DE2750873A1 - ORAL PREPARATION FOR TENTAL INHIBITION - Google Patents

Description

DR. BERG DIFL-ING. STAPF DIPL-ING. SCHWABE DR. DR. SANDM AIR

P.O. Box 860245 8000 Munich 86

Lawyer File 28 5f3 November 14, 1977

MONSANTO COMPANY
ST. LOUIS / MISSOURI / USA

Oral preparation for inhibition; of tartar

The invention relates to "oral preparations", which means products which are to be introduced into the oral cavity in such a way that contact is made with the exposed tooth surfaces. Such products include, for example, pet foods and beverages, chewing gum, and oral care items including mouthwashes, prophylactic pastes, topical solutions, and cleaning agents such as toothpastes, tooth powders, dental creams, and the like.

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D / b. 43-21- ^ 379 A GW

r (0 «9i <* R82 72 telegrams bank accounts Hypo-Bank Manchen 44101221»

9 * 8271 Bf RCiSTAPI PATKNT Munich (BlV 70O2O0I1I Swirt Code HYK) DE MM

988274 TFlIX Bayer Vcreimbank Munich 453100 (BLZ 700202701

Vl Kl (IS 24 VJ) BIRCi d Pmlscheck München 65. ¹ U) mT (BI Z 70010010)

Tartar is a deposit that forms on the surface of the tooth mainly at or near the gumline. Tartar over the gums is most pronounced near the mouth of the salivary duct. Finished tartar contains an inorganic component, mainly calcium phosphate, contained in a hydroxyapatite crystal lattice similar to how it is arranged in bone, tooth enamel and dentin. Furthermore, it is mostly an organic component from exfoliated epithelial cells, saliva deposits, food residues, various microorganisms, etc., available.

Developing tartar is white or yellowish unless it is stained by a foreign substance. He is from from an aesthetic point of view undesirable, furthermore finished tartar deposits are a cause of gum irritation and thus contribute to gingivitis and other diseases of the supporting structures of the teeth, as the irritation Decreases the resistance of the tissue to endogenous and exogenous organisms.

Periodic mechanical tartar removal is a routine procedure in the dental practice. A number of chemical agents have also been used to remove tartar suggested, e.g., alkali metal and ammonium diglycolates

809820/0994 " ^{/ 3}

and diglycolates of organic bases such as urea, guanidine or ethanolamine in GB-PS 995 330. In the French PS 2 108 827 it is stated that the ability of sodium gluconate to separate calcium ions to remove tartar can be used. In US-PS 1 516 206 is described that a tartar-dissolving effect by Use of an aqueous solution of a lactone or anhydride of a weak organic hydroxy acid, e.g. galactonic acid, together with a weak organic acid such as maleic or citric acid. According to US Pat. No. 3,429,963 can remove tartar with a preparation comprising a hydrolyzed copolymer of ethylene and maleic anhydride having an average molecular weight of at least about 1,500.

In some cases, chemical agents are said to be able to delay tartar formation. So is in the aforementioned US-PS 3 t29,963 described that a reduction in tartar formation was observed in rats when the drinking water of the Rats contained 1% of a hydrolyzed ethylene / maleic anhydride copolymer. In the aforementioned GB-PS 995 330 is called that a reduction in tartar formation by using toothpastes containing the above-mentioned diglycolates, was achieved. Another polymer, i.e. a polyester of a polycarboxylic acid having three or more carboxyl groups and a polyalkylene ether with at least two hydro

809820/0994 " ^A.

xyl groups, is described in U.S. Patent 3,542,917 as an anti-tartar agent. U.S. Patent 3,920,837 states that that the formation of tartar can be reduced by cyclohexane hexacarboxylic acid or its water-soluble salts, and in GB-PS 1 373 001 and -003 it is stated that tartar can be removed by using a cleaning agent which contains a contains hardly any water-soluble zinc salt, e.g. zinc citrate, can be reduced. Various phosphorus compounds, such as ethane-l-hydroxyl-l, l-diphosphorous acid (hereinafter EHDP) have been disclosed for this purpose in U.S. Patent 3,488,419 suggested.

