RU2116781C1 - Composition for mouth gargling - Google Patents

Abstract

FIELD: stomatology, in particular, composition for prevention of dental deposit and concrement on teeth. SUBSTANCE: composition contains polyphosphate substance, in particular, tetraalkalimetal pyrophosphate, and, compatible with it, antibacterial agent. It is 2,4,4'-trichlor-2'-hydrooxydiphenyl ether (triclosan) insoluble in water, noncationic, antibacterial agent. Composition action is intensified by anionic polymer which is antibacterial agent. EFFECT: prevention of forming tartar. 13 cl, 2 tbl, 1 expe

Description

 The invention relates to an antibacterial, preventing the formation of plaque and calculus (oral) composition. More specifically, the invention relates to an oral composition containing a polyphosphate, anti-calculus (i.e., calculus) antimicrobial agent and a compatible antibacterial agent effective in preventing the formation of plaque, the effectiveness of which is optimized by the presence of an agent that enhances the effect of the antibacterial agent by enhancing the receipt and retention of an antibacterial agent on intraoral surfaces.

 US Pat. Nos. 4,627,977 to Caffar, Nos. 4,515,772 to Parran and Nos. 4,323,551 to Parran describe oral compositions comprising various polyphosphate compounds. Caffar uses a linear molecular dehydrated polyphosphate salt in combination with a fluoride ion source and linear synthetic polycarboxylate to inhibit calculus formation. In the co-pending European Patent Application 89,200,710.5, anti-calculus formation is optimized by a reduced amount of linear molecularly dehydrated polyphosphate salt in combination with a source of fluoride ions and an increased amount of synthetic linear polymeric polycarboxylate.

 The patran et al. Patents describe the use of water-soluble di-alkali metal pyrophosphate as such or in a mixture with tetra-alkali metal pyrophosphate.

 Oral compositions inhibiting the formation of calculi on the surface of the teeth are necessary because tartar is one of the factors that cause periodontitis. That is, reducing the formation of tartar serves oral hygiene.

 Plaque is a precursor to tartar. But unlike tartar, plaque can form on any part of the tooth surface, including at the edge of the gum. That is, plaque is responsible for the occurrence of gingivitis.

 Thus, it is desirable to include in oral compositions containing an anti-calculus preparation, antimicrobial agents for which the ability to reduce plaque formation is known. Such an approach is described in US Pat. No. 4,022,550 to Vinson, in which a zinc ion-giving compound as an anti-calculus agent is mixed with an antibacterial agent that effectively inhibits the growth of plaque bacteria. A variety of antibacterial agents are provided along with zinc compounds, including cationic materials such as guanides and quaternary ammonium compounds, as well as non-cationic compounds such as halogenated salicylanides and halogenated hydroxydiphenyl ethers.

 To date, cationic antibacterial agents such as chlorhexidine, benzonium chloride and cetyl pyridinium chloride have been the subject of enhanced research as antibacterial plaque-preventing agents. However, despite their use in combination with zinc anti-calculus agents, they are ineffective when used with anionic substances such as polyphosphate anti-calculus agents. Such inefficiency can be considered extremely unexpected, since polyphosphates are chelating agents, and the chelating effect has been found to increase the effectiveness of cationic antibacterial agents (see, for example, Disinfection, sterilization and preservation. 2nd ed., Black, 1977, p. . 915 and "Inhibition and destruction of microbial cells", Hygo, 1971, S. 215). Indeed, the quaternary ammonium compound is present in a pyrophosphate anti-plaque mouthwash (US Pat. No. 4,323,551 to Parran), and bisbiguanide in an anti-calculus oral composition (US Pat. No. 4,515,772 Parran) and other

 Due to the unexpected incompatibility of cationic antibacterial agents with polyphosphates present as anti-calculus agents, it is difficult to expect efficacy from other antibacterial agents.

 An advantage of the present invention is that certain antibacterial agents are effective in preventing calculus formation of oral compositions containing a linear molecularly dehydrated polyphosphate salt, a fluoride ion source and the aforementioned antibacterial agent for inhibiting plaque formation.

 Another advantage of the present invention is that it provides a composition effective in terms of reducing the formation of calculi and optimizing the prevention of plaque formation.

 And another advantage of the present invention is that it provides an anti-calculus and plaque-forming oral composition that is effective in reducing the likelihood of gingivitis.

 Additional advantages of the present invention will become apparent upon consideration of the following description.

 In accordance with some aspects of the present invention, there is provided an oral composition comprising an orally acceptable carrier, an effective anti-calculus quantity of material comprising 0.1-3 wt.%, At least one linear molecular dehydrated polyphosphate salt as anti-calculi an agent effective in preventing plaque formation, an amount of a substantially non-water-insoluble non-cationic antibacterial agent, and preferably up to 4 wt.% Agent that enhances the action of the antibacterial agent, which enhances the intake and retention of the antibacterial agent on the oral surfaces, where, as a rule, the ratio by weight of the polyphosphate ion to the agent enhancing the action of the antibacterial agent is in the range from more than 0.72: 1 to less than 4: 1, for example, from 1: 1 to 3.5: 1, especially from 1.6: 1 to 2.7: 1, preferably from 1.7: 1 to 2.3: 1, and most preferably from 1.9: 1 to 2: 1. For example, in the case of the use of 2% tetrasodium pyrophosphate (TNPF) (forms 1.3% pyrophosphate ion) with 2.5% of an agent that enhances the effect of the antibacterial agent, this ensures a highly desirable ratio by weight of components of 1.9: 1 .

