HK1114574B - Acidic solid oral compositions without erosive potential in saliva and method for determining erosive potential in saliva - Google Patents

Description

Acidic solid oral composition without erosive potential in saliva and method for determining erosive potential in saliva

Technical Field

The present invention relates generally to solid oral compositions that undergo an acidic response when dissolved in an aqueous liquid such as saliva. More particularly, the present invention relates to acidic solid oral compositions having a reduced erosive potential in saliva and to the use of specific amounts of a calcium component and an acid component to reduce erosive potential. The invention also relates to methods of stimulating saliva production and to the use of a calcium component and an acid component to make an acidic solid oral composition for alleviating the pain of an individual with impaired saliva production. Furthermore, the present invention relates to a method for determining the erosive potential of an oral composition in saliva.

Background

Dental erosion refers to the loss of hard dental tissue by a chemical process, involving no bacteria and thus being unrelated to plaque. One of the most important factors causing dental erosion is external exposure to acids. Dental erosion has been found to be an increasing threat to dental health, and frequent consumption of soft drinks and acid-containing foods (citrus fruits and sweets) are important factors in the development of dental erosion. The general concern for dental erosion is growing rapidly. Therefore, it is important for manufacturers to consider developing new methods of food products that meet the consumer's acidic stimulation needs while not causing or reducing dental erosion.

Generally, the low pH in the mouth and around the teeth is the primary cause of dental erosion. Hard parts of human teeth are crystallized from hydroxyapatite (HAp) (Ca)₁₀(PO₄)₆(OH)₂) And (4) forming. In teeth, HAp crystals are arranged in a dense structure, constituting the hardest tissue in the body. However, when teeth come into contact with low pH liquids (such as acidic soft drinks or saliva containing dissolved acidic candies), the HAp crystals will dissolve due to Ca in the liquid²⁺、PO₄ ^3-And OH^-Dental erosion occurs due to a shortage of ions (components of HAp).

The prior art has developed beverages supplemented with significant amounts of calcium for nutritional purposes. Dietary calcium deficiency is responsible for osteoporosis, at least in some people. For example, a positive correlation between calcium uptake and bone mass is found in many age groups. It has also been found that the levels of calcium taken early in life directly affect the peak bone mass at bone maturation.

U5,028,446 discloses a method for preparing a rapidly dissolving calcium fumarate for producing calcium fortified beverages. The process comprises preparing a mixture of fumaric acid and a calcium-containing base wherein the molar ratio of calcium to fumarate is from 1: 2 to about 1: 1. Mixtures of fumaric acid with calcium are indicated to have improved solubility characteristics useful in the preparation of calcium-fortified beverages such as tea.

Another calcium fortified beverage is disclosed in EP 227174. The beverage is substantially free of sugar alcohols and has a weight ratio of calcium to a mixture of citric acid, malic acid and phosphoric acid of from 1/4 to 1/7. The beverage is said to have a satisfactory initial taste and mouthfeel, be substantially free of an unpleasant aftertaste and have the desired calcium absorption/bioavailability. Typically, the pH of the resulting beverage is about 4.3.

A dry mixture for reconstitution comprising citric acid and one or more calcium compounds is disclosed in WO 88/03762. The instant beverage has a calcium/citric acid molar ratio of 0.6 to about 3.0. The solubility of mixtures with different ratios between calcium and citric acid depends on the pH. The solubility was measured at a pH between 2.0 and 7.0, with the pH of the freshly prepared actual beverage being 4.15 and above. The composition can be used as a liquid dietary calcium supplement.

US3,734,742 discloses a sealed or canned bottled aqueous beverage comprising at least about 80% water and having a pH of 2.0-3.4, an ascorbic acid content of 0.056-1.120mg/ml and a ferrous ion content of 0.008-0.15 mg/ml. The purpose of this us patent is to obtain a beverage supplemented with iron and ascorbic acid.

None of the above references mention dental erosion.

As described in the introduction above, acidic compositions for consumption tend to attack dental components, particularly hydroxyapatite components. Several publications address this problem. EP634110a2 relates to nutrient, vitamin and mineral fortified, fruit-based liquid food products having an acid content, measured as tartaric acid, of at least 5 g/l and a calcium phosphate content of at least 2 g/l. The pH is below 4.5, the actual value is between 3.9 and 4.15. Calcium phosphate is believed to reduce the adverse effects of acidic liquid foods on dental substances. Another liquid oral composition comprising a calcium compound and an acid compound is disclosed in WO 97/30601. The liquid composition contains 0.3-0.8 moles of calcium per mole of acid and as an important feature the amount of calcium and acid in the composition is selected so that the pH of the composition is 3.5-4.5. Yet another acidic beverage is disclosed in US5,108,761, which is said to inhibit enamel erosion. The beverage of US5,108,761 comprises calcium citrate malate to reduce dental erosion.

