RU2097021C1 - Composition for oral cavity care - Google Patents

Abstract

FIELD: medicine. SUBSTANCE: composition as a means for teeth cleaning or mouth gargle contains antibacterial agent 2,4,4'-trichlor-2'-hydroxydiphenylene ester (triclosane) which is insoluble in water and prevents formation of dental deposit; synthetic anionic polymeric polycarboxylate with molecular weight 1000-1000000 which intensifies admission and retention of antibacterial agent on intraoral surfaces; and agent allows antibacterial agent to solve effectively in saliva. EFFECT: higher efficiency. 9 cl, 17 tbl

Description

 The invention relates to an antibacterial plaque-preventing oral composition for cleaning teeth containing a substantially water-insoluble non-cationic antibacterial agent effective in preventing plaque formation.

 Plaque is a soft deposit formed on the teeth, in contrast to calculi, hard calcined deposits on the teeth. Unlike calculus, plaque can form on any part of the tooth surface, including especially on the edge of the gums. Therefore, invisible plaque may be responsible for the appearance of gingivitis.

 Accordingly, it is highly desirable to include antimicrobial agents with a known ability to reduce plaque formation in oral compositions. To this end, cationic antibacterial agents have often been proposed. Moreover, in US patent 4022880 in the name of Vinson et al. the compound giving zinc ions, as a means representing the formation of calculi, is mixed with an antibacterial agent effective in slowing the growth of plaque bacteria. A wide range of mixtures of antibacterial agents with zinc compounds are described, including cationic substances such as guanides and quaternary ammonium compounds, as well as non-cationic compounds such as halogenated salicylanilides and halogenated hydroxydiphenyl ethers. In European Patent Publication 0161899 to Saxton et al. A non-cationic antibacterial anti-plaque halogenated hydroxydiphenyl ether triclosan in combination with zinc nitrate trihydrate has been described. Triclosan is also described in European Patent Publication 0271332 to Davis as a component of a toothpaste containing a solubilizing agent such as propylene glycol.

 Cationic antibacterial agents such as chlorhexidine, benzonium chloride and citylpyridinium chloride have also been extensively studied as antibacterial agents to prevent plaque formation. However, as a rule, they are ineffective when used with anionic substances. On the other hand, non-cationic antibacterial agents may be compatible with the anionic components in the oral composition.

 However, oral compositions are usually a mixture of many components, in which even typically neutral substances such as humectants can affect the effect of the entire composition.

 Moreover, even non-cationic antibacterial agents may have limited anti-plaque efficacy in admixture with commonly used substances such as polyphosphate anti-calculus calculating agents described in British Patent Publication 2200551 and Gaffar et al. and European Patent 0251591 to Jackson et al. USSN 398605, assigned on a routine basis, on August 25, 1989, showed that plaque-preventing efficacy increases dramatically when the potentiating antibacterial agent (UAA) is activated, which enhances the flow of antibacterial agents to the mouth surfaces and their retention on these surfaces with an optimization of the incoming quantity and polyphosphate and UAA intake rates.

 Advantages of the invention are that an oral composition is provided that contains a substantially water-insoluble antibacterial agent and an AAA to inhibit plaque formation, and such an oral composition contains a liquid carrier that promotes the dissolution of the antibacterial agent in saliva in amounts effective to prevent tartar.

 Another advantage of the invention is that the UAA enhances the intake and retention of small amounts of antibacterial agent that are effective in preventing the formation of plaque on the teeth and soft tissues inside the mouth.

 Another advantage of the invention is that an oral plaque-preventing composition is provided that is effective in reducing the possibility of gingivitis.

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

 In accordance with some aspects of the invention, there is provided an oral composition comprising an effective amount of a substantially water-insoluble non-cationic non-cationic antibacterial agent 0.005 to 4 wt.% To prevent plaque formation. enhancing the action of an antibacterial agent, enhancing the intake and retention of an antibacterial agent on intraoral surfaces, and an orally acceptable carrier that promotes the dissolution of the antibacterial agent in saliva in an amount effective to prevent plaque formation, and such a composition substantially does not contain a polyphosphate anti-calculus preparation.

 Typical examples of water-insoluble non-cationic antibacterial agents, particularly desirable in terms of efficacy against plaque formation, safety and formulation, include the following substances.

Halogenated diphenyl ethers
2 ', 4,4'-Trichloro-2-hydroxydiphenyl ether (triclosan),
2,2'-dihydroxy-5,5'-dibromodiphenyl ether.

Halogenated salicylanilides
4 ', 5-Dibromosalicylanilide,
3,4 ', 5-Trichlorosalicylanilide,
3,4 ', 5-tribromosalicylanilide,
2,3,3 ', 5-tetrachlorosalicylanilide,
3,3,3 ', 5-tetrachlorosalicylanilide,
3,5-Dibromo-3'-trifluoromethylsalicylanilide (flurofen),
5-n-Octanoyl-3'-trifluoromethylsalicylanilide,
3,5-dibromo-4-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 ether.

Galloid Carbanilides
3,4,4'-trichlorocarbonylidene,
3-Trifluoromethyl-4,4'-dichlorocarbonylidene,
3.3 ', 4-Trichlorocarbonylidene,
phenolic compounds (including phenol and its homologues, mono- and polyalkylphenols substituted in the aromatic nucleus with a halogen (for example: F, Cl, Br, J) phenols, resorcinol, catechin and their derivatives and bisphenol compounds).

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 aralkyl halophenols
methyl p-chlorophenol,
ethyl p-chlorophenol,
n-propyl-p-chlorophenol,
n-butyl-p-chlorophenol,
n-amyl-p-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 p-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-phenylethyl-p-chlorophenol,
o-phenylethyl-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-chlorophenyl,
6-sec-butyl-3-methyl-chlorophenol,
2-isopropyl-3,5-dimethyl-p-chlorophenol,
6-diethylmethyl-3-methyl-p-chlorophenol,
6-sec-octyl-3-methyl-p-chlorophenol,
p-bromophenol,
methyl p-bromophenol,
ethyl p-bromophenol,
n-propyl-p-bromophenol,
n-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,
2-phenylphenol,
4-chloro-2-methylphenol,
4-chloro-3-methylphenol,
4-chloro-3,5-dimethylphenol,
2,4-dichloro-3,5-dimethylphenol,
3,4,5,6-tetrabromo-3-methylphenol,
5-methyl-2-pentylphenol,
4-isopropyl-3-methylphenol,
5-chloro-2-hydroxydiphenolmethane.

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-3,6-dichlorophenyl) sulfide,
bis (2-hydroxy-5-chlorobenzyl) sulfide.

A non-cationic antibacterial agent is present in the oral composition in an effective amount to prevent plaque formation, typically 0.01 to 5% by weight. preferably 0.03 to 1 wt. more preferably 0.25 to 0.5 wt. or from 0.25 wt. up to less than 0.5 wt. most preferably 0.25 to 0.35 wt. for example 0.3 wt. in a dentifrice or preferably 0.03 to 1 wt. in a mouthwash or a liquid dentifrice. The antibacterial agent is essentially insoluble in water, which means that the solubility in water at 25 ^o C is less than 1 wt. but may even be less than 0.1 wt.

