CH646051A5 - COMPOSITION EFFECTIVE AGAINST DENTALIZATION. - Google Patents

Description

The invention relates to orally applicable compositions for preventing tartar formation.

Tartar is a hard mineralized coating on the teeth. Regular brushing prevents these deposits from building up quickly, but even regular brushing is not sufficient to remove all the tartar deposits adhering to the teeth. Tartar forms on the teeth when calcium phosphate crystals begin to deposit in the membrane and the extracellular layer of the dental plaque and are pressed together sufficiently tightly that they are resistant to deformation. There is no complete agreement on how calcium and orthophosphate ultimately form the crystalline material known as hydroxyapatite (HAP). However, there is general agreement that amorphous or microcrystalline calcium phosphate is the precursor for the crystalline hydroxyapatite in a state of higher saturation, ie above the critical saturation limit. Although "amorphous calcium phosphate" is related to hydroxyapatite, it differs from it in its atomic structure, particle morphology and stoichiometry. The X-ray diffraction grating of amorphous calcium phosphate shows broad maxima, which are typical for amorphous materials, while the wide atomic distances, which are characteristic of all crystalline materials, including hydroxyapatite, are missing. This shows that substances that effectively impair the crystal growth of hydroxyapatite act as a remedy for tartar formation.

The mechanism which presumably prevents the formation of tartar in the agents according to the invention is probably based on an increase in the activation energy threshold, so that the conversion of the amorphous calcium phosphate to hydroxyapatite is inhibited or prevented.

Studies have shown that there is a relationship between the ability of a compound in vitro to prevent hydroxyapatite crystal growth and its ability to prevent calcification in vivo.

Cationic, nitrogen-containing antibacterial agents are known, cf. for example the section "Quaternary Am-55 monium and Related Compounds" under "Antiseptics and Disinfectants" in Kirk-Othmer, Encyclopedia of Chemical Technology, 2nd edition, volume 2, pages 632-635. Cationic materials with an antibacterial effect, that is to say germicides, are used against bacteria and are used in compositions which can be used orally in order to counteract the formation of deposits in the oral cavity caused by bacteria.

The most common antibacterial quaternary ammonium compounds used against deposit formation include 65 benzethonium chloride, which is also known as Hyamine 1622 or di-isobutylphenoxyethoxyethyl-dimethyl-benzyl-ammonium chloride. In an orally applicable composition, this is very effective in promoting the

646 051

Oral hygiene by reducing plaque and tartar build-up, which is generally associated with a reduction in tooth decay and dental disease. Other cationic antibacterial substances of this type are described, for example, in US Pat. Nos. 2,984,639,3 325,402, 3,431,208 and 3,703,583 and in British Patent 1,319,396.

Other antibacterial quaternary ammonium compounds effective against deposit formation include those in which one or two substituents on the quaternary nitrogen atom have a carbon chain with 8 to 20 and typically 10 to 18 carbon atoms, in particular alkyl groups, while the other substituents have a smaller number of carbon atoms, for example contain 1 to 7 carbon atoms and are typically alkyl groups, for example methyl or ethyl groups, or benzyl groups. Examples of other typical antibacterial quaternary ammonium compounds are dode-cyl-trimethyl-ammonium bromide, dodecyl-dimethyl- (2-phenoxyethyl) -ammonium bromide, benzyl-dimethyl-stearyl-5 ammonium chloride, cetyl-pyridinium chloride and quaternized 5-amino-1, 3-bis (2-ethylhexyl) -5-methyl-hexahydro-pyrimidine.