Us patent 4.080.440 discloses an acidic drug formulation including a method of remineralizing tooth enamel. The method involves applying a freshly prepared metastable aqueous solution to the tooth surface. The solution has a pH of about 2.5 to 4.0 and comprises soluble calcium salts and soluble phosphate salts in amounts such that the molar ratio of calcium ions to phosphate ions is in a very wide range of 0.01 to 100. The formulation is not intended for consumption.

The prior art also discloses edible or chewable solid or semi-solid compositions that have a reduced tendency to attack teeth. WO98/13013 discloses, for example, chewing gums or candies which are capable of remineralizing dental lesions. The composition comprises: a cationic component comprising at least one partially water-soluble calcium salt, an anionic component comprising at least one water-soluble phosphate salt, and a separate component. The pH of the composition when dissolved in water or saliva is from greater than about 4.0 to about 10.0. Because of the partial solubility of the calcium salt, the calcium cations and phosphate anions in the mixed aqueous composition remain soluble for a period of time sufficient for the cations and anions to diffuse across the tooth surface into the subsurface or dentin where the diffused cations and anions react on the lesion to form an insoluble precipitate to remineralize the lesion.

WO99/08550, which is the same as the inventors of WO97/30601, discloses an acid-containing solid or semi-solid composition with reduced dental erosion. The composition comprises 0.3-0.8 moles of calcium per mole of acid, and the ratio of calcium to acid in the composition is selected such that the composition has an effective pH of 3.5-4.5 when dissolved in a liquid such as water. Although tooth protection can be achieved by using this composition, the taste experience is compromised because the saliva stimulating effect is limited by the relatively high pH. This is especially critical for products such as boiled hard candies, lollipops, jellies, chewing gums, drops, lozenges, pastilles, tablets, ice creams and sherbet (sorbet).

In US2004/0091517A1, the inventor of which is co-inventor of WO97/30601 and WO99/08550, acidic oral compositions are disclosed having an effective pH as low as 2.2, especially acidic beverages having a pH between 2.2 and 5.5. The invention according to said application relates to the use of polyphosphates in the form of phosphate polymers as tooth erosion inhibitors, wherein the number (n) of phosphate groups is at least 3. The polyphosphate may be used in combination with calcium, which is present in an amount up to 0.8 moles per mole of acidulant. However, from a different point of view, polyphosphates are undesirable, especially in the production of cooking hard candies and other products that require heating. By heating the acidic composition, there is a risk of polyphosphate conversion to other phosphates, which conversion is known to produce an unpleasant taste. Furthermore, there is a risk of calcium precipitating as an impractical calcium phosphate compound, with high concentrations of calcium and phosphate present.

The present invention suggests lowering the pH to obtain a better taste experience and a significant saliva stimulating effect. Compositions without erosive potential in saliva can be obtained without the use of polyphosphates as disclosed in US2004/0091517A 1.

Increased saliva production results in increased protection from the components of the saliva itself. As another place of interest, the non-erosive effect of the composition can be obtained even in so-called "xerostomia" individuals with impaired salivation.

This unexpected finding is the result of extensive research carried out by the inventors, and also resulted in a new erosion potential test method which takes into account in a simple and reliable manner the complications in human oral saliva in the presence of acidic oral compositions such as candies. This test method represents a particular aspect of the present invention.

When solid and semi-solid compositions are sucked, saliva becomes the base of the composition, and thus saliva affects all the effects of the composition on teeth. Unlike theoretical calculations based on physico-chemistry, the method of the present invention provides unique features that take into account all protective factors (organic and inorganic) in human saliva. These factors include: salivary proteins (about 2mg/ml), saliva buffer capacity, salivary calcium and phosphate, salivary fluoride, other ions present in trace amounts in saliva. Sialoproteins are capable of forming a protective coating on the tooth surface, also known as a pellicle. Due to this ability, sialoproteins can protect teeth and dental substances from acid-induced erosion. However, the effect of the above-mentioned protein coating on dental erosion cannot be quantified in different individuals by any known calculation method and must be determined. The saliva buffer capacity derived from salivary bicarbonate, phosphate and protein also protects teeth and dental substances from acid-induced erosion, which effect is also calculated by the test method. Thus, when an acidic oral composition dissolves in saliva, the pH will decrease, however, the pH decrease will be counteracted by the three salivary buffer systems, resulting in an increase in the salivary pH and thus a decrease in erosive effects. Saliva also contains some calcium and phosphate, which helps to increase the saturation of hydroxyapatite and thereby reduce acid-induced erosive effects. In this regard, saliva also contains fluoride, primarily from food and toothpaste, which increases the effective saturation of the tooth substance and thus also reduces acid-induced erosive effects. Finally, traces of other ions from food and drinking water can also affect the dissolution of dental substances. Consistently, the last three factors have significant protective effects that cannot be predicted directly by calculation, and therefore need to be determined by the methods provided. The method of the invention provides an effective means of determining the demineralization of hydroxyapatite and thereby assessing the erosive potential of any solid and semi-solid compositions dissolved in saliva.