Typical examples of antibacterial agents that are particularly desirable in terms of efficacy for preventing plaque formation, safety, and formulation preparation include:
2,4,4'-trichloro-2-hydroxydiphenyl ether (triclosan),
2,2'-dihydroxy-5,5'-dibromodiphenyl ether
Halogenated Salicylanilides:
4 ', 5-dibromosalicanilide,
3,4 ', 5-trichlorosalicylanilide.

3,4 ', 5-tribromosalicylanilide,
2,3,3 ', 5-tetrachlorosalicylanilide,
3,3,3 ', 5-tetrachlorosalicylanilide,
3,5-dibromo-3'-trifluoromethylsalicylanilide (fluorophene),
5-n-octanoyl-3'-trifluoromethylsalicylanilide, 3,5-dibromo-4'-trifluoromethylsalicylanilide
Benzoic acid esters:
p-hydroxybenzoic acid methyl ester,
p-hydroxybenzoic acid ethyl ester,
p-hydroxybenzoic acid propyl ester,
p-hydroxybenzoic acid butyl ester
Halogenated Carbanilides:
3,4,4'-trichlorocarbonylanilide,
3-trifluoromethyl-4,4'-dichlorocarbonylidene,
3,3,4'-trichlorocarbonylidene.

 Phenolic compounds (including phenol and its homologs, mono- and polyalkylphenols substituted in the aromatic nucleus with a halogen (for example: G, C1, B) phenols, resorcinol and catechin and their derivatives, as well as bisphenol compounds).

In addition, such phenolic compounds include:
Phenol and its homologues:
phenol,
2-methylphenol,
3-methylphenol
4-methylphenol
4-ethylphenol,
2,4-dimethylphenol,
2,5-dimethylphenol,
3,4-dimethylphenol,
2,6-dimethylphenol,
4-n-propylphenol,
4-n-butylphenol,
4-n-amylphenol,
4-tert-amylphenol,
4-n-hexylphenol,
4-n-heptylphenol,
2-methoxy-4- (2-propenyl) phenol (eugenol),
2-isopropyl-5-methylphenol (thymol),
Mono- and polyalkyl- and aralkylkalo-phenols:
methyl p-chlorophenol,
ethyl p-chlorophenol,
n-propyl-p-chlorophenol,
n-butyl-p-chlorophenol,
n-amyl-n-chlorophenol,
sec-amyl-p-chlorophenol,
n-hexyl-p-chlorophenol,
cyclohexyl-p-chlorophenol,
n-heptyl-p-chlorophenol,
n-octyl-p-chlorophenol,
o-chlorophenol,
methyl o-chlorophenol,
ethyl o-chlorophenol,
n-propyl-o-chlorophenol,
n-butyl-o-chlorophenol,
n-amyl-o-chlorophenol,
tert-amyl-o-chlorophenol,
n-hexyl-o-chlorophenol,
n-heptyl-o-chlorophenol,
p-chlorophenol,
o-benzyl-p-chlorophenol,
o-benzyl-m-methyl-p-chlorophenol,
o-benzyl-m, m-dimethyl-p-chlorophenol,
o-phenethyl-p-chlorophenol,
o-phenethyl-m-methyl-p-chlorophenol,
3-methyl-p-chlorophenol,
3,5-dimethyl-p-chlorophenol,
6-ethyl-3-methyl-p-chlorophenol,
6-n-propyl-3-methyl-p-chlorophenol,
6-isopropyl-3-methyl-p-chlorophenol,
2-ethyl-3,5-dimethyl-p-chlorophenol,
6-sec-butyl-3-methyl-p-chlorophenol,
2-isopropyl-3,5-dimethyl-p-chlorophenol,
6-diethylmethyl-3-methyl-p-chlorophenol
6-isopropyl-2-ethyl-3-methyl-p-chlorophenol,
2-sec-amyl-3,5-dimethyl-p-chlorophenol,
2-diethylmethyl-3,5-dimethyl-p-chlorophenol,
6-sec-octyl-3-methyl-p-chlorophenol,
p-bromophenol,
methyl p-bromophenol,
ethyl p-bromophenol,
n-propyl-p-bromophenol,
p-butyl-p-bromophenol,
n-amyl-p-bromophenol,
sec-amyl-p-bromophenol,
n-hexyl-p-bromophenol,
cyclohexyl-p-bromophenol,
o-bromophenol
tert-amyl-o-bromophenol,
n-hexyl-o-bromophenol,
n-propyl-m, m-dimethyl-o-bromophenol,
4-chloro-2-methylphenol,
2-phenylphenol,
4-chloro-3-methylphenol,
4-chloro-3,5-dimethylphenol,
2,4-dichloro-3,5-dimethylphenol,
3.4,5,6-tetrabrom-2-methylphenol
5-methyl-2-pentylphenol,
4-isopropyl-3-methylphenol,
5-chloro-2-hydroxydiphenylmethane
Resorcinol and its derivatives:
resorcinol
methylresorcinol
ethylresorcinol
n-propylresorcinol,
n-butylresorcinol,
n-amylresorcinol,
n-hexylresorcinol
n-heptylresorcinol,
n-octylresorcinol,
n-nonylresorcinol,
phenylresorcinol
benzylresorcinol,
phenylethylresorcinol
phenylpropylresorcinol,
p-chlorobenzylresorcinol,
5-chloro-2,4-dihydroxydiphenylmethane,
4'-chloro-2,4-dihydroxydiphenylmethane,
5-bromo-2,4-dihydroxydiphenylmethane,
4'-bromo-2,4-dihydroxydiphenylmethane
Bisphenol compounds:
bisphenol A,
2,2'-methylenebis (4-chlorophenol),
2,2'-methylenebis (3,4,6-trichlorophenol) (hexachlorophene),
2,2'-methylenebis (4-chloro-6-bromophenol),
bis (2-hydroxy-3,5-dichlorophenyl) sulfide,
bis (2-hydroxy-5-chlorobenzyl) sulfide.

