solution of methylvinyl ether-male ic anhydride copolymer and the pH is adjusted to 5-6 with ammonium hydroxide. The ratio of magnesium to maleic copolymer is l:lj.. a. magnesium oxide which Is water insoluble. b. magnesium chloride which is water soluble. which c. magnesium glycerophosphate is soluble In water. d. magnesium salicylate which is soluble in water. e. magnesium alpha glucoheptonate which is water soluble. f. magnesium propionate which is soluble in water. g. magnesium salt of 8-hydroxyquinoline which is water 1-npoluble h. magnesium gluconate which is water soluble. i. magnesium pyrophosphate which is insoluble in water, but -16- '1 90 ' i 2 soluble in dilute mineral acids. The final solutions or dispersions containing the magnesium maleic copolymer complex were all clear. Although the ratio of magnesium salt to polycarboxylate in this example is 1:1+, this.ratio may be varied over a wide range, e.g. lUfcO to about J4.1l. While particularly good results in terms of calculus inhibition and other salutary effects in the oral Cavity and on tooth surfaces, have thus far been obtained by applying simply the aqueous solutions or dispersions of the magnesium polycarboxylate complex, it will be understood that it is within the broader aspect of the invention to incorporate said complex into oral compositions generally, such as clear, or. clijndy mouth rinses and transparent or opaque toothpastes, troohes, chewing gum, tablet or powder containing a dental vehicle. Likewise, the complex may be formed-in situ, during the preparation of said oral compositions or even on dilution in the mouth; or the magnesium compound and the polycarboxylate may merely act cooperatively within said oral cavity and not form a detectable complex. The vehicle, often referred to as a dental vehicle contains liquids and solids. In general, the liquid comprises water and/or a humectant such as glycerine, sorbitol, propylene glycol or polyethylene glycol I4.OO including suitable mixtures thereof. It is usually advantageous to use a mixture of both ' ' I water and one or two humectants. The total liquid content is generally about 20-90 percent by weight of the vehicle. In -17- 1 906 1:2 transparent and translucent vehicles, the liquid content of the toothpaste may be about 20-90 percent by weighty; ^itlein opaque vehicles the total liquid content is usually, about 20-50 percent. by weight. The preferred humectants are glycerine and sorbitol. Typically cl^r, that is transparent or translucent, vehicle, contains 0-80. percent by weight of glycerine, about 20-80 percent by weight of sorbitol and about 20-80 percent by weight of water. Opaque vehicles typically contain about 15-35 percent by weight of glycerine and about 10-30 percent by ..weight of water. , V- The solid portion of the vehicle is a gelling agent. In the instant invention the gelling agent includes alkali metal carboxymethyl cellulose in amounts'of at least about 0.25 percent by weight of the vehicles. Additional gelling agents may also be present. Gelling agents which may be additionally present Include viscarin, gelatin, starch, glucose, sucrose, polyvinylpyrrolidone, polyvinyl alcohol, gum tragacanth, gum karaya, hydroxy propyl cellulose, methyl cellulose, carboxyethyl cellulose, sodium alginate. Laponite CP or SP-, which are each synthetic inorganic complex silicate clays sold vinder trademark by Laporte Industries, Ltd., and magnesium aluminum silicate gel. The solid portion or gelling agent of the vehicle is typically present in amounts of about 0.25-10 percent by weight of the toothpaste and preferably about 0.5-8 percent by weight. Alkali metal carboxymethyl cellulose includes the lithium, sodium and potassium salts. Any suitable substantially water-insoluble polishing -18- 11 906 1 2 agent may be added to the gel vehicle. There is a relatively large number of such materials known in the art. , Representative materials include, for example, dicalcium phosphate, tricalcium phosphate, insoluble sodium metaphosphate, aluminum hydroxide, calcined