Summary of The Invention

The present invention provides an acidic solid oral composition having a reduced likelihood of erosion in saliva, the composition comprising a calcium component and an acid component, wherein the amount of the calcium component and the acid component in the solid oral composition are adjusted to provide:

(i) when the solid oral composition is dissolved in an equal weight of highly purified water, the pH is 2.2-3.2, and

(ii) the calcium content in the acidic solid oral composition is in the following range:

the pH is 175-50. the calcium content (mmol/kg) is 660-200. the pH is determined as described above,

with the proviso that the composition does not contain polyphosphate in the form of a phosphate polymer, wherein the number of phosphate groups (n) is at least 3.

It has been surprisingly found that a composition pH of between 2.2 and 3.2 reduces the likelihood of corrosion without the use of any polyphosphate as described in US/2004/0091517A 1.

It is expected that the relatively long contact time between the oral solid composition of the present invention and the teeth will damage the dental hydroxyapatite. Here, it is reported that for compositions of relatively low pH, an amount of the calcium component reduces the likelihood of erosion in saliva, even where the amount of calcium is such that the saliva is unsaturated relative to the calcium.

Typically, beverages have only a few seconds of contact with the teeth before swallowing, while oral compositions intended to be sucked or chewed may remain in the mouth for a few minutes. The acidic solid oral compositions of the present invention achieve significant saliva stimulation, better taste, while significantly reducing the potential for erosion. The taste may be further improved by the addition of one or more sweetening and/or flavouring agents. These additives are also known to stimulate saliva production.

In one aspect of the invention, the saliva stimulating properties of the oral compositions of the invention are used to relieve the pain of individuals with impaired saliva production. Impaired saliva production may be observed in diseases such as sjogren's syndrome, cystic fibrosis, diabetes or eating disorders, or by treatment such as drug therapy or radiation therapy.

Dry mouth patients often use acid candies to alleviate discomfort, but a serious disadvantage of consuming large amounts of candies is the high risk of erosion of the dry mouth patient's teeth.

When healthy individuals enjoy acidic solid oral compositions such as candies, the buffering capacity of saliva offsets the low pH induced dissolution of the oral composition. However, in patients with impaired saliva production, the ability to resist the severe effects of low pH is reduced due to the low buffer concentration in saliva of patients with dry mouth.

Thus, there is a need for acidic oral compositions with high saliva stimulating capacity and no erosive potential. The present invention provides a solution to this need.

As used herein, the term "solid oral composition" refers to a product having a hard or gum-like consistency that is edible, sucked, or chewed in the mouth. The term solid refers to the state at the temperature of use. The invention relates in particular to solid or semi-solid substances for oral administration, such as boiled hard candies, tablets, lozenges, lollipops, jellies, chewing gums, drops and the like. In another aspect of the invention, the semi-solid composition further comprises products such as ice cream and sherbet.

The solid oral compositions of the present invention may be partially or completely soluble in water. Confections such as jellies and candies are typically completely soluble in water, while chewing gums are typically only partially soluble in water. To determine the pH of a solid oral composition, an amount of the composition is mixed with an equal weight of highly purified water (pH. If desired, the oral composition may be physically treated to obtain an aqueous phase in which the soluble components of the oral composition are dissolved. The remainder of the solid composition may remain in the solid phase due to the saturation of the aqueous phase or the insolubility of some of the ingredients in the composition. The pH determined in this manner is referred to herein as the "effective pH".