 The recommended halogenated diphenyl ether is triclosan. Recommended phenolic compounds include: phenol, thymol, eugenol, hexylresorcinol and 2,2'-methylenebis (4-chloro-6-bromophenol). The most recommended antibacterial anti-plaque compound is triclosan. Triclosan is described in the aforementioned US Pat. No. 4,022,880 as an antibacterial agent in combination with an anti-calculus-forming agent giving zinc ions, and also in the description of the German Federal Patent 3532860 in combination with a copper compound. In the description of European patent 0278744, diclosan is described in combination with a desensitizing agent containing a source of potassium ions. Triclosan is also described as an anti-plaque agent in a dentifrice composition containing a layered liquid crystal surface-active phase with a layer spacing of less than 6 nm and which may contain zinc salt (see published European patent application 0161898 in the name of Lane c al.), as well as in a dentifrice containing zinc citrate trihydrate (see published European patent application 0161899 in the name of Saxton et al.).

 The enhancing effect of the antibacterial agent (UAA), which enhances the intake and retention of the antibacterial agent on the surfaces inside the mouth, is used in an amount effective to achieve such an increase in the range of concentrations on the oral composition of 0.005 to 4 wt. preferably 0.1 to 3 wt. more preferably 0.5 to 2.5 wt.

 AAA can be a simple compound, preferably capable of polymerizing by a monomer, more preferably a polymer, the latter term being purely generic and may include, for example, oligomers, homopolymers, copolymers of two or more monomers, ionomers, block copolymers, graft copolymers, crosslinked polymers and copolymers, etc. P. AAA can be natural or synthetic and water insoluble or preferably soluble in water (saliva) or swellable (hydratable, capable of forming a hydrogel). The average molecular weight of the UAA is 100,000,000, preferably 1,000 to 1,000,000, more preferably from 2,000 or 25,000 to 250,000 or 500,000.

The AAA usually has at least one reinforcing group, preferably an acidic group, such as a sulfonic or phosphonic, more preferably a phosphonic or carbonic, or a salt thereof, for example an alkali metal or ammonium salt, and at least one retention enhancing organic group, preferably a series as enhancing admission, and enhancing the retention of groups, with the last formula
- (X) _n -R,
where XO, N, S, SO, SO ₂ , P, PO, Si, etc.

R represents hydrophobic alkyl, alkenyl, acyl, aryl, alkaryl, aralkyl, heterocycle or their inert substituted derivatives, and
n 0 or n ≥ 1.

 The above term “inert substituted derivatives” includes a type of substituents on P that are usually non-hydrophilic and do not significantly affect the target functions of the AAA to enhance the uptake and retention of the antibacterial agent on intraoral surfaces, and such groups include a halogen such as Cl, Br, J, carbonyl and so on. Examples of such retention enhancing groups are given in table. one.

 In the present invention, an admission enhancing group is a group that binds either substantively, adhesively, cohesively or in any other way connecting the AAA (carrying an antibacterial agent) with intraoral (ie, teeth, gums) surfaces with a “delivery” of the antibacterial agent to these surfaces . Organic retention enhancing groups, usually hydrophobic, bind or otherwise bind the antibacterial agent to the UAA and thereby promote the retention of the antibacterial agent on the UAA and indirectly on the oral surfaces. In some cases, the attachment of an antibacterial agent occurs by its physical capture of the 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 in the crosslinked polymer of a higher molecular weight, more hydrophobic crosslinking fragment further promotes the physical capture of the antibacterial agent with the addition or incorporation of the polymer into the AAA.

 It is recommended that the AAA be an anionic polymer consisting of a chain or skeleton comprising repeating units, each of which has at least one directly or indirectly departing monovalent reinforcing reinforcing group and at least one directly or indirectly departing monovalent reinforcing retaining group, geminally , vacinally, or, less preferably, in some other way linked to atoms, preferably carbon atoms of the chain. To a lesser extent, it is recommended that the polymer contains admission enhancing groups and / or retention enhancing groups and / or other divalent atoms or groups in the form of bonds in the polymer chain 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, without both enhancing the intake and enhancing the retention of the groups, can and should preferably be modified chemically 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 substantivity and antibacterial intake of the oral surfaces, so that the repeating units of the polymer chain or skeleton have acidic acid enhancing groups in an amount of at least 10 wt. preferably at least 50 wt. more preferably at least 80 wt. and up to 95mas. or 100 wt. on the polymer.

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

Для применения в изобретении в качестве УАА, содержащем фосфоновую кислоту, рекомендуется поли(бетастиролфосфоновая кислота), содержащая звенья формулы

где Ph фенил, в который усиливающая поступление группа и усиливающая удержание фенильная группа связаны с винильными атомами углерода цепи, или сополимер бета-стиролфосфоновой кислоты с винилфосфонилхлоридом, в котором звенья формулы III перемежаются или неупорядоченно связаны со звеньями формулы I, или поли(альфа-стиролфосфоновая кислота), содержащая звенья формулы

где группы, усиливающие поступление и удерживание, геминально связаны с цепью.According to a preferred embodiment of the invention, the AAA is a polymer containing 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 AAA 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-phosphonoprene) containing units of the formula

For use in the invention as an AAA containing phosphonic acid, it is recommended that poly (betastyrolphosphonic acid) containing units of the formula

where Ph is phenyl, in which the entry-enhancing group and the retention-enhancing phenyl group are bonded to the vinyl carbon atoms of the chain, or a copolymer of beta-styrenephosphonic acid with vinylphosphonyl chloride in which the units of formula III are alternated or randomly linked to the units of formula I, or poly (alpha-styrenephosphonic acid) containing units of the formula

where 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 to 30,000, 2,500 to 10,000. Inert monomers do not significantly affect the intended use of any copolymer used in the invention as an AAA.

поли(аллилбис(фосфонэтиламин) со звеньями формулы

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

poly (allylbis (phosphonethylamine) 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 invention as AAA, provided that they contain or are modified to contain the above organic enhancing retention groups.

 In one aspect of the invention, the oral composition comprises an orally acceptable carrier effective to prevent plaque formation, an amount of a water-insoluble non-cationic antibacterial agent, and an enhancing effect of an antibacterial agent agent with an average molecular weight of 1,000,000,000, containing at least one upstream functional group and at least one an organic retention enhancing group, and such an agent containing said groups is free or substantially TSS is free from water-soluble synthetic anionic carboxylate lineynopolimernoy alkali metal or ammonium salt with a molecular weight of 1000 to 1,000,000.

