SE437324B - USE OF AT LEAST ONE SOLUBLE ALUMINUM SALT IN MIXTURE WITH AN ACID TO MAKE SOME PRODUCTS ANTICARIOGENA - Google Patents

Description

7803801-s a 2 a high proportion of sweeteners such as sucrose and other sugars. It has been suggested that when sugars are introduced into the mouth, they give rise to acids which promote dental caries.

A contributing factor to pediatric dental caries is the adhesion of highly refined sugars and their degradation products to the dental plaque after ingestion, together with the low rate of cleaning of the oral cavity, or the ability to form large amounts of acid, or combinations of such factors.

A number of cariostatic agents have been previously investigated in systems in which the agent is applied or consumed topically (i.e. directly on the teeth) in the form of a toothpaste (i.e. a toothpaste or a tooth powder). However, the knowledge gained regarding the efficacy of the cariostatic agents used in such topical applications has not allowed any possibility to predict the efficacy of these cariostatic agents in other applications, e.g. in foods, and in particular in foods containing a significant proportion of sugars.

Unfortunately, known cariostatic agents generally do not have a significant degree of protection when used in food.

Known cariostatic agents such as fluorides, phosphate, vitamin K, nitrofurans, ammonium compounds, iodoacetic acid and the like, when added separately to a food: containing a high percentage of sugar, thus have little direct topical content. effect in a food environment. For the above and other reasons, dental researchers have continued their efforts to develop new anticariogenic agents, which not only exhibit a high degree of anticariogenic efficacy but are also non-toxic, stable and readily available. It has been suggested that aluminum salts may have a beneficial effect in reducing tooth caries or in facilitating the uptake of fluoride by tooth enamel. Compare in this respect e.g. Manly et al., "Substances Capable of Decreasing the Acid Solubility of Tooth Eklamel", J. Dent. Res. 28: 160 (1948); Regolati et al., "Effects of Aluminum and Fluoride on Caries, Fluorine Content and Dissolution of Rat Molars", Hel. "Odon. Acta. 13:59 (1969); and Kelada," Electrochemical Characteristics of Free and Complexed Fluorides in Drinking Water and The Effects of Aluminum and Iron on Fluoride Inoorporation Into Tooth Enamel ", University of Michigan Thesis (1972). '' In vitro studies have shown that pre-treatment of tooth enamel with aluminum-containing solutions has resulted in increased fluoride uptake. ' when accompanied by treatment with a fluoride solution; treatment / see QUPÛUg s- 3. 7803801-5 with combinations of aluminum and fluoride, however, has not provided any additional advantage over fluoride alone. McCann, “the Effect of Fluoride Complex Formation on Fluoride Uptake and Beten- tion in Human Enamel ", Archs. Oral Biol. l4: 52l (l969); and Gerhardt et al., "Fluoride Uptake in Natural Tooth Surfaces Pretreated with Aluminum Nitrate", Ü. Dent. Res. 51: 87O (1972). In addition, the above-mentioned procedures have primarily been intended for the use of aluminum in combination with fluorides and have not been focused on the effect of aluminum in the absence of fluoride.

»It has previously been suggested that the addition of a source of aluminum to food can reduce the cariogenic potential of food. However, studies to date have shown that aluminum is ineffective as an aticariogenic agent in the diet. Thus, it has been established by Van Reen et al., "Traoe Elements and Dental Caries in Molybdenum, Aluminum and Titanium", Helv. Odont. Acta., 11: 53-59 (1967), page 57, that "aluminum-potassium sulfate upon addition to drinking water for rats in an amount of 10, 50 or 100 ppm aluminum did not provide any protection against dental caries ... “.

The same conclusion was made when aluminum was added to diet-born rats as reported by Wynn et al., "Dental Caries in the Albino Rat on High Sucrose Diets Containing Different Amounts of Aluminum", J. Nutrition, 542285-290 (1954) and with parenterally injected aluminum as reported by Kruger, "The Effect of" Trace Elements "on Experimental Dental Caries in the Albino Rat", Univ. of Queensland Papers, 1: 1-28 (1959).