The actual amounts of the calcium component and the acid component will depend on the formulation of the solid oral composition of the present invention. For example, 10.35 g of candy may be produced using 1kg of calcium lactate pentahydrate, with a calcium concentration of 33.114mmol/kg (33.114 mM). The amount of acidic component is selected to obtain an effective pH in the range of 2.2 to 3.2. The specific amount of acidic component will depend on the type of acidic component, the buffering capacity of the oral composition, etc. For example, the concentration of the acid component is 33-132mM (33-132mmol/kg), corresponding to 5.20g tartaric acid/kg. The calcium component is generally non-toxic and acceptable as a food additive. Furthermore, the calcium component is generally sufficiently soluble in the oral cavity to release free calcium ions. Suitably, the calcium component is selected from: calcium carbonate, calcium hydroxide, calcium citrate, calcium malate, calcium lactate, calcium chloride, calcium glycerophosphate, calcium acetate, calcium sulfate, and calcium formate, or hydrates thereof. The calcium component may also be a combination of two or more of the above compounds. Preferably, the calcium component is calcium lactate.

The acid component of the present invention is suitably selected from edible acids naturally produced by plants or animals. However, artificial acids may also be used. Preferably, the acid component is selected from: citric acid, malic acid, ascorbic acid, tartaric acid, acetic acid, fumaric acid and lactic acid. The acid component may be added during manufacture of the oral composition or may be present in the fruit concentrate or the like, serving as a matrix for the manufacture of the oral composition.

The amount of acid used in the manufacture of the solid oral compositions of the present invention is suitably selected so that when the oral composition is dissolved in an equal weight of highly purified water such asProviding a certain predetermined pH when in water.The water is demineralized, distilled, filtered and ion-exchanged and further subjected to reverse osmosis. For the pH determination, it is critical that the water contains no buffer salts. According to the invention, the acid in the oral composition is adjusted so that the effective pH is between 2.2 and 3.2. In a preferred aspect, the effective pH is from 2.5 to 3.2, especially from 2.6 to 3.1.

The molar ratio of the calcium component to the acid component in the acidic solid oral composition of the invention is in the range of 0.1 to 1.40, preferably O.3-0.8. More preferably, the molar ratio of the calcium component to the acid component is between 0.4 and 0.7.

The composition of the present invention may consist of only calcium and acid components. However, it is preferred that the calcium and acid components are contained in a carrier. The carrier may form a glassy, crystalline or gum-like basic structure. The choice of carrier depends on the intended product. For example, a carrier may be selected that forms a glassy or crystalline structure when making a confection, or a gum-like structure when making a chewing gum or jelly.

Typically, sugar and/or sugar substitutes are selected as carriers when preparing the confectionery. Suitable sugars include: sucrose, isomalt (isomalt), maltose, glucose, fructose, invert sugar, syrup, and the like. The sugar substitute or sweetener is selected from: saccharin, dextrose, levulose, sodium cyclamate (sodium cyclamate), acesulfame-K (acesulfame potassium), and aspartame (aspartame). The sugar component may be a mixture of sugar and sweetener. The sugar component may also be a combination of different sugars. According to one aspect of the invention, the candy is prepared by dissolving the sugar component in water and then cooking the solution until sufficient water has evaporated to obtain a temperature of 105-160 ℃. The resulting mixture was viscous and called a candy. The acid component and the calcium component are added to the confection and then mixed. Typically, the confection is also mixed with flavoring and coloring agents. The candy mass is then cut into suitable pieces and cooled.

Jelly is typically based on gelatin. However, other polymers of natural origin or synthetic polymers may also be used. First, the gelatin is dissolved in water and then a sugar component, such as sucrose or glucose syrup or any other sugar component described above, is added. The homogenous mixture is then cooked until a certain dry matter content is obtained due to evaporation of the water. The remaining components, including the calcium and acid components, are then added to the mixture. Flavors and colors are typically added at this stage. After thorough mixing, the mixture is cast or extruded into a suitable form.

As mentioned above, the erosive potential of a composition in complex liquids such as saliva cannot be theoretically calculated and needs to be determined.

In order to determine the erosive potential, a new test method was developed which considers in a simple and reliable way the influence of oral compositions on saliva production and composition under in vivo conditions. This new test method represents a particular aspect of the present invention.

Accordingly, the present invention provides a method of determining the erosive potential of an oral composition in saliva, the method comprising the steps of:

a) contacting the oral composition to be tested with saliva in the oral cavity,

b) in the prevention of CO₂The saliva sample is collected under conditions that escape from the sample,

c) measuring the pH of the sample collected in step b),

d) removal of CO from samples₂Optionally under vacuum and/or with the aid of a non-volatile acid,

e) adjusting the pH of the sample to the value determined in step c) with a non-volatile acid or, if desired, a non-volatile base,

f) adding dental substance to the sample obtained from step e), observing any increase in pH,

g) if an increase in pH is observed in step f), titrating the sample with an acid to the pH determined in step c),

h) calculating the amount of eroded dental substance based on the amount of acid consumed in step g).

