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ACIDIC SOLID ORAL COMPOSITIONS WITHOUT EROSIVE POTENTIAL IN SALIVA AND METHOD FOR DETERMINING EROSIVE POTENTIAL IN SALIVA

20170216167 ยท 2017-08-03

    Inventors

    Cpc classification

    International classification

    Abstract

    Acidic oral compositions having calcium contents and effective pH-values in the area indicated by grey-tone in FIG. 2 are non-erosive in saliva and capable of stimulating saliva production, even in dry mouth patients. A new multi-step test method for determining erosive potential in saliva has been used for identifying the compositions.

    Claims

    1. An acidic solid oral composition, which is a boiled sweet, a candy, a lollipop, a jelly, a chewing gum, a drop, a pastille, a lozenge, an ice cream, a sorbet or a tablet, with reduced erosive potential in saliva, comprising a calcium component and an acid component, wherein the amounts of calcium component and acid component in the solid oral composition are adjusted so as to provide (i) a pH in the range of 2.2 to 3.2, when the solid oral composition is dissolved in an equal amount by weight of highly purified water, and (ii) a calcium content in the acidic solid oral composition within the following limits:
    175(50.Math.pH)calcium content (mmol/kg)660(200.Math.pH), the pH being as indicated above, with the proviso that the composition does not include a polyphosphate being a phosphate polymer wherein the number of phosphate groups (n) is at least 3.

    2. A solid composition according to claim 1, wherein the mole ratio of calcium component to acid component is in the range of 0.3 to 0.8.

    3. A solid composition according to claim 2, wherein the mole ratio of calcium component to acid component is in the range of 0.4 to 0.7.

    4. A solid composition according to claim 1, wherein the pH, determined as indicated in claim 1, is between 2.5 and 3.2.

    5. A solid composition according to claim 4, wherein the pH, determined as indicated in claim 1, is between 2.6 and 3.1.

    6. A solid composition according to claim 1, wherein the calcium component is selected among calcium carbonate, calcium hydroxide, calcium citrate, calcium malate, calcium lactate, calcium chloride, calcium glycerophosphate, calcium acetate, calcium sulphate, and calcium formate, or hydrates or combinations thereof.

    7. A solid composition according to claim 6, wherein the calcium component is calcium lactate.

    8. A solid composition according to claim 1, wherein the acid component is selected from the group consisting of citric acid, malic acid, ascorbic acid, tartaric acid, acetic acid, fumaric acid and lactic acid.

    9. A solid composition according to claim 1, which is intended for being sucked or chewed.

    10. A method for stimulating the saliva production in an individual comprising orally administering a solid composition according to claim 1 to the individual.

    11. A method according to claim 10, which is not for treatment of the human or animal body by therapy.

    12. A method according to claim 10, for alleviating the sufferings of an individual having impaired saliva production.

    13. A method according to claim 12, wherein the impaired saliva production is caused by a disease such as Sjgren's syndrome, cystic fibrosis, diabetes or an eating disorder.

    14. A method according to claim 12, wherein the impaired saliva production is caused by a therapeutic treatment, such as a medical treatment or radiotherapy.

    15. A method for determining the erosive potential in saliva of an oral composition, comprising the steps of: bringing the oral composition to be tested into contact with saliva in the mouth, collecting a sample of the saliva under conditions so as to prevent CO.sub.2 from escaping from the sample, measuring the pH of the sample collected under b), removing CO.sub.2 from the sample, optionally assisted by vacuum and/or addition of a non-volatile acid, adjusting the pH of the sample to the value measured under c) using a non-volatile acid or, if necessary, a non-volatile base, adding tooth substance to the sample obtained from step e), and observing any rise in the pH, if a rise in pH is observed in step f), titrating the sample to the pH value measured in c) using an acid, and calculating the amount of tooth substance eroded based on the amount of acid consumed in step g).