The antibacterial agent is present in the oral composition in an effective amount to prevent plaque formation, typically 0.01-5mass. %, preferably 0.03-1% and very preferably 0.25-0.5%, and most preferably 0.25-0.35%. The antibacterial agent is essentially insoluble in water, i.e. its insolubility in water at 25 ^o C less than 1%, and may even be less than 0.1%. In the presence of ionizable groups, solubility is determined at pH values at which ionization does not occur.

 Recommended halogenated diphenyl ethers include triclosan. Recommended phenolic compounds include phenol, 2,2'-methylenebis (4-chloro-6-bromophenol), thymol and eugenol. Triclosan is the most recommended antibacterial anti-plaque inhibitor. Triclosan is described in the aforementioned US Pat. No. 40,22880 as an antibacterial agent in combination with a stone formation preventing agent giving zinc ions, and also in the description of the German Federal Patent 3532860 in combination with a copper compound. Triclosan is also described as a plaque-preventing dentifrice in a dentifrice composition containing a layered liquid crystal surface-active phase with a layer spacing of less than 6 nm, which may also include a zinc salt (see published European patent application 0161898 for Lahe c al.), and in a dentifrice composition containing zinc citrate trihydrate (see published European Patent Application 0161899 to Saxton).

The linear molecularly dehydrated polyphosphate salts useful in the present invention are well known. As a rule, they are used in the form of fully or partially neutralized water-soluble alkali metal (for example, potassium, but preferably sodium) or ammonium salts, or any mixtures thereof. Representative examples include: sodium hexametaphosphate, sodium tripolyphosphate, disodium diacid, trisodium monoacid and tetrasodium pyrophosphate, the corresponding potassium salts, and the like. The linear polyphosphates correspond to the formula (NaPO ₃ ) _n , where n = 2-125. In the present invention, polyphosphates are used in oral compositions in approximate amounts by weight of 1-3%, usually 1-2.5%, usually more than 1.5-2%. When n is at least 3 in the formula (NaPO ₃ ) _n , polyphosphate in nature is a glassy substance.

 Particularly desirable anti-calculus agents include tetra-alkali metal pyrophosphates, including mixtures thereof, for example tetrasodium pyrophosphate, tetra-potassium pyrophosphate and mixtures thereof. Thus, the oral composition may contain a polyphosphate calculus-preventing agent that is substantially free of tetrasodium pyrophosphate or substantially free of the combination of tetrapotassium pyrophosphate and tetrasodium pyrophosphate, where the ratio of potassium pyrophosphate and sodium pyrophosphate is 3: 1 or more. An anti-calculus preparation containing about 2% by weight of the oral tetrasodium pyrophosphate is particularly effective.

 The antibacterial enhancing agent (UAA), which enhances the uptake and retention of the antibacterial on the oral surfaces, is used in amounts effective from the point of view of such amplification, in the concentration range, the oral composition is 0.05-4%, preferably 0.1-3% , more preferably 0.5 to 2.5 wt.%.

 AAA can be a simple compound, preferably a polymerizable monomer, more preferably a polymer, the latter term being purely generic, including, for example, oligomers, homopolymers, graft copolymers, crosslinked polymers, copolymers, and the like. The AAA may be natural or synthetic and insoluble in water or preferably soluble in water (saliva) or swellable (hydratable, capable of forming a hydrogel). The average molecular weight of the UAA is 100-1000000, preferably 1000-1000000, more preferably 2000 or 25000-250000, or 500000.

The AAA typically has at least one income enhancing group, which is preferably an acidic group, such as a sulfonic, phosphonic or, more preferably, phosphonic or carbonic, or a salt thereof, for example an alkali metal or ammonium salt, and at least one organic retention enhancing group , preferably a series of both enhancing the intake and enhancing the retention of the group, the latter preferably corresponding to the formula: - (X) _n - R, where X = O, N, S, SO, SO ₂ , P, PO, Si, etc. ., R is hydrophobic alkyl, alkenyl, acyl, aryl, alkaryl, aralkyl, heterocyclic or their derivatives inertnozameschennye and n = 0 or n ≥1. The above term “inert substituted derivatives” includes a type of substituents and P that are usually non-hydrophilic and do not significantly affect the target functions of the UAA to enhance the intake and retention of the antibacterial agent on intraoral surfaces, and such substituents include halogen, for example Cl, Br, I, carbonyl etc. An illustration of such retention enhancing groups is the table.

 In the present invention, an admission enhancing group is a group that binds or connects, in an essential, adhesive, cohesive or other way, the AAA (carrying an antibacterial agent) to the oral (ie, teeth and gums) surfaces with an “delivery” of the antibacterial agent thereto surfaces. Organic retention enhancing groups, usually hydrophobic, combine or otherwise bind the antibacterial agent to the UAA and thereby promote the retention of the antibacterial agent to the UAA and indirectly on intraoral surfaces. In some cases, the attachment of an antibacterial agent occurs by physical capture of its UAA, especially if the AAA is a cross-linked polymer, the structure of which itself creates an increased number of sites for such a capture. The presence of a higher molecular weight, more hydrophobic crosslinking fragment in the crosslinked polymer further promotes the physical uptake of the antibacterial agent with its addition or incorporation into the polymer AAA.

