DK175758B1 - Antibacterial anti-plaque anti-toothpaste oral care - Google Patents

Description

DK 175758 B1

The present invention relates to an antibacterial anti-plaque anti-tartar oral care agent. More particularly, it relates to an oral care agent containing a polyphosphate antifouling agent and a compatible antibacterial agent which is effective in preventing plaque, wherein the antiplaque efficiency is optimized by the presence of an antibacterial enhancer which enhances the delivery of the antibacterial agent. means and retention thereof on mouth surfaces.

US Patents Nos. 4,627,977, 4,515,772 and 4,323,551 disclose oral care agents containing various polyphosphate compounds. In the former patent, a linear, molecularly dehydrated polyphosphate salt is used together with a source of fluoride ion and a synthetic linear polymeric polycarboxylate to prevent tartar formation. In the co-pending European patent application 89.200.710.5, anti-tartar efficiency is optimized with a reduced amount of the linear, molecularly dehydrated polyphosphate, together with sources of fluoride ion and an increased amount of the synthetic linear polymeric polycarboxylate. In the other two US patents, water-soluble dialkali metal pyrophosphate is used alone or mixed with tetraalkali metal pyrophosphate.

Oral care products that inhibit or prevent tartar formation on tooth surfaces are highly desirable, tartar being one of the factors causing periodontal conditions. Reduction thereof therefore promotes oral hygiene.

Dental plaque is a precursor to tartar. Opposite tartar, however, plaque can be formed on any part of the tooth surface, especially including the gingival rim. In addition to being unattractive, it is therefore implicated in the occurrence of gingivitis.

Therefore, it would be highly desirable to include antimicrobial agents known to reduce plaque in oral care agents containing anti-tartar agents. This is actually disclosed in U.S. Patent 4,022,550, wherein a compound which provides zinc ions as an antitouristic agent is admixed with an anti-bacterial agent which is effective in inhibiting the growth of plaque bacteria. Many different antibacterial agents are described

I DK 175758 B1 I

I 2 I

Together with the zinc compounds, including cationic materials such as guanides and I

In quaternary ammonium compounds as well as non-cationic compounds such as halogen-I

In prepared salicylanilides and halogenated hydroxydiphenyl ethers. IN

So far, they have cationic antibacterial materials such as chlorhexidine, benzethonium

In chloride and cetylpyridinium chloride have been the subject of the largest studies as

In anti-plaque antibacterial agents. Despite their use with zinc like I

however, they are not effective when used in conjunction with other

In ionic materials such as polyphosphate as an anti-tartar. This inefficiency I

I10 is considered quite surprising as polyphosphates are chelating agents, and

In the chelating effect, it has been known in the past to increase the efficiency of cation

In spoon, antibacterial agents (see, for example, Disinfection, Sterilization and Preservation, 2nd ed

Gift, Black, 1977, page 915, and Inhibition and Destruction of the Microbial Cell, Hugo, I

In 1971, page 215). Quaternary ammonium compounds are actually found in the plaque rule I

In purging mouthwash containing pyrophosphate according to U.S. Patent No. 4,323,551, and

Bis bis biguanide antiplaque agent is proposed in the anti-tartar pyrophosphate oral care agent I

In U.S. Patent No. 4,515,772. IN

In view of the surprising incompatibility of cationic antibacterial agents

20 with polyphosphates, which are found as anti-tartar agents, it was quite unexpected that

In these antibacterial agents would be effective. IN

It is an advantage of the present invention that certain antibacterial agents are effective

effective in anti-toothpaste oral care products containing a linear, molecular I

In 25 dehydrated polyphosphate salt, a source of fluoride ion and the aforementioned antibacterial

In reinforcing agent to prevent plaque formation. IN

It is a further advantage of the invention that an agent is provided which is effective

effective in reducing tartar formation and optimizing plaque reduction. IN

B 30 I

3 DK 175758 B1

It is a further advantage of the invention that an anti-plaque anti-tooth stone oral agent is provided which is effective in reducing the incidence of gingivitis.

Further advantages of the invention will become apparent from the following description.

In certain embodiments, the invention relates to an oral care agent comprising, in an orally acceptable carrier, an effective anti-dentifrice amount of material comprising 0.1-3% by weight of at least one linear, molecularly dehydrated polyphosphate salt as an anti-dentifrice, an effective antiplaque amount of a substantially water-insoluble, non-soluble -10 cationic, antibacterial agent and suitably up to approx. 4% by weight of an antibacterial or strengthening agent which enhances the delivery of the antibacterial agent and its retention on oral surfaces, typically the weight ratio of antibacterial enhancer to polyphosphation ranges from more than 0.72: 1 to less than 4: 1, e.g. from approx. 1: 1 to approx. 3.5: 1, especially from approx. 1.6: 1 to approx. 2.7: 1, preferably approx. 1.7: 1 15 - approx. 2.3: 1 and most preferably ffa approx. 1.9: 1 to approx. 2: 1. For example, when 2% of tetrasodium pyrophosphate (TSPP) is used (which gives about 1.3% pyrophosphate) together with 2.5% of the antibacterial enhancer, a very desirable weight ratio of approx.

1.9: 1st 1 30

Typical examples of antibacterial agents that are particularly desirable for consideration of antiplaque efficacy, safety, and composition are:

Halogenated diphenyl ethers: 2 ', 4,4'-trichloro-2-hydroxy-diphenyl ether (Triclosan), 2,2'-dihydroxy-5,5'-dibromo-diphenyl ether.

I DK 175758 B1 I

I 4 I

In Halogenated Salicylic Anilides: I

In 4 ', 5-dibromo salicylanilide,

3,4 ', 5-trichlorosalicylanilide, I

In 3,4 ', 5-tribromosalicylanilide,

I 2,3,3 ', 5-Tetrachlorosalicylanilide, I

3,3,3 ', 5-tetrachlorosalicylanilide, I

In 3,5-dibromo-3'-trifluoromethylsalicylanilide I

5-n-octanoyl * 3'-trifluoromethylsalicylanilide, I

In 3,5-dibromo-4'-trifluoromethylsalicylanilide 5L

In 3,5-dibromo-3'-trifluoromethylsalicylanilide (Flurophen). IN

Benzoic acid esters: I

I 15 ----------------------- I

In methyl p-hydroxybenzoic acid ester, I

In Ethyl p-hydroxybenzoic acid ester, I

In Propyl-p-hydroxybenzoic acid ester, I

In 20 butyl p-hydroxybenzoic acid ester. IN

In Halogenated Carbanilides:

I 3,4,4'-trichlorocarbanilide, I

In 3-trifluoromethyl-4,4'-dichlorocarbanilide, I

In 3,3,4 '-trichlorocarbanilide. IN

I 30 I

5 DK 175758 B1

Phenolic compounds (including phenol and its homologue, mono- and polyalkyl and aromatic halogen (e.g.