Nor has the use of aluminum salts in toothpastes given a desired result. Thus, while French patent 3610M discloses a specific combination of aluminum lactate, aluminum fluoride and calcium pyrophosphate, abrasives react with the aluminum by reacting therewith to form insoluble aluminum phosphate. Similarly, according to U.S. Pat. No. 3,095,356, aluminum salts such as aluminum fluoride are used to interact with insoluble sodium metaphosphate as abrasives to reduce the solubility of such abrasives and to increase fluoride uptake but without independent therapeutic benefit of the aluminum.

U.S. Pat. No. 3,282,792 discloses low pH toothpastes containing stannous fluoride which have been stabilized against precipitation and oxidation of stannous ions by the use of hydroxyl-substituted di- and tricarboxylic acids. However, nothing is stated in the patent specification regarding the use of aluminum in systems that do not contain fluoride. While U.S. Pat. No. 3,937,806 relates to oral compositions containing indium and fluoride to which malic acid is added to stabilize indium, it is similarly not clarified that beneficial results can be obtained with aluminum and carboxylic acids without fluoride being present.

Canadian Pat. No. 928,272 discloses acidic toothpastes containing a combination of surfactants and alpha-foam coagulants such as certain carboxylic acid salts of aluminum and other metals. This patent also does not state that significant dental health benefits can be obtained with aluminum-containing foods. Thus, while some elements are known to inhibit dental caries (e.g., F, Mo, Sr, and V) and while others are known to promote caries (e.g., Se, Mg, and Cd), they indicate multiple data on aluminum that it is inert in relation to dental 'caries in classification' according to Navia, "Effect of Minerals on Dental Caries", in Dietary Chemicals v. Dental Caries, ACS, Washington, 13.0. (1970).

U.S. Pat. No. 3,772,43l discloses a mouthwash tablet containing a pair of foaming substances (eg a solid basic material and a solid organic acid such as fumaric acid, citric acid, tartaric acid), which gives CO 2 upon dissolution in water, in combination with an astringent desensitizing agent, which may be (but need not be) an aluminum compound. In addition, the patent states the possible use of vitamin C (ascorbic acid) as a mucin-filling agent in combination with an antimicrobial agent and a chelating agent. However, the patent does not suggest that any anticariogenic therapeutic effects are obtained as a result of the presence of the aluminum compounds in such compositions. Other essential constituents of the tablets are in fact incompatible with aluminum ions, as a result of which they are not therapeutically available.

In summary, it has been said that no therapeutically effective system has been proposed in the past which provides bioavailable aluminum when used in a food in the absence of fluoride.

According to the present invention, 0.01-0.10%, 7 calculated as aluminum ion, of at least one soluble aluminum ion-containing salt in admixture with 0-6%, calculated on the weight of edible material, is used of an acid selected from the group consisting of adipic acid, ascorbic acid and mixtures thereof, in an anticariogenically effective but non-toxic amount to make edible products anticariogenic.

It is desirable that edible materials containing additives also contain a non-cariogenic nutrient-containing sweetener comprising a mixture of at least a first sweetener selected from the group consisting of sorbitol, xylitol and mixtures thereof. at least one second sweetener selected from the group consisting of dextrose, fructose and mixtures thereof. The mixture contains at least approx. 75% of the first sweetener, based on the weight of the mixture, when dextrose is the second agent and at least approx. 60% of the first agent, when fructose is the second agent. The sweetener is added to the edible material in an amount which is effective in sweetening. The use of the cariostatic additive according to the invention reduces the acid solubility of the tooth enamel and, when the sweetener system according to the invention is also used, products are obtained which, when introduced into the mouth, show little or no harmful lowering of the plaque pH (indicating that the origin of degrading oral acids has reduced little or no harmful decalcification of the tooth enamel (decalcification is a precursor to the emergence of dental cariesh and rapid oral cleansing.