 It is recommended that the AAA be an anionic polymer consisting of a skeleton chain comprising repeating units, each of which preferably has at least one carbon atom and at least one directly or indirectly leaving a monovalent receipt enhancing group and at least one directly or an indirectly departing, enhancing retention group geminally, officially, or, less preferably, in some other way connected with atoms, preferably carbon atoms of the chain. It is at least recommended that the polymer contain group enhancing and / or group retention enhancing and / or other divalent atoms or a group in the form of bonds in the copolymer target instead of or in addition to carbon atoms, or as crosslinking fragments.

 It must be emphasized that any UAA, shown as an example or illustration, which does not have both enhancing the intake and enhancing the retention of the groups, can and should preferably be chemically modified by known methods to obtain the recommended UAA having both types of groups, preferably a number of such groups . In the case of the recommended polymeric AAA, it is desirable, to optimize the substance and antibacterial supply to the oral surfaces, that the repeating units of the polymer chain or skeleton have acidic group-enhancing groups in an amount of at least 10%, preferably at least 50%, more preferably at least 80 % and up to 95% or 100 wt.% per polymer.

которая, однако, не имеет усиливающих удержание групп. Группы последнего типа присутствуют, однако, в поли(1-фосфонопропене), содержащем звенья формулы:

Для применения в настоящем изобретении в качестве УАА, содержащем фосфоновую кислоту, рекомендуется поли(бета-стиролфосфоновая кислота), содержащая звенья формулы:

,
где
Ph - фенил, в котором усиливающая поступление фософоновая группа и усиливающая удерживание фенильная группа связаны с вицинальными атомами углерода цепи, или сополимер бетастиролфосфоновой кислоты с винилфосфонилхлоридом, в котором звенья формулы III перемежаются или неупорядоченно связаны со звеньями формулы 1, или поли(альфа-стиролфосфоновая кислота), содержащая звенья формулы:

,
в которой группы, усиливающие поступление и удерживание, геминально связаны с цепью.According to a preferred embodiment of the present invention, the AAA is a polymer consisting of repeating units in which one or more phosphonic acid-enhancing groups are attached to one or more carbon atoms of the polymer chain. An example of such a UAA is poly (vinylphosphonic acid) containing units of the formula:

which, however, does not have retention enhancing groups. Groups of the latter type are, however, present in poly (1-phosphonopropene) containing units of the formula:

For use in the present invention as a AAA containing phosphonic acid, it is recommended poly (beta-styrene phosphonic acid) containing units of the formula:

,
Where
Ph is phenyl in which the phosphonone group and the retention enhancing phenyl group are bonded to vicinal carbon atoms of the chain, or a copolymer of betastirolphosphonic acid with vinylphosphonyl chloride in which the units of formula III are alternated or randomly linked to the units of formula 1, or poly (alpha-styrene phosphon ) containing units of the formula:

,
in which groups that enhance intake and retention are geminally linked to a chain.

 Such polymers of styrene phosphonic acid and its copolymers with other inert monomers with ethylene unsaturation usually have a molecular weight in the range of 2000-30000, preferably 2500-10000. "Inert" monomers do not significantly affect the intended use of any copolymer used in the invention as an AAA.

поли(аллилбис(фосфоноэтиламин) со звеньями формулы:

Другие фосфонированные полимеры, например поли(аллилфосфоноацетат), фосфонированный полиметакрилат и т. д., а также геминальные дифосфонатные полимеры, описанные в опубликованном Европейском патенте 0321233, могут быть использованы в настоящем изобретении при условии, разумеется, что они содержат или модифицированы, чтобы содержать вышеозначенные органические усиливающие удерживающие группы.Other phosphonic acid group containing polymers include, for example, phosphonated ethylene with units of the formula
- / (CH ₂ ) ₁₄ CHPO ₃ H ₂ / -,
Where
n can be, for example, an integer or take values that provide the polymer with a molecular weight of about 3000, poly- (butene-4'4-diphosphonate) sodium with units of the formula:

poly (allylbis (phosphonoethylamine) with units of the formula:

Other phosphonated polymers, for example poly (allylphosphonoacetate), phosphonated polymethacrylate, etc., as well as geminal diphosphonate polymers described in published European patent 0321233, can be used in the present invention, provided, of course, that they contain or are modified to contain the aforementioned organic reinforcing retention groups.

 In one aspect of the present invention, the oral composition comprises an orally acceptable carrier, an agent effective in enhancing the antibacterial effect of the antibacterial agent, with an average molecular weight of 1000-1000000, which contains at least one functional group that enhances the intake of the antibacterial agent, and at least at least one organic group that enhances the retention of a bacterial agent, and such an agent with these groups essentially does not contain a water-soluble alkali a metal or ammonium synthetic anionic linear polymeric polycarboxylate salt with a molecular weight of 1000-1000000, the composition also contains a polyphosphate anti-calculus calculating agent, such as a mixture of potassium and sodium salts, the ratio of potassium and sodium in the composition is less than 3: 1, for example, from 0.37 up to 1.04-1.