5 F, Cl, Br, I) -phenols, resorcin and pyrocatequin and their derivatives and bisphenolic compounds).

These phenolic compounds include, inter alia: 10 Phenol and its homologue:

Phenol, 2-methyl-phenol, 3-methyl-phenol, 4-methyl-phenol, 4-ethyl-phenol, 2,4-dimethyl-phenol, 2,5-dimethyl-phenol, 3,4-dimethyl-phenol, 2,6- dimethyl-phenol, 4-n-propyl-phenol, 4-n-butyl-phenol, 4-n-amyl-phenol, 4-tert-amyl-phenol, 4-n-hexyl-phenol, 4-n-heptyl -phenol, 2-methoxy-4- (2-propenyl) phenol (Eugenol), 2-isopropyl-5-methyl-phenol (Thymol).

30

I DK 175758 B1 I

Mono and polyalkyl and aralkyl halogen phenols: I

Methyl p-chlorophenol, I

Ethyl p-chlorophenol, I

n-propyl-p-chlorophenol, I

n-butyl p-chlorophenol,

n-amyl-p-chlorophenol, I

sec-amyl-p-chlorophenol, I

N-hexyl-p-chlorophenol, I

Cyclohexyl-p-chlorophenol,

n-heptyl-p-chlorophenol, I

n-octyl-p-chlorophenol, I

o-chlorophenol, I

Methyl o-chlorophenol, I

Ethyl-o-chlorophenol,

n-propyl-o-chlorophenol, I

n-butyl-o-chlorophenol, I

n-amyl-o-chlorophenol, I

Tert-amyl-o-chlorophenol, I

n-hexyl-o-chlorophenol, I

n-heptyl-o-chlorophenol, I

p-chlorophenol, I

o-benzyl-p-chlorophenol, I

O-benzyl-m-methyl-p-chlorophenol, I

o-benzyl-m, m-dimethyl-p-ch] orphenol, I

o-phenylethyl-p-chlorophenol, I

o-phenylethyl-m-methyl-p-chlorophenol, I

3-methyl-p-chlorophenol, I

3,5-dimethyl-p-chlorophenol, I

6-ethyl-3-methyl-p-chlorophenol, I

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, n-butyl-p-bromophenol, n-amyl-p-bromophenol, sec-amyl-p-bromophenol, n-hexyl-p-bromophenol,

Cycle ohexyl-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-2-methylphenol, 5-methyl-2-pentylphenol, 4-isopropyl-3-methylphenol,

DK 175758 B1 I

5-chloro-2-hydroxydiphenylmethane. B

Resorcin and its derivatives: B

Resorcin, B

Methyl resorcin, B

Ethyl resorcin, B

n-propyl resorcin, B

N-butyl resorcin, fl n-amyl resorcin, fl n-hexyl resorcin, fl

n-heptyl resorcin, B

n-octyl resorcin, B

N-nonyl resorcin, B

phenyl resorcin, B

benzyl resorcin, fl

phenylethyl resorcin, B

phenylpropyl resorcin, B

20-chlorobenzyl resorcin, B

5-Chloro-2,4-dihydroxydiphenylmethane, B

4'-chloro-2,4-dihydroxydiphenylmethane, B

5-bromo-2,4-dihydroxydiphenylmethane, B

4'-bromo-2,4-dihydroxydiphenylmethane. B

25 I

Bisphenolic Compounds: B

Bisphenol A, B

2,2'-methylene bis (4-chlorophenol), I

2,2'-methylene bis (3,4,6-trichlorophenol) (Hexachlorophen), fl 9,2,2-methylene bis (4-chloro-6-bromophenol), bis (2-hydroxyphenol) 3,5-dichlorophenyl) sulfide, bis (2-hydroxy-5-chlorobenzyl) sulfide.

The antibacterial agent is present in the oral care agent in an effective amount of antiplaque, typically from ca. 0.01 to 5% by weight, preferably from about 0.03 to 1% and very much preferred from approx. 0.25 to 0.5% and most preferably from about 0.25 to 0.35%. The antibacterial agent is substantially water-insoluble, which means that its solubility is less than ca.

1 wt.% In water at 25 ° C and may be even less than ca. 0.1%. If an ionizable group is present, solubility is determined at a pH at which no ionization occurs.

The preferred halogenated diphenyl ether is Triclosan. The preferred phenolic compounds are phenol, 2,2'-methylene bis- (4-chloro-6-bromophenol), thymol and eugenol.

The most preferred antibacterial antiplaque compound is Triclosan. Triclosan is described in the aforementioned U.S. Patent No. 4,022,880 as an antibacterial agent in combination with an anti-tartaric agent which provides zinc ions, and in German Patent No. 35,32860 in combination with a copper compound. It is also disclosed as an antiplaque agent in a dentifrice composition so as to contain a lamellar, liquid crystal surfactant phase having a lamella gap of less than 6.0 nm and which may optionally contain a zinc salt, in published form. European patent application no.

No. 0161,898, and in a dentifrice containing zinc citrate trihydrate in published European Patent Application No. 0,161,899.

The linear, molecularly dehydrated polyphosphate salts which are effective in carrying out the invention as anti-tartar agents are well known and are generally used in the form of their wholly or partially neutralized, water-soluble alkali metal salts (e.g., potassium and preferably sodium) or ammonium salts and mixtures thereof. Representative examples include sodium hexametaphosphate, sodium tripolyphosphate, sodium dihydrogen pyrophosphate, trisodium monohydrogen pyrophosphate and tetrasodium pyrophosphate, the corresponding potassium salts and the like. Linear polyphosphates sva- ^ ---

I DK 175758 B1 I

I 10 I

R is to (NaPO 3) n, where n is approx. 2 - approx. 125. In the present invention, they are used in I

In oral care products in weight amounts of approx. 0.1 to 3%, typically from 1 to 2.5% and more typically I

I from 1.5 to 2%. When n is at least 3 in (NaPO 3) n, the polyphosphates are glassy. IN

Particularly desirable antitanking agents are tetraalkali metal pyrophosphates, including

In things thereof, such as tetrasodium pyrophosphate, tetras potassium pyrophosphate and mixtures I

In that. Thus, the oral care agent may contain polyphosphate as an anti-tooth stone, I

In the main, it is free of tetrasodium pyrophosphate or substantially free of a com

In the combination of tetras potassium pyrophosphate and tetrasodium pyrophosphate, wherein the ratio of

In 10 limes of potassium and sodium pyrophosphate is 3: 1 or greater than 3: 1. An anti-toothstone agent I

In extensive approx. 2% by weight of the tetrasodium pyrophosphate oral care agents is particular

In effectively. IN

The antibacterial enhancer (AEA) which enhances the delivery of the anti-I

15 bacterial agents and their retention on oral surfaces are used in quantities I

there, effective to achieve this enhancement, in the range of the oral care agent of approx. IN

In 0.05% to approx. 4%, preferably from ca. 0.1% to approx. 3% and more preferably from ca. 0.5% to 1

For approx. 2.5% by weight. IN

AEA may be a simple compound, preferably a polymerizable monomer, more preferably

Preferably a polymer, the latter term being completely generic and including e.g. IN

oligomers, homopolymers, copolymers of two or more monomers, ionomers, block I

copolymers, graft copolymers, cross-linked polymers and copolymers, and the like. IN