    16. The method according to claim 15, wherein the non-volatile acid optionally used in step d) is a strong acid.

    17. The method according to claim 15, wherein the non-volatile acid is HCl or HNO.sub.3.

    18. The method according to claim 15, wherein the tooth substance is hydroxyapatite.

    19. The method according to 18, wherein the hydroxyapatite is of non-dental origin.

    20. The method according to claim 15, wherein the acid used for titration is HCl.

    21. A solid composition according to claim 1, which, when tested in randomly selected healthy test persons by a method comprising the steps of: bringing the oral composition to be tested into contact with saliva in the mouth, collecting a sample of the saliva under conditions so as to prevent CO.sub.2 from escaping from the sample, measuring the pH of the sample collected under b), removing CO.sub.2 from the sample, optionally assisted by vacuum and/or addition of a non-volatile strong acid, adjusting the pH of the sample to the value measured under c) using a non-volatile acid or, if necessary, a non-volatile base, adding tooth substance to the sample obtained from step e), and observing any rise in the pH, if a rise in pH is observed in step f), titrating the sample to the pH value measured in c) using an acid, and calculating the amount of tooth substance eroded based on the amount of acid consumed in step g), no rise in pH in step f) is observed, within a period of 5 minutes for at least 90% of the test persons.

    Description

    BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

    [0062] FIG. 1 illustrates the amount of tooth substance lost by dental erosion versus time by testing of a candy according to the invention and a control candy, respectively.

    [0063] FIG. 2 is a graphic representation illustrating calcium content in mmol/kg versus effective pH for compositions according to the invention as well as some compositions, which are not according to the invention.

    [0064] As will appear from the explanations given above, the erosive potential of a composition in saliva cannot be theoretically calculated, but will have to be tested. However based on experiments with compositions, which have been shown to be non-erosive, the following correlation between the amount of calcium component and the effective pH was initially found:


    calcium content (mM)=65010-200.Math.pH

    [0065] The actual pH-ranges, within which the correlation applied were not established initially, but at least the correlation was expected to exist within the pH-range from 2.6 to 3.1.

    [0066] Later experiments have confirmed this pH range and even broadened it to pH 2.2 to 3.2. Likewise the range of calcium content in mM or mmol/kg has been broadened to:


    175-50.Math.pHcalcium content (mmol/kg)660-200.Math.pH.

    [0067] The pH value is the pH obtained when the solid oral composition is dissolved in an equal amount by weight of highly purified water, i.e. the effective pH.

    [0068] The correlation between effective pH and calcium content in mmol/kg has been illustrated graphically in FIG. 2.

    [0069] In the following the invention will be further described by examples, which shall not be regarded as limiting for the scope of the invention.

    EXAMPLES

    Example 1

    Preparation of Solid Candy

    [0070] In a mini cooker 800 ml water is added 3 kg isomalt and 0.3 mg sweetener (Acesulfame-K) during stirring. The stirring is continued until a homogenous solution is obtained. Subsequently the temperature is raised to about 162 C. and the mixture is boiled. When the temperature has decreased to 110 C. the stirring is discontinued and the dough is withdrawn from the mini cooker and applied on a heated table.

    [0071] The dough is added 4.5 ml red colour (camine E120) and kneaded so as to obtain a uniform distribution of the colour. Then, 6 ml aroma (strawberry and rhubarb in 2:1 ratio) is added and kneaded into the dough. Subsequently, 30 g tartaric acid (mol weight: 151 g/mol) and 49.5 g calcium lactate penta hydrate (mol weight: 308 g/mol) are added and mixed thoroughly with the dough. Long strings of dough are prepared and cut into appropriate pieces of candy. The candy is allowed to cool to room temperature.

    [0072] A candy was added an equal amount by weight of water (Millipore), i.e a 1:1 ratio of candy and water was formed, and allowed to stand for 1 hour. After an hour the candy was completely dissolved. In the resulting solution the pH was measured with a calibrated electrode to 2.95.