alumina, magnesium carbonate, calcium carbonate, calcium pyrophosphate, calcium sulfate, bentonite, etc., including suitable mixtures thereof. It is preferred to use the water-insoluble phosphate, sodium metaphosphate and/or a calcium phosphate, such as dicalcium diphosphate dihydrate. The present magnesium polycarboxylate complexes have been found to stabilize the monofluorophosphates in an oral composition containing the diphosphate dihydrate abrasive. In general, these polishing agents will comprise a major proportion by weight of the solid ingredients. The polishing agent content is variable, but will generally be up to about 75 percent by weight of the total composition, generally about 20-75 percent; although, as indicated below, even lower amounts of polishing agent can be employed. Any suitable surface-active or detersive material may be incorporated in the gel vehicle. Such compatible materials are desirable to provide additional detersive, foaming and antibacterial properties depending upon the spebific type of surface-active material and are selected similarly. These detergents are water-soluble organic compounds usually, and may be anionic, nonionic, or cat ionic in structure. It is preferred to use the water-soluble non-soap or synthetic organic detergents, usually. Suitable detersive materials are known 1 and include, for example, the water-soluble salts of higher -19- 9061 2 fatty acid monoglyceride monosulfate detergent (e.g., sodium coconut fatty acid monoglyceride monosulfate )y higher alkyl sulfates (e.g., sodium lauryl sulfate), alkyl aryl sulfonate (e.g., sodium dodecyl benzene sulfonate), higher fatty acid esters of 1,2-dihydroxypropanesulfonate) and the like. The various surface-active materials may be used in any suitable amount, generally from about 0.05 to about 10 percent by weight, and preferably from about 0.5 to 5 percent by weight of the dentifrice composition. It is a further embodiment of the present invention to use the substantially saturated higher aliphatic acyl amides of lower aliphatic amino carboxylic acid compounds, auch as those having 12 to 16 carbons in the acyl radical, and as more particularly described in N.Z., Patent No. 108,236 ' issued September ll+, 195U« The amino acid portion is derived generally from the lower aliphatic saturated monoamino carboxylic acids having about 2 to 6 carbons, usually the monocarboxylic acid compounds. Suitable compounds are the fatty acid amides of glycine, sarcosine, alanine, 3-aminopropanoic acid and valine having about 12 to 16 carbons in the acyl group. It is preferred to use the N-lauroyl myristoyl and palmitoyl sarcoside compounds, however, for optimum effects. The amide compounds may be employed in the form of the free acid or preferably as the water-soluble salts thereof, such as the alkali metal, ammonium, amine and alkylolamine salts Specific examples thereof are sodium and potassium N-lauroyl, myristoyl and palmitoyl sarcosides, ammonium and ethanolamine, 21KOYf^Q -20- .1 906 1 2 N-lauroyl sarcoside, N-lauroyl sarcosine, and sodium N-lauroyl glycine and alanine. For convenience herein, reference to "amino carboxylic acid compound", "sarcoside", and the like refers to such compounds having a free carboxylic group or the water-soluble carboxylate salts. Various other materials may be incorporated in the vehicles of this invention. Examples thereof are preservatives, silicones, chlorophyll compounds, ammoniated materials such as urea, diammonium phosphate and mixtures thereof, materials which can increase contrast with the particles, such as zinc oxide or titanium dioxide and other constituents. These adjuvants are incorporated in the instant compositions in amounts . which do not substantially adversely affect the properties and characteristics suitably selected and used in proper amount depending upon the particular type of preparation involved. Antibacterial agents may also be employed in the gelled vehicles of the instantvinvention. ' fypipal antibacterial agents includes ■ ■ ,-V * ■ ■'-'iW ' N1-(l+-chlorobenzyl )-N^-(2,i+-dichlorobenzy 1) biguanide; p-chlorophenyl biguanide; i+-chlorobenzhydryl biguanide; l(.