AEA may be natural or synthetic and water insoluble or preferably water (saliva) - I

25 soluble or swellable (hydrating, hydrogel-forming). It has a through- I

cut molecular weight by weight of approx. 100 to approx. 1,000,000, preferably from approx. 1,000 to approx. IN

In 1,000,000, more preferably from approx. 2,000 or 2,500 to approx. 250,000 or 500,000. IN

The AEA usually contains at least one delivery enhancing group, preferably

30 are acidic, such as sulfonic acid, phospic acid, or more preferably phosphonic acid or I

carboxylic acid, or a salt thereof, e.g. alkali metal or ammonium, and at least one organ I

B1 nical retention-enhancing group, preferably several of both the delivery-reinforcing and the retention-enhancing groups, the latter groups preferably having the formula - (X) + - R, wherein X is O, N, S, SO, SO2, P, PO or Si or the like, R is hydrophobic alkyl, alkenyl, acyl, aryl, alkaryl, aralkyl, heterocyclic or their independently substituted derivatives, and n is 0 or 1 or more. The aforementioned "inert substituted derivatives" are to be understood as including substituents on R which are generally not hydrophilic and do not significantly interfere with the desired functions of AEA as enhancing the delivery of the antibacterial agent and its retention on mouth surfaces, such as halogen. , eg. Cl, Br, I and carbo and the like. Illustrations of such detention-enhancing groups are shown in the table below:

η X - (X) + - R

0 - Methyl, ethyl, propyl, butyl, isobutyl, t-butyl, cyclohexyl, ally], benzyl, phenyl, chlorophenyl, xylyl, pyridyl, fiiranyl, acetyl, benzoyl, butyryl, terephthaloyl, etc.

Ethoxy, benzyloxy, thioacetoxy, phenoxy, carboethoxy, carbobenzyloxy etc.

20 N Ethylamino, diethylamino, propylamido, benzylamino, benzoylamido, phenylacetamido, etc.

S Thiobutyl, thioisobutyl, thioallyl, thiobenzyl, thiophenyl, thiopropionyl, phenylthioacetyl, thiobenzoyl etc.

SO butylsulfoxy, allylsulfoxy, benzylsulfoxy, phenylsulfoxy etc.

SO2 Butylsulfonyl, allylsulfonyl, benzylsulfonyl, phenylsulfonyl, etc.

30 P Diethylphosphinyl, ethylvinylphosphinyl, ethylallylphosphinyl, ethylbenzylphosphinyl, ethylphenylphosphinyl, etc.

I DK 175758 B1 I

I 12 I

I PO Diethylphosphinoxy, ethylvinylphosphinoxy, methylallylphosphinoxy, me-

In thylbenzylphosphinoxy, methylphenylphosphinoxy etc. I

Si Si trimethylsilyl, dimethylbutylsilyl, dimethylbenzylsilyl, dimethylvinylsilyl, I

In dimethylallylsilyl etc. I

I I

As used in the present specification, the release enhancer I refers

group to one which attaches or is substantially adhesive, cohesive or otherwise

You bind AEA (which carries the antibacterial agent) to mouth surfaces (e.g., dental or I).

10 gum surfaces), thereby "delivering" the antibacterial agent to these surfaces.

In surfaces. The organic retention enhancer group, generally hydrophobic, I

You attach or otherwise bind the antibacterial agent to AEA and promote it

In the retention of the antibacterial agent for AEA and indirectly on the mouth

surfaces. In some cases, attachment of the antibacterial agent occurs through physical I

In capturing it by the AEA, especially when the AEA is a cross-linked polymer, the structure of which I itself

even providing increased locations for such capture. Presence of a more high mole- I

In cooler, more hydrophobic, cross-linking moiety in the cross-linked polymer, I promotes

further, the physical entrapment of the antibacterial agent of the cross-linked I

AEA polymer. IN

20 I

Preferably, AEA is an anionic polymer comprising a chain or skeleton

said repeating units, each preferably containing at least one carbon atom and form I

preferably at least one direct or indirect protruding, monovalent delivery amplifier

the group and at least one direct or indirect projecting, monovalent, withholding I

25, reinforcing group, geminal, vicinal or, less preferably, bound to other I

way to atoms, preferably carbon, in the chain. Less preferably, the polymer may contain

holding delivery-enhancing groups and / or retention-enhancing groups I

and / or other divalent atoms or groups such as the site of or adjacent to carbon I

tomer or as cross-linking molecular moieties. IN

I 30 I

13 DK 175758 B1

It will be understood that examples or illustrations of AEAs described herein which do not contain both delivery enhancement and retention enhancer groups may or, preferably, be chemically modified in a known manner to obtain the preferred AEAs containing both of these groups, and preferably more of 5 each of such groups. In the case of the preferred polymers of AEAs, it is desirable, in order to maximize the substantivity and delivery of the antibacterial agent to mouth surfaces, that the repeating units in the polymeric chain or skeleton containing the acidic release enhancing groups constitute at least about 10%. 10%, preferably at least approx. 50% and more preferably at least approx. 80% and up to 95% or 100% by weight of the polymer.

In a preferred embodiment of the invention, the AEA comprises a polymer containing repeating units in which one or more phosphonic acid release enhancing groups are bonded to one or more carbon atoms in the polymeric chain. An example of such an AEA is poly (vinylphosphonic acid) containing units of formula I. - [CHa - CH] - PO3H2 20, however, which does not contain a retention enhancing group. However, a group of the latter type will be found in poly (1-phosphonopropene) containing units of formula 25 Π. - [CH-CH] -

I I

ch3 po3h2

A preferred phosphonic acid-containing AEA for use in the invention is poly (β-30-styrene phosphonic acid) containing units of formula III. - [CH - CH] -

I I

Ph P03H2

I DK 175758 B1 I

I 14 I

In which Ph is phenyl and the release enhancing phosphonic acid group and the I

In the retention-enhancing phenyl group is bonded to vicinal carbon atoms in I

In the chain, or a copolymer of β-styrene phosphonic acid with vinyl phosphonyl chloride, which I

You have units of formula III alternating with or in random distribution with units of I

In formula I above, or poly (α-styrene phosphonic acid) containing units of I

In the formula I

I IV. - [CH2-C --------] -: I

I 1 'I

I Ph po2h2 I

I 10 I

In which delivery-enhancing and retention-enhancing groups are geminal I

You tied to the chain. IN

These styrene phosphonic acid polymers and their copolymers with other inert, I

In 15 ethylenically unsaturated monomers generally have molecular weights in the range of about IN

In 2000 to approx. 30,000, preferably from ca. 2,500 to approx. 10,000. Such "inert" mo- I

In nomes, the desired function of any copolymer used does not significantly interfere

You as the AEA of the invention. IN

I I

In other phosphonic acid-containing polymers, e.g. phosphonated ethylene having I

In units of formula I

I v. - [(CH2) J4CHPO3H2] n- I

In which n e.g. may be an integer or have a value giving the polymer a molecular I

Weighing approx. 3,000, and sodium poly (butene-4,4-diphosphonate) having units of I

In the formula I

I VI. - [CH2-CH ------] - I

30 I I

CH2 - CH <(PO3Na2) 2 I

and poly (allyl-bis-phosphonoethylamine) having units of formula I

DK 175758 B1. VII. - [CH2 - CH--] CH2 - N <(PO3H2) Other phosphonated polymers, e.g. poly (allyl phosphonoacetate), phosphonated polymethacrylate, etc., and the geminal diphosphonate polymers described in EP Publication No. 0.321,233 can be used according to the invention as AEA, provided, of course, that they contain or are modified to contain the above defined organic retention-enhancing groups.

