NZ231812A

NZ231812A - Polymers comprising alpha- and/or b- styrene phosphonic acid

Info

Publication number: NZ231812A
Application number: NZ231812A
Authority: NZ
Inventors: Abdul Gaffar; John Afflitto; Michael Prencipe; Orum Nabi Nuran Stringer
Original assignee: Colgate Palmolive Co
Priority date: 1989-08-25
Filing date: 1989-12-15
Publication date: 1991-09-25
Also published as: MY107361A; NL8903188A; AU637777B2; AU4677189A; FR2651235A1; DK671189A; CZ751189A3; CA2006707A1; AR244259A1; IL92693A0; PT92735A; HK70497A; GB2235201B; DE3942641C2; CA2006707C; CZ281211B6; PT92735B; GB2235201A; JPH0383910A; CH679674A5

Description

<div id="description" class="application article clearfix"> New Zealand Paient Spedficaiion for Paient Number £31 81 £ % s? AMENDED under Section of the Pst«ntt Act 1953 from ^ ^ i ?c4.fyL ASSISTANT COMMISSIONER OP PATBgtl 9 PiIcfity 0ale(&):.l5.~:&...J.J)..Q..7 . JLS r.a .:cT.i.,a . .sq..2.5. .-.a r.^r.l, \ r.< ]. r.&.J Specif! ■ mion Filed: {b)...C.C.bf.jQ.j.Cxir.,....AUJ.tk. .1 .jll.Kt? P.O. •»■■■■■'■•'■ s % *n\ ^ ,,J , -T-V Patents Form No. 5 Number PATENTS ACT 1953 Dated COMPLETE SPECIFICATION ANTIBACTERIAL ANTIPLAQUE ORAL COMPOSITION CONTAINING1 NOVEL OUWW^ . STYRENE>PHOSPHONIC ACID .COPOLYMERS GSM33!*/* L POL1MECS #WD We, COLGATE-PALMOLIVE COMPANY of 300 Park Avenue, New York, New York ^10022., United States of America, a corporation organised under the laws of the State of Delaware, United States of America, do hereby declare the invention for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be described in and by the following statement: o "i i o This invention relates to styrenephosphonic ' polymers which are effective to enhance antiplaque effectiveness of an antibacterial antiplaque oral s' composition. Dental plaque is a soft deposit which forms on teeth as opposed to calculus which is a hard calcified deposit on teeth. Unlike calculus, plaque may form on any part of the tooth surface, particularly including at the gingival margin. Hence, besides being unsightly, it is implicated in the occurrence of gingivitis. Accordingly, it is highly desirable to include antimicrobial agents which have been known to reduce plaque in oral compositions. Frequently, cationic antibacterial agents have been suggested. Moreover, in U.S. Patent k, 022, 880 to Vinson et al, a compound providing zinc ions as an anticalculus agent is admixed with an antibacterial agent effective to retard the growth of plaque bacteria. A wide variety of antibacterial agents are described with the zinc compounds including cationic materials such as guanides and quaternary ammonium compounds as well as non-cationic compounds such as halogenated salicylanilides and halogenated hydroxydiphenyl ethers. The noncationic antibacterial antiplaque halogenated hydroxydiphenyl ether, triclosan, has also been described in combination with zinc citrate trihydrate in European Patent Publication 0161,899 to Saxton et al. The cationic antibacterial materials such as chlorhexidine, benzthonium chloride and cetyl pyridinium chloride have been the subject of greatest investigation as antibacterial antiplaque agents. However, they are generally not effective when used with anionic materials. Noncationic antibacterial materials, on the other hand, can be compatible with anionic components in an oral composition. However, oral compositions typically are mixtures 2 of numerous components and even such typically neutral materials as humectants can affect performance of such compositions. It is an advantage of this invention that an oral composition can be provided containing a substantially water-insoluble noncationic antibacterial agent and an antibacterial-enhancing agent including novel styrenephosphonic polymer which enhances the delivery of said antibacterial agent to, and retention thereof on, oral surfaces is provided to inhibit plaque formation. It is an advantage of this invention that said antibacterial-enhancing agents enhance the delivery and retention of the antibacterial agent on teeth and on soft oral tissues. It is a further advantage of this invention that the antiplaque oral composition is effective to reduce the occurrence of gingivitis. Additional advantages of this invention will be apparent from consideration of the following specification. In accordance with certain of its aspects, this invention relates to a polymer selected from the group consisting of beta-styrene phosphonic acid polymer, alpha-styrene phosphonic acid polymer and copolymers of either styrenephosphonic acid with at least one other ethylenically unsaturated polymerizable monomer. These polymers are effective to enhance antiplaque effectiveness of oral compositions containing a substantially water-insoluble antibacterial antiplaque agent, for instance in amount of about 0.01-5% by weight, such as the halogenated diphenyl ethers, 2',4,4'-trichloro-2-hydroxy-diphenyl ether (Triclosan) or 2,2'-dihydroxy-5,5'-dibromo-diphenyl ether as well as halogenated salicylanilides, benzoic esters, halogenated carbanilides and phenolic compounds. Theantibacterial-enhancing agent (AEA) which enhances delivery of said antibacterial agent to, and v> retention thereof on, oral surfaces, is employed in amounts effective to achieve such enhancement within the range in the oral composition of about 0.05% to about 4%, preferably about 0.1% to about 3%, more preferably about 0.5% to about 2 . 