The initial determination of the pH in step c) may be performed in any suitable manner. For example, a pH electrode may be placed in the oral cavity to record the pH at the time the sample is ingested. However, to increase user convenience, CO is generally being prevented₂Saliva samples were collected from the closed system where the sample escaped. One suitable way to collect the sample is to draw an appropriate amount of saliva from the mouth with a syringe. A saliva sample is typically withdrawn from the subject's oral cavity prior to administration of the oral composition. The oral composition to be tested is then contacted with saliva in the oral cavity for a sufficient time. For solid oral compositions, the oral composition is typically sucked or chewed for a sufficient period of time before a saliva sample is drawn. Single or multiple samples may be collected. For example, multiple samples are collected by collecting one sample every 30 seconds or every minute for a total of 5 minutes. Where only a single sample is collected, it is desirable to draw after ensuring that there is sufficient oral composition to dissolve in the oral saliva, for example, after 3 minutes. Throughout the test, subjects were asked not to swallow the oral composition or any saliva.

After pH determination, CO was removed from the samples₂. The skilled worker is aware of various CO removal processes₂The method of (4), comprising sonication, vacuum treatment and stripping. Typically, vacuum is used with agitation. The addition of a non-volatile acid helpsCO removal₂. The non-volatile acid is typically a strong acid. The strong acid may be selected from HCl or HNO₃An aqueous solution of (a). CO removal₂Thereafter, the pH of the sample is adjusted to the initially measured pH with a non-volatile acid or, if desired, a non-volatile base. When added to assist in CO removal₂The latter case (addition of base) can occur when the pH of the sample is lower than the pH determined in step c).

The saliva sample has now been freed of CO₂The ingredient still retains its original acidity. Then, tooth substance was added to test whether any erosion occurred. The dental substance may be of human or animal origin or artificial. When the dental material is of human or animal origin, it is usually ground to obtain a high surface area. However, it is preferable to use artificial tooth substances, such as substances of non-dental origin, in order to avoid the differences existing between individuals. The main component of enamel and dentin is hydroxyapatite. Thus, in a preferred embodiment, hydroxyapatite is selected as the dental substance, in particular hydroxyapatite (Ca) having a solubility product at SATP (standard ambient temperature and pressure) of about 117.3(pK)₁₀(PO₄)₆(OH)₂)。

The tooth substance may remain in the saliva for a period of time before the titration is performed. Due to the thermodynamic properties of the solubility product of hydroxyapatite, the sample should be kept at a temperature not higher than body temperature, not lower than 20 ℃, until titration is performed.

The amount of acid used for titration is equal to the amount of dissolved tooth substance. Thus, based on the reaction: ca₁₀(PO₄)₆(OH)₂→10Ca²⁺+6PO₄ ^3-+2OH^-→10Ca²⁺+6H₂PO₄ ^-+2H₂O, 1mM hydroxyapatite (Mw1005) requires 14mM H + (Mw1) provided the pH in saliva is 3-5. Thus, 14 microliters of 1N acid such as 1M HCl (i.e., 14 micrograms H) is used⁺) Back titration found 1005 micrograms of hydroxyapatite dissolved and 1 microliter of 1M HCl found 72 micrograms of HAp dissolved (i.e., 1005/14).

Thus, the amount of hydroxyapatite crystals lost per minute in the candy containing saliva can be calculated back from the microliter number of 1M HCl required to reach the pH of step c) according to the following formula:

the number of lost micro-liters of HAp (microliters of acid used x 72)/minutes of dissolution

When the solid oral composition does not provoke a pH increase in step f), the process does not continue with steps g) and h), it can be concluded: the subject oral compositions are non-erosive. However, if a pH increase is observed in step f), steps g) and h) can be used to quantify the amount of hydroxyapatite lost (or eroded).

The method provides unique features that take into account the effects of complex conditions in saliva in the human mouth on dental erosion. Moreover, CO in the sample is avoided₂The different effect on pH over time. When pH is the single most important factor for dental erosion, the present invention provides an effective way to predict hydroxyapatite demineralization, thereby assessing the erosive potential in saliva.

When tested in randomly selected healthy subjects according to the method of the invention, the acidic solid oral composition of the invention does not cause any increase in the pH of step f) for at least 90% of the subjects within 5 minutes, which represents a preferred aspect.