In another preferred embodiment, the AEA comprises a synthetic anionic polymeric polycarboxylate which is also an inhibitor of alkaline phosphatase enzyme. Synthetic, anionic, polymeric polycarboxylates and their complexes with various cationic germicides, zinc and magnesium have been previously described as anti-tartar agents as such in e.g. U.S. Patent No. 3,429,963; U.S. Patent No. 4,152,420;

3,956,480, U.S. Patent No. 14,138,477 and U.S. Patent No. 4,183,914. However, in descriptions substantially similar to U.S. Patent No. 4,627,977, use of such polycarboxylates has been disclosed to inhibit salivary hydrolysis of pyrophosphate anti-tartar agents in combination with a source of fluoride ion. It is understood that when the synthetic anionic polymeric polycarboxylates thus described in several patents contain or are modified to contain the retention enhancing groups mentioned above, they act as AEAs in the agents. and the methods of the present invention, and to this extent reference may be made to the aforementioned patents.

25 i

These synthetic, anionic, polymeric polycarboxylates are often used in the form of their free acids or, preferably, partially or, more preferably, fully neutralized, water-soluble or water-swellable (hydrable, gelling) alkali metal salts (e.g., potassium and preferably sodium) or ammonium salts. Preferred are 1: 4 to 4: 1 copolymers of maleic anhydride or maleic acid with another polymerizable, ethylenically unsaturated monomer, preferably methyl vinyl ether / maleic anhydride having a molecular weight of approx. 30,000 to approx. 1,000,000. These copolymers can be obtained e.g. as "Gantrez", - ---: _

I DK 175758 B1 I

I 16 I

In e.g. AN 139 (molecular weight 500,000), AN 119 (molecular weight 250,000), and preferably I

In S-97 pharmaceutical grade (molecular weight 70,000) from GAF Corporation. IN

I i I

Other AEA-active polymeric polycarboxylates containing or modifying I

In the right to contain detention reinforcing groups, include those who are

In U.S. Patent No. 3,956,480, such as 1: 1 copolymers of maleic anhydride with I

ethyl acrylate, hydroxyethyl methacrylate, N-vinyl-2-pyrrolidone or ethylene, the latter being

In the above can be obtained e.g. such as "Monsanto" EMA No. 1103 (molecular weight 10,000) and EMA I

grade 61, as well as 1: 1 copolymers of acrylic acid with methyl or hydroxyethyl I

Methacrylate, methyl or ethyl acrylate, isobutyl vinyl ether or N-vinyl-2-pyrrolidone. IN

Other effective polymeric polycarboxylates described in the above-mentioned U.S. Pat

In patents Nos. 4,138,477 and 4,183,914, which contain or are modified to include

In retention-enhancing groups, copolymers of maleic acid include I

In hydride with styrene, isobutylene or ethyl vinyl ether, polyacrylic acid, polyitaconic acid and I

In polymaleic acid and sulfoacrylic acid oligomers with molecular weights as low as 1,000

You can get it as "Uniroyal" ND-2. IN

Suitable generally are polymerized retention-enhancing, group-containing, oleic

In 20 chemically or ethylenically unsaturated carboxylic acids containing an activated carbon carbide

In bon olefinic double bond and at least one carboxyl group, i.e. an acid containing I

In an olefinic double bond which readily acts by polymerization due to its presence

room in the monomeric molecule, either in the α-β position relative to a carboxyl group I

or as part of a terminated methylene group. Illustrative of such acids are you

Acrylic acid, methacrylic acid, ethacrylic acid, α-chloroacrylic acid, crotonic acid, β-acryloxypropyl

unsolicited acid, sorbic acid, cr-chlorosorbic acid, cinnamon acid, β-styyl acrylic acid, muconic acid, itaconic acid

acid, citraconic acid, mesaconic acid, glutaconic acid, aconitic acid, α-phenylacrylic acid, 2-benzyl-I

acrylic acid, 2-cyclohexylacrylic acid, angelic acid, umbellic acid, fumaric acid, maleic acid and I

anhydrides. Other various olefinic monomers which are copolymerizable with I

30 such carboxylic acid monomers include vinyl acetate, vinyl chloride, dimethyl maleate I

17 DK 175758 B1 and the like. Copolymers usually contain enough carboxylic acid * salt groups to be water soluble.

Also useful in the invention are so-called carboxyvinyl polymers described as 5 toothpaste components of U.S. Patent No. 3,980,767, U.S. Patent No. 3,935,306, U.S. Patent No. 3,919,409, U.S. Patent No. 3,911,904 and U.S. Patent No. 3,711,604. They are commercially available, e.g. under the trademarks "Carbopol" 934, 940 and 941 from B.V. Goodrich, and these products consist essentially of a colloidal water-soluble polymer of polyacrylic acid crosslinked with from ca. 0.75% to approx. 2.0% polyallyl sucrose or polyallyl pentaerythrite as crosslinking agent, the crosslinked structures and bonds providing the desired retention enhancement by hydrophobicity and / or physical entrapment of the antibacterial agent or the like. "Polycarbophil" is somewhat similar in that it is polyacrylic acid crosslinked with less than 0.2% divinyl glycol, the lower amount, molecular weight and / or hydrophobicity of this crosslinking agent tending to provide reduced or no retention enhancement. 2,5-dimethyl-1,5-hexadiene is an example of a more effective retention-enhancing crosslinking agent.

The synthetic, anionic polymeric polycarboxylate component is most often a hydrocarbon with any halogen and O-containing substituents and bonds found e.g. in ester, ether and OH groups, and, when found, are generally used in the present compositions in amounts of weight up to approx. 4% (generally at least about 0.05%).

The AEA may also comprise natural, anionic polymeric polycarboxylates containing 25 retention enhancing groups. Caiboxymethyl cellulose and other binders, rubbers and film formers which lack the aforementioned release enhancer and / or retention enhancer groups are ineffective as AEA.

Illustrative of AEAs containing phosphinic acid and / or sulfonic acid release enhancement groups may be mentioned polymers and copolymers containing units or moieties derived from the polymerization of vinyl or allylphosphinic acid and / or

I DK 175758 B1 I

I 18 I

or sulfonic acid, substituted as necessary on the 1 or 2 (or 3) carbon atom by an I

In organic retention enhancing group, e.g. having the formula - (X) n-R, which is de- I

In the veneer above. Mixtures of these monomers can be used, as well as copolymers thereof

In one or more inert, polymerizable, ethylenically unsaturated monomers, I

I 5 as those described above during the discussion of the active, synthetic, other

In ionic polymeric polycarboxylates. In these and other polymeric AEAs that are active

to the invention, as will be noted, is usually only a sour, release-enhancement.

