MXPA98006724A - Liquid oral compositions comprising a compound of calcium and acidula - Google Patents

Abstract

The present invention relates to a liquid composition for oral use containing a calcium compound and an acidulant characterized in that calcium is present in the range of 0.3 to 0.55 moles per mole of acid and because the proportion of calcium and acidulant in the composition is select so that the pH of the composition is 3.5 to 4.5. The use of a calcium compound and an acidulant for the reduction of tooth erosion caused by acid, characterized in that calcium is present in a molar concentration of 0.3 to 0.55 per mole of acid and a pH in the range of 3.5 to 4.5 in the manufacture of the orally acidified liquid composition administer

Description

LIQUID ORAL COMPOSITIONS COMPRISING A COMPOUND OF CALCIUM AND AN ACIDULANT The present invention relates to compositions for oral use, such as acidic beverages and oral compositions for health care and to the use of calcium in said compositions to alleviate or prevent damage to the teeth associated with the consumption of acid. In particular, the present invention alleviates acceptability problems associated with the addition of calcium to beverages. It is thought that the erosion of teeth is caused, among other things, by acidic products that leach calcium from the teeth faster than it can be replaced by normal remineralization processes. When a product, such as a beverage, is prepared according to this invention and is introduced into the oral cavity for consumer or health care purposes, the dissolution or removal of calcium and phosphate from the teeth by processes is significantly reduced. chemical Calcium is the most abundant mineral in the body. The vast majority of calcium is deposited in the bones and teeth but the mineral is also essential for other functions of the body, such as the regulation of nerve function, the contraction of muscles and the coagulation of blood. Calcium is a common beverage constituent that is derived from fruit and hard water ingredients when used in beverage production without pre-softening. The values for calcium concentration that occur in this way are usually in the range of 0.005-0.02% w / w.