Other cationic antibacterial substances which are advantageously used in orally applicable compositions for reducing the formation of deposits and promoting oral hygiene are amidines, such as substituted guanidines, for example chlorhexidine and the corresponding compound alexidine with 2-ethylhexyl groups instead of chlorophenyl groups and other bis-biguanides, such as those described in 15 of DE-OS 2 332 383 with the general formula:

r nh nh I II II a— (x) -n-c-nh-c-nh (ch2)

n nh nh r * II | l I -nh-c-nh-c- n- (x mz.-a "

in which A and A '(1) is a phenyl group which may contain up to 2 alkyl or alkoxy groups with 1 to about 4 C atoms, a nitro group or a halogen atom as substituents, (2) an alkyl group with 1 to about 12 C -Atoms or (3) alicyclic groups having 4 to about 12 carbon atoms, X and X 'are alkylene radicals having 1 to 3 carbon atoms, z and z' are 0 or 1, R and R 'are hydrogen, alkyl radicals having 1 represent up to about 12 carbon atoms or aralkyl radicals with 7 to about 12 carbon atoms, n is an integer from 2 to 12 and the polymethylene chain (CH2) "by up to 5 ether, thio ether, phenyl or naphthyl groups interrupted, which are available as pharmaceutically acceptable salts. Other substituted guanidines are N '- (4-chlorobenzyl) -N5- (2,4-dichlorobenzyl) biguanide, p-chlorobenzylbiguanide, 4-chlorobenzhydrylguanyl urea, N-3-lauroxypro-pyl-N5-p-chlorobenzyl -biguanide, 5,6-dichloro-2-guanidobe-zimidazole and Np-chlorophenyl-Ns-laurylbiguanide.

The long chain tertiary amines also have antibacterial and anti-fouling effects. These antibacterial agents include tertiary amines with a fatty alkyl group of usually 12 to 18 carbon atoms and 2 poly (oxyethylene) groups on the nitrogen atom with typically a total of 2 to 50 ethyleneoxy groups per molecule and their salts with acids of the general formula

(ch2ch20) zh (ch2ch20) xh

/ 2 2X

r-n-ch2ch2n

(ch2ch20) yh in which R is a fatty alkyl group having 12 to 18 carbon atoms and x, y and z together are 3 or more, and their salts. In general, the cationic agents are preferred for their anti-fouling effect.

The antibacterial compound which is effective against deposit formation is preferably one with such an antibacterial

25 rial effect that their phenol coefficient is well over 50 and in particular well over 100, for example about 200 or more compared to S. aureus. For example, the phenol coefficient (A.O.A.C.) of benzethonium chloride compared to S. aureus is given by the manufacturer as 410. The catalytic antibacterial agent generally represents a monomeric or possibly dimeric material with a molecular weight of well below 2000, for example below 1000. However, it is also possible to use a polymeric cationic an-35 in the composition according to the invention to use tibacterial agent. The cationic antibacterial substance is preferably used in the form of an orally acceptable salt, for example as chloride, bromide, sulfate, alkyl sulfonate such as methyl sulfonate and ethyl sulfonate, as phenyl sulfonate such as p-methylphenyl sulfonate, 40 nitrate, acetate, gluconate and the like .

The nitrogen-containing cationic antibacterial substances and the long-chain antibacterial tertiary amines promote oral hygiene, especially by removing the coating. However, their use leads to spots 45 on the tooth surface or to their discoloration.

The reason for this discoloration is not yet clear. However, human tooth enamel contains a high proportion of approximately 95% hydroxyapatite (HAP) with Ca + 2 and P04 3 ions. In the absence of plaque, Ca + 2 and P04 ~ 3 can be deposited on the tooth enamel, especially from saliva, and these deposits can contain dyes that ultimately discolor the tooth enamel as calcified deposits. It is possible that the cationic antibacterial substances or the long-chain antibacterial tertiary amines also denature protein from the saliva in the oral cavity when the deposit is removed, and the denatured protein then acts as a nucleating agent which is deposited on the tooth enamel and on these spots forms or stains it.

The additives used to date, which reduced staining caused by cationic antibacterial anti-fouling agents, also generally reduced the effectiveness of the anti-bacterial anti-fouling agent, such as bis-biguanido compounds, by precipitating with these agents.

The compositions according to the invention contain 0.01 to 10% by weight of 2- in an orally acceptable carrier.