5% by weight. The AEA may be a simple compound, preferably a polymerizable monomer, more preferably a polymer, which latter term is entirely generic, including for example oligomers, homopolymers, copolymers of two or more monomers, ionomers, block copolymers, graft copolymers, cross-linked polymers and copolymers, and the like. The AEA may be natural or synthetic, and water insoluble or preferably water (saliva) soluble or swellable (hydratable, hydrogel forming). It has an (weight) average molecular weight of about 100 to about 1,000,000, preferably about 1,000 to about 1,000,000, more preferably about 2,000 or 2,5000 to about 250,000 or 500,000. The AEA ordinarily contains at least one delivery-enhancing group, which is preferably acidic such as sulfonic, phosphonic, or more preferably phosphonic or carboxylic, or salt thereof, e.g. alkali metal or ammonium, and at least one organic retention-enhancing group, preferably a plurality of both the delivery-enhancing and retention-enhancing groups, which latter groups preferably have the formula -(X)ri-R wherein X is 0, N, S, SO, S02 , P, PO or Si or the like, R is hydrophobic alkyl, alkenyl, acyl, aryl, alkaryl, aralkyl, heterocyclic or their inert-substituted derivatives, and n is zero or 1 or more. The aforesaid "inert-substituted derivatives", are intended to include substituents on R which are generally non-hydrophilic and do not significantly interfere with the desired functions of the AEA as enhancing the delivery of the antibacterial agent to, and retention thereof on, oral surfaces such as halo, e.g. CI, Br, I, and carbo and the 2*3* like. Illustrations of such retention-enhancing group' tabulated below. n X -(X)„R methyl, ethyl, propyl, butyl, isobutyl, t-butyl cyclohexyl, allyl, benzyl, phenyl, chlorophenyl, xylyl, pyridyl, furanyl, acetyl, benzoyl, butyryl, terephthaloyl, etc. 0 ethoxy, benzyloxy, thioacetoxy, phenoxy, carboethoxy, carbobenzyloxy, etc. N ethylamino, diethylamino, propylamido, benzylamino, benzoylamido, phenylacetamido, etc. S thiobutyl, thioisobutyl, thioallyl, thiobenzyl, thiophenyl, thiopropionyl, phenylthioacetyl, thiobenzoyl, etc. 50 butylsulfoxy, allylsulfoxy, benzylsulfoxy, phenylsulfoxy, etc. S02 butylsulfonyl, allylsulfonyl, benzylsulfonyl, phenylsulfonyl, etc. P diethylphosphinyl, ethylvinylphosphinyl, ethylallylphosphinyl, ethylbenzylphosphinyl, ethylphenylphosphinyl, etc. PO diethylphosphinoxy, ethylvinylphosphinoxy, methylallylphosphinoxy, methylbenzylphosphinoxy, methylphenylphosphinoxy, etc. 51 trimethylsilyl, dimethylbutylsilyl, dimethyl-benzylsilyl, dimethylvinylsilyl, dimethylallyl-silyl, etc. As employed herein, the delivery-enhancing group refers to one which attaches or substantively, adhesively, cohesively or otherwise bonds the AEA (carrying the antibacterial agent) to oral (e.g. tooth and gum) surfaces, thereby "delivering" the antibacterial agent to such surfaces. The organic retention-enhancing group, generally hydrophobic, attaches or otherwise bonds the antibacterial agent to the AEA, thereby promoting retention of the antibacterial agent to the AEA and indirectly on the oral surfaces. In some instances, attachment of the antibacterial agent occurs through physical entrapment thereof by the AEA, especially when the AEA is a cross-linked polymer, the structure of which inherently provides 2 5 1 increased sites for such entrapment. The presence of a higher molecular weight, more hydrophobic cross-linking moiety in the cross-linked polymer still further promotes the physical entrapment of the antibacterial agent to or by the cross-linked AEA polymer. Preferably, the AEA is a anionic polymer comprising a chain or backbone containing repeating units each preferably containing at least one carbon atom and preferably at least one directly or indirectly pendent, monovalent delivery-enhancing group and at least one directly or indirectly pendent monovalent retention-enhancing group geminally, vicinally or less preferably otherwise bonded to atoms, preferably carbon, in the chain. Less preferably, the polymer may contain delivery-enhancing . groups and/or retention-enhancing groups and/or other divalent atoms or groups as links in the polymer chain , instead of or in addition to carbon atoms, or as cross-linking moieties. It will be understood that any examples or illustrations of AEA's disclosed herein which do not contain both delivery-enhancing