In those groups attached to a given carbon atom or other atom of the polymeric backbone I

In or branching thereto. Polysiloxanes containing or modified to contain I

10 holding protruding, release-reinforcing groups and retaining-reinforcing I

In groups, can also be used as AEAs according to the invention. Effective as AEAs to I

In the invention are also ionomers containing or modified to contain the release I

In sight-reinforcing and detention-enhancing groups. Ionomers are described in I

In pages 546 - 573 of the Kirk-Othmer Encyclopedia of Chemical Technology, 3rd edition, supra I

In 15 Bonds, John Wiley and Sons, Inc., copyright 1984, to which reference is made. Effective I

Have as AEAs according to the invention, provided they contain or are modified to

You contain retention-enhancing groups are also polyesters, polyurethanes and I

In synthetic and natural polyamides containing proteins and proteinaceous materials

H such as collagen, poly (argenine) and other polymerized amino acids. IN

I 20 I

When the oral care agent is prepared by first dissolving the polyphosphate and the antibacterial I

In any agent in moisture-binding agent and surfactant, and to this add AEA, especially I

In the polycarboxylate, portionwise, the solution becomes clear and can be characterized as an I

In "microemulsion". As the amount of the polycarboxylate grows,

25 complete oral care products contain at least approx. 2.2% by weight thereof will be dissolved

This is unclear and can be characterized as a "macro emulsion". In such means of ma- I

In the cream emulsion type, the antiplaque effect of the antibacterial agent appears to be up

optimized. IN

A desirable weight ratio of the substantially water-insoluble, non-cationic, I

antibacterial agent and the polyphosphate antitanking agent are from ca. 1.6: 1 to approx. 2.7: 1st IN

19 DK 175758 B1

Conveniently, inhibitors of enzymatic hydrolysis of the polyphosphate are present to optimize the antitumar efficacy of the oral care agent. Such agents are an amount of a fluoride ion source sufficient to yield from 25 ppm to 5,000 ppm fluoride ions, and up to 3% or more of the synthetic anionic polymeric polycarboxylate having a molecular weight of about 1,000 to approx. 1,000,000, preferably from approx. 30,000 to approx. 500,000.

The sources of fluoride ions or fluorine-providing component as inhibitor component of acid phosphatase and pyrophosphatase enzyme are well known as anticaries. These precursors may be poorly soluble in water or may be completely water soluble. They are characterized by their ability to release fluoride ions in water and by freedom from unwanted reaction with other compounds in the oral care product. Among these materials are inorganic fluoride salts such as soluble alkali metal and alkaline earth metal salts, e.g. sodium fluoride, potassium fluoride, ammonium fluoride, calcium fluoride, a copper fluoride such as cuprofluoride, zinc fluoride, sodium fluoride, sodium fluorosilicate, ammonium fluorosilicate, sodium fluorosulfonate, ammonium fluorosirconate, ammonium fluorosirconate, Alkali metal and tin fluorides such as sodium and stannofluoride, sodium monofluorophosphate (MFP) and mixtures thereof are preferred.

The amount of fluorine-providing compound depends to a certain extent on the type of the compound, its solubility and the type of oral care agent, but it should be a non-toxic amount, generally from ca. 0.005 to approx. 3.0% in the composition. In a dentifrice, e.g. a tooth gel, toothpaste (including cream), tooth powder, or tooth tablet, a 25 amount of such a compound is considered to release up to approx. 5,000 ppm F-ion by weight, too satisfactory. Any suitable minimum amount of such a compound can be used, but it is preferred to use sufficient compound to release approx.

300 to 2,000 ppm, more preferably from about 800 to approx. 1,500 ppm fluoride ion.

Typically, in the case of alkali metal fluorides, this component is present in an amount up to approx. 2% by weight, based on the weight of the composition, and preferably in the range of

I DK 175758 B1 I

I 20 I

In easy from approx. 0.05% to 1%. In the case of sodium monofluorophosphate, compound I

The part is found in an amount of approx. 0.1 to 3%, more typically approx. 0.76%. IN

In oral care products such as mouthwashes, lozenges and chewing gum are found in

In fluorine-providing compound, typically in an amount sufficient to release up to approx. IN

At 500 ppm, preferably approx. 25 - 300 ppm by weight, fluoride ion. In general, there are

In from approx. 0.005 to approx. 1.0% by weight of such a compound. IN

In some very preferred embodiments of the invention, the oral care

10 are generally of a liquid nature, e.g. a mouthwash or rinse liquid. In one I

such a composition is typically a water-alcohol mixture suitably contained

You hold a moisture-binding agent as described below. Generally, the weight ratio is I

In the between water and alcohol in the range of approx. 1: 1 to approx. 20: 1, preferably from ca. 3: 1 to 1

In 10: 1 and more preferably from ca. 4: 1 to approx. 6: 1. The total amount of water-alcohol I

Typically, the mixture in this type of composition is in the range of about 70 to approx. 99.9% by weight of I

In the preparation. The alcohol is typically ethanol or isopropanol. Ethanol is preferred. IN

The pH of such a liquid preparation or other compositions of the invention is I

Generally, in the range of approx. 4.5 to approx. 9 and typically from ca. 5.5 to 8. The pH is I

Preferably in the range of from ca. 6 to approx. 8.0. It is worth noting that according to I

The invention can be used orally at a pH below 5 without substantially descaling electricity

In other ways, you can damage tooth enamel. The pH can be regulated with acid (e.g., lemon-I

In acid or benzoic acid) or base (e.g. sodium hydroxide) or with buffer (such as I

I with sodium citrate, benzoate, carbonate or bicarbonate, disodium hydrogen phosphate, I

In sodium dihydrogen phosphate etc.). IN

In certain other desirable embodiments of the invention, the oral care agent may be I

Essentially solid or paste-like in character, such as tooth powder, a tooth tablet or an H

In dental care, ie. a toothpaste (toothpaste) or a gel dentifrice. The carrier of I

Such a solid or paste-like oral care composition generally contains dental:

In acceptable polishing material. Examples of polishing materials are water-insoluble sodium I

21 DK 175758 B1 metaphosphate, potassium metaphosphate, tricalcium phosphate, dehydrated calcium phosphate, anhydrous dicalcium phosphate, calcium pyrophosphate, magnesium orthophosphate, tri-magnesium phosphate, calcium carbonate, hydrated alumina, calcined alumina, silicon dioxide, aluminosilicate silica, aluminum silicate

Other suitable polishing materials include the particulate thermosetting resins disclosed in U.S. Patent No. 3,070,510, such as melamine, phenolic and urea formaldehyde and cross-linked polyepoxides and polyesters. Preferred polishing materials include crystalline silica having a particle size up to approx. 5 microns, an average particle size up to approx. 1.1 microns and a surface area up to approx. 50,000 10 cm 2 per grams, silica gel or colloidal silica and complex amorphous alkali metal-aluminum silicates.