646 051 4

Phosphonobutane-1,2,4-tricarboxylic acid (PBTA) the general excess of the antibacterial anti-scale agent, based on the free base, in order to reduce, inhibit or prevent discoloration in an optimal way.

Various embodiments according to the invention are essentially liquid, such as mouthwashes or mouthwashes. The carrier typically consists of a water / alcohol mixture which advantageously contains a humectant described below. In general, the water: alcohol weight ratio is about 1: 1 to about 20: 1, preferably about 3: 1 to 10: 1 and in particular about 4: 1 to about 5: 1. The total amount of the water-alcohol mixture in this type of preparation or an orally acceptable, preferably water-soluble, generally makes up about 70 to about 99.9% by weight of the preparation.

Salt this acid, for example with an alkali metal, such as 15 parates. The pH of these liquid and other inventions, sodium and potassium, ammonium, a Cj-Cjg mono-, preparations according to the invention is usually in the range of di- and trisubstituted ammonium, for example an al- 4.5 to 9 and in particular from 5.5 to 8. Preferably be-kanol-substituted, such as mono-, di- and tri-ethanolammo, the pH is 6 to 8.0. It is noteworthy that the erium cation. compositions according to the invention orally at a pH

A compound of the above formula and method of 20 less than 5 can be used without its manufacture are essentially decalcified in U.S. Patent 3,886,204 and tooth enamel. The pH 3 886 205 is described. Value can be with an acid, for example, or citric acid

The concentration of the PBTA compound or its benzoic acid can be adjusted, or with a base, to the salt in the oral compositions, for example with sodium hydroxide, or buffered to vary over a wide range, typically from 2s example with phosphate buffer. The liquid oral preparations go up 0.01% by weight, unless this can also be a surfactant and / or a

Cost or incompatibility with the carrier-containing fluorine-containing compound.

Right. Concentrations from 0.01 to 10 and other embodiments according to the invention can preferably be used from 0.1 to 6% by weight. Oral ingredients are essentially solid or pasty, such as tooth powder, compositions which, during normal use, could be swallowed by dental tablets, toothpastes or toothpastes. The carrier preferably contains such solid or paste-like preparations in relatively low concentrations the PBTA connection. So generally contains a polishing agent. Examples of polishing agents are a mouthwash according to the invention, preferably less water-insoluble sodium metaphosphate, potassium metal than 2% by weight of the PBTA compound, in particular 0.1 to phosphate, tricalcium phosphate, dihydrated calcium 1.5% by weight. Other dentifrices, such as topical 35 phosphate, anhydrous dicalcium phosphate, calcium pyro-solutions and prophylactic pastes, the latter being phosphate, magnesium orthophosphate, trimagnesiumphos - used by the dentist, 0.1 to 3 wt .-% phate, calcium carbonate, aluminum oxide, hydrated Alu-the PBTA connection included. minium oxide, aluminum silicate, zirconium silicate, silicon di

The deoxidizer, bentonite and mixtures thereof in the composition according to the invention. Preferred polishing agent-containing PBTA compound counteracts nucleation 40 are silica gel or colloidal silica, complex gene, so that the oral additives containing this compound effectively reduce the formation of tartar, alkali metal aluminosilicate and hydrated compositions, aluminum oxide.

without decalcifying the tooth enamel. In contrast to very effective, aluminum oxide is particularly effective

the nitrogen-containing antibacterial alumina described above, which is brought from the Alcoa as C333 in the anti-fouling agents, the PBTA compound and trade, an alumina content of 64.9 composition, which they contain, little or not to the Gew. %, a silica content of 0.008%, a

Discolor teeth. In addition, they prevent gum infections with an effective iron oxide content of 0.003% and a moisture content. at 110 ° C of 0.37%, also the specific weight

Another advantage of the PBTA compounds is 2.42 and a particle size that 100% of the particles are small in that they surprisingly prevent or remove discolorations of 50 microns than 50 microns and 84% of the particles smaller than 20 Mi enamel that are crowned by those above.