    [0073] The mole ratio of calcium component to acid component can then be calculated as

    [00001] 49.5 .Math. .Math. g .Math. .Math. calcium .Math. .Math. lactate .Math. .Math. penta .Math. .Math. hydrate / 308 .Math. .Math. g .Math. / .Math. mole 30 .Math. .Math. g .Math. .Math. tartaric .Math. .Math. acid / 151 .Math. .Math. g .Math. / .Math. mole = 0.82

    Example 2

    Preparation of Jellies

    [0074] 8 g gelatine (250 Bloom) is dissolved completely in 17 g 80 C. water under constant stirring. 4 g dextrose is added to the gelatine solution under constant stirring until the mixture is homogenous. Then, 20 g sucrose and 49 g glucose syrup (48 DE) are added and the stirring is continued until the mixture is homogeneous. This mixture is then boiled until brix 75, which happened at 108 C. (vacuum at 0.6 atm). After the boiling step the mixture is added 10 g tartaric acid (mol weight: 151 g/mol), 16.5 g calcium lactate penta hydrate (mol weight: 308 g/mol), 0.15 ml red colour (camine E120) and 0.6 ml aroma (strawberry and rhubarb in 2:1 ratio) and mixed to obtain a homogenous solution. The pH in the liquid mixture is adjusted with tartaric acid to a pH of 3.2 as measured with a standard pH electrode. A sample was withdrawn and mixed with an equal amount by weight of water. The pH of this diluted sample was measured as pH 3.2. The mole ratio of calcium component to acid component is

    [00002] 16.5 .Math. .Math. g .Math. .Math. calcium .Math. .Math. lactate .Math. .Math. penta .Math. .Math. hydrate / 308 .Math. .Math. g .Math. / .Math. mole .Math. 10 .Math. .Math. g .Math. .Math. tartaric .Math. .Math. acid / 151 .Math. .Math. g .Math. / .Math. mole = 0.82

    [0075] The solution is cast in an adequate shape and allowed to cool to room temperature.

    Example 3

    Test for Erosive Potential of Oral Composition

    [0076] Candies as produced in example 1 were used in this example to illustrate the erosive potential. A control candy comprising the same components as the example 1 candy except for calcium lactate was also produced.

    [0077] Ten randomly selected healthy test persons (5 males and 5 females) sucked 5 grams of the candy habitually for 5 minutes while his/her stimulated whole mouth saliva was collected every 30 seconds for 5 minutes. A closed saliva collection system was used to avoid saliva CO.sub.2 evaporation and thus pH changes during collection.

    [0078] Immediately after collection, the pH of the saliva was determined in a closed system, and the pH was recorded for each of the collections (i.e. first min, second min, etc.). The saliva was then poured into an open glass and salivary CO.sub.2 was removed by vacuum during constant stirring and the sample was acidified (1M HCl) until the pH obtained immediately after collection was reached.

    [0079] Pure hydroxyapatite crystals (HAp) equal to 2 mg per ml saliva (i.e. 2 mM HAp) were added to each of the saliva samples. The grain size of the HAP crystals was 1 m and they were supplied by Merck Crystals. The pH rise, if any, was recorded continuously at 15-second interval for 5 minutes at room temperature. The test procedures mimic an in vivo condition, which is comparable to sucking on 5 gram of the candy for 5 minutes in vivo.

    [0080] In case there was no pH rise, the hard-boiled candy was assessed as non-erosive.

    [0081] A pH rise indicated that dissolution of HAp crystals had taken place and that the candy was erosive. To quantify the amount of dissolved HAp a back titration with acid (1M HCl) was performed 5 minutes after the HAP addition. The amount of HAp crystals lost per minute in the candy containing saliva could then be calculated from the amount of l 1M HCl needed to reach the pH obtained immediately after collection of saliva using the equation stated in example 2.