-chlorobenzhydrylKUanylurea; N-3-lauroxypropyl-*?-p-chlorobenzylbiguanide; 1,6-di-p-chlorophenylbiguanide hexane; l-(lauryldimethylammonium)-8-(p-chlorobenzyldimethyl- aramonium) octane dichloride; , ; 5>,5-dichloro-2-guanidinobenzimidazole; -21- Li 906 1 2 l 5 N -p-chloropheny1-N -laurylblguanlde; S-amino-1,3-bis(2-ethylhexyl)-3-raethylhexahydro pyrimidine; and their non-toxic acid addition salts. The antibacterial agent, when present, is employed in amounts of about 0.1-$ percent by weight, preferably about 0.05-5 percent. Any suitable flavoring or sweetening materials may be employed in formulating a flavor for the compositions of the present invention. Examples of suitable flavoring constituents include the flavoring oils, etc., oils of spearmint, peppermint, wintergreen, sassafras, clove, sage, eucalyptus, marjoram, cinnamon, lemon and orange, as well as methyl-salicylate. Suitable sweetening agents include sucrose, lactose maltose, sorbitol, sodium cyclamate and saccharine. Suitably, flavor and sweetening agent may together comprise from about 0.01 to 5 percent or more of the compositions of the instant invention. A fluorine-containing compound having a beneficial effect on the care and hygiene of the oral cavity, e.g., diminution of enamel solubility in acid and protection of the teeth against decay may also be incorporated in the gelled vehicle. Examples thereof include sodium fluoride, stannous fluoride, potassium fluoride, potassium stannous fluoride (SnPg-KF), sodium hexafluorostannate, stannous chlorofluoride, sodium fluorozirconate, and sodium monofluorophosphate. These materials, which disassociate or release fluorine-containing -22- 1 906 1 2 ions in water, suitably may be present in an effective but nontoxic amount, usually within the range of about 0.01 to 1 percent by weight of the water-soluble fluorine content thereof. The oral preparation may also be a liquid such as mouth rinse which typically contains 20-99# by weight of an aqueous lower aliphatic alcohol, preferably having about 1-30# by weight alcohol such as ethanol, n-propyl, or Isopropyl alcohol. Such oral preparations are typically applied by brushing the teeth or rinsing the oral cavity for 30 to 90 seconds at least once daily. Typical oral preparations of the invention which can be applied in this manner are set forth below. EXAMPLE k Preparation of Magnesium Polycarboxylate Mouthrlnse Total volume - 1 liter Solution A On Mixing with B (Mouthrlnse concentrate) # (gms/100 ml) Final conc: % Ethyl alcohol 20 10 Pluronlc F-100 8 4 Flavor 0,1+ 0«2 Glycerin 20 10 Saccharin 0,06 0.03 t 0.1# FD Se G Color 0.6 0.3 Deionized water q.s.tolOO.OO It A polyalkene oxide block polymer -23- 1 906 1 2 Solution B Magnesium Polycarboxylate Complex A 2% copolymer solution is prepared by adding methylvinyl ether-malelc anhydride copolymer (Gantrez) t&J>db\foi''<*&• water. The pH is adjusted to 5.5 by the addition of 3N ammonium hydroxide. Then 0.050 M of magnesium oxide salt is added with stirring. The mixture is a clear solution. 500 ml of solution A is added to 500 ml of solution B with continuous stirring (e.g. magnetic stirrer). The pH of the mixture is between 1+ and 6, and is a clear mouth rinse. The final concentration of magnesium salt in the mouthrlnse is 0.025 M and of the copolymer is 1 Equilibrium dialysis studies showed that the magnesium maleic copolymer complex in a typical mouth rinse formulation retains its identity in the presence of saliva salts and exhibits a slow rate of dissociation. The slow release of the magnesium ions and the increased retention of the magnesium in the oral cavity enhance the effectiveness of Instant oral compositions containing the magnesium copolymer complex against dental calculus formation and other oral disorders. EXAMPLE 5 Mouthwash _JL_ Ethyl alcohol 5.0 Non-ionic detergent 3.0. (Pluronic F-108)1 Flavor 0.073 -21+- J 906 1 2 * Glycerin 10,0 Saccharin 0,03 Gantrez 119 (20 ml of 0.5# aqueous