DE1668572A1 - New tin (II) compounds and their use in oral care products - Google Patents

Description

The present invention relates to new compounds for use in oral care for the prevention of tooth decay are suitable. In particular, the invention relates to new stannous salts of gem diphoephonic acids and stable oral ones Caries prophylaxis compositions containing the salts together with a water-soluble fluoride ion donor

The expression "oral care ^{product 11"} is understood to mean a product that does not get into the digestive system when used normally, but remains in the oral cavity for a long enough time until all tooth surfaces have come into contact with it Pastes and solutions for caries prophylaxis used by the dentist.

109836 / 1S90

It is known that certain metal ions have a significant influence on the caries-preventing effect of oral care products. For example, it is already known from the literature that when a tin (II) ion dispenser is used together with a fluoride, the caries-preventing effect is improved compared to fluoride alone (JC · Muhler et al., IADA 5 ± 665, 1955).

One difficulty in the production of stable, tin. (II) -containing oral care products, especially aqueous preparations, is the tendency of this metal to _{oxidize to a higher value, to hydrolyze Sn (OH) 2} ζμ and / or with other components of the Means to react to form very stable complexes or insoluble compounds. After one of these phenomena occurs, the tin no longer reacts with the tooth enamel. Z ± in »which is present in this non-reactive state is referred to in the following description as" not available ".

Various attempts have been made to keep tin in the form effective on tooth enamel. For example, the Ü.S. Patent 2,946 «275 the doctrine, a little soluble tin (II) salt such as tin (II) pyrophosphate as a "reservoir" for tin (II) ions along with a Use water soluble tin salt like SnFp. As Tin (II) ions from the soluble salt react with the tooth enamel or are no longer available due to hydrolysis or the like the little soluble tin salt dissolves slowly and replaces the tin (II) ions that have been used up. The pyrophosphate anion however, hydrolyzes to orthophosphate on aging, which leads to the reserve of tin (II) pyrophosphate gradually decreases.

Daa U.S. Patent No. 3,105,798 represents a further development represents, according to which effective on the tooth enamel Permanent divalent tin by complex formation with an aldonic acid to form a water-soluble tin (II) aldonate is obtained. Reached a similar conclusion

109836/15 90

1688572

one trilodfessigsäure ni when using tin complexes of Hydröxyä, _m-t Hydrxybenzoesäure 1,2,3? Topantri ~ carboxylic acid, itaconic acid or malic acid, piping complexes are soluble in water and so strong that the divalent tin of deactivating influences remains free, but , not strong enough to prevent reacting with your tooth enamel. The two above proposals thus represent compromise solutions between stability and reactivity, with the result that the tin supplied from the complexes mentioned is not as freely available as would be the case with a less stable complex.

Greniäß the present invention will now be little releasable g Liehe organic tin (II) salts that will slowly sjeh weak to form tin (II) to solve "complex, whereby reactive divalent tin is provided with greater success. The weak 'of tin (II) complexes are more reactive with respect to the tooth enamel as the complexes used to date, wherein the anions to hydrolysis are more stable than the pyrophosphate, so that a greater resistance to aging re ■ Itisrt "31 e advantages of both proposals according to the prior Tecfcai ^v ^ eripa thus achieved according to the invention at the same time, In addition to the advantages that the tin salts according to the invention provide with regard to the preservation of the divalent tin in a stable and reactive form, there is a further advantage that these compounds delay the formation of Hahnstein, since they disrupt the crystal growth of the calcium hydroxylapatite Oral care products containing them therefore have tooth decay and tartar preventive effect,

The present invention thus relates to new tin compounds for use in oral care products are suitable for the purpose of caries prevention, and the hydrolysis and conversion into ^ E ^ active compounds in this use wi 3tehen.

Another object of the invention are oral care

109836/15 90

BAD ORK3INM.

agent that is a persistent donor for divalent tin in a persistently reactive to tooth enamel Contain form and unfold a caries and cream stone formation preventive effect.