 According to another preferred embodiment of the invention, the AAA may include a synthetic anionic polymer carboxylate. Although not used in the invention for co-acting with a polyphosphate calculus-preventing agent, nevertheless a synthetic anionic polymeric polycarboxylate with a molecular weight of 1,000,000,000, preferably 30,000 to 50,000, was used as an alkaline phosphatase enzyme inhibitor in optimizing the calculus-preventing efficacy of linear molecularly anhydrous polyphosphate salts (see US Pat. No. 4,627,977 to Gaffar et al.). At the same time, British Patent Publication 2,200,551 discloses a polymeric polycarboxylate as a possible component of an oral composition containing linear molecularly anhydrous polyphosphate salts and a substantially water-insoluble non-cationic antibacterial agent. In addition, in the context of the invention, it was noted that such a carboxylate is noticeably effective in terms of enhancing the uptake and retention of a non-ionic antibacterial anti-plaque agent to the surfaces of the teeth when another component (i.e., molecularly dehydrated polyphosphate) co-acts with the component for which there is no joint action with polymer polycarboxylate, for example, when the component with which the polymer carboxylate acts together is a non-cationic antibacterial a common remedy.

 Synthetic anionic polymeric polycarboxylates and their complexes with various cationic bactericides, zinc and magnesium have been previously described as such as anti-calculus agents, for example, US Pat. No. 3,429,963 to Shedlovsky, US Pat. No. 4,152,420 to Gaffar, US Pat. No. 3,956,480 to Dienter et al. US patent N 4138477 in the name of Gaffar and US patent N 4183914 in the name of Gaffar et al. It must be pointed out that the synthetic anionic polymeric polycarboxylates described in the above patents, if they contain or are modified to contain reinforcing retention groups, are applicable in the compositions and methods of the invention, and descriptions of such patents are incorporated by reference into this description.

 The synthetic anionic polymeric polycarboxylates used in the invention are well known and often used as free acids, or preferably partially, but more preferably completely neutralized, water-soluble alkali metal (e.g. potassium, but preferably sodium) or ammonium salts. Copolymers of maleic anhydride or maleic acid with another polymerizable monomer with ethylene unsaturation (1: 4 to 4: 1) are recommended, preferably a copolymer of methyl vinyl ether with maleic anhydride of molecular weight (MV) of 30,000 to 1,000,000, most preferably 30,000 to 50,000. Such copolymers are available, for example, under the brand names Gantrez AN 139 (MV 500000), AN 119 (MV 25000) and preferably S-97 for pharmaceutical purposes (MV 70000) by GAF Corporation.

 Other polymeric polycarboxylates used as UAA, containing or modified to contain retention enhancing groups, include the polycarboxylates described in US Pat. No. 3,956,480 above, for example copolymers of (1 1) maleic anhydride with ethyl acrylate, hydroxyethyl methacrylate, N-vinyl-2-pyrrolide or ethylene, the latter being produced, for example, by Monsanto under the designation EMA N 1103 (MV 10000) and EMA Grade 61, as well as copolymers (1 1) of acrylic acid with methyl or hydroxyethyl methacrylate, methyl or ethyl methacry atom, isobutyl ether or 11-vinyl-2-pyrrolidone.

 Additional applicable polymeric polycarboxylates are described in US Pat. Nos. 4,138,477 and 4,183,914 cited above and they contain or are modified to contain retention enhancing groups, including copolymers of maleic anhydride with styrene, isobutylene or ethyl vinyl ether, polyacrylic, polyitaconic, and also polyaleic acids oligomers with MVs below 1000, sold under the brand name Uniroyal ND-2.

 In general, polymerizable carboxylic acids with an ethylene or olefinic unsaturation and a retention enhancing group containing an activated carbon-carbon olefinic double bond that is readily realized in the polymerization due to the presence in the monomer in the alpha-beta position with respect to the carboxyl or as part of the terminal methylene are generally applicable. Examples of such acids include acrylic, methacrylic, ethacrylic, alpha-chloroacrylic, crotonic, beta-acryloxy-propionic, sorbic, alpha-chlorosorbic, cinnamic, beta-styrene-acrylic, muconic, itaconic, citraconic, mesaconic, glutaconic, alone, acon 2-benzyl acrylic, 2-cyclohexyl acrylic, angelic, umbella, fumaric, maleic acids and anhydrides of these acids. Other various olefin monomers copolymerizable with the above carboxylic monomers include vinyl acetate, vinyl chloride, dimethyl maleate, etc. The copolymers contain in sufficient quantities groups of salts of carboxylic acids to give them water solubility.

 The so-called carboxyvinyl polymers described as components of toothpaste in US Pat. No. 3,980,767 to Chown et al. Are also applicable in the present invention. U.S. Patent 3,935,306 to Roberts et al. U.S. Patent 3,919,409 to Perla et al. US patent 3911904 nor the name Harrison and US patent 3711604 in the name of Colodney et al. These polymers are commercially available, for example, B.F. Coodrich under the brand names Carbopol 934, 940 and 941, and such industrial products are a colloidal water-soluble polymer of polyacrylic acid crosslinked with 0.75% polyallyl sucrose or allyl pentaerythritol as a crosslinking agent, such a crosslinked structure and cross-linking provide targeted retention enhancement by hydrophobia and / or physical uptake of an antibacterial agent, etc. Policarbophil, which is a polyacrylic acid crosslinked with less than 2% divinyl glycol, is somewhat lower. e amount, molecular weight and / or hydrophobicity that as the crosslinking agent does not provide, or provides gain only slightly retention. An example of a more effective retention enhancing crosslinking agent is 2,5-dimethyl-1,5-hexadiene.

The synthetic anionic polymeric polycarboxylate component is mainly a hydrocarbon with possible halogen and oxygen-containing substituents and bonds represented, for example, by ester, ethers and OH groups, and it is used in the present compositions in approximate amounts by weight of 0.05 to 4%, preferably 0 05 3% more preferably 0.1 2%
AAA may also include natural anionic polycarboxylates containing reinforcing retention groups. Carboxymethyl cellulose and other resins and film-forming substances used as binders that do not have the aforementioned admission enhancing and / or enhancing retention groups are ineffective as AAA.

As an illustration of UAA containing phosphinic and / or sulfonic acid in the form of enhancing the intake of polymers, mention may be made of polymers and copolymers containing units or fragments formed during the polymerization of vinyl or allylphosphinic and / or sulfonic acids, substituted, as necessary, with 1 or 2 (or 3) carbon atom retention enhancing group, for example, the above formula - (X) _n -R. Mixtures of such monomers and their copolymers with one or more inert monomers with ethylene unsaturation such as those 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 associated with any given carbon or other atom of the polymer skeleton or its branch. Polysiloxanes containing or modified to contain outgoing reinforcing or retention enhancing groups can also be used as AAA in the present invention. As UAA in the invention are applicable ionomers containing or modified to contain enhancing the receipt and 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 invention, as an AAA, they are applicable provided that they contain or are modified to contain retention enhancing groups, polyesters, polyurethanes and artificial natural polyamides, including proteins and protein compounds such as collagen, poly (arginine) and others polymerized amino acids.

 In one aspect of the invention, an AAA with an average molecular weight of 1,000 to 1,000,000 contains at least one reinforcing functional group and at least one organic retention enhancing group, and such an agent with these groups does not contain or actually does not contain a water-soluble synthetic anionic linear polymer alkali metal or ammonium polycarboxylate salt with a molecular weight of 1,000 to 1,000,000.