Brief description of the drawings

Figure 1 shows a graph of the amount of tooth substance lost due to dental erosion versus time for testing the confectioneries of the present invention and control confectioneries, respectively.

FIG. 2 shows a plot of calcium content (mmol/kg) versus effective pH for compositions of the invention and some non-inventive compositions.

It will be appreciated from the above description that the erosive potential of a composition in saliva cannot be calculated theoretically, but rather determined. Based on experiments with compositions that appear to be non-aggressive, however, a correlation between the amount of the calcium component and the effective pH was first discovered,

calcium content (mM) 650 + -10-200 pH

No correlation was initially established in the actual pH range, but a correlation was expected to exist at least in the pH range of 2.6-3.1.

Subsequent experiments confirmed that the pH range extends even to pHs of 2.2-32. Similarly, the range of calcium content expressed in mM or mmol/kg also extends to

175-50. pH is less than or equal to calcium content (mmol/kg) is less than or equal to 660-pH.

The pH value refers to the pH obtained when a solid oral composition is dissolved in an equal weight of highly purified water, i.e., the "effective pH".

FIG. 2 shows the correlation between effective pH and calcium content (mmol/kg).

The invention will be further described below by way of examples, which should not be construed as limiting the scope of the invention.

Examples

Example 1

Preparation of solid candy

800ml of water are added to a mini cooker, and 3kg of isomaltose and 0.3mg of sweetener (acesulfame-K) are added with stirring. Stirring was continued until a homogeneous solution was obtained. The temperature was then raised to about 162 ℃ and the mixture boiled. When the temperature decreased to 110 ℃, the stirring was stopped and the candy was taken out of the mini cooker and placed on a heating table.

4.5ml of red pigment (camine E120) was added to the candy and kneaded to uniformly distribute the pigment. Then, 6ml of flavor (strawberry and rhubarb 2: 1) was added and kneaded into a candy. Subsequently, 30g of tartaric acid (molar weight: 151g/mol) and 49.5g of calcium lactate pentahydrate (molar weight: 308g/mol) were added and mixed well with the candy. A candy bar is prepared and cut into suitable candy pieces. The candy was allowed to cool to room temperature.

Adding equal weight of water into candyForming 1: 1 candy and water, and standing for 1 hour. After 1 hour, the candy was completely dissolved. In the resulting solution, the pH was measured to be 2.95 using a calibrated electrode.

The molar ratio of the calcium component to the acid component is then calculated,

example 2

Preparation of fruit jelly

8g of gelatin (250Bloom) were completely dissolved in 17g of water at 80 ℃ with continuous stirring. 4g of dextrose was added to the gelatin solution with continuous stirring until the mixture was homogeneous. Then, 20g of sucrose and 49g of glucose syrup (48DE) were added and stirring was continued until the mixture was homogeneous. The mixture was then boiled until the brix (brix) was 75 deg.C, which was 108 deg.C (0.6atm vacuum). After the boiling step, 10g tartaric acid (molar weight: 151g/mol), 16.5g calcium lactate pentahydrate (molar weight: 308g/mol), 0.15ml red pigment (camine E120) and 0.6ml flavor (strawberry and rhubarb 2: 1) were added to the mixture and mixed to obtain a homogeneous solution. The pH of the liquid mixture was adjusted to pH3.2 with tartaric acid according to standard pH electrode assay. Samples were withdrawn and mixed with an equal weight of water. The pH of the diluted sample was determined to be 3.2. The molar ratio of the calcium component to the acid component is

The solution was cast into the appropriate shape and cooled to room temperature.

Example 3

Testing oral compositions for potential erosion

The confectionery prepared in example 1 was used in this example to illustrate the potential for erosion. A control candy containing the same components as the candy described in example 1 but without calcium lactate was also prepared.

A randomly selected 10 healthy subjects (5 males and 5 females) habitually suck 5 grams of candy for 5 minutes while collecting his/her stimulated full oral saliva every 30 seconds for 5 minutes. Use of a closed saliva collecting system to avoid saliva CO₂Volatilise, thereby avoiding pH changes during collection. The pH of the saliva in the sealed system was measured immediately after collection and the pH was recorded for each collection (i.e., first minute, second minute, etc.). Saliva was then poured into an open glass tube and saliva CO removed under vacuum with continuous stirring₂The sample was acidified (1M HCl) until the pH obtained immediately after collection was reached.