Some of those previously suggested for tartar removal or inhibition chemical agents contain functional groups, the effect of which on animals in terms of toxicity, side effects, etc., is uncertain. Of certain other compounds that are only carbon, hydrogen, and oxygen possibly containing physiologically acceptable cations, it is believed that there is virtually no such uncertainty and that they are therefore preferable for oral preparations. Connections are also used for the stated purpose with relatively simple structure and low molecular weight are desirable, as are compounds without a polymerization process can be produced. Oral preparations containing compounds that act as such Withstand criteria and tartar formation is essential

809820/0994

inhibit, are therefore extremely desirable and it is the object of the invention to provide such preparations. Another object is to develop a method for inhibiting tartar formation through the use of such preparations. Further tasks emerge from the following description, in which weight percentages are given, unless otherwise noted.

The invention relates to an oral preparation which inhibits tartar formation. This preparation contains

1) a propanedioic acid compound selected from acids with the structural formula

COOH COOH

i I

X-C-O-Y-O-C-Z

COOH

COOH

therein Y means

-CR ²

or

R '- C

OC- R

R ^- CR

10

and X and Z are independently of one another

-CR R ¹³

12th

when Y - C - means 1.2

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- he -

COOH - 0 - C - R

A «

14th

if Y - C - C

R '

I.
OC- A <

, 10

and in which R to R each independently represent hydrogen or lower alkyl; m means 0 or 1; η means the sum of m and 0, 1, 2 or 3; and the sum of 2 m and η is 0,1,2 or 3,

and physiologically acceptable salts of these acids, and

2) a carrier suitable for use in the oral cavity, with the above compound in the preparation in a sufficient amount The amount and concentration is present to significantly inhibit tartar formation.

It applies to the above structural formulas that the R substituents in the general formulas representing X and Z (ie R ¹¹ , R ¹² , R ¹³ , R ¹⁴ , R ¹⁵ ) for X or Z can in each case be the same or different. Furthermore, "lower alkyl" here means a C ₁ - to C -alkyl, which can be branched (e.g. isopropyl, isobutyl or tert-butyl) or cyclic (cyclopropyl or cyclobutyl), but which preferably has a straight chain (methyl, ethyl, n-propyl or n-butyl).

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In some preferred embodiments of the invention X and Z each independently of one another by the formula

COOH

- 0 - C - R ^1H R ¹⁵

shown. These compounds are referred to herein as bis (carboxyalkoxypropanedioic acid) compounds.

In some of these embodiments, especially when m 1

14 15

R and R preferably in X and Z each independently represent hydrogen or normal alkyl dar; and in some of these embodiments it is even more desirable that the sum of the carbon atoms

14 15
in R and R for X and Z is not greater than 4 in each case.

In many of these embodiments, the average The number of carbon atoms in the R substituents of X, Y and Z is preferably not greater than 2, more preferably not greater than 1. In these embodiments it is particularly preferred that R always denotes hydrogen.

In other preferred embodiments of the invention, Y is ₁

R ¹

I.
- C -

IT
and X and Z are each independent of one another

-/8th

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R ¹¹

- C - R ¹² R ¹³

These compounds are referred to herein as alkylenedioxybis (alkylpropanedioic acid) compounds designated. In these embodiments it is preferred that the R substituents in X, Y and Z each independently represent hydrogen or normal alkyl, even better they each represent independently from each other hydrogen, methyl or ethyl. In some other of these embodiments, preferred is -1 2

wise R or R hydrogen, it is even better if both mean hydrogen. In still other embodiments preferably represent at least two R's in each

R ¹¹

- C - R ¹²

I ₁₃

Radically hydrogen, it is also preferred that the total number of carbon atoms in each of these

R ¹¹

- C - R ¹² R ¹³

Radicals is no greater than 7 .