 According to another preferred embodiment of the invention, the AAA contains a synthetic anionic polymeric polycarboxylate, which is also an inhibitor of the alkaline phosphatase enzyme. Synthetic anionic polymeric polycarboxylates and their kits with various cationic bactericides, zinc and magnesium have been previously described as such as anti-plaque agents, for example, in U.S. Patent No. 3,429,963 to Shediovsky, U.S. Patent No. 4,152,420 to Caffar, U.S. Patent No. 3,954,480 to Dichter and others. US Pat. No. 4,138,477 Caffar, US Pat. No. 4,183,914 Caffar et al. However, only the description corresponding to US Pat. No. 4,627,977 describes the use of such a polycarboxylate to inhibit hydrolysis of saliva pyrophosphate preventing formation of nodule This agent is combined with a compound giving a source of fluoride ions. It is necessary to indicate that the synthetic anionic polymeric polyhydroxylates described in the above patents, if they contain or are modified to contain reinforcing groups, are applicable in the compositions and methods of the present invention as UAA, and the descriptions of these patents with this approach are included in the present description as links.

 Such synthetic anionic polymeric polycarboxylates are often used as free acids, or preferably in the form of partially or more preferably completely neutralized, water-soluble or water-swellable (hydratable, gel-forming) alkali metal (e.g. potassium, but preferably sodium) or ammonium salts. Copolymers (1: 4 to 4: 1) of maleic anhydride or maleic acid with another polymerizable monomer with ethylene unsaturation are recommended, preferably a methyl vinyl ether / maleic anhydride copolymer with a molecular weight (MV) of 30,000-1000000. Such copolymers are manufactured by GAF Corporation under the brand name Gantrez, for example Gantrez AN 139 (MV 500000), Gangrez 119 (MV 250000), but especially Gantrez S-97 for pharmaceutical purposes (MV 70000).

 Other polymeric polycarboxylates useful in the invention as UAA, containing or modified to contain retention enhancing groups, include the polycarboxylates described in US Pat. No. 3,956,480 cited above, such as copolymers of 1: 1 maleic anhydride with ethyl acrylate, hydroxyethyl methacrylate, N-vinyl -2-pyrrolidone or ethylene, the latter being produced, for example, by Monsanto under the designations EMA N 1103 (MV 10000) and EMA Caoe 61, as well as copolymers (1: 1) of acrylic acid with methyl or hydroxyethyl methacrylate, methyl or ethyl acrylate, isobutyl vinyl ether or N-vinyl-2-pyrrolidone.

 Additional applicable polymeric polycarboxylates are described in US Pat. Nos. 4,138,477 and 4,183,914 cited above, they contain or are modified to contain retention groups, including copolymers of maleic anhydride with styrene, isobutylene or ethyl vinyl ether, polyacrylic, polyitaconic, and also oligomeric acids with MB below 1000, supplied under the brand name Uniroal NO-2.

 In general, polymerizable carboxylic acids with ethylene or olefinic unsaturation and a retention enhancing group containing an activated carbon-carbon olefinic double bond and at least one carboxyl, i.e., acids containing an olefinic double bond, are readily realized during polymerization due to its presence in polymerization. the monomer molecule either in the alpha-beta position with respect to the carboxyl, or as part of the terminal methylene. Examples of such acids include acrylic, methacrylic, ethacrylic, alpha-chloroacrylic, crotonic, beta-acryloxypropionic, sorbic, alpha-chlorosorbic, cinnamic, beta-styrene-acrylic, muconic, itaconic, citraconic, mesaconic, glutaconic, alpha-2, acon benzyl acrylic, 2-cyclohexyl acrylic, angelic, umbellic, fumaric, maleic acids and anhydrides. Other various olefin monomers copolymerizable with the above carboxylic monomers include vinyl acetate, vinyl chloride, dimethyl maleate, and the like. The copolymers usually contain carboxyl groups in the form of salts in an amount sufficient to impart water solubility to the copolymer.

 The so-called carboxyvinyl polymers described as components of toothpastes in US Pat. No. 3,980,767 to Chowh et al., US Pat. No. 3,935,306 to Roberts and others, US Pat. No. 3,919,409 to Perla and others, US Pat. No. 3,911,904 to Harrison and US Pat. No. 3,711,604 also apply. Coldney et al. These polymers are sold by VV Goodrich under the brand names Carbapol 934, 940 and 941 and are a colloidal, water-soluble polymer of polyacrylic acid, crosslinked with 0.75 - 2% polyallyl saccharose or polyallipentaerythritol as a crosslinking agent, such a crosslinked structure and cross-links provide targeted reinforcement of retention due to hydrophobicity and / or physical capture of an antibacterial agent, etc. To some extent, polycarbophil is similar, which is a polyacrylic acid crosslinked with less than 2% divinyl glycol, lower amounts, molecular weight and / or hydrophobicity of which as a crosslinking agent do not provide or provide only a slight increase in retention. An example of a more effective retention enhancing crosslinking agent is 25-dimethyl-1,5-hexadiene.

 The synthetic anionic polymeric polycarboxylate component is most often a hydrocarbon with possible halogen or oxygen-containing substituents and bonds represented, for example, by ester, ether or OH groups, and if present, this component is used in the present compositions in approximate amounts up to 4 wt. % (usually at least 0.05%).

 AAA can also include natural anionic polymeric polycarboxylates containing retention enhancing groups. Carboxymethyl cellulose and other binders, resins and film-forming substances that do not have the aforementioned admission enhancing and / or retention enhancing groups are ineffective as AAA.