Pure hydroxyapatite crystals (HAp) equivalent to 2mg per ml of saliva (i.e. 2mM HAp) were added to each saliva sample. The particle size of the HAP Crystals was 1 micron, supplied by Merck Crystals. Any pH increase was recorded continuously at 15 second intervals over 5 minutes at room temperature. The test procedure simulates in vivo conditions, which corresponds to sucking 5 grams of candy for 5 minutes under in vivo conditions.

If there is no pH increase, the boiled hard candy is considered non-erosive.

An increase in pH indicates dissolution of HAp crystals and the candy is erosive. To quantify the dissolved HAp, back titration with acid (1M HCl) was performed 5 minutes after HAp addition. The amount of HAp crystals lost per minute in the candy containing saliva was then calculated from the number of microliters of 1M HCl needed to reach the pH obtained immediately after collection of the saliva, according to the formula described in example 2.

From the data obtained, the erosive potential (micrograms HAp lost per minute upon exposure to candy-containing saliva) was calculated from the slope of the curve by linear regression. The results of the experiment are shown in fig. 1, where the confectionery according to the invention was a confectionery prepared according to example 1 and the control confectionery was a confectionery lacking calcium lactate. The results show that the candy modified with calcium according to the invention is acidic and non-erosive due to the interaction between the calcium component, the saliva buffer capacity and the protein protection of the solution.

Example 4

Confections having the compositions shown 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 shown in the following table.

TABLE 1

Testing	Calcium component g	Calcium mmol/kg	Acid component g	Acid mmol/kg	Calcium/acid component molar ratio	Effective pH	Aggressive nature
								1	0.0	0	7.0	47	0.00	2.00	Is that
2	0.0	0	5.0	33	0.00	2.25	Is that
								3	0.0	0	3.0	20	0.00	2.60	Is that
4	49.1	160	60.2	400	0.40	2.40	Whether or not
								5	11.0	36	13.0	87	0.41	2.20	Is that
6	16.5	54	18.0	120	0.45	2.50	Whether or not
								7	43.0	140	46.8	311	0.45	2.50	Whether or not
8	10.0	33	10.0	67	0.49	2.40	Is that
								9	16.5	54	16.0	107	0.50	2.64	Whether or not

10	9.0	29	8.0	53	0.55	2.60	Is that
								11	8.1	26	7.0	47	0.56	2.70	Is that
12	16.5	54	14.0	93	0.57	2.76	Whether or not
								13	12.3	40	10.0	67	0.60	2.87	Whether or not
14	36.8	120	30.1	200	0.60	2.64	Whether or not
								15	15.4	50	12.5	83	0.60	2.84	Whether or not
16	18.5	60	15.0	100	0.60	2.73	Whether or not
								17	16.5	54	12.0	80	0.67	2.81	Whether or not
18	7.0	23	5.0	33	0.68	2.85	Is that
								19	27.6	90	22.1	147	0.70	2.81	Whether or not
20	15.0	49	10.0	67	0.73	2.87	Whether or not
								21	16.5	54	10.0	67	0.80	2.91	Whether or not
22	37.0	120	15.0	100	1.20	3.24	Whether or not
								23	31.0	101	12.5	83	1.21	3.20	Whether or not
24	25.0	81	10.0	67	1.22	3.27	Whether or not
								25	10.7	35	7.3	48	1.25	3.32	Whether or not

It has been found that some non-aggressive compositions are otherwise unsatisfactory, either because the effective pH is too high to develop adequate saliva stimulating effect, or because the calcium content is too high to produce an acceptable taste.

Figure 2 shows the dependence of the effective pH on the calcium content (mmol/kg) in tests 1-25, where the area in the range of X2.2 to 3.2, indicated as grey area, between the straight line Y660-X and Y175-50-X, indicates that the composition of the invention (labelled +), i.e. a composition determined to be non-erosive in human saliva by the above tests, is sufficiently acidic to provide the desired salivary stimulation, and the calcium content is sufficiently low to provide a suitable taste. The composition labeled ÷ is erosive, while the composition labeled + + is non-erosive but has an unacceptable taste due to excess calcium, and the composition labeled + + + is non-erosive but too acidic to provide the desired salivary stimulation.

Example 5

Testing saliva stimulating effects

20 healthy individuals were given a candy of test composition 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 in the same individual without any stimulation of saliva production over the same period of time. Tests have shown that sucking a candy increases the amount of saliva more than 10 times.

Corresponding tests carried out in 10 patients with dry mouth showed that sucking a candy of the composition of test 21 produced a 10-fold increase in the amount of saliva.

