US3655867A - Dental preparations - Google Patents

Abstract

DENTAL PREPARATION CONTAINING A FLUORIDE AND A POLISHING ABRASIVE AGENT, A MIXTURE OF MAGNESIUM AMMONIUM PHOSPHATE AND CALCIUM HYDROGEN PHOSPHATE.

Description

United States Patent 3,655,867 DENTAL PREPARATIONS Ludwig Schoernig, Frankfurt am Main, Germany, assignor to Farbwerke Hoechst Aktiengesellschatt vormals Meister Lucius & Bruning, Frankfurt am Main, Germany No Drawing. Continuation-impart of application Ser. No. 601,312, Dec. 13, 1966. This application May 1, 1970,

Ser. No. 33,916

Int. Cl. A6lk 7/16 US. Cl. 424--52 1 Claim ABSTRACT OF THE DISCLOSURE Dental preparation containing a fluoride and a polishing abrasive agent, a mixture of magnesium ammonium phosphate and calcium hydrogen phosphate.

This patent application is a continuation-in-part application of patent application Ser. No. 601,312 filed Dec. 13, 1966, now abandoned.

The present invention relates to dental preparations which contain fluorides and, as abrasive and polishing agents, magnesium ammonium phosphate and calcium hydrogen phosphate.

The term dental preparation as used herein is intended to encompass in a general sense tooth pastes, tooth powders and tooth soaps.

Tooth pastes generally consist of an abrasive and polishing agent, an aqueous solution of humectants and binders, tensides, coloring and flavoring substances, and other additives which may have antiseptic, deodorizing, bleaching, astringent and anticarious action.

Tooth powders generally consist of the same basic substances as tooth pastes but they do not contain the aqueous solution of humectants and binders.

Tooth soaps generally contain a polishing agent, tensides, soaps, flavoring and coloring substances and only a small amount of humectants.

As abrasive and polishing agents, there are generally used sparingly soluble substances such, for example, as those described in Ullmann, Enzykl. techn. Chemie, (Urban and Schwarzenberg, Munchen-Berlin), 3rd Edition (1958, volume 10, pages 714-716 and 718).

For the usability of a dental preparation intended for permanent use, the abrasiveness of the abrasive and polishing agent contained in the preparation is of decisive importance. It depends on the size and the hardness of the particles of the abrasive and polishing agent.

Powders having coarse particles feel sore and sandy in teeth cleaning. They also affect the gum, because coarse and in addition, sparingly soluble powder residues may remain behind dental preparations with odontolithe removing action. For teeth which are free from dental calculus, these preparations are less suitable.

As regards the calcium phosphates, calcium pyrophosphate and calcium hydrogen phosphate are also used as abrasive and polishing agents. Calcium pyrophosphate has a hard grain and is strongly abrasive. It is very difficultly soluble, which fact leads to disagreeable secondary reactions if this compound is not completely removed from the dental area. In contradistinction to the pyrophosphate, the calcium hydrogen phosphate has a very soft grain. -It is only very weakly abrasive even if it is not ground to a microfine crystaline powder and has still a good and effective cleaning power.

Magnesium salts too are used as abrasive agents in dental preparations: magnesium carbonate is quite abrasive, and magnesium ammonium phosphate is, even in unground state, a very mild polishing agent with a good cleaning effect.

Patented Apr. 11, 1972 ice Regarding the harmlessness of a teeth cleaning preparation, it is of importance to know the dependence of the abrasive action on the surface of the teeth on the hardness and the size of the grains of the polishing agent. Numerous methods and devices for measuring the abrasion are known, which permit to determine and to compare extent of the polishing action. A simple and suitable test method consists in introducing an aqueous suspension of the polishing agent or of the corresponding dental preparation into a metal cup, for example, a copper cup, and to allow a round brush to rotate and to slide along the wall. The amount of metal abraded from the wall of the cup is then a measure of the abrasion. This apparatus permits the gradual determination of the abrasiveness of abrasive agents and, simultaneously, the determination of the influence of the grain size. Just as regards the grain size, there have been found quite considerable differences in abrasiveness, for example those described above for calcium carbonate.