In a particularly preferred embodiment, each R in X, Y and Z is hydrogen.

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The embodiments described above are general preferred due to their relatively low molecular weight.

The compound represented by the above formula is

when X and Z are COOH

i
- 0 - C - H ₂ ,

m and η are each 1, and all R in Y are hydrogen, as 2,2'-bis- (carboxymethoxy) -2,2 '- (oxydiäthylendioxy) -bis- (propanedioic acid) and hereinafter referred to as BCOBPDA for the sake of simplicity. This acid and its relatives can be prepared by the following procedure, which is described in further detail in U.S. Patent 3,950,388.

To produce these compounds, a diol (divalent Alcohol) with the formula

R '

HO-C-

R "

I -C-

i OC-

R "■ C

OH

where R ″ to R, m and η have the meaning given above, reacted with a base strong enough to deprotonate the hydroxyl groups of the diol (for example metallic sodium or potassium or sodium or potassium hydride, tert-butoxide or amide ) and to form a conjugate base in which the deprotonated oxygen atoms of the diol with von

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Cations delivered with this base are associated (e.g. sodium or potassium ions). From this it follows that to the diols preferred for this purpose include diethylene glycol, ethylene glycol and other straight chain alkanediols, both of which are terminal hydroxyl groups, e.g. 1,3-propanediol, 1,4-butanediol and 1,5-pentanediol, but that many other diols can also be used equally, e.g. 1,3-butanediol, 3,7-decanediol, 3-methyl-2,6-heptanediol, 3-ethyl-5-propyl-2,6-octanediol, etc.

The conversion of alcohols to their conjugate bases is known. The reaction can conveniently be carried out between 0 ° C. and 115 ° C. in any solvent for the alcohol that does not react adversely with the strong base. Suitable solvents are, for example, tetrahydrofuran, dimethyl sulfoxide, dimethylformamide, ethyl ether, 1,2-dimethoxyethane, bis (2-methoxyethyl) ether, and the like. If the diol reactant is a liquid, an excess of this diol can be used as the solvent. Mixtures of solvents can also be used if desired. For a more detailed discussion of the conversion of alcohols to conjugate bases, see: Morrison and Boyd, Organic Chemistry , 3rd Edition, Allyn and Bacon, Inc. (1973) pp. 526, 527; Feuer and Hooz, The Chemistry of the Ether Linkage, editors Patai, Interscience Publishers (1967), Chapter 10, page 4U7; and Schmidt and Bayer, Methods

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Der Organic Chemie (Houben-Weyl) Volume VI / 2, Georg Thieme Verlag, (1963) Oxygen Compounds 1, Part 2, as well as in the associated bibliographies.

The conjugate base of the diol is then combined with a ketomalonate ester COOA

C = O

COOA

implemented, which the deprotonated oxygen atoms of the diol to

COOA

I _

-OCO

COOA

Converts substituents. In the above ester formula, A is an organic component which, for example due to its chemical reactivity or steric hindrances, will not interfere and will not prevent the desired ester-base reaction. The reaction proceeds normally in all cases where A is methyl or ethyl and the use of diethyl ethomalonate is most preferred. The reaction is usually carried out at -60 ⁰ C to +50 ⁰ C (preferably from -20 ⁰ C to +30 ° C) and preferably effected in the material used for the preparation of the conjugate base of the solvent. The amount of ketomalonate ester present and the reaction conditions should be controlled so that each molecule of the ester reacts with a deprotonated oxygen atom in the conjugate base of the diol. -/1?