groups and retention enhancing groups may and preferably should be chemically modified in known manner to obtain the preferred AEA's containing both such groups and preferably a plurality of each such groups. In the case of the preferred polymeric AEA's, it is desirable, for maximizing substantivity and delivery of the antibacterial agent to oral surfaces, that the repeating units in the polymer chain or backbone containing the acidic delivery enhancing groups constitute at least about 10%, preferably at least about 50%, more preferably at least about 80% up to 95% or 100% by weight of the polymer. According to a preferred embodiment of this invention, the AEA comprises a polymer containing repeating units in which one or more phosphonic acid delivery-enhancing groups are bonded to one or more carbon atoms in 6 2 the polymer chain. An example of such an AEA is poly (vinyl phosphonic acid) containing units of the formula: which however does not contain a retention-enhancing group, group of the latter type would however be present in poly (1-phosphonopropene) with units of the formula: A preferred phosphonic acid-containing AEA for use herein is poly (beta styrene phosphonic acid) containing units of the formula: wherein Ph is phenyl, the phosphonic delivery-enhancing group and the phenyl retention-enhancing group being bonded on vicinal carbon atoms in the chain, or a copolymer of beta styrene phosphonic acid with vinyl phosphonyl chloride having the units of formula III alternating or in random association with units of formula I above, or poly (alpha styrene phosphonic acid) containing units of the formula: in which the delivery - and retention - enhancing groups are geminally bonded to the chain. These styrene phosphonic acid polymers and their copolymers with other inert ethylenically unsaturated monomers generally have molecular weights in the range of about 2,000 to about 30,000, preferably about 2,500 to about 10,000. Such "inert" monomers do not significantly interfere with the intended function of any copolymer employed as an AEA herein. Other phosphonic-containing polymers include, for example, phosphonated ethylene having units of the formula. I -tCH2 yCH]-P03H2 III -[CH yCH]-Ph P03H2 ]- V -[CH2)CHP03H2]„ 7 'V; ;>!'I' i.ipi-n where n may for example be an integer or have a value giving the polymer a molecular weight of about 3,000; and sodium poly (butene-4,4-diphosphonate) having units of the formula: VI -[CH2 - CH ]- / CH2 - CH < (P03Na2) 2 and / poly (allyl bis (phosphonoethyl amine) having units of the formula: j VII -[CH2 -.CH ]- dH2 - N < (P03H2)2 Other phosphonated polymers, for example poly (allyl / phosphono acetate) , phosphonated polymethacrylate, etc. arjd the geminal diphosphonate polymers disclosed in EP Publication 0321233 may be employed herein as AEA's, provided of course that they contain or are modified to contain the /' above-defined organic retention-enhancing groups. / The novel alpha- and beta- styrene phosphonic acid polymers and copolymers with other ethylenically unsaturated monomers may in general be prepared by heating the monomers or mixtures of monomers, preferably under nitrogen, in the presence of an effective amount, e.g. . abou.t 3-5%, of a radical initiator, e.g. AIBN, benzoyl peroxide, t-butyl ! hydroperoxide, persulfate or the like, neat or as solutions in an inert solution such as acetonitrile, methylene chloride or 1,2-dichloromethane; at elevated temperatures, e.g. about 125°C or at solvent reflux, for periods of about 8 to 200 hours. The crude polymeric products after removal of any inert solvent, is mixed with water and the aqueous mixture adjusted,to a pH of about 8-10, e.g. with aqueous sodium hydroxide. After filtration of any solid impurities, tjtie filtrate solution is dialyzed against water (e.g. at 35^0 Dalton cutoff), and the purified polymer / isolatedJnrom the retentate solution as by lyophilization. According to another preferred embodiment, the AEA may comprise a synthetic anionic polymeric polycarboxylate. Although not use^ in the present invention to coact with 8 J c. ,H2 - CH < (POaNa2) 2 and VI -[CH2 - CH ]- poly (allyl bis (phosphonoethyl amine) having units of the formula: VII - [ CH2 -.CH ]- :H2 - N < (C2H^PO3H2)2 Other phosphonated polymers, for example poly (allyl phosphono acetate), phosphonated polymethacrylate, etc. and the geminal diphosphonate polymers disclosed in EP Publication 0321233 may be employed herein as AEA's, provided of course that they contain or are modified to contain the above-defined organic retention-enhancing groups. The novel alpha- and beta- styrene phosphonic acid poljrmers and copolymers with other ethylenically unsaturated monomers may in general be prepared by heating the monomers or mixtures of monomers, preferably under nitrogen, in the presence of an effective amount, e.g. about 2.5-5o by weight of the monomers of a radical initiator, e.g. AIBN, benzoyl peroxide, t-butyl hydroperoxide, persulfate or the like, neat or as solutions in an inert solvent such as acetonitrile, methylene chloride or 1,2-dichloromethane; at elevated temperatures, O e.g. up to about 125 C or at solvent reflux, for periods of about 8 to 200 hours. The crude polymeric products after removal of any inert solvent, is mixed with water and the aqueous mixture adjusted to a pH of about 8-11, e.g. with aqueous sodium hydroxide. After filtration of any solid impurities, the filtrate solution is dialyzed against water (e.g. at 3500 Dalton cutoff), and the purified polymer isolated from the retentate solution as by lyophilization. 