In the present context, the term "edible material" and the like as encompassing any of a variety of diverse food products suitable for human consumption including, but not limited to,. selection of products such as sweets, bakery products, chewing gum, artificial beverages; fruit preparations and the like. In the present context, the term "ascorbic acid" is intended to include its isomeric epimer, isoascorbic acid which is also known as erythorbic acid and D-ertro-hex-2-enonic acid gamma-lactone, which can be used as ascorbic acid for the purpose of the invention.

The adipic acid and / or ascorbic acid are preferably present in an amount of 3% by weight.

The choice of the particular soluble aluminum salt used is not critical and substantially any non-toxic, water-soluble aluminum ion-containing salt may be used. Suitable aluminum salts include aluminum potassium sulfate, AlK (SO) 4) 2.12H 2 O; aluminum chloride, AlCl3.6H2O; aluminum sodium sulfate, AlNa (SO4) 2. 12H2O; aluminum ammonium sulfate, AlNH4 (SO4) 2.12H2O; aluminum sodium phosphate, NaAl3Hl4 (PO4) 8.4H2O; aluminum sulfate, Al2 (SO4) 3.18H2O; aluminum nitrate, Al (NO3) 3 and sodium aluminate, NaAlO2. Aluminum potassium sulfate dodecahydrate (AlK (SO4) 2.12H2O) and aluminum chloride hexahydrate (AlCl6.6H2O) are preferred. When using aluminum potassium sulphate dodecahydrate and aluminum chloride hexahydrate, the respective salts are present in an amount ev o, 2-2 t, preferably o, 1-1, o t, by weight. The cariostatic additive according to the invention can be used in all types of sweetened edible products such as hard caramel, caramel and the like, chocolate and chocolate coatings and in other caraway. However, when the caramel products are prepared from a variety of individual ingredients (such as in caramels in which the central part is based on cooked sugar and which is covered with chocolate), the additive according to the invention can be used. in one or more of the constituents or in all of them.

According to the invention, it is important to find that in comparison with other conventionally used carboxylic acids, such as citric acid and malic acid, ascorbic acid and adipic acid are relatively safe and do not decalcify the teeth when present in the mouth during the rapid oral cleaning period. which are produced with the sweets according to the invention. In addition, these acids (1) do not interfere with the aluminum ions as many other carboxylic acids do; (2) temporarily helps to obtain a pH of 3.5-4.5 in the mouth, at which pH the aluminum ions are most actively incorporated into the tooth enamel, and (3) to some extent opens the apatite crystal structure of the tooth enamel so that aluminum ions react better with enamel.

The sweets prepared according to the invention are essentially the same as those previously prepared, except that by using the cariostatic additive according to the invention the sweets can be consumed in a safe manner without causing or promoting tooth decay.

The anticariogenic caramel products prepared in accordance with the present invention contain common and commonly occurring complementary components conventionally found in confectionery products, e.g. dyes, flavorings, dairy and vegetable fats, foaming agents, texturing agents, such as crispy rice, nuts and the like. However, some conventional confectionery components are not desirable for dental reasons. Significant amounts of fats and texturing agents such as brittle rice may, for example, adversely affect the oral purification of the sweetener.

Nevertheless, by using the additive according to the invention, the sweets are made less harmful to the teeth. The sweets can be produced using manufacturing methods of a hitherto known nature. The additive can be added at any suitable point as long as it is present in the final product at the desired level.

"Compositions exemplifying anticariogenic sweets of the invention are set forth in the examples below.