The salts according to the invention are tin (II / salts of gem-diphosphonic acids of the following formula:

PO ₃ H ₂

PO ₃ H ₂

in which R _{1 is} hydrogen, halogen, a hydroxyl benzyl or alkyl radical, a hydroxyalkyl, methoxyalkyl or carboxyalkyl radical with 1 to 12 carbon atoms, and E, hydrogen, halogen, a hydroxyl, acetyl, phenyl, Benzyl, or alkyl, hydroxyalkyl, methoxyalkyl, or Caiooxyalkylrest with 1 to 12 0 atoms.

The gem-diphosphonic acids, of which those according to the invention Tin (II) salts can be derived, for example are obtained by alkylating the central carbon axome of tetraalkylmethanediphosphonates with an alkyl halide according to the method of Kosolopoff, J. Amer. Chem. Soc. 75 1500, 1S53 * Preferred processes for the preparation of various gem-diphosphonic acids are in the following patents described?

U.S. * Patent No. 3,213,030,

BeIg. Patent No. 672 205,

BeIgο Patent No. 691 788,

BeIg. U.S. Patent No. 684,702, Example I.

The diz-inn (II) salt of methandipho sphonsäure was prepared as follows: 35.2 g methanediphosphonic acid 99, Seiger Purity prepared by the method of U.S. Patents 3,213,030 were in 1000 ml of oxygen-free distilled

109836/1590

lated water dissolved under nitrogen. Then 81.0 g of SnCl _{2 of} 93.6% purity (anhydrous) were dissolved in 750 ml of oxygen-free distilled water under nitrogen. The SnClp solution was added to the methanediphosphonic acid solution with vigorous stirring. After 3 minutes of stirring, the precipitate under nitrogen in a Buchner filter was filtered off It was washed three times with acetone, the acetone was abged ₄ damps _e was obtained 76 g of product having the following analysis:

Found: Calc .:

C. 3.2 2.93 H 1.0 0.49 ^P 24- 14.3 15.15 Sn 53.6 58.0

Example II

The ditin (II) salt of ethane-1-hydroxy-1,1-dipho8-phonic acid was prepared as follows: 51.6 g of ethane-1-hydroxy-1,1-diphosphonic acid (prepared in accordance with Belgian patent 684,702 ) ml of oxygen reiem distilled water were dissolved under nitrogen in 99.4 · 750 g SnCl ₂ (anhydrous, 99 # pure) "that was moistened with 20 ml 12n-HCl, were also dissolved under nitrogen in oxygen free distilled water.

The SnClp solution quickly became the diphosphonic acid solution and added with vigorous stirring. After stirring for 3 minutes after the addition was complete, the precipitated salt was under Sucked off nitrogen. The solid was washed three times with acetone. A yield of. 57.9 g, Ana

^lysei Gef .: Ber.j

C. 5.3 5.46 H' 1.2 0.91 P. 12.9 14.1 Sn 51.4 54.0

103 μ j 6/1590

Example III

The ditin (II) salt of ethane-1,1-diphosphonic acid was prepared from an aqueous solution of ethane-1,1-diphqsphonsäure (s _e Belg. Pat. 684 702) and an aqueous solution of SnCIp according to the procedure of Examples I and II, the molar ratio of divalent tin to gem-diphosphonic acid being 2: 1.

The following compounds are prepared according to the method of the preceding examples by reacting aqueous solutions of the appropriate acids with SnCl ₂ in the appropriate molar ratio: ditin (II) propane-2,2-diphosphonate ditin (II) methane hydroxydiphosphonate dichloromethylene diphosphonate ditin (II) bromomethylene diphosphonate din (II) dibromomethylene diphosphonate ditin (II) methanphenylhydroxydiphosphonate ditin (II) butane 1,1-diphosphonate ditin (II) nonane-5,5-diphosphonate 1,1-diphosphonate ditin (II) dodecane-2,2-diphosphonate ditin (lI) -tetradecane-3,3-diphosphonate ditin (II) -pentadecane-8,8-diphosphonate ditin (II) -ethane-2- hydroxy-1,1-diphosphonate ditin (II) -decane-1-hydroxy-1,1-diphosphonate ditin (II) -hexane-1-hydroxy-1,1-diphosphonate ditin (IIJ-methanobenzyldiphosphonate dizinnClIJ -ethane-i- methoxy-i, 1-diphosphonate, din (II) methoxymethylene dipho-sphonate

The oral care product according to the present invention contains a water-soluble fluoride and a tin (II) salt of a G-em-diphosphonic acid of the above type. 1,1-diphosphonate (hereinafter referred to as Sn ₂ MDP and Sn ₀ EHDP) are particularly preferred.