 In the invention, the recommended oral composition is a dentifrice containing about 0.3 wt. antibacterial agents (for example, triclosan) and 1.5 to 2 wt. polycarboxylate as UAA.

Not wanting to be bound by a specific theory, it is nevertheless believed that UAA, in particular polymer UAA, is usually an anionic film-forming material that is believed to attach to the surface of the teeth and forms a continuous film on this surface that prevents teeth from accessing bacteria. It is possible that a non-cationic antibacterial agent forms a complex or some other form of bond with UAA, resulting in a complex film or similar formation on the surface of the teeth. The ability of the UAA to form a film, as well as the increased receipt and retention of an antibacterial agent on the surface of the teeth under the influence of the AAA, apparently makes the tooth surface unfavorable for the accumulation of bacteria, especially because the direct bacteriostatic effect of the antibacterial agent prevents the growth of bacteria. Thus, a combination of three types of exposure, namely
1) enhanced revenue,
2) a long retention time on the surface of the teeth and
3) preventing the binding of bacteria to the surface of the teeth
makes the oral composition effective to reduce plaque formation. A similar anti-plaque effect applies to soft intraoral tissues on or near the gum line.

 According to the invention, an orally acceptable carrier is effective in converting amounts of a water-insoluble non-cationic antibacterial agent to a state dissolved in saliva in order to prevent plaque formation.

 In an oral composition, an orally acceptable carrier comprises an aqueous phase with a humectant present therein. In a dentifrice in the form of a gel, usually containing 5 to 30 wt. silicon polishing agent, water, as a rule, is present in an amount of at least 3 wt. usually 3 to 35 wt. and a humidifier, which is recommended as glycerin and / or sorbitol, is usually present in an amount of 6.5 to 75 wt. or 80 wt. on an oral composition for cleaning teeth in the form of a gel. The reference here to sorbitol implies a commercial product, usually in the form of 70% aqueous solutions.

 Means for brushing your teeth in the form of a gel containing an antibacterial agent in an amount of 0.25 0.35 wt. they do not require an additional component in an oral carrier that solubilizes an antibacterial agent, although the presence of such a solubilizer is possible. If the amount of antibacterial agent is below 0.25 wt. for example in the range of 0.01 to 0.25 wt. in this case, the presence of a salubilizer is necessary to guarantee sufficient solubilization in saliva in effective prevention of plaque formation. If the amount of antibacterial agent exceeds 0.35 wt. for example, the range is 0.35 to 0.5% wt. or higher, say 5 wt. in this case, it is all the more necessary, since otherwise a significant part of the antibacterial agent will remain undissolved.

 If the oral composition is a dentifrice containing 30 to 75 wt. polishing agent acceptable for brushing teeth, the presence of a solubilizer is also possible.

 If the oral composition is a mouthwash or a liquid dentifrice, then the oral carrier includes at least one surfactant, an oil perfume or a non-toxic alcohol, each of which helps to dissolve the antibacterial agent, in which case a solubilizer is also possible .

 If a solubilizer is present in the compositions of the present invention, it is contained in an amount of 0.5 to 20 wt. lower limit of 0.5 wt. It is sufficient at a low content, say, up to 0.3 wt. water-insoluble non-cationic antibacterial agent. When the content of the antibacterial agent in large quantities, for example at least 0.5 wt. especially in the presence of 5-30 wt. silicon polishing agent, it is desirable that the solubilizer is present in an amount of at least 5 wt. usually up to 20 wt. or more. It is noted that in the presence of a solubilizer in amounts exceeding 5 wt. there is a tendency to separate dentifrices into liquid and solid parts.

 An agent present or which may be present to solubilize the antibacterial agent in saliva may be incorporated into a carrier consisting of water and a humectant. Such solubilizers include moisturizing 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 12 carbon atoms in a straight chain, such as olive oil, castor oil and petrolatum, as well as esters such as amyl acetate, ethyl acetate and benzyl benzoate. As used herein, “propylene glycol” refers to 1,2-propylene glycol and 1,3-propylene glycol. Significant amounts of polyethylene glycol, especially those with a molecular weight of 600 or higher, should be avoided since polyethylene glycol effectively inhibits the antibacterial activity of a non-cationic antibacterial agent. For example, polyethylene glycol (PEG) 600 mixed with triclosan with a weight ratio of 25 triclosan 1 PEG 600 lowers the antibacterial activity of triclosan by a factor of about 16 compared to the amount of activity in the absence of polyethylene glycol.

In accordance with some aspects of the invention, an oral dentifrice composition may be a gel in nature, for example, a gel dentifrice. Such oral gel preparations include a kermni-containing dentifrice. Recommended polishing agents include crystalline silicon oxide with a particle size of up to 5 μm, an average particle size of up to 1.1 μm and a specific surface area of up to 50,000 cm ² / g, silica gel or colloidal silicon oxide and complex amorphous alkali metal aluminosilicates.

 When visually transparent or opaque gels are used, colloidal silicon oxide, such as sold under the trade name Siloid, for example Siloid 72 and Siloid 74, or under the trade name Santogel, such as Santogel 100, or alkaline metal aluminosilicate complexes, is especially useful as a polishing agent. i.e., silicon oxide included in the alumina matrix), since they impart consistency to a gel-like texture and have refractive indices close to those of the system I use a liquid-forming gel (including water and / or a humectant) commonly used in dentifrices.

 Polishing material is usually present in an oral dentifrice composition, such as toothpaste or gel compositions, in amounts of 5-30 wt.

 In the same aspect of the present invention, in which the oral preparation is a dentifrice, it contains an orally acceptable carrier comprising an aqueous phase with a humectant, preferably glycerin and / or sorbitol, and water is usually present in an amount of 25 35 or 40 wt. . the amount of glycerol and / or sorbitol in general is usually 20 75 wt. on a preparation for brushing your teeth, more typically 25 to 60 wt. In this case, reference to sorbitol refers to material commonly sold as 70% aqueous solutions.

 In the invention, the composite dentifrice may be pasty in nature, such as toothpaste (tooth cream), although if a silicon-containing polishing agent is used (the case is uncharacteristic, since this material is not used in amounts exceeding 30 wt.) character may be gelatinous. The carrier of the composite dentifrice includes a dentifrice polishing agent, examples of which include water-insoluble sodium metaphosphate, potassium metaphosphate, tricalcium phosphate, dehydrated dicalcium phosphate, anhydrous dicalcium phosphate, calcium carbonate, aluminum silicate, hydrated alumina, silica and mixtures thereof, benton with each other or with solid polishing materials, such as calcined alumina, zirconium silicate, a material comprising particles of thermosetting resins described in atente US N 3070510, issued 15 December 1962, such as melamine, phenolic, and urea-formaldehyde resins, and crosslinked polyepoxides and polyesters. Recommended polishing materials include insoluble sodium metaphosphates, licalcium phosphate and hydrated alumina.