An important requirement which abrasive and polishing agents in dental preparations must meet is their compatibility with the other components and the active substances of the dental preparations, for example, their compatibility with fluorides which are of increasing interest and importance as additives having anticarious action.

The human organism is able to excrete the fluorine it has taken up, in a daily quantity of about 2.5 mg. This dose is, therefore, considered the harmless and tolerated dose and it is generally contained in about 1 g. of a fluorine-containing tooth paste. On the average, about 1.5 g. of tooth paste are used for tooth cleaning. This amount thus contains about 34 mg. of fluorine. Only a negligible part thereof is taken up by the stomach. Hence the extensive prevention of dental caries is to be attributed above all to a local action in the mouth. If about 20-30 ml. of water are used during tooth cleaning, which is in general the case, a fluorine concentration during tooth cleaning of about meg. (p.p.m.) per ml. of mouth liquid can be expected. In order to be able to react with the surface of the tooth within the short period during which the teeth are cleaned, the fluorine must be in the dissolved state. It must not be bound by the abrasive or polishing agent or if bound then it should be bound to a very small extent only.

However, some, especially microfine polishing agents, bind fluorine ions easily and rapidly. For example, calcium carbonate forms with alkali metal fluoride a sparingly soluble calcium fluoride. In addition thereto, the said fluoride is adsorbed by calcium carbonate. The degree of adsorption depends on the pH-value of the suspension. If alkali metal carbonates are added, a greater quantity of fluorine ions remain behind in the aqueous solution, according to the self-establishing balance. Tooth pastes of this type, however, have a strong alkaline action, which affects the mucuous membrane of the mouth on prolonged application. Magnesium carbonate also adsorbs alkali metal fluoride. When sodium polyphosphate is used as abrasive agent in dental preparations, no linkage with the fluorine takes place. However, the polyphosphate is in most cases used in combination with calcium pyrophosphate. The latter is compatible with fluorine ions, because it is extremely sparingly soluble. But sodium polyphosphate as well as calcium pyrophosphate are not satisfactory in dental preparations for permanent use, because of their above described abrasive action.

For the anticarious action of a dental preparation, it is important that the dental preparation contains calcium and phosphate together. The presence of calcium is of considerable importance also with regard to the adaptation of the preparation to the calcium ion content of the saliva. With a view to obtaining a thorough cleaning effect and a very mild abrasive action and, at the same time, a good anticarious elfect, it seemed interesting to combine in a dental preparation calcium hydrogen phosphate which also has a good anticarious action when 4 neither turn acidic nor solidify upon storage, so that they are unusable, and when used do not show a reduction of the concentration of dissolved fluorine in the mouth liquid to a therapeutically ineifective value.

MgNH4PO4.6H2O, Molar ratio, Weight ratio Fluorine Stability of the paste 03111 0421120, mols m Ca/Mg of CazMg salt ions, mols pH change at room temperature 0.219 l. 334 0. 164 :90 1 After 1 year O.3 units Paste after 1 year unchanged. (Constant viscosity within the limit of error.) 12. 8 0.423 22. 2:77. 8 1 .do Do. 10. 5 0.495 25:75 1 do Do. 8. 11 1. 42 49:51 -do Do.

3. 9 4. 52 75.4:24. 6 1 do Do. 0. 307 70. 4 98:2 1 do Do. 0.078 285 99. 510.5 1 do Do. 100:0 1 pH 7.41 ediately after Paste solid already alter the manufacture. pH 4.3 4 Weeks. after one year.

applied orally, with a fluoride, for example, an alkali This behaviour which 15 evident from the table was not metal fluoride or an alkaline earth metal fluoride. In corresponding tests, the following results were obtained.