■■ M 0

iS a large number of fluorides are suitable for. ^'T - ~ r application in the inventive agents, particularly can be water-soluble fluorides used that emit at least 2,5ppI, I fluoride ions in aqueous solution.

The following fluorides, for example, are suitable for the purposes of the present inventions:

Inorganic fluorides

Tin (II) fluoride. Copper (II) fluoride

Sodium fluoride lead fluoride

Potassium fluoride Iron (III) fluoride

Lithium fluoride palladium fluoride

Cesium fluoride, nickel fluoride

Ammonium fluoride silver fluoride

Aluminum fluoride zirconium fluoride

Organic fluorides (I) Water-soluble amine hydrofluorides such as, for example _,

Hexylamine hydrofluoride

Laurylamine hydrofluoride

Myristylamine hydrofluoride

Decanolamine hydrofluoride

Octadecenylamine hydrofluoride

Myris toxyamin-hydx'of luoride

Diethylaminoethyloctoylamide hydrofluoride

DiethanolaMinoethyl oleylamide hydrofluoride

Diethanolamine propyl-N'-octadecenylamine-

dihydrofluoride

1-ethanol-2-hexadecylimidazoline dihydrofluoride

Octoylethanolamine hydrofluoride

Compounds of this group which contain at least one hydrocarbon "remainder, e.g. an alkyl, alkylol, alkenyl

109836/1590

or have an alkylene radical with 8 to 20 carbon atoms special due to their surface-active properties preferred. These and other usable amine hydrofluorides and a process for their preparation are described in the U «So patent Fr. 5.083.H3 described.

■ (II) Compounds of the formula (HOC _x H _2x ) _n N ⁺ (CLH _2. ,) ⁺ ₄ " _n P" * in which χ and y are integers from 1 to 4 and η is an integer from 1 to 3 These compounds include, for example, dimethyl diethanolammonium fluoride, trimethylethanolammonium fluoride and methyltriethanolammonium fluoride. Further examples and processes for the preparation of these compounds are described in US Pat. No. 3,235,459.; III) Water-soluble addition compounds of amino acids and hydrofluoric acid or fluorides, e.g.

Betaine hydrofluoride sarcosine tin (II) fluoride Alanine tin (II) fluoride glycine potassium fluoride Sarcosine potassium fluoride G-lycin hydrofluoride Lysine hydrofluoride Alanine hydrofluoride betaine zirconium fluoride

Further compounds from this class that can be used and a method of preparation are described in Canadian patent IJr. 594,553.

The amount of fluoride salt in the agents must be sufficient to at least about 25 parts per 1 million parts Fluoridio- nen of the total mixture to deliver. Excessive amounts of fluoride ions do not improve the intended properties of the agent, but can make it toxic. The agents according to the invention therefore contain no more than 4000 ppM fluoride ions, in the case of toothpastes preferably no more than 3000 ppM.

109836/1590

The dizinn (II) gem diphosphonates can be from about 0.05 "to 5" 0 weight-fo of the agents according to the invention. Less than $ 0.05 will not be a sufficient amount of reactive tin guaranteed during the normal storage time of the product. Made with over $ 5.0 get an astringent taste. Preferably amounts from about 0.1 to about 1.0 weight £ $ are used.

The preferred additional tin donor is SnPp used in amounts necessary to provide at least 3000 ppM tin and a maximum of 4000 ppM fluoride. In the agents according to the invention, however, the entire divalent tin from the tin (II) gem diphosphonate come. In any case, the total tin content can be around 15 to about 10,000 ppM with the preferred range is between about 50 and about 8000 ppM

It is obvious to the person skilled in the art that oral care products according to the invention can also be produced by a gem-diphosphonic acid of the one described above Art is added to a water-soluble tin (II) salt such as SnFp or SnCIp, with the corresponding diphosphonate in situ arises.