 Many of the so-called "water-insoluble" polishing materials are anionic in nature and also include small amounts of soluble material. Thus, insoluble sodium metaphosphate can be obtained by any suitable method, for example, given in the Thorpe Dictionary of Applied Chemistry, Volume 9, 4th Edition, p. 510 511. Insoluble sodium metaphosphate, known as the Madrell salt and the Currol salt, is a further example of acceptable materials. Such metaphosphates exhibit only limited solubility in water, as a result of which they are often called insoluble metaphosphates (NMPs). In the form of impurities, they contain small amounts of soluble phosphate product, usually in the amount of several percent, for example up to 4 wt. The amount of soluble phosphate product, which is believed to include soluble sodium trimetaphosphate in the case of insoluble metaphosphate, can be reduced or negated by washing if desired. Insoluble alkali metal metaphosphate is usually applied to the form of a powder with a particle size such that no more than 1% of the material is made up of particles larger than 37 microns.

Hydrated alumina is an example of a non-ionic polishing material in nature. As a rule, the particle size of aluminum oxide is small, i.e. at least 85% of the particles have a size of less than 20 microns, and the representative of aluminum oxide is gibbsite (aliphoxide trihydrate), corresponding to the chemical formula Al ₂ O ₃ • 3H ₂ O or Al (OH) ₃ . The average particle size of gibbsite is usually 6 to 9 microns. A typical gibbsite has the following particle size distribution:
Mkm
30 94 99
20 85 93
10 56 67
5 28 40
Polishing material is usually present in the composition in the form of a paste or gel within 30 to 75 wt.

Toothpastes or tooth creams for cleaning teeth, as well as gel cleaning products, typically contain a natural or synthetic thickener or gel-forming agent in an amount of 0.1 to 10%, preferably 0.5 to 5%, Synthetic colloidal complex clay is an acceptable thickener, which is a silicate of magnesium and an alkali metal and sold under the brand name Laponite (for example: CP, SP 2002, D) manufactured by Laport Industries Limited. Analysis of Laponite D gives the following distribution of components (by mass): 58% SiO ₂ , 25.4% MgO, 3.05% Na ₂ O, 0.98% Li ₂ O, some water and traces of other metals. Its true specific gravity is 2.53 and an apparent bulk density (g / ml or 8% moisture) of 1.0.

 Other suitable thickeners or gel-forming agents include Irish moss, iota-carrageenan, tragacanth gum, starch, polyvinylpyrrolidone, hydroxyethylpropylcellulose, hydroxybutylmethyl cellulose, hydroxypropyl methylcellulose (for example, sodium hydroxide), for example, produced in the form of the smallest powder under the brand names Siloid 244 or Silo dent 15.

 In that aspect of the invention in which the oral composition is a mouthwash or a liquid dentifrice, such a liquid composition, especially in the case of a mouthwash, contains a water-alcohol mixture as a carrier. 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 this type of preparation is usually in the range of 70 - 99.9 wt. Alcohol is a non-toxic alcohol such as ethanol or isopropanol. In an amount of 10 to 30 wt. a humectant such as glycerin and sorbitol may be present. Liquid dentifrices containing 50 to 85 wt. water may contain 0.5 to 20 wt. non-toxic alcohol and may also contain 10 to 40 wt. a humectant such as glycerin and / or sorbitol. The reference to sorbitol refers to material commonly produced by industry in the form of 70% aqueous solutions. Ethanol is the recommended non-toxic alcohol. Alcohol is believed to contribute to the dissolution of a water-insoluble non-cationic antibacterial agent, and flavoring oil is believed to serve the same purpose.

 As indicated, the non-cationic antibacterial agent is substantially insoluble in water. However, in the present invention, in which an AAA, such as a polycarboxylate, is believed to be present in an oral rinse or a liquid dentifrice, an organic surfactant, a fragrance oil and a non-toxic alcohol are believed to aid in the dissolution of the antibacterial agent to facilitate its access to the soft intraoral tissues on or near the gums, as well as on the surface of the teeth. Organic surfactants and / or aroma oils, if present in oral dentifrice compositions, can help dissolve antibacterial agents.

 Organic surfactants are also used in the compositions of the present invention with the aim of increasing the prophylactic effect of the compositions, with the aim of promoting the ubiquitous and complete spread of plaque-preventing antibacterial agents in the oral cavity and with the goal of giving the compositions a more acceptable cosmetic appearance. The organic surfactant is preferably anionic, nonionic or ampholytic in nature, and it is recommended that a detergent be used as a surfactant that imparts detergent and foam properties to the composition. Examples of suitable anionic surfactants include water-soluble salts of monosulfate monosulfates of higher fatty acids, such as the sodium salt of monosulphonated coconut oil fatty acids monoglyceride, higher alkyl sulfates, such as higher alkyl sulfoacetate esters of higher fatty acids acylamides of lower aliphatic amino acid compounds, for example, having 12 16 carbon atoms in a fatty acid, alkyl m or acyl radicals, and m. p. Examples of the above amides include N-lauroyl sarcosine, the sodium, potassium and ethanolamine salts of N-lauroyl, N-myristoyl or N-palmitoyl sarcosine, which should not contain soap or similar higher fatty acid derivatives. The use of these sarcosine derivatives in the oral compositions of the present invention is especially promising, since these derivatives have a long and noticeable effect from the point of view of inhibiting the formation of acids in the oral cavity as a result of the decomposition of carbohydrates and, in addition, to some extent reduce the solubility of tooth enamel in acid solutions . Examples of water-soluble non-ionic surfactants are the condensation products of oxide and ethylene with various reactive compounds having active hydrogen and long hydrophobic chains (for example, aliphatic chains with 12 to 20 carbon atoms), and such condensation products ("ethoxamers") 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 gender propylene oxide (e.g., pluronic products).

 Surfactant is usually present in an amount of 0.5 to 5 wt. preferably 1 to 2.5 wt.

 If the oral composition is a liquid dentifrice, 0.1 to 10%, preferably 0.5 to 5% of the above described natural or synthetic thickener or gel forming agent is usually present in amounts.

 Typically, such a dentifrice does not contain a polishing agent. However, as indicated in US Pat. No. 3,506,757 to Salzmann, in a liquid dentifrice, 0.3 to 2% high molecular weight polysaccharide with a molecular weight higher than 1,000,000 containing fragments of mannose, glucose, potassium gluconate and acetyl in an approximate ratio of 2 1 can be used. 1 1, and the same composition may contain 10 20% of a polishing agent such as hydrated alumina, dicalcium phosphate dihydrate, calcium pyrophosphate, insoluble sodium metaphosphate, anhydrous dicalcium phosphate, calcium carbonate, magnesium carbonate, ma rot, silicon oxide, mixtures of these substances, etc.

 Not wanting to be bound by a certain theory, as a result of which the advantages of the present invention are achieved, we nevertheless believe that an aqueous carrier with a humectant is solubilized in micelles of a surfactant into the mobile phase (not including gel-forming and polishing agents if they are present in the composition of the cleaning agent teeth). The solution of the mobile phase of the dentifrice during use is diluted with saliva, which leads to the deposition of triclosan. So, it was found that even in the absence of a special solubilizer, if the amount of triclosan is 0.25 0.35 wt. and UAA, such as polycarboxylate, is present, triclosan is present in amounts sufficient to create an excellent anti-plaque effect on soft gum tissue. Similar remarks apply to other water-insoluble non-cationic antibacterial agents used in the invention.