The interest in the general nutritional benefits of diet fortification by calcium ions has led to an investigation of practical ways to incorporate this ion in beverages at levels higher than 0.2% w / w at 2% w / w. The use of calcium as a supplement for beverages has been described in WO88 / 03762. It is well known that the addition of malic acid will help maintain the solubility of calcium in calcium fortified beverages by minimizing losses due to precipitation. This is due to the formation of a soluble complex "calcium citrate malate". On the other hand, Lussi et al. (1995, Caries Res 29, 349-354) have associated the titratable acidification of a beverage with its erosive potential; The greater the concentration of acid in the drink, the greater the damage to the teeth. US Pat. No. 91 / 071-17 discloses a method for preventing tooth enamel erosion by consuming an acidic beverage (having a pH less than 5.5) comprising from 0.02% to 0.15% calcium in the form of a complex. of calcium citrate malate that has a molar ratio of citrate to malate from 1: 0.5 to 1: 4.5. in the calcium citrate malate complexes the molar ratio of total moles of calcium: total moles of citrate: total moles of malate may be from about 2: 1: 1 to about 6: 3: 4. A preferred complex for beverages has the molar ratio 4: 2: 3. We have found that the inclusion of high levels of calcium in beverages gives acceptance problems. The present invention is based on the discovery that effective reduction of the Erosion of the teeth in oral acid compositions can be achieved with lower amounts of calcium relative to the acidulant when the pH of the composition is also controlled. In one aspect, the present invention provides a liquid composition for oral use containing a calcium compound and an acidulant characterized in that calcium is present in the range of 0.3 to 0.8 moles per mole of acid and that the amount of calcium and acidulant in the composition it is selected so that the pH of the composition is from 3.5 to 4.5. In another aspect, the present invention provides the use of calcium as an inhibitor of tooth erosion in an acidic liquid composition for oral use by adding a calcium compound to the composition so that calcium is present in the range of 0.3 to 0.8. moles per mole of acid, the amount of calcium and acidulant in the composition is selected such that the pH of the composition is 3.5 to 4.5. In a further aspect, the present invention provides a method for reducing the erosion properties of the teeth of an oral acid composition which comprises adding a calcium compound to the liquid oral acid composition so that calcium is present in the scale of 0.3 to 0.8 moles per mole of acid and if necessary, or desired, adjust the pH by the addition of an alkali so that the pH of the composition is 3.5 to 4.5. In a still further aspect, the present invention provides a process for preparing a composition of this invention that it comprises adding a calcium compound to an acidic liquid oral composition so that calcium is present in the range of 0.3 to 0.8 moles per mole of acid and if necessary, or desired, adjusting the pH by adding an alkali of so that the pH of the composition is 3.5 to 4.5. The present invention can be applied to acidic substances for oral consumption, such as acid drinks, fruit juices, ciders, wines, vinegars and pickles and various acid dairy products and also or other liquid substances that will be taken orally such as mouth rinses and medicines. acids. The practice of the present invention does not cause taste flaws in beverages. Although it could be expected that the increase in pH of a beverage at around pH 4 reduces the sharpness in taste provided by the acidulant, surprisingly the inclusion of calcium according to this invention mitigates this. An additional advantage arises from the use of low calcium levels according to this invention in the form of an alkaline salt. The pH-regulating capacity of the formulation is reduced by the partial neutralization of the acid, which allows the saliva to more quickly neutralize the residues in the mouth. The absolute concentration of calcium used in the present invention is critical since this will vary according to the nature and concentration of the acids present. The acid solution may contain organic and / or inorganic acids and may be supplemented with vitamins such as ascorbic acid. In a concentrated drink that will be diluted with up to five parts of water before consumption, the calcium concentration can vary from 0.001 moles per liter to more than 0.05 moles per liter. In a ready-to-drink beverage the concentration of calcium ions can vary from 0.002 moles per liter to more than 0.01 moles per liter. Calcium can be added as any convenient salt such as calcium carbonate, calcium hydroxide, calcium citrate, calcium maleate, calcium lactate, calcium chloride, calcium glycerophosphate or calcium formate or any other salt to minimize any contribution of adverse taste to the composition. The invention can be carried out by mixing the acid (e.g., citric acid) with its corresponding calcium salt (e.g., calcium citrate) or another calcium salt. It may be advantageous to mix the acid with an alkaline calcium salt such as calcium carbonate or calcium hydroxide thereby minimizing the concentration of acid applied to the formulation. The acid can also be mixed with inorganic calcium salts such as calcium chloride. The molar ratio of calcium to acid can be from 0.3-0.75, more usually from 0.3-0.65, preferably from 0.3-0.55. Even more preferably the molar ratio is at least 0.4 and a value of about 0.5 has been found to be especially effective. The pH of the formulation can be adjusted to the desired scale by the addition of the calcium compound at the appropriate ratio relative to the acid. If necessary, depending on the acid present, the pH can also be adjusted by the application of an alkali, e.g. , sodium hydroxide or a suitable salt, for example, sodium citrate, sodium malate or sodium lactate. The pH of the composition preferably is not greater than 4, more preferably from 3.7 to 3.9. It has been found that compositions with a pH of about 3.8 are especially effective. The normal concentration of citric or malic acid in a concentrated fruit drink would be on the scale from 0.1% w / w to 4% w / w. In a ready-to-drink beverage, acid concentrations are usually in the range of 0.01% w / w to 1% w / w. Other conventional drinking acids can also be used for beverages also such as lactic acid. Mixtures of drinking acids can be used. In a preferred embodiment, the acid composition is a beverage concentrate prepared from a natural fruit juice, such as cassis juice, for example a flavored syrup concentrate. Calcium can be added in a suitable form to either the concentrate, especially when the beverage is sold to the consumer as a concentrate for dilution before drinking, or when diluting the syrup concentrate for the preparation of a diluted concentrate "ready to be drunk " Preferably, the product contains reduced levels of sugar or carbohydrate or is low calorie type containing intense sweeteners.

The oral composition may contain magnesium or other ions as adjuncts for remineralization. It may also contain an effective amount of malic acid or potable salts thereof to maintain the solubility of calcium so as to avoid or minimize the precipitation of insoluble calcium salts. The added malic acid can provide as little as 10% of the total acidity of the beverage, the rest of the acidity being provided by other acids, preferably present in nature such as citric acid or ascorbic acid. The invention can be applied in a variety of beverages such as concentrates, distilled fruit drinks, or soft carbonated beverages in particular to health drinks such as cassis fruit drinks or drinks with added vitamin. The invention is advantageously applied to beverages containing natural or added citric acid. The beverages can be unsweetened or sweetened with sugar or intense sweeteners such as saccharin, aspartyl phenyl alanyl methyl ester or other sweeteners known in the art. The beverages may also contain other conventional additives such as sodium benzoate, sorbic acid, sodium metabilsulfite, ascorbic acid, flavorings, colorants and carbon dioxide. The drinks can be prepared by mixing the ingredients according to conventional methods. If required, the solid ingredients can be dissolved in water or in hot water before addition to the other components. Usually the Beverages are pasteurized before filling in bottles or cans or other packaging or "pasteurized in their packaging" after filling.

The invention is illustrated by the following Examples: Example 1 A concentrated beverage product, for dilution with five parts of water before consumption was prepared by mixing the ingredients in the following manner. Calcium carbonate was added to the other ingredients as a final addition.