The pH of the agents according to the invention is between about 2.5 and 7, preferably between about 4.0 and 6.3. Above pH 7, the loss of tin (II) ions available to react with tooth enamel can become too rapid. Certain flavorings, especially esters, also decompose too quickly. A pH value that is too low, i.e. below about 2.5, causes an unpleasant, astringent taste. At low pH values, the hydrolysis of certain foaming agents is also accelerated, causing a taste of fatty acids to appear and foaming to decrease during use. At pH values below 2.5, the metal tubes in which the agent is appropriately stored also corrode, and there is a tendency for other components to hydrolyze, for example condensed phosphates, which are used as cleaning bodies

109836/1590 ".

can serve. Such hydrolysis reactions can also Reduce the availability of tin (II) ions by supplying anions which are very stable complexes with the tin ions or form insoluble compounds.

In addition to the above-mentioned essential constituents, the agents according to the invention can contain the usual constituents of toothpastes, mouthwashes and the like. For example, toothpastes always contain a cleaning agent, foaming agent, binding agent, humectant, aroma and Sweeteners.

The cleaning bodies should preferably be relatively insoluble and relatively stable in the above-mentioned pH ranges « They aren't supposed to be too hard so they don't scratch the tooth surface or excessively remove dentin, however have enough grinding effect to clean the teeth. Any cleaning body can be used for the purposes according to the invention use that meets these requirements and is compatible with tin (II) and fluoride ions »

Preferred cleaning bodies for use in toothpastes according to the invention include insoluble condensed phosphates and the waterproof crosslinked thermosetting resins. Examples of condensed phosphates are Calcium pyrophosphate, insoluble, highly polymerized calcium polyphosphate (also called calcium polymetaphosphate) and insoluble highly polymerized sodium polyphosphate (also called insoluble sodium metaphosphate). examples for Usable resins are particulate condensation products of formaldehyde and / or urea and other resins according to U.S. Patent No. 3,070,510. Also mixtures of plaster bodies can be used.

The total amount of cleaning bodies in toothpastes according to the invention is 0.5 to 95 weight based on the paste. Toothpastes preferably contain from 20 to 60 weight i * _f dentifrice powder 60 to 95 wt ^ plaster body.

Toothpastes usually contain foaming agents, but for the purposes of the provisional invention are not

I 0 8 l- ■ < 6/1 5 8 0

absolutely necessary. Any foaming agent that is sufficiently stable in the specified pH range and Generate foam can be used. Examples of suitable foaming agents are the water-soluble alkyl sulfates with alkyl groups of about 8 to 18 carbon atoms, such as sodium coconut monoglyeeride sulfonate, salts of fatty acid amides of taurines such as sodium-N-methyl-N-palmitoyl-tauride, 3 salts of fatty acid esters of isethionic acid and essentially saturated aliphatic acylamides of saturated aliphatic monoaminocarboxylic acids with 2 to 6 carbon atoms, in where the acyl radical has 12 to 16 carbon atoms, such as sodium N-lauroyl sarcoside, Mixtures of 2 or more foaming agents can also be used »

The foaming agents can be used in the agents according to the invention be used in an amount of 0.5 to 5.0% by weight, based on the total mixture.

Thickening agents must be added in the manufacture of toothpastes. Preferred thickeners are water-soluble salts of cellulose ethers such as sodium carboxymethyl cellulose and sodium carboxymethyl-hydroxyethyl cellulose. Natural gums such as gum karaya. Gum arabic and tragacanth can also be used and can occasionally lead to a deterioration in smell or taste. To improve the structure, such thickeners can also contain colloidal magnesium aluminum silicate or finely divided silicic acid are added. in order to produce satisfactory toothpastes thickening agents may in amounts of _t 5 to 5 0 wt _r ^, based on the total weight of the paste are added.

Suitable detergents include glycerine, Sorbitol and other polyhydric alcohols. The humectants can make up to 35 Gewients- # of the paste

Oral care products also contain small amounts of Aromatic substances, e.g. wintergreen oil, peppermint oil, mint oil, Sassafras oil and anisole. Furthermore, they are usually small Amounts of soda such as saccharin, dextrose, or levulose

109 836/1590

BAD ORIOlNAt

Sodium cyclamate added.