Tooth pastes which, for example, contained about 40% of calcium hydrogen phosphate and 0.2% of fluorine (as sodium fluoride) showed at the beginning a neutral reaction (pH 7.2-7.4), but became then acidic (pH 4.2-4.4). Upon storage, they hardened and could not be pressed out from the tubes and were thus unusable. From the calcium hydrogen phosphate and the fluoride, for example, an alkali metal fluoride, there formed fluorine-apatite, sodium dihydrogen phosphate and free phospheric acid.

When, for example, 0.5 mol of calcium hydrogen phosphate and 0.1 mol of sodium fluoride were suspended in 0.3 l. of water, the soluble fluorine rapidly disappeared from the liquid. At 37 C., 55.4% of the fluorine used were found after 3 minutes, 71% after 5 minutes and 95.4% were found after 10 minutes in the deposit.

In this reaction, the pH- value of the suspension fell from 7.4 to 2.2. An attempt to increase the portion of soluble fluorine by alkalinization with sodium carbonate or sodium hydroxide, as described above for calcium carbonate and sodium fluoride, had the contrary result: when a suspension containing calcium hydrogen phosphate and sodium fluoride in the usual ratio for tooth pastes (40% of abrasive and polishing agent and 0.2% of fluorine) and in the concentration expected during tooth cleaning, was adjusted to a pH-value of 7-7.2 by dropwise addition of dilute sodium hydroxide solution, the fluorine was bound at 38 C. within a short time by the polishing and abrasive body. Only 0.8 p.p.m. of dissolved fluorine were found in the filtrate. When the pH-value was adjusted to 8-8.5, only 0.2 p.p.m. of soluble fluorine could be detected in the filtrate. Hence, the quantity of fluorine given off by the apatite decreases considerably with increasing pH- value.

Not only the addition of alkali, but also calcium hydro gen phosphate reduces the concentration of dissolved fluorine in an apatite suspension. For example, in a fluorine apatite suspension containing only 10% of calcium hydrogen phosphate, calculated on the apatite, 0.6 ppm. were found at 23 C., and at 40 C. only 0.9 p.p.m. of dissolved fluorine were found in the filtrate. Thus, the calcium hydrogen phosphate largely binds the small amount of fluorine given oif by the fluorine apatite. Dental preparations, however, whose content of soluble fluorine is below that of a fluorine apatite suspension, will not have a therapeutic action.

Now, we have found that, surprisingly, it is possible to add calcium hydrogen phosphate to dental preparations, preferably tooth pastes, which contain a soluble fluoride in a therapeutically effective dosage, in the presence of magnesium ammonium phosphate as the abrasive and polishing body; the dental preparations thus prepared to be expected, since it was rather to be expected that in the paste which owing to the magnesium ammonium phosphate showed a weakly alkaline or neutral reaction or in its aqueous suspension formed during tooth cleaning, the fluoride would be bound by the calcium hydrogen phosphate to form a sparingly soluble fluorine apatite and that the concentration of soluble fluorine would be below the therapeutically effective level, which would have been expected especially with an excess addition of calcium hydrogen phosphate.

Salulzky (U.S. Pat. 3,155,454) discloses that magnesium ammonium phosphate may react with calcium ions to form insoluble calcium ammonium phosphate and magnesium ions. That this reaction cannot explain the present invention can be seen from the fact, that the tooth pastes containing fluoride ions with a ratio of calcium: magnesium of more than 1 do neither become solid nor acid (cf. the above table). It is surprising that even a very small amount of magnesium ammonium phosphate of about 2% or even less as for example of 0.5% results in a tooth paste which does not become solid whereas a paste containing no magnesium ammonium phosphate is solid (and acid) already after 4 weeks.

Since, according to the present invention, the fluorine remains soluble in a therapeutically effective concentration, the physiologically harmless dose of about l-3 mg. of fluorine, preferably 2 mg. of fluorine, for 1 g. of tooth paste, is sufiicient. As fluorides which may be used according to the invention, there may be mentioned, for example, alkaline earth metal fluorides, preferably alkali metal fluorides such, for example, as sodium fluoride, potassium fluoride or magnesium fluoride. The fluorides may also be used in admixture with one another or in form of their double salts.

