Dental composition

DESCRIPTION

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B 69 784 TO attached to a request for

BELGIAN PATENT filed by

Israel KLEINBERG having for subject: Composition for combating dental caries

Qualification proposed: PATENT OF INVENTION

Priority of a patent application filed in the United States of America on June 18, 1976 under the number 697 538

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Β 63,734

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The present invention is based on two well accepted operations. Cavities are most likely to occur when the pH of the mouth drops below a certain critical level depending on the individual's resistance and the length of time the critical level is exceeded. The second observation is the recognition of the fact that the saliva itself exerts a beneficial effect on the factors causing the cavities mentioned above and includes certain substances making it possible to raise the oral pH.

It has been clear for some time that when an abundance of carbohydrates, especially sugar, is present in the mouth, it is certain that we are in the presence of conditions favoring the production of an acid pH in dental plaques. The microflora of the plates generates an acid from exogenous or endogenous carbohydrates. It has been observed that the compensation of this acid production takes place by means of alkalogenic substances neutralizing the cariogenic acids coming from carbohydrates and bringing the pH of the dental surfaces to a level higher than that at which caries occurs.

The present invention relates to a means for increasing the body's natural defenses against cavities when the latter are the result of the attack of the teeth by cariogenic acids. The invention also relates to replacement or assistance^{7 ;} - '; g

-3 the natural protective function of saliva when the latter is reduced by atrophy of the salivary glands or other disorders of the latter which reduce the secretion of saliva or its protective power.

The subject of the invention is also a substitute or a product for complementing the part of the saliva which plays a protective role with regard to caries.

The subject of the invention is also the reduction or elimination of caries in individuals sensitive to the latter by providing appropriate sources of compounds for adjusting the pH or of precursors thereof.

The invention also has for ^!subject of the use of arginine precursors, in particular oligomeric peptides having from 2 to 4 amino acid links, one or more of them being arginine, as alkallogenic agents.

It has been observed that the plates, that is to say the spongy organic matter strongly adhering to the surfaces of the der. + S, accept molecules of certain shapes and dimensions in its matrix. Oligomers of peptides are among the compounds that can penetrate plaques. These compounds have been shown to enter bacteria found in the mouth. It has been found that the material that most readily counteracts the acid produced when a •; “·· · Λ

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abundance of carbohydrates, especially sugar, was present, was the amino acid called 'argi-nina. It has been determined, not without surprise, that an oligomeric peptide comprising from 2 to 4 amino acid links, one or more of these being ar gigine, is even more effective in bringing the pH of the mouth to a non-toxic level. cariogenic.

It has been determined that in general, cavities

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coming from an acidic pH, almost invariably occurred when a pH of about 5 or 5.1 was manifested for a sufficient period of time, while with only rare exceptions, caries occurred when the pH was maintained at 6.1 or more than 6.1.

The question of the duration of exposure of the enamel to a pH below about 5 varies with the individuals, but certain generalities have been determined.

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: Two activity patterns can be established

According to the first, the mouth is exposed to an amount

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? . \ ment- sugar, 'after which the bacteria present in. -plates, transform carbohydrates into acids, -7 - mainly into acetic, lactic and propionic acids.

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-o aa a "· ♦ -" at rates such as the drop in pH which occurs within about 5 to 15 minutes, usually reaches the critical pH level for cavity formation, unless their factor for raising the pH which has been found to be arginine and its precursors, is not present and is activated by bacteria in the mouth, so that the drop in pH is reduced and the pH is brought down at normal value after approximately 45 minutes to 1 hour, depending on the particular mouth involved.

A second situation is represented by the availability of larger quantities of fermentable carbohydrates present for a longer period of time. The pH of the mouth drops, in this case, below 5, which leads to the formation of caries after about 15 minutes and this pH remains at this value as long as the excess of fermented carbohydrates target is present. This can happen during one. period of two hours or more. It is under these conditions that the most serious cariogenic attack occurs, but this duration is reduced in the presence of one; pH rise factor.

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The effective oligomeric peptide which occurs naturally in saliva has the glycine-glycine-lysine - arginine arrangement with amino and carboxyl endings. This compound was synthesized using conventional methods and found to be effective for the purposes of the present invention and to be the preferred pH raising factor since it is the compound which naturally produced, it is obviously the first choice substance, but the possibility of an oligomeric peptide having two or more of two arginine units could prove to be even more effective.

The arginine-containing peptide quickly penetrates the plaques and also penetrates the bacteria themselves. The oligomeric peptide is stored there, protected from dilution, and provides a potential source of alkaline substance to counteract the formation of activated acid by the presence of edible carbohydrates. ”This storage capacity suggests the inclusion of the factor pH-elevation in common dental products, such as toothpaste, tooth powders, mouthwashes and the like.

It has also been found that the pH raising factor of the oligomeric peptide type is effective even when it is introduced into the mouth simultaneously with substances containing carbohydrates. -are; activated by bacteria, · plaques

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- 7 so as to generate acids. Adding the pH raising factor to substances containing carbohydrates is an effective way to supplement the body's natural defenses against cavities.

The arginine-containing oligomeric peptides are particularly suitable as food additives, since several of them are natural products, in particular the preferred substance according to the invention.

They are odorless, tasteless, thermally stable, and soluble in quantities well beyond their effective rate. They are aesthetically acceptable as used.

Differences in pH in the mouths of people who are susceptible to cavities and are free from cavities can be minimized by providing additional pH elevation to the first appointees. This is effective in proportion to the amounts of arginine-containing oligomeric peptides supplied. A significant effect is obtained with an amount as low as 0.05 mM, while there is still an improvement with an amount as high as 3 mM and more.

Particularly interesting cooperation may occur with the whole pH raising factor and fluoride ions. Fluoride ions in minor amounts such as about 5 ppm generally reduce dental solubility.

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These quantities of fluoride ions further inhibit the drop in pH when the pH drops below about 5. The drop in pH in the case of a high sugar availability up to 4.8 is kept at 5, 1 when 5 ppm of fluoride are present. This is approximately the highest pH value that fluoride ions can bring back. Only When a pH elevation factor is also present, fluoride always inhibits the drop in pH, but the pH returns more quickly to higher levels. sure that when the factor in question is not present *.

The examples which follow illustrate the present invention without however limiting it.

Four sets of three 10 x 75 mm test tubes of 0.2 ml of an 8.4 ml aqueous glucose solution were filled. Series I was filled with 0.2 ml of collected supernatant saliva. 0.2 ml of 9.9 mM series II was packed with the glycine-glycinearginine oligomeric peptide. Series III was parked with 0.2 ml of arginine and the TV series was filled with 0.2 distilled. 0.2 ml of a 50:50 aqueous buccal bacteria was then added to each test. The test tubes thus prepared were kept at 37^eC in a double boiler. The pH was raised to /,^s- “/ where we added the bacteria, as well as at the end

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It is clear from the above data that supernatant saliva and an arginine supplement lower the pH decrease in a carbohydrate environment. It is also clearly evident that an oligomeric peptide containing arginine is more effective than arginine alone. In similar experiments, an oligomeric peptide supplement containing arginine also serves to moderate the drop in pH more than when saliva or arignin is present alone and brings the pH back to its initial value or even better.

The identification of the pH elevation factor suggests other areas where it might be possible to use oligomeric peptides containing arginine. These compounds could be used for the regulation of numerous processes involving microorganisms, such as bacterial fermentations, wine making, the production of antibiotics, the formation of citric acid and other processes.

The present invention has been described by some of its preferred embodiments, but it is understood that many modifications and variants can be made to the process and compositions according to the invention without departing from the scope and spirit of the invention.

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