Several toothpastes of the invention were made using conventional mixing techniques and tested for stability and reactivity with tooth enamel tested.

The shelf life of toothpastes in terms of

2+ the provision of reactive tin was determined using an accelerated aging test, which is as follows was carried out:

A test sample is maintained at 50 ° C and in particular Zeitabsxänden the concentration of leslichem bivalent tin is determined as follows: Mix 1 part distilled toothpaste for 10 minutes with 3 parts; / ater _e The Peststoffe are then "away by a long 30 minutes centrifuged at 12,000 rpm. The tin (II) concentration in the supernatant solution is then determined iodometrically * The second part of the test sample is adjusted to pH 6.2 and maintained at this point, mixed with water (1 part paste, 3 parts water) for 1 hour and how centrifuged at the top, whereupon a second tin analysis is carried out. Since the increase in the pH value to the specified value leads to the dissolution of the undissolved portion of the Z ± nn (II) salt, the 2nd value gives a measure of the "reservoir" effect of the salts. The results are shown in Tab. 2 divalent tin soluble in ppM *

The caries-preventing effect of the oral care products according to the invention was ^{investigated in the W} ESS test ⁿ (reduction in the solubility of tooth enamel). In this test, the reduction in the solubility of the cream melt is chemically determined by treatment with a solution or toothpaste.

The test is done on healthy human teeth, usually molars or canines. The teeth will cleaned and polished and the roots are then cut about 6.4 mm below the lowest enamel point. Parts of the teeth that appear damaged are covered with blue sealing wax. The teeth are in 180ml beakers (tall form), the bottom of which is covered with blue

109 836/1590

casting wax is covered. The teeth are then cemented in attached so that only intact areas of the tooth enamel are exposed to later treatment «

The experiments were carried out with 4 beakers with 6 teeth carried out. The teeth were prepared by adding about 100 ml of 0, in-lactate buffer solution, pH 4.5, to the G-las given and the contents at a constant rate (1725 Uep.ItU) «was stirred twice for 1 hour each time, with the buffer solution was renewed for each period.

During the test, the teeth are placed in a water bath kept constant at 37 ° C up to about half of their length immersed. The teeth are held at this height with brackets. The stirrer is lowered so that it is about 12.5 mm above the teeth in the beaker and held in this position during the test. 40 ml lactate buffer are added and the stirrer is started. After 15 minutes the lactate buffer is removed and retained for analysis, and the teeth are washed three times with distilled water and returned to the water bath spent.

15 g of the toothpaste to be tested is mixed with about 45 ml of water and about 15 ml of this mixture is centrifuged. 40 ml of the supernatant liquid after centrifugation is poured to the teeth and the stirrer is started again. After 5 minutes the treatment solution is removed. The teeth are washed with distilled water and kept in 40 ml lactate buffer for 15 minutes, stirring at 1725 TJ.pM. The for pre- as well as for post-lactate used are analyzed for phosphorus by the method of Martin and Doty. The percentage decrease in the solubility of the tooth enamel is calculated from the difference between the amount of phosphorus in the pre- and post-treatment solution, divided by the amount in the pre-treatment solution.

Formulations for various tooth according to the invention

1 09836/1590

Pastes are given in Table 1, while Table 2 shows the aging and LiSR values. The numbers in Tab. 1 are percentages. The numerical values (apart from ESR and pH values) give ppM soluble divalent tin at.