The mixing proportion of calcium hydrogen phosphate to magnesium ammonium phosphate can be varied within wide limits. In tooth pastes which as a rule contains 20- 60%, preferably 35-50% of abrasive and polishing agent, the mixture of polishing and abrasive agent may be composed of about 5-99.5% of calcium hydrogen phosphate and 95-0.5% of magnesium ammonium phosphate. A prepared composition of abrasive and polishing agent comprises 20-50% of calcium hydrogen phosphate and EEO-50% of magnesium ammonium phosphate. For tooth powders, which for example, contain up to about 95% of abrasive and polishing agent, it may be suitable to use a greater amount of calcium hydrogen phosphate and a smaller amount of magnesium ammonium phosphate. For tooth soaps, an amount of up to about of abrasive and polishing agent is generally used.

Among the known hydrates of magnesium ammonium phosphate and calcium hydrogen phosphate, there are preferably used the magnesium ammonium phosphate hexahydrate and the calcium hydrogen phosphate dihydrate.

In addition to the abrasive and polishing agents, the dental preparations of the present invention may also contain the other additives generally used for such purposes. Thus, for example, the dental preparations may contain humectants, for example, glycerol, sorbitol, urea, etc., dissolved in water; tooth pastes may contain such humectants in amounts of about 10-50%; tooth soaps may contain smaller amounts of up to about 20%. For tooth powders humectants are not necessary. As binders, there are suitable, among others, carboxymethyl cellulose, tragacanth, agar-agar, in a quantity of 0.l%, preferably 0.52%. The dental preparations of the present invention can be flavoured, depending on the requirements, with a quantity of about 0.54%, preferably about 1%, of essential oils. The quantity of foaming agent is suitably adjusted to the quantity of foam considered to be agreeable during usage. A quantity of about 0.3-5 of the known tensides is generally suflicient. In tooth powders, it is not necessary to use such tensides.

The quantity ranges of the other ingredients, which may be added, are not critical. If particular properties of the dental preparations are to be obtained, the proportions of the additives may be considerably greater or smaller. In general, however, the required components will be added in the usual amounts, because the dental preparations of the present invention do not become acidic upon storage and thus do not affect the additives, especially the flavoring agents and special active substances.

The dental preparations can be prepared by the methods which are usual in the production of dental preparations, for example, by the method described in Ullmann, Enzykl. techn. Chemie (Verlag Urban und Schwarzenberg, Munchen-Berlin), 3rd Edition, volume 10, page 714 et seq.

The dental preparations of the present invention, which contain fluorine and, as abrasive and polishing agents, a mixture of calcium hydrogen phosphate and magnesium ammonium phosphate, represent a considerable advance in the art, because the preparations do not become unusable by solidification or hardening and have a very mild abrasiveness owing to their content of magnesium ammonium phosphate. By the addition of calcium hydrogen phosphate the requirement of a simultaneous presence of calcium and phosphate to promote anticarious activity is met and the abrasive action, especially the cleaning effect, of a paste containing only magnesium ammonium phosphate, which has a very soft grain, is increased and the dental preparation is adjusted in the required manner to the calcium ion content of the saliva. Furthermore, the fluorine ion binding effect of the calcium hydrogen phosphate is suppressed to the utmost extent, despite the weakly alkaline to almost neutral reaction which is adapted to the biological state of the mouth liquid, and thus prevents the concentration of dissolved fluorine falling below the therapeutically effective value which should be at disposal during teeth cleaning.

The following examples serve to illustrate the invention but they are not intended to limit it thereto. The quantitative proportions may be varied within the scope of the aforegoing disclosure without impairment of the effects obtained according to the present invention.

EXAMPLE 1 29.6 g. of magnesium ammonium phosphate hexahydrate, 29.6 g. of calcium hydrogen phosphate dihydrate, 0.9 g. of potassium fluoride and 0.2. g. of flavor oil were intimately mixed in a mixing drum or in a tumbling mixer.

06 g. of the tooth powder was suspended in 30 ml. of water (37 C.). The suspensio. showed a pH-value of 8.2.