9 " Q 1993 According to another preferred embodiment, the AEA , c ' / < " ' N may comprise a synthetic anionic polymeric polycarboxylate. Although not used in the present invention to coact with polyphosphate anticalculus agent, synthetic anionic polymeric polycarboxylate having a molecular weight of about 1,000 to about 1,000,000, preferably about 30,000 to about 500,000, has been used as an inhibitor of alkaline phosphatase enzyme in optimizing anticalculus effectiveness of linear molecularly dehydrated polyphosphate salLs, as disclosed in U.S. Patent 4,627,977 to Gaffar et al. Indeed, in published British Patent Publication 22 00551, the polymeric polycarboxylate is disclosed as an optional ingredient in oral compositions containing linear molecularly dehydrated polyphosphate salts and noncationic antibacterial agent. It is further observed, in the context of the present invention that such polycarboxylate when containing or modified to contain retention-enhancing groups is markedly effective to enhance delivery and retention of the noncationic antibacterial, antiplaque agent to dental surfaces when another ingredient with which the polymeric polycarboxylate would coact (that is, molecularly dehydrated polyphosphate) is absent; for instance, when the ingredient with which the polymeric polycarboxylate coacts is especially the noncationic antibacterial agent. Synthetic anionic polymeric polycarboxylates and their complexes with various cationic germicides, zinc and magnesium have been previously disclosed as anticalculus agents per se in, for example U.S. Patent No. 3,429,963 to Shedlovsky; U.S. Patent No. 4,152,420 to Gaffar; U.S. Patent No. 3,956,480 to Dichter et al; U.S. Patent No. 4,138,477 to Gaffar; and U.S. Patent No. 4,183,914 to Gaffar et al. It is to be understood that the synthetic anionic polymeric polycarboxylates so disclosed in these several patents when containing or modified to contain the retention-enhancing groups defined above are operative as AEA's in the compositions and methods of this invention and such disclosures are to that extent incorporated herein by reference thereto. These synthetic anionic polymeric polycarboxylates are often employed in the form of their free acids or preferably partially or more preferably fully neutralized water soluble or water-swellable (hydratable, gel forming) alkali metal (e.g. potassium and preferably sodium) or ammonium salts. Preferred are 1:4 to 4:1 copolymers of maleic anhydride or acid with another polymerizable ethylenically unsaturated monomer, preferably methyl vinyl ether/maleic anhydride having a molecular weight (M.W.) of about 30,000 to about 1,000,000, more preferably about 30,000 to about 500,000. These copolymers are available for example as Gantrez e.g. AN 139 (M.W. 500,000), AN 119 (M.W. 250,000); and preferably S-97 Pharmaceutical Grade (M.W. 70,000), of GAF Corporation. Other AEA-operative polymeric polycarboxylates containing or modified to contain retention-enhancing groups include those disclosed in U.S. Patent No. 3,956,480 referred to above, such as the 1:1 copolymers of maleic anhydride with ethyl acrylate, hydroxyethyl methacrylate, N-vinyl-2-pyrollidone, or ethylene, the latter being available for example as Monsanto EMA No. 1103 M.W. 10,000 and EMA Grade 61, and 1:1 copolymers of acrylic acid with methyl or hydroxyethyl methacrylate, methyl or ethyl acrylate, isobutyl, isobutyl vinyl ether or N-vinyl-2-pyrrolidone. Additional operative polymeric polycarboxylates disclosed in above referred to U.S. Patent No. 4,138,477 and 4,183,914, containing or modified to contain retention enhancing groups include copolymers of maleic anhydride with styrene, isobutylene or ethyl vinyl ether, polyacrylic, polyitaconic and polymaleic acids, and sulfoacrylic oligomers of M.W. as low as 1,000, available as Uniroyal ND-2. Suitable generally are retention-enhancing group-containing polymerized olefinically or ethylenically unsaturated carboxylic acids containing an activated carbon- 10 to-carbon olefinic double bond and at least one carboxyl ii ^ ^ iL, group, that is, an acid containing an olefinic double bond which readily functions in polymerization because of its presence in the monomer molecule