Concentrate of cassis juice SG 1 .27 84 liters Aspartyl phenyl alanyl methyl ester * 1. 15 Kg Acesulfame K 1 .8 Kg Ascorbic acid 0.8 Kg Sodium Benzoate 0.325 Kg Sodium metabisulphite 0.145 Kg Casis flavoring 0.3 liters Water up to the final volume of 1000 liters Calcium Carbonate 4.2 Kg 'sold as Aspartame (RTM) The molar ratio of calcium: acid is 0.5 The concentrate was adjusted to pH 3.7 with sodium hydroxide solution. When diluting the concentrate with five parts of water (to reinforce the drink), the pH of the composition is usually found to be 3.85.

In vitro planometry tests were carried out in which the flat sections of dental enamel were exposed to test solutions at a temperature of 37 ° C for 30 minutes. The erosive potential was assessed by physically measuring the depth of enamel loss during the procedure. Whereas in a control formulation comprising 14 mM citric acid, the pH of 3.2 resulted in a loss of 4 enamel microns and an additional control formulation of 14 mM citric acid, pH 3.85, removed 1.8 microns , a test formulation with adjusted pH and added calcium comprising 14 mM citric acid, 7 mM calcium, pH 3.85 removed only 0.17 microns of enamel, demonstrating the utility of the invention. Example 2 A ready-to-drink beverage was prepared by mixing the ingredients as follows: Ingredients% w / w Sugar 10 Sodium Benzoate 0.01 Orange juice 5.04 Ascorbic Acid 0.03 Citric acid monohydrate 0.15 Flavoring 0.005 Coloring 0.004 Water by difference 86 Calcium Carbonate 0.048 Sodium Hydroxide sufficient to adjust to pH 3.9 Carbon Dioxide 0.48 In this drink the molar ratio of calcium: acid is 0.46 (orange juice is usually 1% w / w citric acid). Example 3 A ready-to-drink beverage was prepared by mixing the ingredients as follows: Ingredients% w / w Sugar 8 Sodium Benzoate 0.01 Apple juice 10 Ascorbic Acid 0.03 Malic acid 0.15 Flavoring 0.005 Coloring 0.004 Water by difference 82 Calcium Carbonate 0.093 Sodium hydroxide sufficient to adjust to pH 3.9 In this drink, the molar ratio of calcium: acid is 0.74 (apple juice is normally 0.6% w / w malic acid).

Example 4 In vivo study A drink was produced by mixing the ingredients as follows: Blackcurrant concentrate 16.78 liters Phenyl alanyl methyl ester aspartyl 0.54 kg Acesulfame K 0.1 1 kg Ascorbic acid 0.45 kg Flavor 0.55 liters Calcium hydroxide 0.52 kg Water up to 1000.00 liters The calcium hydroxide was added as a slurry with a portion of the water as a final addition and was sufficient to produce a beverage containing calcium in a molar ratio of 0.5: 1 of calcium to citric acid. The resulting beverage had a pH of 3.8. The batch was pasteurized instantaneously and packaged in 250 ml "Tetra-Brik" containers. In this study, the loss of human enamel was compared between three drinks: the previous example, an orange juice as a positive control (pH 3.8) and water as a negative control. Twelve volunteers participated in the study in a cross-shaped square "Latin" of three treatments. Each study period consisted of three weeks counting each one with five days of the week. In each study period, a section of enamel of a healthy extracted tooth was carried on a device for seven hours each day of the week. On four occasions during this period 250 ml of the test drink was sipped gradually under supervision, for a period of ten minutes. The subjects were allowed to remove the apparatus to consume a food at noon but were not allowed to consume food or other beverages while the apparatus was in place. The enamel specimen was measured by planometry (the principles of the method have been described by Davis and Winter (1977) British Dental Journal 143. 116-119) at the beginning of the treatment period and at the end of each week of treatment. All readings were carried out in duplicate. After a washout period, each subject then began the next treatment period with a fresh enamel specimen. The results are given in the following table and represent the microns of enamel lost by the treatment provided after the given exposure time and the means found for the twelve subjects.