described nitrogen-containing antibacterial anti-plaque - If visually clear, anti-calculus agents are preferably caused without them failing or their effective gels are used, the polishing agents are col-antibacterial and anti-plaque effects, disadvantageously loidal silicon dioxide, as is impaired under the trademark Sy. Not all 55 loid 72 and Syloid 74 or Santocel 100, which are effective against nucleation, are sold, and agents prevent discoloration by such antibacterial-alkali metal-aluminosilicate complexes, particularly useful, rational agents. Victamide, also known as Victamine C because its refractive indices are close to the refractive indices of and a condensation product of ammonia with systems of gelling agent and liquid, water

Phosphorus pentoxide, including increased discoloration itself and / or humectants included, are the usual in the absence of such antibacterial agents. 60 are usually used in dentifrices. From similar

If preferred, the usually given reasons are alkali metal aluminosilicate complex anti-bacterial anti-discoloration stains - particularly useful as a polishing agent in visually clear gels, used in commonly effective amounts, usually for the PBTA compound in combination with example in such a way that the oral product this contains the described nitrogen-containing antibacterial antibacterial amounts from 0.001 to 15% by weight. It preferably contains 65 agents.

Amount to achieve a desired anti-deposit effect Many of the so-called «water-insoluble» polishing agents

0.01 to 5 and in particular 0.25 to 1.0% by weight, based on are anionic and also contain small amounts of soluble free base. The PBTA connection in mola material is advantageous. So insoluble sodium metaphosphate can mean ho «

o ch2-cooh p — c cooh ho-

h -ch-ch2-cooh

be produced in a suitable manner, as described in the Dic-tionary of Applied Chemistry, volume 9.4. Ed., Pages 510-511, by Thorpe. Insoluble forms of sodium metaphosphate, known as Madrell's and Kurrol's salts, are further examples of suitable materials. These metaphosphate salts have minimal solubility in water and are therefore usually referred to as insoluble metaphosphates. They contain a small amount of soluble phosphate material as an impurity, usually a few percent up to 4% by weight. The amount of soluble phosphate material believed to include soluble sodium trimetaphosphate in the insoluble metaphosphate can be reduced, if desired, by washing with water. The insoluble alkali metal metaphosphate is typically used in powder form with a particle size that is no more than about 1% of the material is greater than about 37 microns.

The polishing agent is generally present in an amount from about 10 to about 99 percent by weight of the oral composition. It is preferably about 10 to about 75% in toothpaste and about 70 to about 99% in tooth powder.

In the manufacture of tooth powders, it is usually sufficient to mechanically mix the various solid constituents in suitable amounts and particle sizes, for example by grinding.

In pasty compositions, the PBTA compound should be compatible with the other components. In a toothpaste, the liquid carrier can contain water and a humectant and typically make up about 10 to about 90% by weight of the composition. Glycerin, propylene glycol, sorbitol or polyethylene glycol oil 400 can be present as a humectant or binder. Mixtures of water, glycerin and sorbitol are particularly useful liquid components.

In the case of clear gels, in which the refractive index is of particular importance, about 3 to 30% by weight of water, 0 to about 80% by weight of glycerol and about 20 to 80% by weight of sorbitol are preferably used. A gelling agent, such as natural or synthetic gums or rubber-like materials, typically Irish moss, sodium carboxymethyl cellulose, methyl cellulose, hydroxyethyl cellulose, hydroxypropylmethyl cellulose, the carbopoles, for example 934,940 and 941, tragacanth gum, polyvinylpyrrolidone, starch or mixtures thereof among others is usually used in a toothpaste in amounts of up to about 10% by weight, preferably from about 0.5 to about 5% by weight. In a toothpaste or a gel, the liquid and solid substances are generally used in such proportions that a creamy or gel-like mass is formed, which can be expressed from a pressurized container or a compressible tube, for example from aluminum or lead.