either in the alpha-beta position with respect to a carboxyl group or a part of a terminal methylene grouping. Illustrative of such acids are acrylic, methacrylic, ethacrylic, alpha-chloroacrylic, crotonic, beta-acryloxy propionic, sorbic, alpha- chlorosorbic , cinnamic, beta-styrylacrylic, muconic, itaconic, citraconic, mesaconic, glutaconic, aconitic, alpha-phenylacrylic , 2-benzyl acrylic, 2-cyclohexylacrylic, angelic, umbellic, fumaric, maleic acids and anhydrides. Other different olefinic monomer copolymerizable with such carboxylic monomers include vinylacetate, vinyl chloride, dimethyl maleate and the like. Copolymers ordinarily contain sufficient carboxylic salt groups for water- solubility . Also useful herein are so-called carboxyvinyl poljrmers disclosed as toothpaste components in U.S. 3,980,767 to Chown et al; U.S. 3,935,306 to Roberts et al; U.S. 3,919,409 to Perla et al; U.S. 3,911,904 to Harrison, and U.S. 3,711,604 to Colodney et al. They are commercially available for example under the trademarks Carbopol 934, 940 and 941 of B.F. Goodrich, these products consisting essentially of a colloidally water-soluble polymer of polyacrylic acid crosslinked with from about 0.75% to about 2.0% of polyallyl sucrose or polyallyl pentaerythritol as cross linking agent, the cross-linked structure and cross-linkages providing the desired retention-enhancement by hydrophobicity and/or physical entrapment of the antibacterial agent or the like. Polycarbophil is somewhat similar, being polyacrylic acid cross-linked with less than 0.2% of divinyl glycol, the lower proportion, molecular weight and/or hydrophobicity of this cross-linking agent tending to provide little or no retention enhancement. 2,5- 11 _ 3 1 diraethyl-l,5-hexadiene exemplifies a more effective retention-enhancing cross-linking agent. The synthetic anionic polymeric polycarboxylate component is most often a hydrocarbon with optional halogen and O-containing substituents and linkages as present in for example ester, ether and OH groups. The AEA may also comprise natural anionic polymeric polycarboxylates containing retention-enhancing groups. Carboxymethyl cellulose and other binding agents gums and film-formers devoid of the above-defined delivery-enhancing and/or retention-enhancing groups are ineffective as AEA's. As illustrative of AEA's containing phosphinic acid and/or sulfonic acid delivery enhancing groups, there may be mentioned polymers and copolymers containing units or moieties derived from the polymerization of vinyl or allyl phosphinic and/or sulfonic acids substituted as needed on the 1 or 2 (or 3) carbon atom by an organic retention-enhancing group, for example having the formula -(X)„-R defined above. Mixtures of these monomers may be employed, and copolymers thereof with one or more inert polymerizable ethylenically unsaturated monomers such as those described above with respect to the operative synthetic anionic polymeric polycarboxylates. As will be noted, in these and other polymeric AEA's operative herein, usually only one acidic delivery-enhancing group is bonded to any given carbon or other atom in the polymer backbone or branch thereon. Polysiloxanes containing or modified to contain pendant delivery-enhancing groups and retention enhancing groups may also be employed as AEA's herein. Also effective as AEA's herein are ionomers containing or modified to contain delivery-and retention-enhancing groups. Ionomers are described on pages 546-573 of the Kirk Othmer Encyclopedia of Chemical Technology, third edition, Supplement Volume, John Wiley & Sons, Inc. copyright 1984, which description is incorporated herein by reference. Also effective as AEA's herein, provided they contain or are modified to contain retention-enhancing groups, are polyesters, 12 2 3.1 0 polyurethanes and synthetic and natural polyamides including proteins and proteinaceous materials such as collagen, poly (arginine) and other polymerized amino acids. Without being bound to a theory, it is believed that the AEA, especially polymeric AEA, is generally and desirably an anionic film forming material and is thought to attach to tooth surfaces and form a continuous film over the surfaces, thereby preventing bacterial attachment to tooth surfaces. It is possible that the noncationic antibacterial agent forms a complex or other form of association with the AEA, thus forming a film of a complex or the like of the two over tooth surfaces. The film forming property of the AEA and the enhanced delivery and film forming property of the AEA and the enhanced delivery and retention of the antibacterial agent on tooth surfaces due to the AEA appears to make tooth surfaces unfavorable for bacterial accumulation particularly since the direct bacteriostatic action of the antibacterial agent controls bacterial growth. Therefore, through the combination of three modes of actions: 1) enhanced delivery, 