When visually clear gels are used, a colloidal silica polishing agent such as those sold under the trademark "Syloid" as "Syloid" 72 and "Syloid" 74, or under the trademark "Santocel" as "Santocel" 100, alkali metal aluminum silicate compound plexes, particularly useful as they have refractive indices close to the refractive indices of the gelling and liquid systems (including water and / or moisture-binding agent) commonly used in dentifrices.

Many of the so-called "water-insoluble" polishing materials are of anionic nature and also contain small amounts of soluble material, thus insoluble sodium metaphosphate can be formed in any suitable manner, as illustrated in Thorpe's Dictionary of Applied Chemistry, Volume 9, 4th Edition, page 510 - 511. The forms of insoluble sodium metaphosphate known as Madrell's salt and Kurrol's salt are other examples 25 of suitable materials. These metaphosphate salts exhibit only very little solubility in water and are therefore generally referred to as insoluble metaphosphates (IMPs). There is a smaller amount of soluble phosphate material as impurities, usually a few percent, e.g. up to 4% by weight. The amount of soluble phosphate material, which is believed to include a soluble sodium trimetaphosphate, in the case of insoluble metaphosphate, can be reduced or removed by washing with water if desired.

I DK 175758 B1 I

I 22 I

Typically, the insoluble alkali metal metaphosphate is used in powder form with a partial I

In a cell size such that no more than 1% of the material is greater than 37 microns. IN

The polishing material is generally found in solid or paste-like agents in weight concentrations

In 5 tions of approx. 10% to approx. 99%. Preferably, it is present in amounts ranging from approx. 10% I

I to approx. 75% in toothpaste, and from approx. 70% to approx. 99% in tooth powder. When the polishing material is I

In the silica-containing nature of toothpastes, it is generally found in amounts of about IN

In 10-30% by weight. Other polishing materials are typically found in an amount of approx. 30 - 75 I

In weight%. IN

I 10 I

In a toothpaste, the liquid carrier may comprise water and moisture-binding agent, typically in 1

In an amount ranging from approx. 10% to approx. 60% by weight of the composition. Glycerin, propylene- I

glycol, sorbitol and polypropylene glycol are examples of suitable moisture binding agents / - I

In carriers. Also advantageous are liquid mixtures of water, glycerine and sorbitol. I I

In 15 clear gels where the refractive index is of importance, preferably approx. 2.5 - 30 I

In weight% water, from 0 to approx. 70% by weight glycerine and approx. 20 - 80% by weight sorbitol. IN

Toothpastes, creams and gels typically contain a natural or synthetic thickening agent

agent or gelling agent in amounts of approx. 0.1 to approx. 10, preferably from ca. 0.5 to approx. IN

20% by weight. A suitable thickener is synthetic hectorite, a synthetic, colloidal magnet

In sium alkali metal silicate complex obtainable e.g. such as "Laponite" (e.g., CP, SP 2002, I

D), negotiated by Laporte Industries Limited. "Laponite" D analysis shows by weight approx. IN

58.00% SiO2, 25.40% MgO, 3.05% Na2O, 0.98% Li2O and some water and trace metals. IN

Its true density is 2.53 and it has an apparent mass space weight (g / ml at 1

In 25% humidity) of 1.0. IN

In Other suitable thickeners include Irish moss, iotacarragenan, tragacanth, starch,

In polyvinylpyrrolidone, hydroxyethylpropylcellulose, hydroxybutylmethylcellulose, hy-I

droxypropylmethylcellulose, hydroxyethylcellulose (for example available as "Natrosol"),

30 carboxymethyl cellulose and colloidal silica such as finely ground "Syloid"

(e.g., 244). In some of the dental preparations of the invention, especially when

23 DK 175758 B1 is used more than approx. 0.35% by weight of the water-insoluble antibacterial agent, and a silicon-containing polishing agent is present in an amount of less than about 30 weight percent, it may be desirable to include an agent which dissolves the antibacterial agent. Such solubilizing agents include moisture-binding polyols such as propylene glycol, dipropylene glycol and hexylene glycol, cellos solvents such as methylcellosolve and ethyl cellosolve, vegetable oils and waxes containing at least about 100%. 12 carbon atoms in a straight chain such as olive oil, castor oil and petrolatum, and esters such as amyl acetate, ethyl acetate and benzyl benzoate.

10 It will be appreciated that the oral care agents must be negotiated or otherwise distributed in suitable labeled packages in the usual manner. Thus, a glass with mouthwash will have a label describing it as a mouthwash or mouthwash, as well as a user manual, and a toothpaste, cream or gel will usually be in a collapsible tube, typically of aluminum, lined lead or plastic, or other squeeze dispensing apparatus, pump or pressure meter for measuring the contents, and having a label describing it as a toothpaste, gel or toothpaste.

Organic surfactants are used in the compositions of the invention to achieve increased prophylactic effect, help to achieve thorough and complete distribution of the antitumor and antiplaque agent in the oral cavity, and to make the present agents cosmetically more acceptable. The organic surfactant is preferably anionic, nonionic or ampholytic in nature, and it is preferred to use as a surfactant a purifying material which imparts the scavenging and foaming properties of the agent. Suitable examples of anionic surfactants are water-soluble salts of higher fatty acid monoglyceride monosulphates, e.g. the sodium salt of monosulfated monoglyceride of hydrogenated coconut oil fatty acids, higher alkyl sulfates such as sodium lauryl sulfate, alkylarylsulfonates such as sodium dodecylbenzenesulfonate, higher alkyl sulfoacetates, higher fatty acid esters of 1,2-dihydroxypropane sulfonate, . those having 12-16 carbon atoms in the fatty acid, alkyl or acyl radical, and the like. Examples of the latter amides are N-lauroylsarcosine and sodium,

I DK 175758 B1 I

I 24 I

In the potassium and ethanolamine salts of N-lauroyl, N-myristoyl or N-palmitoylsarcosine, I

In it must be substantially free of soap or similar higher fatty acid material. Use I

of these sarcosinate compounds in the oral care agents of the invention are particularly preferred.

In part, as these materials exhibit a prolonged and pronounced effect to inhibit the system

In 5 oral cavity formation due to carbohydrate breakdown, in addition to

In any reduction in the solubility of tooth enamel in acidic solutions. Examples of water I

In soluble, nonionic surfactants, condensation products of ethylene are I

In oxide with various compounds containing reactive hydrogen which is real

In actionable thus, and which have long, hydrophobic chains (e.g., aliphatic chains with I

For 10 approx. 12 to 20 carbon atoms), which condensation products ("ethoxamers") contain I

hydrophilic polyoxyethylene molecules such as poly (ethylene-I condensation products)

In oxide) with fatty acids, fatty alcohols, fatty amides, polyhydric alcohols (e.g. sorbitan I

In monostearate) and polypropylene oxide (eg "Pluronic" materials). IN

Typically, the surfactant is present in an amount of ca. 0.1-5% by weight, preferably I

For approx. 1 - 2.5%. It is worth noting that surfactant can help to dissolve I

In the non-cationic, antibacterial agent, thereby reducing the amount of emergency use