The preferred solid or pasty oral composition which typically has a pH of 4.5 to 9, generally 5.5 to 8, and preferably 6 to 8.0, as measured on a 20% slurry.

may also contain a surfactant and / or a fluorine-providing compound.

The oral preparations are generally marketed or otherwise distributed in suitable labeled packages. For example, a bottle containing a mouthwash is provided with a label that describes it as a mouthwash or mouthwash and gives instructions for its use. A toothpaste is usually in a squeezable tube, usually made of aluminum, clad lead or plastic, or in some other squeezable delivery device

646051

for dosing their content, which is provided with a label that contains the content as toothpaste or toothpaste.

Organic surfactants can be used in the compositions according to the invention in order to enhance the prophylactic effect, to bring about a complete dispersion of the PBTA compound in the oral cavity and to make the compositions cosmetically acceptable. The commonly used organic surfactant is preferably anionic, nonionic or ampholytic. It is advantageous to use a surface-active agent which gives the composition cleaning and foaming properties. Suitable examples of anionic surfactants are water-soluble salts of higher fatty acid monoglyceride monosulfates, such as the sodium salt of the monosulfated monoglyceride of hydrogenated coconut oil fatty acids, higher alkyl sulfates, such as sodium lauryl sulfate, alkylarylsulfonates, such as sodium dodecylbenzenesulfonate sulfate, higher alkyl sulfonate sulfonate, higher alkyl sulfonate sulfonate, higher alkyl sulfonate sulfonate, higher alkyl sulfonate sulfonate, higher alkyl sulfonate fatty acid sulfonate, higher alkyl sulfonate sulfonate, higher alkyl sulfonate fatty acid sulfonate, higher alkyl sulfonate fatty acid sulfonate, higher alkyl sulfonate fatty acid, higher alkyl sulfonate fatty acid, higher alkyl sulfonate, and higher alkyl sulfonate, sulfonate, and higher alkyl sulfonate, higher alkyl sulfonate, and higher alkyl sulfate, 1,2-diol sulfonate, and higher alkyl sulfonate, sulfonate, and higher alkylsulfonate di-sulfonate, higher alkylsulfonate, and higher alkyl sulfonate, 1,2-di-sulfonate, and higher alkyl sulfonate, sulfonate, and higher alkyl sulfonate substantially saturated higher aliphatic acylamides of lower aliphatic aminocarboxylic acid compounds, for example those having 12 to 16 carbon atoms in the fatty acid, alkyl or acyl radicals and the like. Examples of the latter amides are N-lauroylsarco-sin and the sodium, potassium and ethanolamine salts of N-lauroyl, N-myristoyl or N-palmitoylsarcosine, which should be essentially free of soap or similar higher fatty acid materials. The use of these sarcosinates in the dentifrices according to the invention is particularly advantageous since they substantially and permanently inhibit the formation of acids at the mouth level due to a carbohydrate breakdown and reduce the solubility of the tooth enamel in acidic solutions.

Examples of preferred water-soluble nonionic surfactants are the condensation products of ethylene oxide with various reactive hydrogen-containing compounds which have long hydrophobic chains, for example aliphatic chains with about 12 to 20 carbon atoms. These condensation products (“ethoxamers”) contain hydrophilic polyoxyethylene components, for example the condensation products made of poly (ethylene oxide) with fatty acids, fatty alcohols, fatty acid amides, polyhydric alcohols, for example sorbitan monostearate, and polypropylene oxide, that is to say the Plu-ronics .

According to certain embodiments of the invention, the oral composition contains a fluorine-providing compound. These compounds can be slightly or completely soluble in water. They are characterized by the ability to release fluoride ions in water and essentially not to react with the other compounds of the composition. These materials include, in particular, inorganic fluoride salts, such as soluble alkali metal, alkaline earth metal and heavy metal salts, for example sodium fluoride, potassium fluoride, ammonium fluoride, copper fluorides, such as copper (I) fluoride, zinc fluoride, tin fluorides, such as tin (IV) fluoride or tin ( II) chlorofluoride, barium fluoride, sodium fluorosilicate, ammonium fluorosilicate, sodium fluozirconate, sodium monofluophosphate, aluminum mono- and di-fluorophosphate and fluorinated sodium calcium pyrophosphate. Alkali metal and tin fluorides such as sodium and tin (II) fluorides, sodium monofluophosphate and mixtures thereof are preferred.