    [0082] From the data obtained the erosive potential can be computed as the slope of curve (g HAp lost per minute of exposure for candy containing saliva) by linear regression. The result of the experiment is shown on FIG. 1, in which the candy acc. inv. is the candy according to example 1 and the control candy is the candy lacking calcium lactate. The results show that the calcium-modified candy according to the invention was acidic as well as non-erosive due to the interplay between calcium component, saliva buffer capacity, and salivary protein protection.

    Example 4

    [0083] Candies of the compositions indicated in Table 1 were prepared in a similar manner to Example 1 and tested for erosive potential using the test method described in example 3 with the results likewise indicated in the table.

    TABLE-US-00001 TABLE 1 Ca comp. Ca Acid comp. Acid Ca/acid Effective Test (g) (mmol/kg) (g) (mmol/kg) mole ratio pH Erosive 1 0.0 0 7.0 47 0.00 2.00 YES 2 0.0 0 5.0 33 0.00 2.25 YES 3 0.0 0 3.0 20 0.00 2.60 YES 4 49.1 160 60.2 400 0.40 2.40 NO 5 11.0 36 13.0 87 0.41 2.20 YES 6 16.5 54 18.0 120 0.45 2.50 NO 7 43.0 140 46.8 311 0.45 2.50 NO 8 10.0 33 10.0 67 0.49 2.40 YES 9 16.5 54 16.0 107 0.50 2.64 NO 10 9.0 29 8.0 53 0.55 2.60 YES 11 8.1 26 7.0 47 0.56 2.70 YES 12 16.5 54 14.0 93 0.57 2.76 NO 13 12.3 40 10.0 67 0.60 2.87 NO 14 36.8 120 30.1 200 0.60 2.64 NO 15 15.4 50 12.5 83 0.60 2.84 NO 16 18.5 60 15.0 100 0.60 2.73 NO 17 16.5 54 12.0 80 0.67 2.81 NO 18 7.0 23 5.0 33 0.68 2.85 YES 19 27.6 90 22.1 147 0.70 2.81 NO 20 15.0 49 10.0 67 0.73 2.87 NO 21 16.5 54 10.0 67 0.80 2.91 NO 22 37.0 120 15.0 100 1.20 3.24 NO 23 31.0 101 12.5 83 1.21 3.20 NO 24 25.0 81 10.0 67 1.22 3.27 NO 25 10.7 35 7.3 48 1.25 3.32 NO

    [0084] Some of the compositions, which were found non-erosive by the test, were found unsatisfactory from other points of view, either because of the effective pH being too high to give an adequate saliva stimulating effect or because of the calcium content being to high to give an acceptable taste.

    [0085] The correlation between effective pH and calcium content in mmol/kg for tests 1-25 has been illustrated graphically in FIG. 2, wherein the area between the lines Y=660-200.Math.X and Y=175-50.Math.X in the range from X=2.2 to 3.2 (marked in grey tone) illustrates compositions according to the invention (marked with +), i.e. compositions, which have qualified as non-erosive in human saliva by the above test, have an adequate acidity to provide the desired saliva secretion stimulation, and a calcium content, which is sufficiently low to provide an agreeable taste. Compositions marked by have been found erosive, whereas compositions marked by ++ have been found non-erosive, but with an unacceptable taste because of an excessive amount of calcium, and the composition marked by +++ non-erosive, but with too low acidity to provide the desired saliva secretion 15 stimulation.

    Example 5

    Test for Saliva Stimulating Effect

    [0086] A group of 20 healthy individuals was given a candy of the composition according to test 21, and the amount of saliva produced by sucking the candy was recorded. The amount of saliva produced by sucking the candy was compared with the amount of saliva produced by the same individuals within the same period of time without any stimulation of the saliva production. The test showed a more than tenfold increase in saliva production by sucking the candy.

    [0087] A corresponding test carried out on a group of 10 dry mouth patients showed a fold increase in saliva production by sucking a candy of the composition according to test 21.