As an illustration of the UAA, containing phosphinic and / or sulfonic acid in the form of enhancing the supply, polymers and copolymers containing units or fragments formed during the polymerization of vinyl or allylphosphinic and / or sulfonic acids, substituted, as necessary, in 1 or 2 (or 3) carbon atoms, a retention enhancing group, for example a group of the above formula: (X) _n —R. Mixtures of such monomers and their copolymers with one or more inert polymerizable ethylene unsaturated monomers of the type described above in relation to the synthetic anionic polymer polycarboxylates used can be used. As will be noted, in these and other polymeric AAAs useful in the present invention, usually only one acidic acid-enhancing group is bonded to any given carbon atom or other atom of the polymer skeleton or its branch. Polysiloxanes containing or modified to contain, waste reinforcing receipts and enhancing retention groups can also be used as AAA in the present invention. As UAA in the present invention, ionomers are used, containing or modified to contain, enhancing the intake and enhancing the retention of the group. Ionomers are described on p. 546-573 Encyclopedia of Chemical Technology by Kirk Othmer, Third Edition, Supplementary Volume, John Wiley and Sons, Inc., 1984, which is incorporated herein by reference. In addition, in the present invention, as an AAA, they are applicable provided that they contain or are modified to contain retention enhancing groups, polyesters, polyurethanes, artificial or natural polyamides, including proteins and protein compounds such as collagen, poly (argenin ) and other polymerized amino acids.

 Upon receipt of an oral preparation by the initial dissolution of polyphosphate and an antibacterial agent in a moisturizer and a surfactant, followed by the gradual addition of UAA to them, especially polycarboxylate, the solution becomes transparent and can be characterized as a "microemulsion". With an increase in the amount of polycarboxylate so that the complete oral preparation contains at least 2.2 wt.% Polycarboxylate, the solution becomes cloudy and can be described as a “macroemulsion”. In compositions such as "macroemulsions" the anti-bacterial action that prevents the formation of plaque is apparently optimal.

 The target ratio by weight of the water-insoluble non-cationic antibacterial agent to the prevention of calculus formation of polyphosphate from more than 0.72: 1 to less than 4: 1, for example, from 1: 1 to 3.5: 1, especially from 1.6: 1 to 2.7: 1.

 To optimize the effectiveness against calculus formation of the oral composition, the presence of inhibitors of enzymatic hydrolysis of polyphosphate is desirable. Such inhibitors are used in an amount sufficient to provide a fluoride ion source of 25-5000 ppm fluoride ions and contain up to 3% or more synthetic anionic polymeric polycarboxylate with a molecular weight of 1000-1000000, preferably 30000-500000.

 Sources of fluoride ions or fluoride-supplying components as inhibitors of acid phosphatase and pyrophosphatase enzymes are well known as anticaries agents. Such compounds may be slightly soluble in water or be completely insoluble in it. The compounds are characterized by the ability to release fluoride ions in water and the inability to enter into undesirable reactions with other compounds of the oral preparation. Such substances include inorganic salts of hydrofluoric acid, such as soluble alkali metal and alkaline earth salts, for example sodium fluoride, potassium fluoride, ammonium fluoride, calcium fluoride, copper fluoride such as copper (I) fluoride, zinc fluoride, barium fluoride, fluorine sodium silicate, ammonium fluorosilicate, sodium fluorozirconate, ammonium fluorozirconate, sodium monofluorophosphate, aluminum mono- and difluorophosphate, fluorinated sodium calcium pyrophosphate. Alkali metal and tin fluorides are recommended, such as sodium and tin (II) fluorides, sodium monofluorophosphate (NFF), and mixtures thereof.

 The amount of fluorine-containing compound to a certain extent depends on the type of compound, its solubility and the type of oral preparation, but this should be a non-toxic amount, usually 0.005-3% per preparation.

 Typically, in the case of alkali metal fluorides, this component is present in an amount up to 2 wt.% Based on the weight of the preparation, preferably in the range of 0.05-1%. In the case of sodium monofluorophosphate, the compound may be present in an amount of 0.1-3%, more typically about 0.76%.

 In oral formulations such as mouthwashes, lozengis, and chewing gum, the fluorine supplying compound is usually present in an amount sufficient to isolate up to 500 ppm, preferably 25-300 ppm by weight of fluoride ion. Typically, 0.005-1% by weight of such a compound is present.

 In certain particularly recommended forms of the invention, the oral composition may be liquid in nature and may be a means for washing or rinsing the mouth. In such a preparation, the carrier is usually a water-alcohol mixture, preferably comprising a humectant, as described below. Typically, the ratio by weight of water to alcohol is in the range from 1: 1 to 20: 1, preferably from 3: 1 to 10: 1, and more preferably from 4: 1 to 6: 1. The total amount of water-alcohol mixture in a preparation of this type is usually in the range of 70-99.9 wt. % on the drug. Ethanol or isopropanol is usually used, of which ethanol is preferred.

The pH value in liquid preparations, as a rule, is in the range of 4.5-9, usually 5.5-8. Recommended pH values are 6-8. It is worth noting that the compositions of the invention can be used at oral pH below 5 without significant decalcification or other damage to the tooth enamel. The pH value can be adjusted by adding an acid (e.g. citric or benzoic acid) or a base (e.g. sodium hydroxide) or a buffer (e.g. citrate, benzoate, sodium carbonate or bicarbonate, disodium hydrogen phosphate, sodium dihydrogen phosphate, etc.)
It must be indicated, as is customary, that oral preparations must be sold or otherwise distributed in packages with appropriate labels. So, a vessel with a mouthwash should have a label describing the tool in composition, method of use for rinsing or rinsing the mouth.