2) long retention time on tooth surfaces, and 3) prevention of bacterial attachment to tooth surfaces the oral composition is made efficacious for reducing plaque. Similar antiplaque effectiveness is attained on soft oral tissue at or near the gum line. In the oral preparation, an orally acceptable vehicle including a water-phase with humectant is present. The humectant is preferably glycerine and/or sorbitol. Significant amounts of polyethylene glycol, particularly of molecular weight of 600 or more, should be avoided since polyethylene glycol effectively inhibits the antibacterial activity of the noncationic antibacterial agent. For instance, polyethylene glycol (PEG) 600 when present with triclosan in a weight ratio of 25 triclosan:1 PEG 600 reduces the antibacterial activity of triclosan by a factor of about 16 from that prevailing in the absence of the polyethylene glycol. Materials which substantially dissolve the d 0 I b i £. antibacterial agent, to permit its delivery to the soft oral tissues at or near the gum line, may be employed to dissolve the antibacterial agent in saliva. Typical solubilizing materials include the humectant polyols such as propylene glycol, dipropylene glycol and hexylene glycol, cellosolves such as methyl cellosolve and ethyl cellosolve, vegetable oils and waxes containing at least about 12 carbon atoms in a straight chain such as olive oil, castor oil, and petrolatum esters such as amyl acetate, ethyl acetate, glyceryl tristearate and benzyl benzoate. Propylene glycol is preferred. As used herein, "propylene glycol" includes 1,2-propylene glycol and 1,3-propylene glycol. The pH of oral preparation is generally in the range of about 4.5 to about 9 or 10 and preferably about 6.5 to about 7.5. It is noteworthy that the compositions may be applied orally at a pH below 5 without substantially decalcifying or otherwise damaging dental enamel. The pH can be controlled with acid (e.g. citric acid or benzoic acid) or base (e.g. sodium hydroxide) or buffered (as with sodium citrate, benzoate, carbonate, or bicarbonate, disodium hydrogen phosphate, sodium dihydrogen phosphate, etc.). The oral preparation may be substantially liquid such as a mouthwash or may be a dentifrice containing a dentally acceptable polishing agent. The oral dentifrice composition typically contains a natural or synthetic thickener or gelling agent. The oral composition may also contain a source of fluoride ions, or fluorine-providing component, as anti-caries agent. It will be understood that, as is conventional, oral preparations are to be sold or otherwise distributed in suitable labelled packages. Thus a dentifrice gel will usually be in a collapsible tube, typically aluminum, lined lead or plastic, or other squeeze, pump or pressurized dispenser for metering out the contents, having a label describing it, in 14 substance, as a dentifrice gel or the like. Organic surface-active agents are used in oral compositions to achieve increased prophylactic action, assist in achieving thorough and complete dispersion of the antiplaque antibacterial agent throughout the oral cavity, and render the compositions more cosmetically acceptable. The organic surface-active material is preferably anionic, nonionic or ampholytic in nature, and it is preferred to employ as the surface-active agent a detersive material which imparts to the composition detersive and foaming properties. Various other materials may be incorporated in the oral preparations such as whitening agents, preservatives, silicones, chlorophyll compounds and/or ammoniated material such as urea, diammonium phosphate, and mixtures thereof. These adjuvants, where present, are incorporated in the preparations in amounts which do not substantially adversely affect: the properties and characteristics desired. Significant amounts of zinc, magnesium and other metal salts and materials which are generally soluble and which would complex with active components of the instant invention are to be avoided. Any suitable flavoring or sweetening material may also be employed. The oral composition is preferably applied regularly to dental enamel and soft oral tissues, particularly at or near the gum line, such as every day or every second or third day or preferably from 1 to 3 times daily, at a pH of about 4.5 to about 9, generally about 5.5 to about 8, preferably about 6.5 to 7.5, for at least 2 weeks up to 8 weeks or more up to lifetime. The AEA and the antibacterial agent can be incorporated in lozenges, or in chewing gum or other products, e.g. by stirring into a warm gum base or coating the outer surface of a gum base, illustrative of which may be mentioned jelutong, rubber latex, vinylite resins, etc., desirably with conventional plasticizers or softeners, sugar or other sweeteners or carbohydrates such as glucose, sorbitol and the like. 15 The following Examples are further illustrative of