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AS

The product of this ester-base reaction is then combined with a bromine or iodine carboxylate of the structural formula

\
DCCOOA

i «

IM x 15 implemented, in which D is bromine or iodine, and R, R and A have the abovementioned meaning, the radicals -0 of the conjugate base to _1U

\
-OCCOOA

i "

Converting substituents and thereby obtaining the ester forms of the acids and / or salts used in the invention. The bromine or iodine carboxylate can be added as such or generated in situ by, for example, adding a mixture of sodium iodide or bromide and a suitable chlorocarboxylate, such as ethyl chloroacetate, methyl 2-chloropropionate, ethyl 2-chlorobutyrate, methyl 2- chloroisobutyrate or the like. Used. A reaction temperature between -20 C and +100 ⁰ C is usually satisfactory, and it can be elevated or atmospheric pressure are used.

The reaction of the hexacarboxylic acid esters obtained with an alkali metal (for example sodium or potassium) hydroxide gives the alkali metal salts which can be used for the invention. Each of these salts can be obtained by treatment with a strong acid such as HCl, H-SO ₁ , or a strongly acidic ion exchange resin

809820/0994 _ / i ₃

converted to the corresponding acid (e.g. BCOBPDA). The corresponding ammonium, mono- or di- (C ₁ - to C_-alkyl) -ammonium or mono- or di- (C ₁ - to C_-alkanol) -ammonium salts can be prepared by reacting such acids with ammonia or one of its suitable Alkylamines, alkanolamines or hydroxides can be prepared using one of the known processes.

In the above process for preparing the bis (carboxyalkoxypropanedioic acid) compounds (e.g. BCOBPA) of the invention, the diol can optionally be mixed first with the ketomalonate ester and the mixture then reacted with a strong base of the type described above. In an alternative method, which is particularly useful when the aufzu- through one or both R in said compound

14th
taking R

i
- CCOOA

Radical possibly steric hindrance is, is

14 a monoalcohol form of this radical R

(HOCCOOA)

reacted with a strong base to form the conjugate base of this alcohol i the conjugate base is reacted with the ketomalonate ester, and two molecules of the product of this

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VT -

1?

Ester-base reaction will be with each molecule of a dihalide counterpart of the above-mentioned diol, for example a dibromide of the formula

Br

R '

I.
OC-

> 8

10

3 10
wherein R to R, m and η have the meaning given above

to have.

The compound represented by the above formula, here, when Y is -CH-- and X and Z are both -CH, it becomes 2,2'-dimethyl-2 , 2 '- (methylenedioxy) bis (propanedioic acid) (hereinafter referred to as DMBPDA for the sake of simplicity). The tetrasodium salt of this acid can be prepared by a suitable diester of methyl tartronic acid, e.g. a di (lower alkyl) ester such as diethyl methyl tartronate, contacts with a base strong enough to deprotonate the hydroxy group of that diester (e.g. metallic sodium or potassium or sodium or potassium hydride, tert-butoxide or amide), and a conjugate base to form, in which the deprotonated oxygen atom of the diester with a cation supplied by this base (e.g. a sodium or potassium ion) is associated; then this conjugate base is exposed to a dihalomethane (e.g. Dibromomethane) in a molar ratio of 2: 1 to the tetraester

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the DMBPDA, and saponify this tetraester with sodium hydroxide.

Sodium salts of the acids of the above formula can, if

X and Z _R ll

- R ¹²

mean, and at least one of R, R and R is lower alkyl, can be prepared by a process analogous to that just described, but in which the methyl tartronate diester is at least partially replaced by a tartronic acid diester which has an alkyl substituent on its hydroxylated carbon atom _i the appropriate is greater than methyl, e.g. ethyl, n-propyl, n-ßutyl, isopropyl, isobutyl, tert-butyl, etc.

Sodium salts of the acids of the above formula in which Y

R ¹

-ΟΙ ²

1 means 2 and at least one of R and R is lower alkyl can be carried out using a method analogous to that just described be prepared, but in which the dihalomethane is replaced by a dihaloalkane, in which two Halogen atoms are directly linked to the same carbon atom of an alkylene radical that is appropriately larger

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as methylene, e.g. dihaloalkane such as 1,1-diiodoethane, 1,1-dibromopropane, 2,2-dibromopropane, 2,2-dibromobutane, 2-methyl-3,3-dibromopentane, 2,2-dimethyl-3,3-dibromo-5-methylhexane, etc.