 Organic surfactants are used in the compositions of the present invention to achieve an enhanced prophylactic effect, to promote the complete spread of an anti-calculus agent in the oral cavity and to prevent the formation of plaque, and also to make the present compositions more cosmetically acceptable. Organic surfactants are preferably anionic, non-ionic or ampholytic in nature, and detergents are recommended as surfactants that impart detergent and foaming properties to the composition. Suitable examples of anionic surfactants include: water-soluble salts of monosulfates of monoglycerides of higher fatty acids, such as the sodium salt of monosulfonated monoglyceride of fatty acids of hydrogenated coconut oil, higher alkyl sulfates, such as sodium lauryl sulfate, alkyl aryl sulfate, sodium sulfate sulfonates 1,2-dehydroxypropanesulfonate and saturated higher aliphatic acylamides of lower aminocarboxylic acids, the same both having 12-16 carbon atoms in the fatty acid, alkyl or acyl radicals, and the like Examples of the latter amides are N-lauroylsarcosine, as well as the sodium, potassium and ethanolamine salts of N-lauroyl-N-myristoyl with N-palmitoylsarcosine, which should not contain soaps and similar derivatives of higher fatty acids. The use of these sarcosinates in the oral compositions of the present invention is especially promising, since these substances exhibit a long and noticeable effect on the inhibition of acid formation in the oral cavity, associated with the decomposition of carbohydrates, and also slightly reduce the solubility of tooth enamel in acid solutions. Examples of water-soluble non-ionic surfactants include the condensation products of ethylene oxide with various compounds reacting with it having an active hydrogen atom and long hydrophobic chains (for example, aliphatic chains with 12-20 carbon atoms), such condensation products ("atoxamers") contain hydrophilic polyoxyethylene moieties, including condensation products of poly (ethylene oxide) with fatty acids, fatty alcohols, fatty amides, polyhydric alcohols (e.g. sorbitan monostearate) and polyprop ilenoxide (e.g., pluronic substances).

 Surfactants are usually present in an amount of 0.1-5 wt. %, preferably 1-2.5%. It should be noted that surfactants contribute to the dissolution of non-cationic antibacterial agents and thereby reduce the required amount of solubilizing moisturizer.

 Various other substances, such as brighteners, preservatives, silicones, chlorophilic compounds and / or ammonium-containing compounds, for example urea, diammonium phosphate and mixtures thereof, can also be incorporated into the oral preparations of the present invention. Such auxiliary substances, if present, are introduced into the preparations in amounts that do not undesirably affect the target properties and parameters. It is necessary to avoid the presence of significant amounts of salts of zinc, magnesium and other metals, usually soluble, capable of forming complexes with the active components of the present invention.

 Any suitable flavoring and sweetening agents may be used. Examples of suitable flavoring components include flavoring oils, for example: spearmint, peppermint oil, peppermint oil, sintofras oil, clove oil, sage oil, eucalyptus oil, marjoram oil, cinnamon oil, lemon oil and orange oil, as well as methyl salicylate. Suitable sweeteners include sucrose, lactose, maltose, sorbitol, xylitol, sodium cyclamate, perillartine, aspartyl phenylalanine methyl ether (AMP), saccharin, and the like. Flavoring and sweetening agents, individually or together, are preferably present in an amount of 0.1-5% or more per formulation. Moreover, aromatic oil, apparently, helps to dissolve the antibacterial agent.

 In the recommended practice of the present invention, the oral composition of the invention, for example, in the form of a mouthwash containing the composition of the invention, is applied regularly to tooth enamel, for example, daily or every second or third day, or preferably 1-3 times a day at pH 4, 5-9, usually 5.5-8, preferably 6-8, for at least 2 weeks and up to 8 weeks or throughout life.

 The following examples illustrate the present invention, but it should be pointed out that the invention is not limited to them. All quantities and ratios given are by weight.

 In the following examples, triclosan (2,4,4'-trichloro-2'-hydroxydiphenyl ether) is abbreviated as TCHE, sodium lauryl sulfate is abbreviated as NLS, a copolymer of maleic anhydride with methyl vinyl ether manufactured by GAF Corporation under the brand name "Gantrez S-97" is designated as "Gantrez," tetrasodium pyrophosphate is designated simply as "pyrophosphate" and sodium fluoride is designated as NaF.

 Example 1

 The effectiveness of the adsorption and excretion of a tooth mineral to prevent plaque formation (tartar formation) is determined by the adsorption of an antibacterial agent with saliva covering the disks from the tooth mineral (hydroxyapatite) in the presence of pyrophosphate and various amounts of polycarboxylate.

To detect the receipt of an antibacterial agent in the saliva covering the disks made of hydroxyapatite (hydroxyapatite (GA) manufactured by Monsanto Co.), it is intensively washed with distilled water, collected by vacuum filtration and allowed to dry for a day at 37 ^o C. The dried HA is ground into powder with a pestle in a mortar . 150 mg of HA was placed in a KBr tablet compression chamber (Barnes Analytical Stanford, CT) and pressed for 6 minutes under 10,000 pounds in a Carver laboratory press. The resulting 13 mm discs are sintered for 4 hours at 800 ^° C. in a Thermolyhe furnace. Parafilm-stimulated hollow saliva is collected in an ice-cooled glass bottle. The saliva is clarified by centrifugation at 15,000 x g (multiple gravity) for 15 min at 40 ^o C. Sterilization of the clarified saliva is carried out at 4 ^o C and stirring by irradiating the sample for 1 h with UV radiation.