In poem solubilizing, moisture-binding agent. IN

Various other materials may be incorporated into the oral care compositions of the invention, I

such as whitening agents, preservatives, silicones, chlorophyll compounds and / or I

clay ammoniated materials such as urea, diammonium phosphate and mixtures thereof. IN

Where these additives are present, they are incorporated into the compositions in amounts which I

You have no significant detrimental effect on the desired properties. Significant I

25 amounts of zinc, magnesium and other metal salts and materials, generally soluble

In ge, which could form complex with active components of the invention, must be avoided

goose. IN

In Any suitable flavored or sweetening material may also be used. Examples of I

In suitable flavoring ingredients, essential oils, e.g. garden mint oil, pepper- I

mint, evergreen, sassafras, spice, sage, eucalyptus, marjoram, cinnamon, lemon I

DK 175758 B1 25 and orange, and methyl salicylate. Suitable sweeteners include sucrose, lactose, maltose, sorbitol, xylitol, sodium cyclamate, perillartin, AMP (aspartylphenylalanine, methyl ester), saccharin and the like. Conveniently, the aroma and sweetener, individually or together, may amount to approx. 0.1% to 5% or more of the composition. In addition, 5 essential oils appear to help dissolve the antibacterial agent.

In the preferred practical application of the invention, a mouth care agent according to the invention, such as a mouthwash liquid or dentifrice containing the composition of the invention, is preferably applied regularly to tooth enamel, such as 10 every day or every other or every three days, or preferably from 1 to 3 times a day. , at a pH of approx. 4.5 to approx. 9, generally approx. 5.5 - 8, preferably from ca. 6 to 8, for at least 2 weeks and up to 8 weeks or more or throughout life.

The compositions of the invention may be incorporated into lozenges or in chewing gum or other products, e.g. by stirring in a hot rubber matrix or by coating the outside of a rubber matrix, examples of which may be mentioned gelatin, rubber latex, vinylite resins, etc., conveniently with conventional plasticizers or plasticizers, sugars or other sweetening agents, such as glucose, and the like.

20

The following examples further illustrate the nature of the invention, but it will be understood that the invention is not limited thereto. All quantities in the specification and claims are by weight, unless otherwise stated.

In the following examples, the agent Triclosan, 2,4,4'-trichloro-2, hydroxydiphenyl ether, designated "TCHE", sodium lauryl sulfate is designated "SLS", the copolymer of maleic anhydride and methyl vinyl ether available from GAF Corporation as "Gantrez" S-97, is designated "Gantrez", tetrasodium pyrophosphate is designated "pyrophosphate" and sodium fluoride is designated "NaF".

30

DK 175758 B1 I

EXAMPLE 1. I

The adsorption and release of dental minerals for antiplaque / anti-tooth effect H

The activity of agents is assessed by adsorption of antibacterial agent into saliva-coated slices H

of the dental mineral hydroxyapatite in the presence of pyrophosphate and various amounts of H

polycarboxylate. IN

The compositions of the assessed toothpastes are:

10 parts by weight H

AB I

Glycerin 10,000 10,000 I

Iota-carrageenan 0.750 0.750 I

Sorbitol (70% solution) 30,000 30,000 I

Propylene glycol 0.500 0.500 I

"Gantrez" (13.02% resolution) 19,000 19,000 I

Titanium dioxide 0.500 0.500 I

Water (Deionized) 9,957 13,457 I

NaF 0.243 0.243 I

Sodium saccharin 0.300 0.300 I

Pyrophosphate 2,000 2,000 I

Sodium hydroxide (50%) 1,000 1,000 I

25 Silicon dioxide polish H

("Zeodent" 113) 20,000 20,000 I

Silica Thickener I

("Sylodent" 15) 2,500 2,500 I

Aroma oil 0.950 0.950 I

30 TCHE 0.300 0.300 I

SLS 2,000 2,000 I

27 GB 175758 B1 "Gantrez" is available as an active ingredient in an amount of 2.5 parts in toothpaste A and 2.0 parts in toothpaste B.

To test the delivery of antibacterial agent to a saliva-coated hydroxyapatite disc 5, hydroxyapatite (HA) from Monsanto Co. washed thoroughly with distilled water, collected by vacuum filtration and allowed to dry overnight at 37 ° C. The dried HA is ground to a powder with a mortar. 150.00 mg of HA is placed in a chamber in a KBr pill matrix (Barnes Analytical, Stanford, CT) and pressed together for 6 minutes at 10,000 pounds in a Carver laboratory press. The resulting 13 mm slices are sintered for 4 hours at 800 ° C in a Thermolyne oven. Whole saliva stimulated with parafilm is collected in an ice-cooled beaker. The saliva is prepared by centrifugation at 15,000 x g for 15 minutes at 4 ° C. Sterilization of the cleared saliva is performed at 4 ° C with stirring and irradiation of the sample with UV light for 1.0 hour.

Each sintered disk is hydrated with sterile water in a polyethylene test tube. The water is then removed and replaced with 2.00 ml of saliva. A saliva is formed by incubating the disc overnight at 37 ° C while still shaking in a water bath. After this treatment, the saliva is removed and the slices are treated with 1.00 ml of a solution containing antibacterial agent (Triclosan) in a liquid dentifrice phase and incubated at 37 ° C with constant shaking in the water bath. After 30 minutes, transfer the slice to a new glass and add 5.00 ml of water, followed by shaking the slice gently with a vortex. The disc is then transferred to a new glass and the washing procedure repeated twice. Finally, the disc is gently transferred to a new glass to avoid the co-transfer of any liquid along with the disc. Then add 1.00 ml of methanol to the disc and shake vigorously with a vortex. The sample is left at room temperature for 30 minutes to extract the Triclosan adsorbed in the methanol. The methanol is then extracted and cleared by centrifugation in a Beckman Microfuge 11 at 10,000 rpm. minute for 5 minutes. After this treatment, the methanol is transferred to HPLC (high performance liquid chromatography) vials to determine the concentration of antibacterial agent. Three tests are taken for all tests.

DK 175758 B1 I

28 I

The table below summarizes these data:

TABLE. IN

Toothpaste Delivery of TCHE to saliva coated I

hydroxyapatite discs (micrograms) I

10 A 130 I

B 30 1

The data shows that with the increasing amount of "Gantrez" (toothpaste A) there is a lot I

large increase in the delivery of TCHE to salivary tooth minerals. IN

EXAMPLE 2. I

The following toothpaste is effective as an antiplaque and anti-toothpaste:

20 I

Weight parts I

Sorbitol (70%) 22.00. IN

25 Irish moss 1.00 I

Sodium hydroxide (50%) 1.00 l

"Gantrez" (13.02% solution) 19.00 I

Water (deionized) 2.69 l

Sodium monofluorophosphate 0.76 I

Sodium Saccharin 0.30 I

Pyrophosphate 2.00 I

29 DK 175758 B1

Hydrated alumina 48.00

Flavor Oil 0.95 TCHE 0.30 SLS 2.00 EXAMPLE 3.