The conversion of hydroxylated compounds to their conjugate bases is known and has already been described. Reactions of such conjugated bases with HaIogenaikanen to form compounds with ether bridges are also known. In the above-described process for preparing alkylenedioxybis (alkylpropanedioic acid) compounds (e.g., DMBPDA), it is generally desirable to use a diiodoalkane or, more generally, a dibromoalkane. Both can be added to the alkyl tartronate diester as such or prepared in situ, for example by adding a mixture of sodium iodide or bromide and a suitable dichloroalkane, such as dichloromethane, 1,1-dichloroethane, 1,1-dichloro-n-propane, 2, 2-dichloropropane, 2,2-dichloro-n-butane, or the like. Used. A reaction temperature between -20 ⁰ C and + 100 ⁰ C is generally satisfactory and it can increased or atmospheric pressure are applied.

Each of the alkylenedioxybis (alkylpropanedioic acid) salts mentioned can be purified by treatment with a strong acid, for example HCl, H _? SO _U or a strongly acidic ion exchange resin to the

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corresponding acid (e.g. DMBPDA). Other metal salts of the acids obtained can be neutralized with the appropriate metal hydroxide, e.g., an alkali metal hydroxide such as potassium hydroxide. The corresponding ammonium, mono- or di- (C, - to C_-alkyl) -ammonium- or mono- or di-CC.- to C_-alkanol) Ammonium salts can be obtained by treating these acids with ammonia, or a suitable alkylamine or alkanolamine or hydroxide thereof, can be prepared by known methods.

In the oral preparations according to the invention, the amounts in which the propanedioic acid compounds are present as acids and / or their partially or fully substituted salts depend on the pH of the preparation. This pH is usually between about U and 11, although in some cases it can be higher or lower. At a pH of less than about 4, the risk of damage to the tooth enamel is greater, despite the relative safety of the said acid and its salts. If the pH is greater than about 11, it is difficult to produce products with satisfactory taste and mildness. A preferred pH range is between about 6 and 10. In many embodiments, the physiologically acceptable salts used are preferably water-soluble salts, such as, for example, sodium, potassium or ammonium salts, which are easily absorbed

809820/0994 ~ ^{/ 18}

dissolve in saliva.

As mentioned earlier, there are some embodiments of the invention Oral care items such as detergents, mouthwashes, prophylactic pastes and solutions for topical use. A cleaning agent, especially toothpaste, that contains an anti-tartar amount of an acid of the above formula and / or contains one of its physiologically acceptable salts, represents a preferred embodiment of the invention, likewise a mouthwash which contains such an acid and / or a salt. Many compositions of such products are known, but none of them contain a propanedioic acid compound. Typical toothpaste and mouthwash recipes, which are compatible with anti-tartar compounds of the present invention are disclosed, for example, in U.S. Patents 3,639,569, 3,544,678, 3,678,154, and 3,959,458, which are incorporated herein by reference.

When used normally, the preparations according to the invention are physiologically compatible, i.e. they can be incorporated into the Oral cavity can be introduced without a significant adverse effect on the tooth structure or other health damage entry. The anti-tartar amounts and concentrations can be used within these tolerance limits of the propanedioic acid compounds in the oral preparations according to the invention vary widely. Also are

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809820/0994

- rf -

these amounts and concentrations can easily be determined by those skilled in the art for the individual oral preparations. in the in general, concentrations of about 0.01 to 10% are preferred. Oral preparations, with normal use Accidentally or deliberately ingested, concentrations can be relatively low, but nonetheless highly effective contain. Of course, all such preparations taken should be physiological (i.e. im Digestive system). For example, a mouthwash according to the invention usually contains about 0.1 to 3% of the anti-tartar agents Link. Dentifrices, solutions for topical use and prophylactic pastes that are normally used administered by the dentist may desirably contain up to 10% and more of this compound, however, they usually contain about 0.1 to 5%, mostly about 1 to 2%.