The amount of the fluorine-providing compound depends to some extent on the compound used, its solubility and the nature of the oral composition, but must not be toxic. In a solid oral composition, for example a toothpaste or a toothpaste

5

5

10th

15

20th

25th

30th

35

40

45

50

55

60

65

646051

ver, an amount of such a compound is considered satisfactory that releases a maximum of about 1% by weight of the composition. Any minimum amount is suitable, but it is preferred to use a compound in an amount sufficient to release about 0.005 to 1%, preferably about 0.1%, of fluoride ion. In the case of the alkali metal fluorides and stannous fluoride, this component is typically present in an amount of up to about 2% by weight based on the weight of the composition, preferably in an amount of about 0.05 to about 1% .%. In the case of sodium monofluophosphate, the compound can be present in an amount of up to 7.6% by weight and in particular about 0.76%.

In a liquid oral preparation, such as in a mouthwash, the fluorine-providing compound is typically contained in an amount that is up to about 0.13 and preferably about 0.0013 to 0.1 and especially about 0.0013 to 0.5 % By weight of fluoride ion are released.

Various other materials can be incorporated into the oral compositions according to the invention, for example whitening substances, preservatives, silicones, chlorophyll compounds, other anti-calculus agents, antibacterial anti-scaling agents and / or ammoniated substances such as urea, diammonium phosphate and mixtures thereof. If used, these auxiliaries can be used in amounts such that they do not impair the desired properties of the composition.

Suitable flavoring or sweetening agents can also be used. Examples of these are flavor oils, for example the oil of spearmint, peppermint, wintergreen, sassafras, clove, sage, eucalyptus, marjoram, cinnamon, lemon and orange oil and methyl salicylic lat. Suitable sweeteners are, for example, sucrose, lactose, maltose, sorbitol, xylitol, sodium cyclamate, perillatin, the methyl ester of aspartylphenylalanine (APM), saccharin and the like. The flavoring and sweetening agents are suitably used together in an amount of about 0.01 to 5% or more of the composition.

In the preparation of the oral compositions according to the invention, it is advantageous but not essential to add the PBTA compound after the mixing of the other constituents, with the exception of a little water, in order to prevent possible precipitation of the PBTA compound.

For example, a mouthwash or mouthwash can be made by mixing ethanol and water with the flavor oil, surfactant, humectant, optionally antibacterial anti-fouling agent such as cetylpyridinium chloride, benzethonium chloride or chlorhexidine, sweetener and colorant thereon add the PBTA connection and then, if desired, additional water.

A toothpaste can be produced by first preparing a gel from the humectant, the rubber, the thickening or the gel-forming agent, such as hydroxyethyl cellulose, and the sweetener, then adding the polishing agent, flavoring agent, optionally antibacterial anticoagulant and further water and then adding water the PBTA connection. If sodium carboxymethyl cellulose is used as a gelling agent together with a bis-biguanide as an anti-bacterial anti-fouling agent, one can use the procedure set forth in U.S. Patent 3,842,168 or U.S. Patent 3,843,779, modified by the addition of the PBTA compound , apply.

An oral composition according to the invention, such as a mouthwash or toothpaste, is regularly applied to the tooth enamel, preferably about one to about three times a day with a pH of 4.5 to 9, in general from 5.5 to 8 and preferably from 6 to 8.

In the following examples, all quantities are by weight unless otherwise stated.