The quantity of fluoride which remained in solution was determined in the filtrate of the suspension, which had been shaken for one minute. 78 mcg. (=microgram) of soluble fluorine were found in 1 ml. of filtrate.

A tooth powder, obtained by mixing 44.4 g. of magnesium ammonium phosphate hexahydrate, 14.8 g. of calcium hydrogen phosphate dihydrate, 0.9 g. of potassium fluoride and 0.2 g. of flavor oil, had 76 mcg. of soluble fluoride per ml. of filtrate (test temperature 37 C.).

Av tooth powder obtained by mixing 53.3 g. of magnesium ammonium phosphate hexahydrate, 5.9 g. of calcium hydrogen phosphate dihydrate, 0.9' g. of potassium fluoride and 0.2 g. of flavor oil, had 72 mcg. of soluble fluoride in the filtrate (test temperature 37 C.).

A tooth powder obtained by mixing 56.6 g. of magnesium ammonium phosphate hexahydrate and 2.6 g. of calcium hydrogen phosphate dihydrate, 0.9 g. of potassium fluoride and 0.2 g. of flavor oil, gave mcg. of soluble fluorine per ml. of filtrate of the suspension (test temperature 37 C.).

EXAMPLE 2 When for cleaning the teeth a greater quantity of tooth powder was used with an equal quantity of water or the same quantity of tooth powder with a smaller quantity of water, the concentration of fluorine that remained soluble was increased.

The following table shows the concentration of fluorine, in tooth powders with increasing calcium hydrogen phosphate contents and falling magnesium ammonium phosphate contents, determined in the filtrate of the suspension which was shaken for one minute.

12 g. of tooth powder containing about 8.88 g. of abrasive and polishing agent, the composition of which may correspond to the values given in the following table, were intimately mixed with 0.135 g. of potassium fluoride and 0.3 g. of flavor oil. 0.92 g. of this tooth powder was suspended in 30 ml. of water having a temperature of 37 C. and the suspension was shaken for one minute; the quantity of dissolved fluorine was then determined. The results are shown in the following table.

TABLE Calcium Magnesium ammohydrogen Dissolved nium phosphate, phosphate, Mixing fluorine, grams grams ratio p.p.m. pH

When the tooth powder containing 6.69 g. of magnesium ammonium phosphate and 2.23 g. of calcium hydrogen phosphate was shaken for one hour at 37 C. with water, 79 p.p.m. of soluble fluorine could be detected in the filtrate of the suspension.

The content of dissolved fluorine in the filtrate shows that a tooth powder which contains 510% of magnesium ammonium phosphate and 95-90% of calcium hydrogen phosphate already assures, with the usual dosage of fluorine, a sufficient concentration of soluble fluorine in the mouth rinsing liquid during teeth cleaning.

The tests furthermore show that, after an addition of magnesium ammonium phosphate, the calcium hydrogen phosphate does not bind essential quantities of fluorine.

EXAMPLE 3 700 g. of glycerol, 50 g. of carboxymethyl cellulose, 1.25 g. of sodium salt of saccharin, 25 g. of sodium cyclamate, 25 g. of potassium benzoate, 22.5 g. of sodium fluoride, 250 g. of urea, 1000 g. of distilled water were thoroughly mixed in a kneader. As soon as the mass was homogenous, 1750 g. of magnesium ammonium phosphate hexahydrate and 500 g. of calcium hydrogen phosphate dihydrate were added.

The mass was then kneaded for 30 minutes at a slightly reduced pressure (40-50 mm./Hg) and a mixture of 300 g. of glycerol, 100 g. of lauryl sulfate, 70 g. of flavor oil and 206.25 g. of distilled water were added. After a further kneading for 30 minutes without application of reduced pressure, the paste was introduced on a roller mill, aerated and filled into tubes. The content of abrasive and polishing substance, referred to tooth paste, amounted to 45%. Directly after preparation, a viscosity of 37 7 poises was measured with a recording structural viscosimeter.