109836/1590

/ he sch. 3Pär b-. Aromas tcff β

λ λ

• 3- in in <n in in in - ■; : n τΐ- ^ - Tt * Tt * ^ - - ^ *

HHHHHHHH

8th L. cn cn Γ- C- cn a \ cn Tf ": O ί- τ} - cn cn ro cn cn cn HSC ⁰ ΙI ro • ο ro ro ro Ti ro ro ro ro , - \ H H H

O O

O O O O O

O O O O C

ro ro oo

α o

Φ «» ι «*

- »» - -4

cm cm Oj ιτν in

O O C O O

γ-Τ H H'Η * H *

tr «
O Oj
O Oi
O CvI
O CV
O O CV
O H H H H H H H H
CO , 78 , 78 OO co
tv co CO

MgSO

r-. cn cn c- C- c-

^ cTcT

SAS

oo co co H H

C "- C ~ - t - CO CO

cT ο ο ο ο

ο ο ο

O

a * co <o

Ό ro f * o

in in in ro

pr »m ro ^ - in

vD ^! sO ^; i5 VO vo ro ro ΓΟ ro! -O

C * CM CM ro ro OJ CVI OJ CM OJ ro OJ OJ CN! CSi CM CM ΆΙ

α α) 3-p ca 4 =: 3-H cn S

cTooocodo cTcTcTo cTo c

Cape

OJ

c—

04

U ο pi

cn cn σ ^ν . cn cn cn cn

SnP, rrj

cn cn

cn cn

»5 ft Λ

O O O O O

Sn ₂ MDP

ο cn <· cn in co «si-

C \ "! J · CvI ** ■« ^ Ci

O O O O O O

C-O

Sn ₂ EHDP

co «a

»Te

■ "* · CO

CSi · «* ·

O

Pi U : o

UP "

in in in η ei

• k «k ^ ΨΊ * fe

Λ 'OJ CVI CJ ^

O »CM CM C \ i Oi

O O OO O

• it «». «^

ro ro C \ i ro

CM (M (M CVJ

MUP '

t— t— c— cn cn

· «4k Ct Λ 0 *

<e · · «* Ti- ■« * · 'S »· HHHHH ο ο ca ο

IT ₁ m in in HHHH

GO CO CO

«T · * Λ

c- t- r ~

ro ro ro

CQ CO CO CO GO VO

οΗ

HHHH

ro ro ro ro ro

CO CO CO CO CO CO

C— t— C— C— t— C—

r * - \ m ro ro ro ro

C- C- C- C- C- C-

cn cn cn cn cn cn

co co co

VD VO VO ¹ ^ t ro ro OOOO

S orb c

H ₂ O

mcTiCnHHcncncno ocy ocncncncncnai

HHHOiCMHHHOJOJOJ (MHHHHHH

incn

H H H H i>

109836/1590

1o sorbitol - J> Ofo aq. solution

2, Precipitated melamine-urea-formaldehyde condensation product

3. Precipitated urea-formaldehyde condensation product 4ο sodium lauryl sulfate

5. Sodium coconut monoglyceride sulfonate

6. Sodium carbonyl ethyl cellulose

7. Magnesium aluminum silicate 8ο hydroxyethyl cellulose

9. The comparison preparation is a commercially available tin (II) fluoride Containing toothpaste which, in addition to the specified components, contained 0.97 wt. ^ Tin (II) pyrophosphate.

109836/1590

Dew. 2

Dwell time at 50 G.

Example fresh 2 days 7 days 11 days 21 days 28 days

IV at: 922 (4.4) 8o2 (4.1) 62o (4.1) - 767 (4.2) 582 (4.4) 2? Days 7o.5 pH 6.2 1655 172o 1617 ~ 1744 177o

V at: 91o (4.2) 737 717 (4.3). - 752 (4.3) 671 (4.3) 28 days 64.6 pH 6.2 957 Io84 9_8_2 - Ic96 Io31

VI at: 826 (4.3) 723 (4.5) 582 (4, o) 652 (4.5) - 64I (4.2) pH 6.2 537 532 54o 642 - 666

VII / at: 956 (3.6) - 577 528 - 457 (3.8) pH 6.2 653 - ___: ί__ _ ⁶ J _- ⁸ .