While it is not intended to be specific or limiting of this invention Theories about their mode of action have been created, however, it appears that the propanedioic acid compounds inhibit tartar formation by converting calcium phosphate dissolved in saliva into crystalline ones Obstruct deposits like calcium hydroxyapatite. The preparations according to the invention therefore preferably contain not so many soluble polyvalent cations as the crystal growth inhibiting ability of these compounds could be weakened to the extent that your tartar

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inhibitory effect would be practically neutralized.

Examples I to V

A. Evaluation of calculus inhibition

The evaluation of the effectiveness of the invention for inhibition Preparations used for calculus formation were carried out essentially as described in "A Method and Apparatus for Studying In Vitro Calculus "by Yankelowitz, S. et al. Of Colgate-Palmolive Co., Journal of Dental Research Mj + (No. Ό, 6U8-53 (1965). According to In this now well-known process, artificial oral tartar deposits are formed on glass plates, by rotating these plates upright and vertically at 0.5 rpm so that each plate alternately through a Sample of undiluted human saliva containing 0.1% monocalcium phosphate was added, and then passed through an air blower that each plate at least partially dries before it runs through the saliva sample again. As stated in the referenced article, the tartar deposits obtained were both compositional as well as oral tartar deposits according to their X-ray diffraction pattern similar.

In the reviews listed here, stimulated saliva (50 ml / day) was used over a period of three days. collected from a donor, from his saliva previously

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it was found that there was a marked tendency towards tartar formation. The saliva collected was also of the type in which, under the present test conditions, the formation of tartar is significantly more inhibited by EHDP than by water used instead of the EiIDP in a comparative test. Each 50 ml portion of saliva was stored frozen until used. At this point the combined 150 ml sample was neutralized to pli 7 + _ 0.05 after the addition of 0.1% monocalcium phosphate, stirred thoroughly and divided into aliquots of 25 ml. 1 ml of a 0.1 mol / 1 solution of the tetrasodium salt of DHBPDA or the hexasodium salt of BCOBPDA was added to one aliquot, and 1 ml of a 0.1 mol / 1 solution of the known anti-tartar compound LHDP was added to a second aliquot after each these solutions had been previously neutralized with NaOH or H "SÜ _U. To a third aliquot was added 1 ml of distilled water.

For comparison purposes, the three aliquots were then placed in identical side-by-side trough-like containers in a warming cabinet equipped with a device for holding a separate set of three 22 χ 44 mm glass plates (those in relation to the rotating shaft on which they were mounted were attached at a distance of about 120) could be rotated through the individual saliva containers. In addition, an even horizontal air flow

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current directed against the plates and perpendicular to their axis of rotation. All the plates used were convenient identical and mounted on the shaft in such a way that the same longitudinal section (24 mm) of each plate passes through the corresponding Saliva sample ran.

The calculus formation test was carried out uninterruptedly for 20 hours in the heating cabinet described, the inside of the heating cabinet being kept at 37 ± 1 ° C. and a relative humidity of 76 to 78%. The spoke samples were then removed from the oven, but the plates rotated in the air stream for an additional hour before they were also removed from the oven. The weight of each plate and the deposit remaining thereon was then compared with the weight of the plate prior to use in the test, and visual evaluations of the deposits were made using photographs taken under the same conditions of each plate to determine confounding factors to exclude these evaluations. The results were recorded separately for each of the three plates in each set and then averaged. In the test with the hexasodium salt of BCOBPDA, the entire procedure was repeated using saliva from the same donor. Both for the sodium salt of BCOBPDA and for the tetrasodium salt of DMBPDA, the whole procedure was carried out with

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Another donor's saliva repeated. In any case

was made from the results of the various runs

Average averaged to obtain the results below.