In order to test the properties of the paste, samples thereof were stored in a refrigerator, at room temperature, and in an incubator at 40 C.

After a period of 12 months, the sample stored in the refrigerator at about 4-5" C. showed a viscosity of 438 poises. The sample stored at room temperature showed a viscosity of 361 poises and the sample stored in the incubator at 40 C. showed to have a viscosity of 387 poises. The samples measured in the meantime showed the variations usual in the determination of the viscosity.

The pH-value of a suspension of 2.25 g. of paste in 30 ml. of water amounted to 8.2, directly after the preparation. The paste stored in the refrigerator had a pH- value of 7.9; the sample stored at room temperature had a pH-value of 7.8 and the paste stored in the incubator a pH-value of 7.4.

The paste extruded from the tube was uniform, smooth and viscous with all three samples stored.

The test for the amount and the speed of formation of foam carried out with the stored samples showed no observable difference to a fresh paste.

For determining the soluble fluorine to be expected in the mouth liquid during teeth cleaning, 1.5 g. of paste were suspended in 20 ml. of distilled water and the suspension was shaken for one minute. The suspension was then pressed through a clarifying filter (B.K.-filter). A freshly prepared paste showed to have 40.2 mcg. of soluble fluorine per ml. of filtrate. The sample stored for 12 months at 40 C. in an incubator, showed to have a fluorine content of 34.4 mcg. per ml. of filtrate. The fluorine values of the sample stored for 12 months in a refrigerator correspond to this content of fluorine. The abrasiveness measured on a copper cylinder did not change in all three samples. I

A tooth paste containing only calcium hydrogen phosphate dihydrate and fluoride, but no magnesium ammonium phosphate hexahydrate, showed the following behaviour:

8 COMPOSITION OF THE PASTE G. Calcium hydrogen phosphate 500 Glycerol 150 Lauryl sulfate 15 Hydroxyethyl cellulose 15 Sodium benzoate 5 Urea 125 Sodium fluoride 4.4 Flavor oil 16 Distilled water--Ad 1000.

The tooth paste was prepared as described above in a kneader. The viscosity was measured shortly after the preparation and found to be 300 poises. After storage for 4 weeks at room temperature (24 C. the tooth paste could no be extruded from the tube.

The pH-value of the suspension (2.25 g. of paste in 30 ml. of water) was, with a fresh paste, 7.3-7.4, after storage for 18 days 4.7 and after 5 weeks 4.3. The pH-value then remained constant.

We claim:

1. In a dental preparation which includes calcium hydrogen phosphate and a source of soluble fluoride and which provides a therapeutically eflective fluoride concentration in mouth liquid, the improved composition which comprises:

(a) a carrier consisting of 5% to 99.5% calcium hydrogen phosphate and to 0.5% magnesium ammonium phosphate, said percentages being by weight of total phosphates; and

(b) a physiologically harmless but therapeutically effective amount of an alkaline metal fluoride.

References Cited UNITED STATES PATENTS 2,018,410 10/1935 McDonald et al. 424-57 2,078,498 4/ 1937 Klarmann et al. 424-57 3,105,013 9/1963 Saul et al. 424--52 3,155,454 11/1964 Salutsyl et al. 23-----1 OTHER REFERENCES Sagarin, Cosmetics: Science and Technology, published by Interscience Publishers, Inc., New York, 1957, pp. 342 and 343.

RICHARD L. HUFF, Primary Examiner US. Cl. X.R. 42457 UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No. 6: 86? Dated April 11 197 InventO1-( Ludwig fichoergig It is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:

In the Heading:

After "'Ser. No. 55,916" insert Claims priority, Germany, December 17, 1965, F 7,950".

Signed and sealed this 18th day of July 1972.

(SEAL) Attest:

EDWARD M.FLETCHER,JR. ROBERT GOTTSCHALK Attesting Officer Commissioner of Patents 7 FORM uscoMM-Dc 60376-P69 U.5. GOVERNMENT PRINTING OFFICE 1 '99 0" 356'33