the nature of the present invention, but it is understood that the invention is not limited thereto. All amounts and proportions are by weight, unless otherwise indicated. EXAMPLE A Poly (beta-styrenephosphonic acid) A mixture of 18 .1 g . ( 0 .1 M) of beta-styrenephosphonic acid and 0.82 g. (0.005 M) of 1 I azobisisobutyronitrile (AIBN) in 300 ml. of anhydrous / acetonitrile is stirred under reflux under dry nitrogen for 96 hrs. The mixture is cooled and the crude product precipitate is isolated filtration, washed with acetonitrile, and air dried. The crude product is dissolved aqueous sodium hydroxide (to pH 11) and dialyzed against water at 3000/Dalton cutoff. The retentate solution is reduced to 100,ml., in vacuo, and freeze- 7 / dried to yield the purified product/polymer as a white powdery f solid in 0.91 g. yield. Infrared .spectrum: 1610, 1550, 7 45 cm-1 (aryl,5 adjacent H); 1240,,1020, 950 cm-1 (phosphonate). Proton nmr (D20) : tr, 6 . 4 ppm. (H on carbon bearing phosphonate); m,7.3 ppm (aryl and benzylic protons); area ratio 1 to 6. Phosphorus nmr (D20): m,6.2 ppm. (alkyl phosphonate). EXAMPLE B Copoly (beta-styrenephosphonic acid/vinylphosphonic acid) A mixture of 10/. 68 g. (0.058 M) of beta-styrenephosphonic acid, 6.0 ml. (8.4 g. , 0.058 M) of vinylphosphonyl dichloride, and 0.5 g. of AIBN is heated, with stirring, under ail anhydrous nitrogen atmosphere intermittently for a few hours/then overnight at 80-90°C. The material is transferred tp a beaker with 60-70 ml. of water. A crystalline precipitate/^orms as the warm solution cools. The mixture is filtered, ,6he aqueous filtrate is diluted to 125 ml. with water, / and the resulting solution is dialyzed vs. water at 3500 Dalton cutoff. The retentate solution is evaporated in vacuo to give 0.600 g. purified acid form of the copolymer. Proton nmr (D20) 16 are by weight, unless otherwise indicated. c-n EXAMPLE A ' '\/ Poly (beta-styrenephosphonic acid) A mixture of 18 .1 g . (0 .1 M) of beta-styrenephosphonic acid and 0.82 g. (0.005 M) of azobisisobutyronitrile (AIBN) in 300 ml. of anhydrous acetonitrile is stirred under reflux under dry nitrogen for 96 hrs. The mixture is cooled and the crude product precipitate is isolated filtration, washed with acetonitrile, and air dried. The crude product is mixed with water, into the mixture is dissolved aqueous r.odium hydroxide (to pi! 11) and the mixture dinlyzerl ng.iimt- writer nl; 300fl Dalton cutoff. The retentate solution is reduced to 100 ml., in vacuo, and dried to yield the purified product polymer as a white powdery solid in 0.91 g. yield. Infrared spectrum: 1610, 1550, 745 cm-1 (aryl,5 adjacentll); 1240, 1020, 950 cm"1 (phosphonate). Proton nmr (D20) : tr,6.4ppm. (H on carbon bearing phosphonate); m,7.3 ppm (aryl and benzylic protons); area ratio 1 to 6 . Phosphorus nmr (D20): m,6.2 ppm. (alkyl phosphonate) . EXAMPLE B Copoly (beta-styrenephosphonic acid/vinylphosphonic acid) A mixture of 10.68 g. (0.058 M) of beta-styrenephosphonic acid , 6.0 ml. (8.4 g. , 0. 058 M) of vinylphosphonyl dichloride, and 0.5 g. of AIBN is heated, with stirring, under an anhydrous nitrogen atmosphere intermittently for a few hours, then overnight at 80-90"C. The material is transferred to a beaker with 60-70 ml. of water. A crystalline precipitate forms as the warm solution cools. The mixture is filtered, the aqueous filtrate is diluted to 125 ml. with water, and the resulting solution is dialyzed vs. water at 3500 Dalton cutoff. The retentate solution is evaporated in vacuo to give 0.600 g. purified acid form of the copolymer. Proton nmr (D20) shows to broad regions at 1.0-2.8 (alkyl, 11H) and 6.9-7.5 ppm -(aryl, 5H) . These data indicate a ratio of beta-styrenephosphonic acid to vinylphosphonic acid of 1:3 in the copolymer. Phosphorus nmr (D20) shows two main phosphorufe signals centered at about 23. A and 29.2 ppm. respectively. EXAMPLE C Poly (alpha-styrenephosphonic acid) / A mixture of 2.21 g. (O.OlM)of alpha- . / styrenephosphonyl dichloride and 0.01 g. of AIBN is stirred / under a nitrogen atmosphere at 115°C. At 12 hour intervals , successive 0.01 g. AIBN portions are added to, the mixture/ After 96 hours, the mixture is allowed to cool and dissolve in water. The pH is adjusted to 8-10 with aq. sodium hydroxide in / a total volume of 125 ml. The solution is filtered a,nd the filtrate is dialyzed against water in a 3500 Dalton Cutoff cellulose bag. The retentate is reduced to about'50 ml. in / vacuo, then freeze dried. The polymer is obtained as a tan / powdery solid in 0 . 08 g . yield. Proton nmr (D20): 23-25 ppm. (m) . This invention has been described with respect to certain preferred embodiments and it will be understood that modifications and variations thereto pbvious to those skilled in art are to be included within the purview of this application / and the scope of the appended Claims. / / / / / /' 17 MAY 1991 1 ! ' 17 </div>