@ Poon ancutALlnfr 7803801-5 Example I - Tableted caramel Ingredients Weight parts Sucrose 95, 0 Adipic acid 3.0 Aluminum potassium sulphate 0.2 Magnesium stearate in 1.0 Flavors, color, etc. 0.8 Example II - Boiled hard-caramel Ingredients' Weight parts Sack 98.0 Acetic acid in Aluminum chloride 0.5 Flavorings, color, etc. - 0.5 It is desirable that the cariostatic additive be used in sweetened edible products containing, instead of sucrose or other cariogenic sweeteners, a non-cariogenic Nutrient sweetener system comprising a mixture of at least a first sweetener selected from the group consisting of sorbitol, xylitol and mixtures thereof, and at least a second sweetener selected from the group consisting of dextrose, fructose and mixtures thereof, the mixture containing at least about 75% of the first agent, based on the weight of the mixture, when dextrose constitutes the second agent and at least approx. 60% of the first agent, when fructose is the second agent.

Sorbitol is the preferred first agent and dextrose is the preferred second agent, depending on cost and availability. It is desirable to use homogeneous mixtures of the first and second agents.

When using mixtures of sorbitol-dextrose or xylitol-dextrose, a mixture consisting of 75% sorbitol and / or xylitol -25% dextrose is preferred. When fructose is used, slightly larger amounts of the second sweetener may be used. Thus, about 40% fructose is preferred for mixtures of sorbitol-fructose and xylitol-fructose.

The sweetener mixtures are generally used in the same amounts as the sugar or other cariogenic sweetener systems used heretofore. Thus, when non-cariogenic nutrient sweetener systems are used in a confectionery product, they are preferably used in an amount of approx. 40-100% by weight, calculated on the confectionery product. Caramel products obtained according to the invention are essentially the same as previously known caramel products with the exception that, due to the addition of the cariostatic additive and the use of the non-cariogenic nutrient sweetener system, they can be safely consumed with a reduction in the presence and severity of dental caries. Sweets obtained according to the invention can be prepared using the above-mentioned non-cariogenic nutrient-containing sweetener system according to hitherto used methods. The preparation methods are generally the same, although some modifications must be made due to the use of sorbitol or xylitol as the essential component of the sweetener system.

Thus, in the case of tableted sweets, the same technique was used with respect to mixing the components ooh: Forming them into tablets, but somewhat greater control of humidity must be applied because sorbitol and xylitol are desiccants. An agent such as magnesium stearate may also be added at low levels to facilitate removal of the tablets from the mold. With knowledge of these properties of sorbitol- and / or xylitol-containing sweeteners, those skilled in the art can readily adapt existing methods of making sweets to the preparation of other confectionery products according to the invention. The composition of examples of anticariogenic sweets prepared using the mixture of the invention is given in the following examples.

Example III - Tableted sweet Ingredients Weight components Sorbitol 71.3 Dextrose 23.8 'Flavorings, color, etc .; 0.7 'Adipic acid a - I 3,0 Aluminum potassium sulphate -' 0,2 _____, ______, i _____k 0 v_a_____ PALN "g É 1803801-5 Example IV - Tableted sweet Ingredients Weight components Sorbitol 81.0 Dextrose - _ 14.0 Ascorbic acid »3, C Flavorings, color, etc. 0.5 Aluminum chloride 0.5 Magnesium stearate '1.0 Example V - Tableted sweet Ingredients Å Weight components Sorbitol 57.2 Fructose 38.1 Adipic acid' 1, 5 Ascorbic acid ~ 1.5 Aromas, color, etc. 0.5 Magnesium stearate '1.0 Aluminum potassium aulphate 0.2 Example VI - Tableted aötsgg Ingredients e Weight parts xylitol e 72.0 Dextrose 1. 24.0 Acetic acid '03 Aromas, color, etc. 0.2 Magnesium stearate 1.0 Aluminum chloride 0.5 Example VII - Tableted sweet Ingredients Weight components Sorbitol 64.1 Dextrose ü 15.5.