 Oral dentifrice compositions may also include a fluoride ion source or a fluorine-containing component as an anti-caries agent in an amount sufficient to provide 25 5000 ppm fluoride ions. Such compounds may be slightly soluble in water or may be water insoluble. The compounds are characterized by the ability to produce fluoridion in water and the inability to enter into undesirable reactions with other compounds of the oral composition. Such compounds include inorganic salts of hydrofluoric acid, such as soluble alkali metal salts, alkaline earth metal salts, for example sodium fluoride, potassium fluoride, ammonium fluoride, calcium fluoride, copper fluoride such as copper (I) fluoride, zinc fluoride, barium fluoride , sodium fluorosilicate, ammonium fluorosilicate, sodium fluorozirconate, ammonium fluorozirconate, sodium monofluorophosphate, aluminum mono- and difluorophosphate and sodium calcium pyrophosphate. Alkali metal and tin fluorides, such as sodium and tin fluorides, sodium monofluorophosphate (MFF), and mixtures thereof are recommended.

 The amount of fluoride-forming compound to some extent depends on the type of compound, its solubility and the type of oral preparation, but this should be a non-toxic amount, usually 0.0005 3% per drug. In a dentifrice, for example, in the form of a gel, such an amount of a compound is considered satisfactory that it releases up to 5000 ppm G-ions per mass of the preparation. Any minimum amount of such a compound may be used, but it is recommended that the compound be used in an amount sufficient to form 300 to 2000 ppm, more preferably 800 to 1500 ppm of fluoridion.

Typically, in the case of alkali metal secondary, this component is present in an amount of up to 2 wt. for the whole preparation, preferably in the range of 0.05 to 1%. In the case of sodium monofluorophosphate, the compound may be present in an amount of 0.1 to 3%, more typically about 0.76%
It must be emphasized that, as usual, oral preparations should be sold or otherwise distributed in packages provided with appropriate labels. So, a gel-type dentifrice should be packaged in a crease tube, usually made of aluminum, lined lead or plastic, or in a dispersant with pressurized contents, measured by a dispersant that has a label with information about what substance it contains, e.g. gel for brushing teeth, etc.

 Various other substances, such as brighteners, preservatives, silicones, chlorophyll derivatives and / or ammonium-containing products, for example urea, diammonium phosphate and mixtures thereof, can be incorporated into the oral preparations of the present invention. These auxiliary substances, if present, are introduced into the preparations in an amount that does not have a noticeable undesirable effect on the target properties and characteristics of the drug. Significant amounts of salts or compounds of zinc, magnesium and other metals, usually soluble, which can form complexes with the active components of the present invention, should be avoided.

 Any suitable flavoring or sweetening material may also be used. Examples of suitable flavoring components include flavoring oils, for example, spearmint, peppermint, vitegren oil, sassofras oil, clove oil, sage oil, eucalyptus oil, marjoram oil, cinnamon oil, lemon oil, orange oil and methyl salicylate. Suitable sweeteners include sucrose, lactose, maltose, xylitol, sodium cyclamate, perillartine, aspartylphenylalanine methyl ester (AMP), saccharin, etc. It is desirable that the flavoring and sweetening agents separately or together be from 0.1 to 5% or more per drug. Moreover, as a surfactant, a flavoring oil is believed to contribute to the dissolution of the antibacterial agent together or even in the absence of a surfactant.

 In the recommended practice of the present invention, the oral composition is recommended to be applied regularly to tooth enamel and soft intraoral tissues, especially on or near the gum line, with a periodicity of, for example, every day or every second or third day, or preferably 1 to 3 times a day, at pH 4, 5 9 or 10, usually 5.5 to 8, preferably 6 to 8, and most preferably 6.5 to 7.5 for at least 2 to 8 or more weeks or throughout life.

 The compositions of the invention can be incorporated into losingis or chewing gum or into other products, for example, by mixing with a heated rubber base or by applying a rubber base to the outer surfaces, an illustration of which is gelutong, rubber latex, vinyl resin and the like. preferably with conventional plasticizers and softeners, sugar or other sweeteners or carbohydrates such as glucose, sorbitol, etc.

 The following examples continue to illustrate the nature of the invention, but it should be pointed out that the invention is not limited to them. All quantities shown are by weight unless otherwise indicated.

 Example 1. Received a dentifrice, the composition of which is given in table.2.

 Dentifrice A supplies triclosan to the teeth and soft gum tissue essentially the same as dentifrice B containing a special triclosan solubilizer. In other words, the presence of a special solubilizer is not necessary for the effectiveness of the dentifrice of the present invention. In addition, an appropriate dentifrice that lacks polycarboxylate (Gantrez) is significantly worse in terms of triclosan intake.

 In the above example, improved results can be achieved by replacing triclosan with other indicated antibacterial agents, such as phenol, thymol, eugenol and 2,2'-methylenebis (4-chloro-6-bromophenol) and / or by replacing Gantrez with other UAA, such as a copolymer (1: 1) of maleic anhydride and ethyl acrylate, a sulfoacrylic oligomer, Carbopol (e.g. 934) and polymers of monomeric alpha or beta styrene phosphonic acids and copolymers of these monomers with each other or other polymerizable monomers with ethylene unsaturation, such and as vinylphosphonic acid.

 Example 2. Listed in table. 3 liquid-phase solutions of dentifrices were tested for isolation and retention of triclosan in saliva on disks coated with hydroxyapatite (HA) according to the test procedure described in example 1. The results are shown in table. 3.

 The results (Table 3) show that a solution (D) containing polyvinyl alcohol that is not in the UAA gives only 36 μg of triclosan, which is similar to the results of control solution (A) (31 μg) that does not contain an additive. In contrast, solution (C) with poly (alpha-styrenephosphonic) acid gives 86 mcg of triclosan, which is more than double the results for solutions (A) and (D), and solution (B) with poly (beta-styrenephosphonic acid) ) gives an income that is more than 5 times higher than the results for solutions (A) and (D), which additionally indicates the best results in the case of an official substitution of an income-enhancing group. The above results also show an unexpectedly good retention of triclosan on HA discs for solution (B) containing poly (beta-styrene phosphonic acid) (MV 3000 10000).

 Example 3. The effect of synthetic anionic linear polycarboxylate on the intake, retention and release from the tooth surface of a water-insoluble non-cationic antibacterial agent is tested in vitro in saliva on hydroxyapatite-coated discs and exofolated buccal epithelial cells. In vitro tests correlate with in vivo uptake and retention on intraoral surfaces.