1. DMBFDA

In the experiments with the tetrasodium salt the DMBPDA was found that the weight of the artificial tartar on the glass plates, the saliva containing this salt had been exposed, averaged 0.32 mg, on the glass plates in the comparative experiments with EIIDP 0.30 mg, and on the glass plates in the comparative experiments with water 0.67 mg. In the experiments with the DMBPDA-SaIz the artificial tartar formation was on average 52% less than in the comparative tests with water, while in the comparison tests with EHDP it was on average 55% lower than in the comparison tests with Water. The visual evaluations recorded the amounts of the opaque material deposited on the glass plates exposed to the saliva containing the DMBPDA salt averaged about estimated the same size as the deposits on the glass plates from the comparison tests with EHDP, and much less than half of the deposits on the glass plates from the comparative tests with water.

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a *

2. BCOBPDA

In the tests with the hexasodium salt of BCOBPDA it was found that the weight of the artificial tartar had an effect on the Glass plates exposed to saliva containing this salt averaged 0.26 mg the glass plates from the comparison experiments with EHDP 0.26 mg, and on the glass plates from the comparison experiments with water 0.78 mg. In the tests with the hexasodium salt of BCOBPDA, the artificial tartar formation was therefore average 67% less than in the comparison tests with water, while in the comparison tests with EHDP was also 67% lower than in the comparative tests with water. In the visual evaluation, the amounts were the opaque material deposited on the glass plates, the one containing the BCOBPDA sodium salt Saliva had been exposed, on average, estimated to be practically the same size as the debris on it the glass plates from the comparative tests with EHDP, and on much less than half of the deposits on the Glass plates from the comparison tests with water.

B. Manufacture of the oral preparations The preparations examined in Part A of these examples, the corresponding acids and other physiologically compatible salts of these acids are used to inhibit the formation of tartar useful when they are in suitable carriers

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809820/0994

a?

usual way. The following examples are dog water preparations that contain at least one such compound.

Examples Component I II III IV

Glycerin 10.0 10.0 10.0 10.0

Ethyl alcohol 16.5 16.5 16.5 16.5

Water 67.172 67.172 67.172 70.192

Tween 80 ¹ 0.12 0.12 0.12 0.12

Saccharin 0.045 0.045 0.045 0.02

Sodium cyclamate 0.75 0.75 0.75 0.04

Flavor 0.088 0.088 0.088 0.088

Salt of DMBPDA 2- _n 3 4 5 _fi or BCOBPDA ''''

pH ⁶ 7.0 7.0 8.5 10.0

Polyoxyethylene (20 mol ethylene oxide) sorbitol monooleate nonionic Atlas Powder Co.

2
Tetraammonium salt of DMBPDA or hexaammonium salt of BCOBPDA.

Tetra (triethanolammonium) salt of DMBPDA or hexa (triethanolammonium) salt by BCOBPDA.

4th
Tetrasodium salt of DMPDA or hexasodium salt of BCOBPDA.

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Tetrapotassium salt of DMPDA or hexapotassium salt of

BCOBPDA.

Set to the specified value with NaOiI or H "SO,

The following example is a toothpaste preparation that contains at least one such compound.

component

W ater Sorbitol Saccharin Calcium Pyrophosphate Glycerin Sodium Alkyl (Coconut) Sulphate Sodium Coconut Monoglyceride Sulphonate Sodium carboxymethyl cellulose Magnesium aluminum silicates Flavor DMBPDA or BCOBPDA

Example V

Parts by weight ₃ 1.58

6.25

0.12 39.00 18.00

0.40

0.75

1.15 0.40

0.85 1.00 5.90

manufactured according to US Pat. No. 3,112

"Adjusted to the specified pH value with sodium hydroxide solution.