solution)2, 0.1 Magnesium chloride O.ij. Water q.s. to 100 1 A polyalkene oxide block polymer 2 . Copolymer of maleic anhydride and methylvinyl ether having a molecular weight of 250,000. The magnesium chloride powder is added to a 0.5# aqueous solution of the copolymer and stirred until dissolved and the pH is adjusted to 7.00 with ammonium hydroxide and then the mouth rinse concentrate containing the remaining ingredients is added to the magnesium copolymer solution. A clear mouthwash having a pH of 5.3 is produced which is very effective in inhibiting dental calculus formation over a protracted period of time. The ratio of magnesium salt to polycarboxylate is l+sl. EXAMPLE 6 A mouth wash is prepared in accordance with the procedure of Example 5, except that 1.0# of the sulfoacrylic oligomer ND-2 defined in Table I is substituted for the 0.1# of the maleic copolymer. A clear mouthrlnse having a pH of 7.8 is produced which is an effective anti-calculus composition ' » for a protracted period of time. The ratio of magnesium salt to oligomer is 2:5. -25- v1 90612 EXAMPLE 7 : i- A mouthrlnse in accordance with Example £ la prepared except that 0.5# of the tricarboxylate 0TB defined, in Table IV, is substituted for the 0.1# of the maleic copolymer. Thei resultant mouthrinse is clear and has a pB of 7•0, and a magnesium : polycarboxylate ratio of l+:5. EXAMPLE 8 ' \ -V-;. Dental Cream •; ■'''■■' i $ - Copolymer of Example 1 1.0 : Magnesium chloride 0.025 Nonionic detergent 1.00 Glycerine 22.00 Sodium pyrophosphate 0.25 Carboxymethyl cellulose 0.85 Sodium saccharin 0.20 Sodium benzoate 0.50 Calcium carbonate (precipitated) 5.00 Dicalcium phosphate dihydrate M>»75 Flavor 0.80 Water q.s. to 100.00 ^Tween 80-Polyoxyethylene (20 moles ethylene oxide) sorbitan raonooleate. ■ ■ :V : t -26- J 906 1 2 The magnesium copolymer complex is prepared in accordance with the procedure of Example If. The remaining Ingredients . are admixed with agitation to font a base paste, which is then mixed with the magnesium copolymer complex, using either equal volumes or weights of the base paste and the preformed maghpsiTan ' ' . -T ' \. copolymer complex. An effective amount, e.g., about 0.01-556 magnesium compound and 0.1 to 10$ polycarboxylate may alao be incorporated in an inert carrier or dissolved in a suitable vehicle in the formulation of chewing gums and lozenges. Similarly, the magnesium polycarboxylate complex may also be incorporated into a mouth spray. A typical lozenge formula Contains the following ingredients, in percent by weight, based on the weight of the total formulation: 75£ to VS. CO Sugar 1% to 20 i Corn Syrup .1% to Flavor oil 0% to .03$ Colorant(s) .1% to 5:% Tableting Lubricant . 2jo to Water .1% to 10# Polycarboxylate 01% to 5£ Magnesium compound Sugarless pressed candy may also be formulated to include the complex of this invention. For products of this type, which usually contain powdered sorbitol instead of sugar, synthetic sweeteners are mixed with the powdered sorbitol and tl 906 i 2 flavor(s), colorant(s) and a tablet lubricant are then added. The formula is introduced into a tablet machine to shape the final product. A typical sugarless pressed candy contains the following ingredients, in percent by weight, based on the weight of the total formulation: 98$ to 99.5# Sorbitol .1$ to .9$ Flavor(s) 0$ to .02$ Synthetic Sweeteners 0$ to .03$ Colorant(s) .05$ to 1.00$ Tableting Lubricant Obviously many variations of the above described procedures may be used to prepare pressed candies. A typical chewing gum may contain the following ingredients, in percent by weight based on the weight of the total gum formulation: Ingredients height Percent Gum Base From about 10$ to about \\0% Sucrose From about 50$ to about 75% Corn Syrup or Glucose From about 10% to about 20% Flavor Material From about 0,[|.