Example 1

Inhibition of crystal growth of hydroxyapatite 1.0 ml of an aqueous solution of 1 x 10 ~ 4M to 1 x 10 ~ 5M of the anti-tartaring agent to be investigated and 0.1 M monosodium phosphate are combined with 22 to 23 ml of distilled water in one Flask were given and constantly stirred in a nitrogen atmosphere. For this, 1 ml of 0.1 M CaCl2 is added and the pH is adjusted to 7.5 + 0.05 with NaOH (final concentration of Ca ++ and P043 ~ = 4 x 10_3M). The consumption of the 0.1 N NaOH is determined automatically (radiometer). In this test, the formation of the hydroxyapatite takes place in two distinct phases. First, one observes a rapid base consumption (1 to 4 minutes), which then decreases until a second rapid base consumption occurs 15 to 20 minutes later. A delay in the time until the second rapid base consumption or a complete absence of the second rapid base consumption indicates a disturbance in the crystal growth of the hydroxyapatite. Agents that interfere with crystal growth of hydroxyapatite are effective anti-tartar agents. Examination of PBTA in the above procedure gave the following results:

Table 1

remedy for

Tartar formation,

concentration

Time to delay in

Hydroxyapatite Formation of Hydroxyapatite Formation

40

Water, control PBTA, 4ppm PBTA, 8ppm PBTA, 10ppm PBTA, 20ppm

15 minutes 25 minutes 75 minutes 129 minutes 33.8 hours

10 min. 60 min. 114 min.

The above values show that PBTA effectively inhibits the crystal growth of hydroxyapatite in vitro and that this inhibition is not due to the conversion of calcium into complexes or chelates, since substoichiometric ratios of PBTA: calcium are used.

The following are examples of a mouthwash according to the invention which contains Pluronic F108 as a polyalkylene oxide block polymer.

55

example

2nd

3rd

4th

5

Flavoring

0.22%

0.22%

0.22%

0.22%

Ethanol

15.0

15.0

15.0

15.0

Pluronic F108

3.0

3.0

3.0

3.0

Glycerin

10.0

10.0

10.0

10.0

Na saccharin

0.03

0.03

0.03

0.03

PBTA

0.1

0.2

0.5

1.0

Water to

Filling up

100

100

100

100

pH, with NaOH

7.4

7.4

7.4

7.4

Appearance clear clear clear clear

The following example explains a toothpaste effective against tartar formation according to the invention:

example

6

Silicon dioxide 30

Glycerin 16

Sorbitol (70%) 6

Pluronic F-108 3

Hydroxyethyl cellulose 1.2

PBTA 2

Sodium saccharin 0.17

Flavor 0.8

Water to fill up to 100

7 646 051

Table 2 below explains mouthwash formulations according to the invention and the activity against discoloration of the preferred PBTA additive used in them. The tooth-discoloring properties of the formulations are determined by slurrying hydroxyapatite (Biogel), a specific oral saliva protein, a car bonyl source, for example acetaldehyde, and a pH 7 phosphate buffer with or without the mouthwash formulation to be examined. The mixture is shaken at 37 ° C. for 18 hours. The colored hydroxyapatite powder is filtered off and dried and the color values are determined in a Gardner color difference measuring device in reflection units.

15

Table 2

example

Clear mouthwash formulations 7 8 9

10th

11

12

13

Ethanol

10%

10%

10%

10%

10%

10%

10%

Glycerin

10th

10th

10th

10th

10th

10th

10th

Pluronic F1081

3.0

3.0

3.0

3.0

3.0

3.0

3.0

Flavoring

0.146

0.146

0.146

0.146

0.146

0.146

0.146

Sodium saccharin

0.03

0.03

0.03

0.03

0.03

0.03

0.03

CPC2

0.1

0.1

0.1

0.1

0.1

0.1

PBTA

0.1

0.2

0.3

0.5

1.0

Water to

Filling up

100%

100%

100%

100%

100%

100%

100%

pH, with IN NaOH

7.0

7.0

7.0

7.0

7.0

7.0

7.0

Reflection

56.8

39.6

42.1

43.6

46.2

47.8

55.9

difference

+ 17.2

-2.5

-4.0

-6.6

-8.2

-16.3

RD

<

Comparison to example

8th

>

1 polyalkylene oxide block polymer

2 cetylpyridinium chloride

Using the example of the PBTA, the above values illustrate that the additives according to the invention substantially reduce the tooth staining which is usually caused by antibacterial anti-scaling agents, for example by CPC. A PBTA concentration of around 1.0% leads to excellent results. These additives also prevent or reduce gingivitis caused by tartar and do not significantly reduce the anti-plaque effect of the specified anti-plaque agents.