The results show that the cassis formulation was minimally erosive, a little more erosive than water and highly significant, less erosive than orange juice. Example 5 In vitro test To investigate the importance of calcium supplementation by exposing the enamel to citric acid solutions, the five experiments were carried out, each using eight teeth. The teeth were first subjected to prophylaxis, washed with saline and then covered in an acid-resistant wax with the exception of an experimental window of 5 μm in diameter. In each experiment, the teeth were subjected to six consecutive exposures of 5 min utes with citric acid solutions at 0.3% at a flow rate of 0. 1 μl / m in. The citric acid solutions were supplemented with 0.0, 0.5, 2.5, 5.0, 7.5, 10 or 15 mM calcium in the form of calcium hydroxide and the pH was adjusted to 3.5 or 3.8 using 1.0 M sodium hydroxide. . Samples of residual citric acid were collected after every 5 minutes of tooth exposure and then gelled at -4 ° C, before phosphorus analysis by the method of Chen et al. (1956) Analytical Chemistry, Vol. 28 , p 1 956-8. The summaries are illustrated below This experiment clearly illustrates that the addition of calcium to a 0.3% citric acid solution reduces its potential erosive. The effect is greater up to a molar ratio of calcium to acid of approximately 0.5 (approximately 7.5 mM calcium). A justifiable decrease in erosive potential can not be achieved by increasing the molar ratio of calcium: acid beyond this point. Example 6 A flavored concentrate was prepared by mixing the following ingredients with stirring. The calcium hydroxide was added to the latter as a slurry in cold water and the volume was adjusted to 1000 liters with water. Ingredient Unit Quantity Blackcurrant concentrate L 67. 1 Binder Kg 3.33 Ascorbic Acid Kg 2.28 Preservatives Kg .0.45 Flavors L 1 .2 Calcium Hydroxide Kg 2.96 Water up to 1000 liters The beverage concentrate was pasteurized instantaneously at 93 ° C for 42 seconds and filled into 600 ml bottles. The molar ratio of calcium and citric acid was of p.4 and the final pH was 3.7. When diluted with five parts of water to make the beverage stronger, the pH of the composition was found to be 3.85 and the taste of the beverage was described as normal cassis fruit. The beverage concentrate was tested for storage stability at both room temperature and 30 ° C. After a period of 9 months, no insoluble calcium precipitation was observed. Example 7 In vivo study A drink was produced by mixing the ingredients as follows: Cassis concentrate 10.07 liters E: ester Aspartyl phenyl alanyl methyl 0.21 kg Acesulfame K 0.07 kg Ascorbic acid 0.27 kg Lactic acid at 80% w / w 0.66 liters Potassium sorbate 0.1 kg Sodium metabisulfite 0.02 kg Flavor 0.56 liters Calcium hydroxide 0.52 kg Water up to 600.00 liters Calcium hydroxide was added as a slurry with a portion of the water as a final addition and was sufficient to produce a beverage containing calcium in a molar ratio of 0.45: 1 calcium to citric acid / lactic acid. The resulting beverage had a pH of 3.85. The batch was packed in 250 ml containers and pasteurized "in the package". In this study, the loss of human enamel was compared between four drinks: the previous example, a commercially available blackcurrant fruit drink with a pH of 3.0 without added calcium, an orange juice drink as a positive control (pH 3.9) and water as a negative control. Twelve volunteers participated in the study. Each study period consisted of three weeks each consisting of five days of the week. In each period of the study, a section of enamel of a healthy extracted tooth was carried in an appliance for seven hours each day of the week. On four occasions during this period, 250 ml of the test drink was sipped gradually, under supervision, for a period of 10 minutes. Subjects were allowed to remove the device to consume a half-day meal, but were not allowed to consume food or other beverages while they were wearing the device. The enamel specimen was subjected to measurements by planometry (the principles of the method have been described by Davis and Winter (1977) Britsh Dental Journal 143, 1 16-1 19) at the beginning of the treatment period and at the end of each week of treatment . All readings were carried out in duplicate. After a washout period, each subject then began the next treatment period with a fresh enamel specimen. The results are given in the following table and represent enamel loss microns for the treatment given after the given exposure time.

The results show that the blackcurrant formulation was found to be minimally erosive, almost no more erosive than water, and highly significantly less erosive than orange juice or commercial blackcurrant drink. Example 8 A concentrate of cola was prepared by mixing the following ingredients A cola syrup with a 1 +5 strip was then prepared by mixing the following ingredients Calcium hydroxide was added as a slurry with a portion of the water as a final addition and the cola syrup was then diluted with carbonated water, canned and pasteurized in the package to produce a finished product with a pH of 3.5 yu Molar ratio of calcium to acid of 0.6.