Mouthwash Liquid: Parts 10 --------

Tetrasodium pyrophosphate 2.00 "Gantrez" S-97 2.50

Glycerin 10.00

Sodium fluoride 0.05 Sodium lauryl sulfate 0.20 TCHE 0.06

Aroma oil 0.40

Water q.s. to 100.00 Example 4.

, Suction tablet: 75-80% sugar 1-20% corn syrup 0.1-1.0% flavor oil 2% tetrasodium pyrophosphate 2.50% "Gantrez" S-97

0.01-0.05% NaF

0.01-0.1% TCHE

DK 175758 B1 I

30 I

1-5% magnesium stearate lubricant I

0.01-0.2% water I

EXAMPLE 5. I

5 ------------------- I

Chewing Gum: Parts I

Rubber matrix 25.00 H

Sorbitol (70%) 17.00 I

TCHE 0.50 - 0.10 I

2.00 H tetrasodium pyrophosphate

"Gantrez" S-97 2.50 I

In a variant example of the preceding example, "Gantrez'1 S-97 may be omitted

EXAMPLE 6. I

20 Chewing Gum: Parts I

Rubber matrix 30.00 H

TCHE 0.50 I

"Gantrez" 2.00

NaF 0.05. IN

Glycerin 0.50 I

Crystalline Sorbitol 53.00 I

2.00 H tetrasodium pyrophosphate

Aroma oil and water q.s. to 100.00 I

In the preceding examples, improved results can also be obtained when TCHE is replaced with each of phenol, 2,2'-methylene bis (4-chloro-6-bromophenol), eugenol and thymol, and / or when "Gantrez "Is replaced by other AEAs such as" Carbopol "(e.g., 934) or styrene phosphonic acid polymers having molecular weights in the range of about 3,000 to 5,000, such as poly (/ 3-styrene phosphonic acid), copolymers of vinyl phosphonic acid with β · styrene phosphonic acid and poly (α-styrene phosphonic acid) or sulfoacrylic acid oligomers, or a 1: 1 copolymer of maleic anhydride with ethyl acrylate.

Similarly, similar results can be obtained when pyrophosphate (tetrasodium pyrophosphate) 10 is replaced with tetrasodium pyrophosphate and tetracassium pyrophosphate, the weight ratio of potassium to sodium being a) 0.37: 1, b) 1.04: 1, c) 3: 1 and 3.5 : 1st

Thus, the invention is described with reference to certain preferred embodiments, and it will be understood that modifications and variations thereof obvious to those skilled in the art will be included and are within the scope of the following claims.

Claims (24)

An oral care agent, characterized in, comprising in an orally acceptable carrier an effective anti-toothstone amount of a material comprising approx. 0.1-3% by weight of at least one Li-H molecular, dehydrated polyphosphate salt as an anti-inflammatory agent, an effective HI antiplaque amount of a substantially water-insoluble, non-cationic, antibacterial H agent, and up to ca. 4% by weight of an antibacterial enhancer which enhances the delivery of the antibacterial agent to and retention thereof on oral surfaces, HI 10, the weight ratio of antibacterial enhancer to polyphosphation agent being H 1.6: 1 to approx. 2.7: 1st IN Oral care agent according to claim 1, characterized in that the antibacterial agent is H I selected from the group consisting of halogenated diphenyl ethers, halogenated salicylic anilides, benzoic acid esters, halogenated carbanilides and phenolic compounds. H Oral care agent according to claim 2, characterized in that the halogenated diphenyl-H ether is 2,4,4'-trichloro-2'-hydroxyphenyl ether. H Oral care according to claim 2, characterized in that the phenolic compound is H selected from the group consisting of phenol, thymol, eugenol and 2,2'-methylene-bis (4-chloro-H 6 -bromophenol). H Oral care agent according to claim 2, characterized in that the antibacterial agent is present in an amount of approx. 0.01-5% by weight. IN Oral care agent according to claim 1, characterized in that the linear molecularly de-H I hydrated polyphosphate salt is an alkali metal pyrophosphate which is present in an amount of H 1 - 2.5% by weight. I I 30 I DK 175758 B1 Oral care agent according to claim 6, characterized in that the alkali metal pyrophosphate is tetrasodium pyrophosphate. Oral care agent according to claim 7, characterized in that the weight ratio of polyphosphate to antibacterial enhancer is approx. 1.7: 1 to approx. 2,3: 1st Oral care agent according to claims 1-8, characterized in that the carrier comprises water, moisture-binding agent and a gelling agent, which oral care agent contains a dental acceptable, water-insoluble polishing agent and is a dentifrice. 10 Oral care composition according to claims 1 - 8, characterized in that the carrier comprises water and a non-toxic alcohol and that the oral product is a mouthwash liquid. Oral care agent according to claims 1-10, characterized in that the antibacterial-enhancing agent has an average molecular weight of approx. 100 to approx. 1,000,000. Oral care agent according to claim 11, characterized in that the antibacterial-enhancing agent contains at least one delivery-enhancing, functional group and at least one organic, retention-enhancing group. 20 Oral care agent according to claim 12, characterized in that the release enhancing group is selected from the group consisting of carboxylic acid, phosphonic acid, phosphinic acid and sulphonic acid and their salts and mixtures thereof. Oral care agent according to claim 13, characterized in that the organic retention enhancing group comprises the formula - (X) n R wherein X is O, N, S, SO, SO 2, PO or Si, R is hydrophobic alkyl, aryl, alkenyl, acyl, alkaryl, aralkyl, heterocyclic or their inert substituted derivatives, and n is 1 or 0. I DK 175758 B1 II 34 I Oral care agent according to claim 13, characterized in that the antibacterial enhancer is an anionic polymer containing a chain containing gene units, each containing at least one carbon atom. I I 5 Oral care agent according to claim 15, characterized in that each unit contains at least one delivery enhancing group and at least one organic, retention-enhancing group attached to the same or vicinal or other atoms in the chain. IN Oral care agent according to claim 13, characterized in that the release-enhancing I-10 group comprises a carboxyl group or a salt thereof. IN Oral care agent according to claim 17, characterized in that the antibacterial enhancer is a copolymer of maleic acid or anhydride with another ethylenically unsaturated polymerizable monomer or a salt thereof. I I I Oral care agent according to claim 18, characterized in that the second monomer is methyl vinyl ether in a 4: 1 to 1: 4 molar ratio with the maleic acid or anhydride. IN Oral care agent according to claim 19, characterized in that the copolymer has a molecular weight of approx. 30,000 to 1,000,000. IN Oral care agent according to claim 13, characterized in that the release enhancer I group comprises a phosphonic acid group or a salt thereof. I I 25 Oral care agent according to claim 21, characterized in that the antibacterial-enhancing agent is polγ (β-styrene phosphonic acid), poly (of-styrene phosphonic acid) or a co II polymer of either styrene phosphonic acid with the other or with another inert In polymerizable, ethylenically unsaturated monomer or its salts. IN Oral care agent according to claim 22, characterized in that the antibacterial enhancer has a molecular weight of approx. 1,000 to approx. 30,000. In DK 175758 B1 Oral care agent according to claims 1-23, characterized in that it contains a source which provides fluoride ion. 5 i »