To test the intake of an antibacterial agent in the saliva covering the discs, hydroxyapatite (HA) manufactured by Monsanto is intensively washed with distilled water, separated by vacuum filtration and allowed to dry for 37 ^° C. Dried HA is ground with a pestle in a mortar, 150 mg of HA are placed in a chamber for compressing tablets KV (Barnes Analytical, Stanford, CT) and pressed for 6 min under a pressure of 10,000 feet in a laboratory press Carver. The resulting 13 mm discs are sintered for 4 hours at 800 ^° C. in a Thermolyne furnace. Stimulated paraphilic saliva is collected in an ice-cooled bucks. The saliva is clarified by centrifugation at 1500 xg (multiple gravity) and 4 ^o C for 15 minutes Sterilization of clarified saliva is carried out at 4 ^o C and stirring by irradiation of the sample with UV radiation for 1 hour

Each sintered disk 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 one 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 a liquid-phase dentifrice with an antibacterial agent (triclosan), and incubated at 37 ^° C with continuous shaking in a water bath. After 30 minutes, the disc is transferred to a new tube, 5 ml of water is added, after which the discs are 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 any entrainment of any liquid along with the disc. Then, 1 ml of methanol is added to the disk and vortexed vigorously. The sample is left for 30 minutes at room temperature to extract the absorbed triclosan into methanol. Methanol is then purged and clarified by centrifugation in a Beckman Model II microcentrifuge at 10,000 rpm for 5 minutes. After this treatment, methanol is transferred to vials for high performance liquid chromatography (HPLC) to determine the concentration of the antibacterial agent. In all experiments, samples were duplicated three times.

To test the retention of an antibacterial agent on HA saliva-coated discs, the discs are suspended with a dentifrice as described above. After incubation for 30 min at 37 ^° C, HA disks are removed from the suspension of dentifrices, washed twice with water, and then again incubated with paraphilic stimulated holistic human saliva, clarified by centrifugation. After incubation at 37 ^° C and constant shaking for various periods, HA disks are removed from saliva and the amount of antibacterial agent (triclosan) retained on the disk and excreted into saliva is determined analytically by HPLC.

To determine the inflow of an antibacterial agent to the buccal epithelial cells, this inflow is determined in order to identify the effect of PVM / MA on the inflow of an antibacterial agent (triclosan) to soft intraoral tissues from a dentifrice. Buccal epithelial cells are harvested using a tool for local application of the drug in the form of a wooden stick by carefully scraping the oral mucus. Cells are suspended in a buffer of residual saliva salts (Pss) (50 nM NaCl, 1.1 nM CaCl ₂ and 0.6 nM KH ₂ PO ₄ , pH 7) to a concentration of (5 6) • 10 ⁰ cells / ml using a hemocytometer for counting cells that are stored on ice until use. A suspension of cells (0.5 ml), previously incubated at 37 ^o C in a water bath, is added to 0.5 ml of the solution of the tested antibacterial agent and incubated at 37 ^o C. The solution of the antibacterial agent (triclosan) is delivered to the soft intraoral tissues from the means for brushing your teeth. Buccal epithelial tissues are harvested with a wooden stick by carefully scraping intraoral mucus. Cells are suspended in a buffer of residual saliva salts (Pss) (50 nM NaCl, 1.1 nM CaCl ₂ and 0.6 KH ₂ PO ₄ , pH 7) to a concentration of (5 - 6) • 10 ⁵ cells / ml using a hemocytometer for counting cells that are stored on ice until use. A cell suspension (0.5 ml), previously incubated in a water bath at 37 ^° C, is added to 0.5 ml of the solution of the tested antibacterial agent and incubated at 37 ^° C. The solution of the antibacterial agent in the incubation mixture is diluted at least 10 times with the goal of lowering the concentration of surfactant and preventing the destruction of cell membranes. After 30 minutes of incubation, the cells are collected by centrifugation in the form of a lump, which is washed 3 times with Pss buffer and treated with 1.5 ml of methanol. The sample is vigorously mixed and analyzed by HPLC for the presence of an antibacterial agent.

 Obtained dentifrices, the composition of which is given in table. 4.

 The intake of triclosan in saliva covering the disks made of hydroxyapatite and buccal epithelial cells in the presence and absence of polymeric polycarboxylate Gantrez S-97 are shown in table. 5.

 The above results show that Gantrez (present in the preparation B) significantly enhances the intake and absorption of triclosan by saliva covering the disks of hydroxyapatite and exofolated cheek epithelial cells.

 Similar results were obtained with 0.3 parts of triclosan in the dentifrice.

 Example 4. In tests with saliva-coated hydroxyapatite discs and exfoliated buccal epithelial cells, in contrast to Example 1, dentifrice B containing 2% S-97 gantrez and 0.2% triclosan, 10% propylene glycol and 2% sodium lauryl sulfate, and a dentifrice (B ′) similarly formulated, but not containing 0.3% triclosan, is compared to a commercial dentifrice (C) containing hydrated alumina and (a) 0.2% triclosan as a polishing agent, (b) lack of gantrez, (c) lack of cuts glycol, (d) 0.5% zinc citrate, (e) 2.5% surfactants, (f) sodium monofluorophosphate and a hydrated aluminum mixture as a polishing agent, and the following dentifrice composition (C '), similar a sales composition (C) but containing 0.3% triclosan.

 Dentifrice C ', wt.

Sorbitol (70%) 27.00
Sodium carboxymethyl cellulose 0.80
Sodium Monofluorophosphate 0.85
Zinc Citrate 0.50
Sodium Saccharin 0.18
Water 16.47
Hydrated Alumina (Polishing Agent) 50.00
Ethanol 0.20
Sodium lauryl sulfate 1.875
Sodium dodecylbenzenesulfonate 0.625
Triclosan 0.3
Fragrance 1.20
Since compositions C and C 'in total contain 2.5 surfactants, more surfactants are used to dissolve triclosan than in the case of formulations B and B' containing 2 surfactants. However, the presence of propylene glycol in formulations B and B 'containing a silicon-containing polishing agent (in contrast to hydrated alumina in formulations C and C') ensures optimal dissolution of triclosan.

 The superiority of compounds B and B '(containing propylene glycol and Gantrez) over compositions C and C' in terms of the absorption of triclosan by saliva covering the disks made of hydroxyapatite and exofolated cheek epithelial cells is shown in Table. 6.

 Additional experiments with the dentifrice composition B '(0.3% triclosan, Gantrez, propylene glycol) in a 50% suspension of the composition in order to determine the retention of triclosan in the saliva covering the hydroxyapatite discs over time show excellent retention of triclosan, as evidenced by the results reflected in the table. 7.

 The results show that dentifrices, including triclosan, gantrez and propylene glycol, can provide enhanced intake and retention of triclosan on the surface of the teeth and soft tissues of the oral cavity, resulting in an improved anti-plaque formation and antibacterial effect.

 Example 5. Comparison of obtaining composition a and b are shown in table. eight.

 Composition a is a dentifrice containing Gantrez (polycarboxylate and 0.5% triclosan as an antibacterial anti-plaque agent and does not contain a solubilizer. Propylene glycol is present as part of the solubilizer.

 Composition a poorly delivers triclosan to buccal epithelial cells, while composition b is noticeably more effective.

 The above results indicate the excellent intake of triclosan from the dentifrices containing it.