Each fused disc is hydrated with sterile water in a polyethylene test tube. Then the water is removed and 2 ml of saliva is replaced. A thin film of saliva is formed by incubating the disk for a day at 37 ^° C. and continuously shaking in a water bath. After this treatment, the saliva is removed and the discs are treated with 1 ml of a solution containing an antibacterial agent (triclosan) in the liquid phase of the dentifrice solution and incubated at 37 ^° C. with continuous shaking in a water bath. After 30 minutes, the disk is transferred to another tube, 5 ml of water is added, after which the disk is gently shaken with a swirl. Then the disk is transferred to a new tube and the washing procedure is repeated twice. Finally, the disc is carefully transferred to a new tube so as to avoid the joint transfer of any liquid along with the disc. After this, 1 ml of methanol is added and the disk is vigorously shaken with a swirl. The sample is left for 30 min at room temperature in order to extract adsorbed triclosan with methanol. The methanol is purged and clarified by centrifugation in a Beckman II microcentrifuge at a speed of 10,000 rpm for 5 minutes. After this treatment, methanol is transferred into vessels for high performance liquid chromatography (HPLC) in order to determine the concentration of the antibacterial agent. In all experiments, samples were duplicated three times.

 The data obtained is summarized below.

Mouthwash - Parts
Tetrasodium pyrophosphate - 2.00
Dumbbell S-97 - 2.50
Glycerin - 10.00
Sodium Fluoride - 0.05
Sodium lauryl sulfate - 0.20
TCGE - 0.06
Flavoring Oil - 0.40
Water - The rest is up to 100.

 In the above example, improved results are also achieved when replacing TCHE with phenol, 2,2'-methylenebis (4-chloro-6-bromo-phenol), eugenol and thymol and / or when replacing the Gantrez with another UAA, such as Carbopol (for example, Carbopol 934 ) or polymers of styrenephosphonic acid with a molecular weight of 3000-10000, such as poly (beta-styrenephosphonic acid), copolymers of vinylphosphonic acid with beta-styrenephosphonic acid and poly (alpha-styrenephosphonic acid), sulfoacrylic oligomers or maleoid anhydride copolymer (1: 1) with ethyl acrylate.

 Similar results are achieved when replacing pyrophosphate (tetrasodium pyrophosphate) with a mixture of tetrasodium pyrophosphate and tetracal pyrophosphate with a ratio by weight of potassium and sodium a) 0.37: 1, b) 1.04: 1 and c) 3.5: 1.

 The invention has been described in terms of certain preferred embodiments, but it must be emphasized that modifications and modifications obvious to those skilled in the art should be included within the scope of this application and the scope of the appended claims.

Claims (13)

 1. An oral composition for rinsing the mouth, including an acceptable carrier containing 70 to 99.9 wt.% Water-alcohol mixture with a mass ratio of water to alcohol from about 1: 1 to 20: 1 and in the specified carrier about 0.1 to 3 wt. % of at least one linear molecularly dehydrated polyphosphate salt, which is a fully or partially neutralized water-soluble alkali metal or ammonium polyphosphate, as an anticalculus agent and said polyphosphate is selected from tripolyphosphate or pyrophosphate, an effective anti-flying amount of 0.01 - 5 wt.% Mainly water-insoluble non-cationic antibacterial agent selected from the group consisting of halogenated diphenyl ethers, halogen carbonated or phenolic compounds, characterized in that it contains from about 0.05 to 4 wt.% agent that enhances the delivery of an antibacterial agent, which enhances the delivery and retention of the agent on the surface of the oral cavity, with the mass ratio of the agent that enhances the antibacterial effect to polyphosphate ion , from about 1.6: 1 to 2.7: 1, the specified antibacterial enhancing agent is a copolymer of maleic acid or anhydride with another ethylene unsaturated polymerizable monomer and has a medium non-molecular weight of 30,000 - 1,000,000.  2. The composition according to claim 1, characterized in that the halogenated diphenyl ether is 2,4,4'-trichloro-2'-hydroxydiphenyl ether.  3. The composition according to claim 1, characterized in that the linear molecularly dehydrated polyphosphate salt is alkali metal pyrophosphate, present in an amount of 1 to 2.5 wt.%.  4. The composition according to claim 1, characterized in that the alkali metal pyrophosphate is tetrasodium pyrophosphate.  5. The composition according to claims 1 to 4, characterized in that the ratio of the agent that enhances the antibacterial effect to the polyphosphate ion is 1.7: 1 - 2.3: 1.  6. The composition according to p. 1, characterized in that the agent that enhances the action of the antibacterial agent is an anionic polymer having a number of groups that enhance the intake and organic groups that enhance the retention.  7. The composition according to claim 6, characterized in that the anionic polymer is a chain of repeating units, each of which consists of at least one carbon atom.  8. The composition according to claim 7, characterized in that the unit contains at least one reinforcing receipt group and at least one organic retention enhancing group attached to the same or official or other chain atoms.  9. The composition according to p. 1, characterized in that the gain-enhancing group is carboxyl or its salt.  10. The composition according to claim 9, characterized in that the agent that enhances the action of the antibacterial agent is a copolymer of maleic acid or maleic anhydride with another polymerizable monomer with ethylene unsaturation or its salt.  11. The composition of claim 10, wherein the other monomer is methyl vinyl ether in a ratio of 4: 1 to 1: 4 to maleic acid or maleic anhydride.  12. The composition according to claim 11, characterized in that the average mol.m. copolymer of about 70,000.  13. The composition according to any one of claims 1 to 12, characterized in that it contains a source supplying fluoridions.

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