Fructose _ 15.5 Adipic acid 1.5 Ascorbic acid e 1.5 Flavorings, color, etc. 0.5 Magnesium stearate 1.0 Aluminum chloride 0.5 ee, ______, _, I ...___ 5 QUALITY 1 ~ 10 7803801-5 Example VIII - Tableted sweetness Ingredients Sorbitol Xylitol Dextrose Adipic acid Flavorings, color, etc.

Magnesium stearate Aluminum chloride Exemgel: x - Boil near-caranial Ingredients Sorbitol, (70% solution) Dextrose _ ¶ Adipic acid Aromas, color, etc.

Aluminum potassium sulphate Exemgel X - Caramel Besånasaelar sørbitol (mß-ig solution) Dextros' Egg albumin (45.27% solution) Coconut oil 92 degrees Adipic acid- Sodium alginate Calcium acetate Emulsifier Flavorings, color, etc.

Aluminum moria _ Weight parts 35.7 35.7 23.8 3.0 0.2 1, o 0.5 ¶ folding errors ¶ 81.8 17.3 0.8 0.2 0.2 ¶ weighting year 70.1. 16.3 2.4 8.9 1.7 ào .3 0.1 0.1 0.2 o .5 í // f / f / .Å _ ¶ 1 QUALLTL 11 7803801-5 Example XI - Chocolate coating for caramel Ingredients Weight components Sorbitol '42.0 Dextrose p 14.0 Kaomel (hard-butter) f'. 30,9 Cocoa powder _ I 7, 8 Fatty dry dry milk 4, 2 Lecithin '0,3 Salt g' 0,1 Vanilla powder 0,9 Aluminum potassium sulphate 0,2 Experimental evaluation The anticariogenic properties of the products have been verified in the following experimental studies.

A primary criterion for evaluating an anticariogenic agent is its ability to reduce the solubility of tooth enamel, namely enamel solubility reductions ("ESR"). In vitro studies on ESR are performed as follows, Healthy bovine teeth are mounted in self-curing acrylic resin with the labial the surface is exposed and is given a careful prophylaxis with pumice flour. A "window" is then formed on the labial. the surface by dropping wax over a circle of aluminum foil with a diameter of 1.0 cm. A sharp drawing pin is then used to draw the foil window which is then peeled off to expose a round surface of enamel of reproducible size. The windowed teeth are descaled four times in succession at 20 minute intervals with 25 ml portions of a 0.2 N acetic acid solution (buffered to pH 4.0) at a stirring speed of 60 rpm using an ESR stirrer. . Through the fourth descaling, the amount of calcium and phosphorus demineralized from the tooth has reached a constant level. The teeth are then treated with 25 ml of a superficial caramel (1 part caramel diluted with 3 parts redistilled water to mimic the dilution that occurs in the mouth upon ingestion) stirred at a rate of about 60 rpm. - After treatment, the teeth are decalcified again with 25 ml portions of the acetic acid buffer for an additional 20 minute intervals. The fifth and eighth descaling solutions are referred to as the first descaling after the treatment (first PTD) and fourth descaling after treatment (fourth PTD). i___, 7Pi fifi Mli__lgs i QUALITY 7803801-5 i i i; _ _ The difference in the amount of calcium and phosphorus in the fourth descaling solution before treatment and that in the fifth and eighth descaling solutions after treatment divided by the amount in the fourth descaling times 100 was used to determine the ESR values for the first PID and the fourth PTD. Calcium is determined using atomic absorption spectroscopy and phosphorus using the Fiske-Subbarow method.

In order to demonstrate that repeated ingestion of sweets containing the cariostatic additive used according to the invention for short periods of time has an accumulative effectiveness in reducing the solubility of tooth enamel, the teeth are treated a number of times of relatively short duration (eg 5 minutes, the typical oral cleaning time for candies of this type. - Using this technique, a grape flavored tableted sweet with the composition set forth in Example III was evaluated.