-VIII at: 911 (3.7) - 469 (3.7) 523 (3.7) 4 35 (3.8)

ο pH 6.2 393 - 373 443 - 398 co

co IX at: 793 (4.2) - 448 (4.9) 478 (5.0) - 474 (5.1) - -

ι ω pH 6.2 926 -. 567 575 ₌ 523 -

c- ΪΧ at » 529 (4.3) 28o (4.6) 257 (5.1) 257 (5.1) - 21o (5.2) fresh 69.0 '

PH 6.2 564 365 281 2j55 ₌ 225 30 days 52.3

'£ xi at: 631 (4.3) - 442 (4.6) 422 (4.8) - 4o6 (4.7) -

ο pH 6.2 73o - 424 434 - 4oo

XII at:
pH 6, 2 688 (4.4)
313 628
395 (4, 3) 54o
47o (4.4) 5o2
443 (4, 3) 148
158 466
417 (4, 3) friech
Thirty days 65.5
73.9 XIII at:
pH 6, 2 212 (4.8)
225 212
2o5 (4, 8th) itn
173 (4, 8th) 153
162 (4, 8th) 3o ~ 47.3
54.9 i sch
location

XIV at i " _7o2 (4.5) 711 (4.3) 593 (4.2) 526 (4.3) 448 (4.1) fresh 69.8.

pH 6.2 3_gg! 55 797 276 281 - 30 days 74.1

_- _—. _ __ _____ ___ ^ - ^ - ζτ ~ - τ ^ (4,8) frlsah 30 ^ 5

pH 6.2 9 * 47 40 43 _ ^ 3 - ^ 3Q £ age_ ^ o, 2 cn

XVI at: 513 (4.8) 363 (4.8) 295 (5.2) 274 (5.3) 248 (5.6) - fresh 60.6 Y ³ ? pH 6.2 49o 375_ 291 264- j? 27 3o days 4_1.4 ^

¹⁷¹¹ ^ ¹ I. 755 (4.6) - 519 (4.9) 487 (5.1) - 4o6 (5.3) 64.8 ^ fresh pH o, 2 öo7 - 54o 532 - 5o5 3o days 4o, 2

When aging at 50 G, this results in ^: / the same principle as shown in Table 1, the following values;

fresh. 2 days 3 days 4 days 7 days fa JS

483. (4.7) 232 96 100 4b fresh 66.8 867 297 132 81 35 30 days 35.0

It can be seen that the -; n (II) content of the comparative preparation has fallen by more than £ 50 after just 2 days. After 7 days at 50 ° ö was the Jn (Π) -Sehalt below 1/10 of the initial values a "from the notches for the Yergleichspräparat is further seen ilerts a corresponding decrease in the Sli ^ ^"

Provide the toothpastes according to the preceding examples in contrast, even after aging for longer periods of time (28 days) under the extraordinary conditions relatively constant ün (II) - 'ffert, xiie given for the examples BtjR-values remain at the initial values after aging relatively similar, the toothpastes of examples IV and 7 also caused a noticeable reduction in tartar formation in comparison with the previous reference preparation.

Further i / Iun according to the invention: ipflegemit -.el were like is formulated as follows:

Example XXl

A mouthwash was made by mixing the following components obtain;

component

Ethyl alcohol (50p Äethol, .50> ί TTasser)

Glycerin methyltriethanol amiaonium fluoride

Dizinn (II) ji than-1-hydroxy-1,1-diphO3phonate

Aroma

Saccharin pH adjusted to 6.5 »

10 9 8 3 6/1590

33 _? 00 12th , 00 2 , 68 1 »15 0 , 35 0 , 12

Before use, this mouthwash is diluted by adding 20 ml of water to 2 ml of the above mixture.

The mouthwash holds a high concentration with the

2+
Tooth enamel is reactive Sn over long periods of time

and sets the solubility of the enamel, too Aging, coming down. When used 1 to 2 times a day, Jas i, iundwasser is an effective means of preventing caries dar «,

The ditin (II) ethane-1-hydroxy-1,1-diphosphonate can also by another salt such as ditin (II) propane-2,2-diphosphonate, Mtin (II) methane hydroxydiphosphonate, ditin (II) dichlorinethylenediphosphonate, Ditin (II) bromomethylene diphosphonate or jizinn (II) -niethanphenylhydroxydiphosphoiiat can be replaced in corresponding lengths with income.

Example XXlI

Another mouthwash was formulated as follows:

component Gew.9b Ethanol 35.00 Glycerin 10.00 Laurylamine hydrofluoride C, 72 Sn Cl ₂ 0.016 Ditin (lI) methanediphosphonate 0.15 Aroma 0.16 Saccharin 0.12 water rest pH adjusted to 6.0.