45 The use of equivalent amounts of the following antibacterial anti-scaling agents instead of CPC results in formulations which also lead to a surprising reduction in tooth staining and tartar.

Example antibacterial anti-scale agent

14 benzethonium chloride (BC)

15 chlorhexidine diacetate

16 chlorhexidine digluconate

17 Dodecyl trimethyl ammonium bromide

CH2CH2OH

i ^ -ch2ch2oh

18 C12_] 8-alkyl-N-CH2CH2N <r x: h2ch2oh

19 Alexidine dihydrochloride

646051 8

The following formulations explain toothpastes with an anti-plaque effect, which simultaneously lead to reduced discoloration and tartar formation.

Example, parts 20 21 22

hydrated alumina

30th

30th

30th

Polyethylene glycol 600

22

22

22

Pluronic F-108

3rd

3rd

3rd

Hydroxypropylmethyl cellulose

1.2

1.2

1.2

BC

0.5

-

Hibitans

-

4,725

CPC

-

0.5

PBTA

1.0

1.0

1.0

Sodium saccharin

0.17

0.17

0.17

Flavoring

0.8

0.8

0.8

Water to fill up

100

100

100

20th

25th

30th

35

40

45

60

Claims (11)

646 051 PATENT CLAIMS 1. Composition against tartar formation from an orally acceptable carrier containing 0.01 to 10% by weight of 2-phosphonobutane-l, 2,4-tricarboxylic acid of the general formula o ch2-cooh p-c- -cooh (I) h-ch- -ch2-cqoh or an orally acceptable salt of this acid. 2. Composition according to claim 1, characterized in that it additionally contains up to 15 wt .-%, based on the free base, of a nitrogen-containing antibacterial anti-scaling agent, which the tooth surfaces in the absence of the 2-phosphonobutane-I, 2 , 4-tricarboxylic acid discolored. 3. Composition according to claim 2, characterized in that the antibacterial anti-fouling agent is cationic and is present in an amount of at least 0.001% by weight. 4. Composition according to one of claims 1 to 3, characterized in that it contains the phosphono compound in an amount of 0.1 to 6 wt.%. 5. Composition according to one of claims 2 to 4, characterized in that it contains a substituted guanidine as an antibacterial anti-fouling agent. 6. Composition according to claim 5, characterized 5 indicates that the antibacterial anti-scale agent is a pharmaceutically acceptable water-soluble salt of chlorhexidine or alexidine. 7. Composition according to one of claims 2 to 4, characterized in that it is used as an antibacterial anti- io lagmittel contains benzethonium chloride. 8. The composition according to any one of claims 2 to 4, characterized in that it contains a quaternary ammonium compound with I to 2 C8 to C20 alkyl groups as an antibacterial anti-coating agent. 15 9. Composition according to claim 8, characterized in that it contains cetyl-pyridinium chloride as an antibacterial anticoagulant. 10. Composition according to one of claims 1 to 9, characterized in that the carrier from a water 20 alcohol mixture exists and the composition is in the form of a mouthwash with a pH of 4.5 to 9. 11. The composition according to any one of claims 1 to 9, characterized in that the carrier is liquid and a 2s contains gel-forming agent and a dental acceptable polishing agent and the composition is in the form of toothpaste with a pH of 4.5 to 9. 12. Composition according to one of claims 2 to 10 in the form of a mouthwash, characterized in that 30 that it contains the anti-scale agent in an amount of 0.01 to 5 wt.%.