$ to about 5% Polycarboxylate From about 0.1$ to about 10$ Magnesium Compound From about 0.01$ to about 5% An alternate chewing gum formulation is as follows: -28- 1 906 11 Ingredients Weight Percent Gum Base Prom about 10$ to about 50# Binder Prom about 3# to about 10# Filler (Sorbitol, Mannitol From about 5# to about 80# or combinations thereof) Artificial Sweetener and From about 0.1# to about 5# Flavor Polycarboxylate From about 0.1# to about 10j£ Magnesium Compound From about 0.01# to about 5% In certain sugarless gums, there is used as the binder ingredient a solution of sorbitol in water containing from about 10# to about 80#, preferably from about $0# to about 75# by weight of sorbitol in HgO. In others, there is used a gum acacia-in-water system containing from about 30# to about 60#, preferably from about 1+5# to about 50# by weight of gum acacia powder. The above chewing gum formulations are exemplary only. Many additional formulations are described in the prior art, and in carrying out this invention, such formulations can be employed. It is also possible to prepare an acceptable chewing gum product containing a gum base, flavoring material and magnesium polycarboxylate complex according to the teaching of this invention. The ingredient referred to heretofore in the formulations simply as "gum base" is susceptible to many variations. In general, a gum base is prepared by heating and blending various ingredients, such as natural gums, synthetic resins, * waxes, plasticlzers, etc. in a manner well known in the art. -29- 1 906 1 2 Typical examples of the ingredients found in a chewing gum base are masticatory substances of vegetable origin, such as chicle, crown gum, nispero, rosidinha, jelutong, pendare, perillo, niger gutta, tunu, etc.; masticatory substances of synthetic origin such as butadiene-stylene polymer, isobutylene-isoprene copolymer, paraffin, petroleum wax, polyethylene, polyisobutylene, polyvinylacetate, etc.; plasticizers such as lanolin, stearic acid, sodium stearate, potassium stearate, etc* A preferred ingredient of instant composition is a non-ionic organic surfactant which provides increased prophylactic action, assists in achieving thorough and complete dispersion of instant compositions throughout the oral cavity and renders instant compositions more cosmetically acceptable. The non-ionic surfactant imparts to the composition detersive and foaming properties, as well as maintains the flavoring materials in solution (i.e., solubilizes flavor oils). In addition, the non-ionics are completely compatible with the magnesium polycarboxylate complex of this invention, thereby providing for a stable, homogeneous composition of superior anti-calculus control. The non-ionic organic surface active compounds which are contemplated are commercially known and comprise water-soluble products which are derived from the condensation of an alkylene oxide or equivalent reactant and a reactive-hydrogen hydrophobe. The hydrophobic organic compounds may be aliphatic, aromatic or heterocyclic, although the first two classes are , preferred. The preferred types of hydrophobes are higher -30- 1 906 1 2 aliphatic alcohols and alkyl phenols, although others may be used such as carboxylic acids, carboxamides, mercaptans, sulphonamides, etc. The ethylene oxide condensates with higher-alkyl phenols represent a preferred class of non-ionic compounds. Usually the hydrophobic moiety should contain at least about 6 carbon atoms, and preferably at least about 8 carbon atoms, and may contain as many as about $0 carbon atoms or more. The amount of alkylene oxide will vary considerably, depending upon the hydrophobe, but as a general guide and rule, at least about £ moles of alkylene oxide per mole of hydrophobe should be used. The upper limit of alkylene oxide will vary also, but no particular criticality can be ascribed thereto. As much as 200 or more moles of alkylene oxide per mole of hydrophobe may be employed. While ethylene oxide is the preferred and predominating oxyalkylating reagent, other lower alkylene oxides such as propylene oxide, butylene oxide, and the like, may also be used or substituted in part for the ethylene oxide. Other non-ionic compounds which are suitable are the polyoxyalkylene esters of the organic acids such as the higher fatty acids, the rosin acids, tall oil acids, acids from petroleum oxidation products, etc. These esters will usually contain from about 10 to about 22 carbon atoms in the acid moiety and from about 12 to about 30 moles of ethylene oxide or its equivalent. Still other non-ionic surfactants are the alkylene oxide condensates with the higher fatty acid amides. The'fatty \ -31- </div>