Example 9 A mouthwash was prepared by mixing the following ingredients: The ethanol, cetylpyridinium chloride, Tego Betaine CK-KB5 (trademark for a cocamide propyl betaine) and flavoring, were mixed together to form a clear solution. In a separate container, the rest of the ingredients were mixed. The ethanolic solution was then added to the aqueous solution to produce a mouthwash with a pH of 4.5 and a molar ratio of calcium to acid of 0.4. E-example 10 A ready-to-drink beverage was prepared by mixing the following ingredients: Ingredients% p / v Sodium Benzoate 0.01 Malic Acid 0.30 Flavoring 0.1 Artificial Sweetener 0.05 Water by Difference 99.5 Calcium Hydroxide 0.083 The resulting pH of the composition is usually found to be 3.85 and has a molar ratio of calcium to acid of 0.5. In vitro planometry tests were carried out in which the flat enamel sections were exposed to test solutions at a temperature of 37 ° C for 30 minutes. The erosive potential was evaluated by physical erosion of the depth of enamel loss during the procedure. Whereas a control formulation lacking the addition of calcium hydroxide gave a pH of 2.5 and resulted in a loss of 8.1 microns of enamel and an additional control formulation in which the pH of the beverage was increased. { or at pH 3.85 having sodium hydroxide 1.65 microns removed, the detailed composition before removed only 0.6 microns of enamel. Demonstrating its usefulness to reduce tooth erosion.

Claims (22)

1. CLAIMS 1. A liquid composition for oral use containing a calcium compound and an acidulant characterized in that calcium is present in the range of 0.3 to 0.55 moles per mole of acid and that the proportion of calcium and acidulant in the composition is selected from so that the pH of the composition is 3.5 to 4.5.
2. 2. A composition according to claim 1, wherein the calcium is present in an amount of at least 0.4 moles per mole of acid.
3. 3. A composition according to claim 1 or 2, wherein the pH of the composition is not greater than 4.
4. 4. A composition according to any of claims 1 to 3, wherein the pH is 3.7. to 3.9.
5. 5. A composition according to any of claims 1 to 4, wherein the acid is citric acid or malic acid or lactic acid or mixtures thereof.
6. 6. A composition according to any of claims 1 to 5, wherein the calcium compound is calcium carbonate, calcium hydroxide, calcium citrate, calcium malate, calcium lactate, calcium chloride, calcium glycerophosphate or calcium format.
7. 7. A composition according to any of claims 1 to 6, which is a beverage.
8. 8. A composition according to claim 7, wherein the beverage is distilled fruit drink or a soft carbonated beverage or preferably a healthy beverage.
9. 9. A composition according to claim 8, wherein the healthy drink is drink of blackcurrant juice or a drink with added vitamin.
10. 10. A composition according to any of claims 1 to 6, which is a beverage concentrate for the preparation of a beverage.
11. 1 1. A composition according to claim 10, which is a concentrate for a fruit drink or healthy beverage.
12. 12. A composition according to any of claims 1 to 6, which is an oral composition for health care.
13. 13. A composition according to claim 12, which is a mouth rinse.
14. 14. Use of calcium as an inhibitor of tooth erosion in an acidic liquid composition for oral use by adding a calcium compound to the composition so that calcium is present in the range of 0.3 to 0.55 moles per mole of acid, the amount of calcium and acidulant in the composition being selected so that the pH of the composition is 3.5 to 4.5.
15. 15. Use according to claim 14, wherein the calcium is present in an amount of at least 0.4 moles per mole of acid.
16. 16. Use according to claim 14 or 15, wherein the pH of the composition is not greater than 4.
17. 17. Use according to any of claims 14 to 16, wherein the pH is from 3.7 to 3.9.
18. 18. Use according to any of claims 14 to 16, in which the liquid acid composition is a natural fruit juice beverage concentrate.
19. 19. A process for preparing a composition according to any of claims 1 to 13, which comprises adding a calcium compound to an acidic oral liquid composition such that calcium is present in the range of 0.3 to 0.55 moles. per mole of acid and if necessary or you want to adjust the pH by adding an alkali so that the pH of the composition is 3.5 to 4.5.
20. 20. A process according to claim 19, wherein the acid liquid composition is a beverage concentrate of natural fruit juice. twenty-one .
21. A method for reducing the erosion properties of teeth of an oral acid composition which comprises adding a calcium compound to the acidic oral liquid composition such that calcium is present in the range of 0.3 to 0.55 moles per mole of acid. , and if necessary or it is desired to adjust the pH by the addition of an alkali so that the pH of the composition is from 3.5 to 4.5.
22. 22. A method according to claim 21, wherein the liquid acid composition is a natural fruit juice beverage concentrate. RESU MEN Acid oral compositions that have reduced tooth erosion characteristics, especially known beverages such as fruit juice beverage concentrates or oral health care products such as mouth rinses, are prepared by adding a calcium compound to the acid composition so that the molar ratio of calcium to acid varies from 0.3 to 0.8, and the pH of the composition, if necessary after adjustment with an alkali, is 3.5 to 4.5.