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809820/0994

Other toothpaste preparations that contain at least one of the propanedioic acid compounds are handy with identical to the above toothpaste preparation, except that the corresponding potassium or ammonium salt of DMBPDA or bCOBPDA, or the sodium, potassium or ammonium salt of 2,2'-DiUthy1-2,2 '- (methylenedioxy) -bis- (propanedioic acid), 2,2'-Diisopropy1-2,2 '- (methylenedioxy) -bis- (propanedioic acid), or a 2,2'-bis (carboxymethoxy) -2,2 '- (C "- to C ^ -polymethylenedioxy) -bis- (propanedioic acid), e.g. 2,2'-bis- (carboxymethoxy) -2,2 '- (ethylenedioxy) -bis- (propanedioic acid) is used.

Other examples of oral preparations containing at least one such compound are mouthwash and toothpastes, Tooth powders, dental creams and prophylactic pastes made by a dentist or dental technician after removal of tartar can be used to polish teeth. Examples of such preparations, but none Containing anti-dental compounds according to the invention are disclosed in the aforementioned US Pat. Nos. 3,544,678, 3,639,569, 3,678,154 and 3,959,458. Toothpastes are usually aqueous preparations that contain a polishing agent, a surfactant, a binder, a humectant, contain a preservative, flavoring and sweetening agents, and optionally therapeutic agents. Mouthwashes usually contain water, ethanol, flavored »

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Sweeteners and colorants and optionally a surface active one Middle. Oral preparations which contain at least one of the compounds according to the invention include Foods and beverages such as soft drinks, candy, pastries, etc., animal feed, chewing gum, etc. Such In contrast to pure drinking water, beverages contain a flavor, nutrient or sweetener and, optionally, therapeutic ones Fabrics. Chewing gum contains raw materials, plasticizers, sugar or other suitable carbohydrates such as Glucose, sorbitol, etc. Sugar-free chewing gum can contain other sweeteners such as saccharin or sodium cyclamate. The components of these oral preparations, with the exception of the propanedioic acid compounds, as well as various mixtures Such constituents are examples of suitable carriers which are used according to the invention for the oral cavity can be.

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809820/0994

Claims (9)

Patent claims: (ij Oral preparation effectively inhibiting tartar formation, characterized in that it a) a propanedioic acid compound from the group of acids with the structural formula COOH COOH I I X-C-O-Y-O-C-Z COOH wherein Y is R ¹ or R ³ -C- ir —C- COOH R ⁵ -C R ' OC- R- • C 10 means, and X and Z are each independently of one another R ¹¹ -CR R ^1: 12th mean if Y - C - means ι » COOH - 0 - C - I A « if Y - C R ^v C- R ' R ' I OC- R " I • c- , 10 denotes, and in which R to R each independently of one another denote hydrogen or lower alkyl, m 0 or 1 - / 30 809820/0994 means η is the sum of m and 0, 1, 2 or 3, and the sum of 2 m and η is 0, 1, 2 or 3, and is more physiologically tolerable Salts of these acids, and b) contains a carrier suitable for use in the oral cavity, furthermore, this compound is present in the preparation in an amount and concentration sufficient for the formation to effectively inhibit tartar. 2. Preparation according to claim 1, characterized in that the carrier is a dental polish, a Contains flavor, gum base, or human or pet food. 3. Toothpaste preparation according to claim 2. 4. Mouthwash preparation according to claim 2. 5. Oral care preparation according to claim 2. 6. Chewing gum preparation according to claim 2. 7. Food preparation according to claim 2 for consumption by humans or animals. - / 31 809820/0994 8. Preparation according to claim 2, characterized in that the propanedioic acid 2,2'-bis- (carboxymethoxy) -2,2 '- (oxydiäthylendioxy) -bis- (propanedioic acid) is. 9. Preparation according to claim 2, characterized in that the propanedioic acid 2,? '- dimethyl-2,2' - (methylenedioxy) -bis- (propanedioic acid) is. 809820/0994