Claims

<div id="claims" class="application article clearfix printTableText"> 1 906 12 acid group will generally contain from about 8 to about 22 carbon atoms and this will be condensed with about 10 to about 50 moles of ethylene oxide as the preferred illustration. The corresponding carboxamides and sulphonamides may also be used as substantial equivalents. Still another class of non-ionic products are the oxyalkylated higher aliphatic alcohols. The fatty alcohols should contain at least 6 carbon atoms, and preferably at least about 8 carbon atoms. The most preferred alcohols are lauryl, myristyl, cetyl, stearyl and oleyl alcohols and the acid alcohols should be condensed with at least about 6 moles of ethylene oxide, and preferably about 10 to 30 moles of ethylene oxide. A typical non-ionic product is oleyl alcohol condensed with 15 moles of ethylene oxide. The corresponding alkyl mercaptans when condensed with ethylene oxide are also suitable in the compositions of the present invention. The amount of non-ionic may generally be varied from about 0.2-3.0^ by weight of the total formulation, depending on the specific nature of the non-ionic utilized, as well as on the amounts and nature of the other ingredients in the oral formulation. . Although this invention has been described with refer-once to specific examples, it will be apparent to one skilled in the art that various modifications may be made thereto which fall within its scope. -32- 190612 WHAT WE CLAIM IS: glaimqi ■ 1. An oral composition containing as the essential anticalculus of magnesium compoundandpolycarboxylate compound agent, a magnesium polycarboxylate complex/wherein said polycarboxylate -complex contains ionizable carboxyl groups selected from the group consisting of: 1. a copolymer of maleic acid or anhydride and of an olefin having 2 or more carbon atoms per molecule, 2. sulfoacrylic oligomers having an average molecular weight of less than 1000, and f 3. a tricarboxy-oxa-butanol or pentanol, wherein bonding between said complex and said magnesium compound comprises ionic bonding and said magnesium compound is dissociable and physiologically acceptable. 2. A composition in accordance with Claim 1, wherein the copolymer of maleic acid or anhydride has recurring groups: - X - CH - CH - ii C00M COOM-l wherein M and are individually hydrogen, sodium, potassium or ammonium and may be the same or different, and X i3 selected from the group consisting of ethylene, styrene, isobutylene, methylvinyl ether, and ethyl vinyl ether. 3. A composition in accordance with Claim 1, wherein the sulfoacrylic oligomer is represented by the following structure: MO-jS wherein M is an alkali metal or the ammonium ion, and n is less than 10 and greater than 6. U. A composition in accordance with Claim 1, wherein the tricarboxy compound is the trisodium salt of 3-oxa-2,2jij. tri-carboxybutano1-1. 5. A composition in accordance with Claim 1, wherein the l magnesium compound constitutes 0.01 to 5% by weight of the composition. 6. A composition in accordance with Claim 1, wherein the polycarboxylate constitutes 0.1 to 10$ by weight of the composition. 7. A composition in accordance with Claim 2, wherein said polycarboxylate is a copolymer of maleic anhydride and methylvinyl ether. 8. A composition in accordance with Claim 1, wherein said magnesium compound is magnesium oxide. * * 9. A composition in accordance with Claim 1, wherein said magnesium compound is magnesium chloride. . K | - 5 _ — WEST-WALKER, McCAEE ■. IgJSisj.; - por; gomA^scJU±ur 'C~ ' ATTORNEYS FOR THE APPLICANT H i -C i H H t C H i C i H i C i H COOH H COOH, n </div>