Claims

<div id="claims" class="application article clearfix printTableText"> 5 1 b 1 2 copolymer. Phosphorus nmr (D20) shows two main phosphorus ' signals centered at about 23.4 and 29.2 ppm. respectively. EXAMPLE C Poly (alpha-styrenephosphonic acid) A mixture of 2.21 g. (0.01 M) of alpha-styrenephosphonyl dichloride and 0.01 g. of AIBN is stirred under a nitrogen atmosphere at 115°C. At 12 hour intervals, successive 0.01 g. AIBN portions are added to the mixture. After 96 hours, the mixture is allowed to cool and dissolve in water. The pH is adjusted to 8-10 with aq . sodium hydroxide in a total volume of 125 ml. The solution is filtered and the filtrate is dialyzed against water in a 3500 Dalton Cutoff cellulose bag. The retentate is reduced to about 50 ml. in vacuo, then freeze dried. The polymer is obtained as a tan powdery solid in 0.08 g. yield. Proton nmr (D?0): 23-25 ppm. (m) . This invention has been described with respect to certain preferred embodiments and it will be understood that modifications and variations thereto obvious to those skilled in art are to be included within the purview of this application and the scope of the appended Claims . 2 5 AUG 1993',: * 17 WHAT WE CLAIM IS: f" Al "'l" >l'!)

1. A polymer selected from the group consisting of beta-styrenephosphonic acid polymer, alpha-styrenephosphonic acid polymer, and copolymers of either styrenephosphonic acid with at least one other ethylenically unsaturated polymerizable monomer

2. A method of preparing a polymer as defined in Claim 1 comprising polymerizing the monomer or mixture of monomers at elevated temperatures in the presence of a radical initiator, mixing the crude polymeric product with water, adjusting the resulting solution to a pH of substantially 8-10, dialyzing the solution against water and isolating the purified polymer therefrom. / /

3. The polymer claims in Claim 1, wherein said polymer has ,a j t molecular weight of substantially 2,000-10,000. J f

4. The polymer claimed in Claim 1 wherein said polymer is alpha-styrene phosphonic acid polymer. /

5. The polymer claimed in Claim 1 wherein said polymer is beta-styrene phosphonic acid polymer. /

6. The polymer claimed in Claim 1 wherein said , styrenephosphonic acid copolymer is copolymerized with at least one other ethylenically unsaturated monomer.

7. The method claimed in Claim 2 wherein said purified polymer has a molecular weight of substantially 2,000-10,000. west-walker. mcgabf per: pf. ca i h< ATTORNEYS FOR TUP A. / 1 7 MAY 1991 18 / j 1 811 •'V-. A, ■O WHAT WE CLAIM IS:

1. A polymer selected from beta-styrene phosphonic acid homopolymer and copolymers with vinyl phosphonic acid.

2. Beta styrene phosphonic acid homopolymer.

3. Beta styrene phosphonic acid/vinyl phosphonic acid copolymer.

4. A polymer according to any one of Claims 1-3 having a molecular weight of substantially 2,000 to 10,000.

5. A method of preparing a polymer as defined in any of Claims 1-4 comprising polymerizing the precursor monomer or mixture of monomers at elevated temperatures in the presence of a free radical initiator, mixing the crude polymeric product with water, adjusting the resulting solution to pH of substantially 8-11, dialyzing the solution against water and isolating the purified polymer therefrom. WESJ-WALKER, iMcCABE , ir: ATTOniJCYS roft THE APPLICANT 2 </div>