Bas I'.undwasser maintains an effective Sn (II) concentration over several months. When used in undiluted form, the gown lowers the solubility of the tooth enamel and the susceptibility to tooth decay is considerable.

Instead of the luethandiphosphonate you can use the same

109 8 36/1590

Success Dizinn (II) nonane-5,5-diphosphonate, Dizinn (II) -decane-1,1-diphosphonate, Ditin (II) dodecane-2,2-diphosphonate, ditin (lI) -tetradecane-3,3-diphosphonate and ditin (II) butane-1,1-diphosphonate can be used.

Example XXIII

A chewing gum was made from the following ingredients:

Component weight;

x) gum-base sugar

Corn syrup (Baume 45) flavor

NaF.

Ditin (lI) pentadene-8,8-diphosphonate

pH adjusted to 4.5.

x)

Ester rubber

Oumarone resin latex (dry) paraffin wax (F. 82 ° C)

This is an effective means of preventing tooth decay. When chewing will reduce solubility

2+ dee tooth enamel sufficient amounts of tin and fluoride

ions dissolved in saliva.

The chewing gum retains high concentrations of active Sn (II) even after long periods of storage.

The diphosphonate used in the above example can be replaced by ditin (II) -ethane-2-hydroxy-1,1-diphosphonate, ditin (II) < decane-1-hydroxy-1,1-diphosphonate, din (II) -methanbenzyldiphosphonat, Ditin (II) ethane-1-methoxy-1,1-diphosphonate or ditin methoxymethylene can be successfully replaced.

The gem diphosphonates used in the above examples can also be replaced by ditin (II) ethane-1-acetyl-1,1-diphoephonate or propane-1,3-diphenyl-2,2-diphosphonate

109836/1590

- Dnat 21.50 Parts 59.50 Parts 18.20 Parts 0.25 ph < 0.55 30th 45 15th

with good results as well will.

1 0 9 ö G / 1 B 9 0

Claims (1)

- 22 claims in which R / hydrogen, halogen, a hydroxyl, benzyl, or an alkyl, hydroxyalkyl, methoxyalkyl or carboxyalkyl radical with 1 to 12 O atoms, and R _{2 is} hydrogen, halogen, a hydroxyl, acetyl, Denotes phenyl, benzyl or an alkyl, hydroxyalkyl, methoxyalkyl or carboxy alky 1 radical with 1 to 12 carbon atoms,
2 · Ditin (II) methanediphosphonate
3 ο ditin (II) ethane-1-hydroxy-1,1-diphosphonate
4. Oral care products, especially for caries prophylaxis, characterized in that it (1) a water-soluble fluoride in an amount sufficient to provide about 25 to about 4000 ppivl of fluoride ion and (2) about 0.05 to about 5.0 wt Ditin (II) salt of a G-em-diphosphonic acid of the formula R ₁ JO ₃ H ₂ Contains, in the R. contains hydrogen, halogen, a hydroxyl, benzyl, or an alicyl, hydroxyalkyl, I * ain.oxyalK: ylodosr narboxyalkyl radical with 1 to 2 carbon atoms, and R ^ V / hydrogen, halogen , a hydroxyl, acetyl, Pneuyi-, Benayl- or elö »n alkyl, hydroxyalkyl, teethoxyalkyl or Carböxyalkylreet with 1 Ms 12 C-atoms mean, wcbäi da & 10 9836/1590 BATH ORIGINAL Means a pH from 2.5 to 7.0 has ₀ 5. «lundpflegemittel according to claim 4», characterized in that it contains SnF ₂ as a fluoride. 6. itiundpflegemittel according to claim 4, characterized in that that it is as I) tin (II) salt ditin (II) methanediphosphonate contain 7. Oral care product according to claim 4, characterized in that it is ditin (II) ethane-1-hydroxy-1,1-diphosphonate as the din (II) salt contains. For Procter & Gamble Company Cincinnati, Ohio, V.St.A. Lawyer 109836/1590