 Example 6. The study "at home" on a group of volunteers to identify the effects of specific means for brushing your teeth on the re-occurrence of plaque. The technique described in Addy, Wilis, Morem, J. Clin Perio, 1993, v. 10, p. 89 99. Tested dentifrices include a placebo (control) free of triclosan (I) and a dentifrice in accordance with the present invention containing 0.3% triclosan, 10% propylene glycol (instead of 3% 600 polyethylene glycol) and 2 % Gantrez S-97, and as a humectant propylene glycol and sorbitol (II). Means for cleaning teeth have the following composition (table. 9).

With regard to reducing the formation of plaque on the teeth of volunteers compared with placebo (I), the composition of the invention (II) gives a significant decrease of 20%
Since smaller amounts of propylene glycol can dissolve 0.3% of triclosan present in toothpaste (II), similar results can be expected when the amount of propylene glycol is reduced to 0.5 parts and the amount of sorbitol is increased to 39.5 parts. Similarly, other solubilizers, such as dipropylene glycol, hexylene glycol, methyl cellosolve, ethyl cellosolve, olive oil, castor oil, petrolatum, amyl acetate, ethyl acetate, glycerol tristearate and benzyl benzoate instead of propylene glycol, can efficiently supply triclosan to soft tissues. Moreover, similar results are expected in case of exclusion from toothpaste (II) containing 0.3% triclosan, propylene glycol or another solubilizer.

 Example 7. Obtained dentifrices, the compositions of which are given in table. ten.

 In the above examples, improved results can be obtained by replacing triclosan with other already mentioned antibacterial agents, such as phenol, thymol, eugenol and 2,2'-methylenebis (4-chloro-6-bromophenol) and / or when replacing Gantrez with other UAA, such as a copolymer of (1 1) maleic anhydride with ethyl acrylate, sulfacrylic oligomers. Carbopols (e.g., Carbopol 934), polymers of monomeric alpha or beta styrene phosphonic acids and copolymers of these monomeric styrene phosphonic acids with each other or other polymerizable ethylenically unsaturated monomers such as vinyl phosphonic acid.

 Example 8. Received a dentifrice, the compositions of which are given in table. eleven.

 The above formulations deliver triclosan to the teeth and soft gum tissue significantly more efficiently than the corresponding formulations that do not contain polycarboxylate (Gantrez).

 Example 9. Obtained dentifrices, the compositions of which are given in table. 12.

 The above dentifrice formulations deliver triclosan to the saliva covering the hydroxyapatite discs more efficiently than polycarboxylate-free formulations (Gantrez).

 Example 10. Received a means of preventing the formation of plaque for brushing the following composition, wt. h

Glycerin 15.00
Propylene glycol 2.00
Sodium carboxymethyl cellulose 1.50
Water 24.93
Maleic anhydride copolymer of vinyl methyl ether (42% solution) 4.76
Sodium Monofluorophosphate 0.76
Sodium Sarin 0.30
Insoluble sodium metaphosphate 47.00
Titanium dioxide 0.50
Sodium lauryl sulfate 2.00
Triclosan 0.30
Fragrance 0.95
In the above examples, improved results are also achieved when replacing triclosan with phenol, 2,2'-methylenebis (4-chloro-6-bromophenol), eugenol and thymol and / or when replacing the Gantrez with other UAA, such as Carbopol (for example, Carbopol 934) polymers of styrene phosphonic acids with molecular weights in the range of 3000 to 10000, such as poly (beta-styrene phosphonic acid), copolymers of vinyl phosphonic acid with beta-styrene phosphonic acid, poly (alpha-styrene phosphonic acid), sulfo-acrylic oligomers or copolymers of maleic anhydride ethyl acrylate.

 Example 11. Mobile phases of dentifrices containing triclosan (see table. 13).

The concentration of the components corresponds to 1.33% in such a dentifrice, for the complete completion of which an abrasive additive of 25% was required
The above mobile phases of these dentifrice formulations have been tested for triclosan absorption by saliva covering HA discs. The results are shown in table. 14.

 The results are shown in table. 14 show a more than twofold increase in the absorption of triclosan achieved in the case of a composition containing a Gantrez, in comparison with a composition A not containing a Gantrez.

 Example 12. The concentration and absorption of triclosan HA from the liquid part of the suspension (1 1) means for cleaning teeth in water (table. 15).

 The liquid part of the suspension (1 1) of the dentifrices in water is tested for the concentration of triclosan and for the absorption of triclosan with saliva covering HA discs. The results show that the use of 50% alumina as an abrasive significantly increases, under conditions of small dilution (1 1), the concentration of triclosan (from 1650 and 1905), which leads to a significant increase in the absorption of triclosan (from 52 to 74).

 Example 13. Compositions for rinsing the mouth (table. 16) are effective in reducing the formation of plaque or increasing the absorption and retention of triclosan by the oral surfaces.

 Example 14. Liquid dentifrices shown in the table. 17 are also effective in reducing plaque formation by absorption and retention of triclosan on intraoral surfaces.

 In the above examples, improved results are also achievable when replacing triclosan with phenol, 2,2'-methylenebis (4-chloro-6-bromophenol), eugenol and thymol and / or when replacing the Gantrez with another UAA, such as Carbopolis (e.g. Carbopol 934), styrene phosphonic acid polymers with molecular weights in the range of 3,000 10,000, for example poly (beta-styrene phosphonic acid), vinyl phosphonic acid copolymers with beta-styrene phosphonic acid, poly (alpha-styrene phosphonic acid), sulfoacrylic oligomers or maleic acid anhydride copolymer (1 1) Rilat.

 The present invention is described from the point of view of certain recommended options, but it must be emphasized that modifications and modifications obvious to a person skilled in the art should be included in the scope of this application and the scope of the attached claims.

Claims (9)

 1. An oral composition containing a water-insoluble non-cationic antibacterial substance, a polishing agent, characterized in that it further comprises polyvinyl phosphonate with a mol.m. 1,000,000,000 and a solvent with a pH of 4.5 of 10.0.  2. The composition according to p. 1, characterized in that it is a toothpaste and additionally includes about 5 to 30 wt. siliceous polishing substance and antibacterial substance in an amount of 0.25 to 0.35 wt.  3. The composition according to p. 2, characterized in that it is a toothpaste containing 0.01 to 5 mass. antibacterial substances and material that promotes the dissolution of antibacterial substances in saliva.  4. The composition according to one of claims 1 to 3, characterized in that it is a toothpaste, comprising 30 to 75 wt. water-insoluble polishing agent.  5. The composition according to claim 1, characterized in that it is a mouthwash or a liquid dentifrice, and the specified acceptable oral carrier is an aqueous carrier in which a non-toxic alcohol is present.  6. The composition according to claim 2, characterized in that said antibacterial substance is selected from the group consisting of halogenated diphenyl esters, halogenated salicylanilides, benzoic acid esters, halogenated carbanilides and phenolic compounds.  7. The composition according to claim 6, characterized in that the antibacterial substance is a halogenated diphenyl ether. 8. A composition according to claim 7, characterized in that said halogenated diphenyl ether is 2,4,4 ^{'trichloro-2 '} hydroxyphenyl ether.  9. The composition according to PP.1 to 8, characterized in that the polyvinyl phosphonate is present in an amount of 0.5 to 2.5 wt.

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