Claims (23)

1. An acidic solid oral composition having a reduced likelihood of erosion in saliva, said composition being a confection, jelly, chewing gum, drops, lozenge, ice cream, sherbet or tablet, said composition comprising a calcium component and an acid component, wherein the amounts of the calcium component and the acid component in the solid oral composition are adjusted to meet the following requirements:

(i) when the solid oral composition is dissolved in an equal weight of highly purified water, the pH is 2.2-3.2, and

(ii) the calcium content in the acidic solid oral composition is in the following range:

the calcium content in mmol/kg of 175-50 & ltpH & gt is & lt, 660 & lt, 200 & gtpH, which is determined as described above,

with the proviso that the composition does not contain polyphosphate in the form of a phosphate polymer having a number of phosphate groups of at least 3.

2. The solid composition of claim 1 wherein the candy is a boiled hard candy, lollipop or lozenge.

3. The solid composition of claim 1, wherein the molar ratio of the calcium component to the acid component is from 0.3 to 0.8.

4. The solid composition of claim 3 wherein the molar ratio of the calcium component to the acid component is from 0.4 to 0.7.

5. The solid composition according to any one of claims 1 to 4, wherein the pH determined according to claim 1 is from 2.5 to 3.2.

6. The solid composition of claim 5, wherein the pH determined in claim 1 is from 2.6 to 3.1.

7. The solid composition of claim 1, wherein the calcium component is selected from one or more of the following: calcium carbonate, calcium hydroxide, calcium citrate, calcium malate, calcium lactate, calcium chloride, calcium glycerophosphate, calcium acetate, calcium sulfate, and calcium formate, or hydrates thereof.

8. The solid composition of claim 7, wherein the calcium component is calcium lactate.

9. The solid composition of 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.

10. The solid composition of claim 1, wherein the composition is for sucking or chewing.

11. A method of stimulating saliva production in an individual, the method comprising orally administering the solid composition of any one of claims 1-10, for a non-therapeutic purpose.

12. The method of claim 11, wherein the method is not a treatment of the human or animal body.

13. Use of a calcium component and an acid component for reducing the erosive potential of an acidic solid oral composition in saliva, said composition being a candy, a jelly, a chewing gum, a drop, a lozenge, an ice cream, a sherbet or a tablet, wherein the amount of the calcium component and the acid component in the solid oral composition is adjusted to meet the following requirements

(i) When the solid oral composition is dissolved in an equal weight of highly purified water, the pH is 2.2-3.2, and

(ii) the calcium content in the acidic solid oral composition is in the following range:

the calcium content in mmol/kg of 175-50 & ltpH & gt is & lt, 660 & lt, 200 & gtpH, which is determined as described above,

with the proviso that no polyphosphate in the form of a phosphate polymer having a number of phosphate groups of at least 3 is used, for non-therapeutic purposes.

14. Use according to claim 13, wherein the confectionery is a boiled hard candy, a lollipop or a lozenge.

15. Use according to claim 13, wherein the molar ratio of the calcium component to the acid component is between 0.3 and 0.8.

16. Use according to claim 15, wherein the molar ratio of the calcium component to the acid component is between 0.4 and 0.7.

17. Use of a calcium component and an acid component for the manufacture of a solid oral composition for alleviating the pain of an individual with impaired saliva production, said composition being a confection, a jelly, a chewing gum, a drop, a lozenge, an ice cream, a sherbet or a tablet, wherein the amount of the calcium component and the acid component in the solid oral composition is adjusted to meet the following requirements:

(i) when the solid oral composition is dissolved in an equal weight of highly purified water, the pH is 2.2-3.2, and

(ii) the calcium content in the acidic solid oral composition is in the following range:

the calcium content in mmol/kg of 175-50 & ltpH & gt is & lt, 660 & lt, 200 & gtpH, which is determined as described above,

with the proviso that no polyphosphate in the form of a phosphate polymer having a number of phosphate groups of at least 3 is used.

18. Use according to claim 17, wherein the confectionery is a boiled hard candy, a lollipop or a lozenge.

19. Use according to claim 17, wherein the molar ratio of the calcium component to the acid component is between 0.3 and 0.8.

20. Use according to claim 19, wherein the molar ratio of the calcium component to the acid component is between 0.4 and 0.7.

21. The use of any one of claims 17-20, wherein said impaired saliva production is due to a disease of sjogren's syndrome, cystic fibrosis, diabetes, or an eating disorder condition.

22. The use of claim 17, wherein the impaired saliva production is due to therapy.

23. The use of claim 22, wherein the treatment is drug therapy or radiation therapy.