For comparison purposes, a caramel of the same composition, but without the aluminum salt, was tested as a control. ESR data for the sweetener of Example III were determined after ten 5-minute treatments and also after twenty 5-minute treatments. The ESR data given in Table I show that repeated 5-minute treatments with this dissolved sweetener give an accumulated significant ESR effect; After twenty such treatments, an ESR of 70% is obtained.

TABLE I aa Number 54 - Treatment- - minutes ~ cl Esa (%) 1 = ESR (at) solution treatments 1st PTDr 4th PTD 1st PTD 4th PQQ Example III, but no A1K (so4) 2,121 {2o (pH set to 4.0) (Average of 7 '_ 3 readings) 20 9 in 5 l2 3 _ Example III (pH set to 4.0) i (Average of 4 3 readings) 10 41 _ 30 - 44 Example III (pH set to 4.0) (Average of _ _ 3 readings) 20 69 f 43 74 43 Poo IQLML 13 I 77søsso1-5 While ESR values indicate the effectiveness of an anticariogenic agent, it is also highly desirable that determine the amount of agent actually absorbed by the tooth enamel to further determine the effectiveness. Six windowed healthy bovine teeth were treated with the sweetener of Example III diluted with redistilled water in a ratio of 1: 3. The teeth were treated twenty times in succession for separate 5-minute periods with 25 ml of the sweet solution. After the treatment, the teeth were descaled for 30 seconds in 15.0 ml of 2.0 HClO 4 and the amount of calcium and aluminum was determined. Calcium was determined by atomic absorption and aluminum according to the "Aluminon method"; the data given in Table II clearly show that a significant amount of aluminum ions react with and are absorbed into the tooth enamel. Treatment of teeth with redistilled water in a similar manner resulted in an aluminum uptake equal to 0. These accumulative aluminum uptake values correspond to and should be associated with the accumulative ESR values given in Table I. Collectively, they demonstrate the cariostatic. the effect of the additives according to the invention.

TABLE II _ g aluminum / calcium- Total g nluminium- Total gg calcium _3 Eggp gon, ppm calcium Ion ppm aluminum xl0 1 1,14 1710 0,579 i 11,85 6,93 2 o, 89 1335 o, 5o- 7,50 . 5.62 g 3 0.68 1020 0.54 8.10 7.95 4 1.22 - p 1830 0.88 A 13.20 7.21 5 0.97 1455 _ '0.88 13.20 9, 07 6 1, oo isoo 0.97 i 14.55 9.70. The anticariogenic effect of the additives has also been demonstrated in an in vivo study in rats performed as follows.

Ten 35-day-old rats of the species "Wistar" were randomly divided into two equal groups according to sex, body weight and littermates. Groups of two rats served as a control and were fed a low fluoride barley flour diet and fluoride-free water in the desired amount. Rat group I in group number 1 was kept on the same diet except that their barley diet was supplemented with 3% adipic acid and 1% AlCl3.6H2O. At the end of one month, the rats were killed and the acid solubility of the cheek teeth was determined. The data obtained are given in Table III. _ / "a” \ ¿<šï

Claims (4)

1, 7305301-5 PATENT CLAIMS Use of 0.01-0.10%, calculated as aluminum ion, of at least one soluble aluminum ion-containing salt in a mixture with 0-6%, calculated on the weight of edible material, of an acid selected from the group consisting of adipic acid, ascorbic acid and mixtures thereof, in an anticariogenically effective but non-toxic amount to make edible products anticariogenic. _ Use according to claim 1, characterized in that the acid is adipic acid. ' Use according to claim 1, characterized in that the aluminum salt consists of aluminum potassium sulphate dodecahydrate, AlK (SO4) 2.l2H2O ~ Use according to claim 1, characterized in that the aluminum salt consists of aluminum chloride hexahydrate, AlCl 3 .6H 2 O. s Üíftítïl * alla V _; auAurv i