WO2006007839A1

WO2006007839A1 - Composition comprising minerals and uses thereof

Info

Publication number: WO2006007839A1
Application number: PCT/DK2005/000454
Authority: WO
Inventors: Carsten Andersen; Lene Jorsal
Original assignee: Fertin Pharma AS
Current assignee: Fertin Pharma AS
Priority date: 2004-07-01
Filing date: 2005-07-01
Publication date: 2006-01-26
Anticipated expiration: 2007-01-01

Abstract

The present invention relates to a composition comprising an inner core which e.g. may be a chewing gum core, said composition furthermore comprising a coating comprising a very high load of a mineral. The invention furthermore pertains to processes for preparing the composition and to various medical uses.

Description

COMPOSITION COMPRISING MINERALS AND USES THEREOF

TECHNICAL FIELD OF THE INVENTION

The invention relates to the field of formulation of a pharmaceutical oral dosage form, in particular chewing gum formulations comprising high load of elemental calcium and/or high load of minerals. The invention also pertains to the field of treating and/or preventing diseases, which are associated with insufficient intake minerals such as e.g. osteoporosis.

BACKGROUND

Supplementary intake of vitamins and minerals are important means for reducing the prevalence of human diseases. In recent years it has become clear that osteoporosis (decalcifying of bones) is an overall and growing treat to the health of ageing women and men. It has also been revealed that sufficient intake of calcium in the younger males and females may reduce the risk of decalcifying of the bones later in life.

Therefore, acceptable, convenient and easily administrable calcium-containing products with therapeutically relevant doses of calcium are needed so as to increase the overall intake of calcium in different groups of the population.

The required dose of calcium is rather high such as about 400-1000 mg per day dependent on the age.

A plethora of calcium-containing products is already commercially available in the form of tablets. In general high amounts of elemental calcium in the products are required for achieving therapeutically relevant doses. For that reason the tablets are rather large (more than 1.5 g) and thus rather inconvenient to swallow. A number of chewable tablet formulations also exist. Advantageously, chewable tablets disintegrate quickly in the mouth into smaller sizes of particulate matter that are more easily swallowed than entire conventional tablets. However, it is still concerned that a large bulk of particulate matter ought to be swallowed unless a significant amount of the ingredients in the chewable tablet is dissolvable. Therefore, there is a need for providing alternative calcium-containing products for oral administration, in which a limited amount of the ingredients besides the calcium are released to the saliva and meant to be swallowed. Advantageously, such products are more convenient to administer in that the bulk of ingredients to be swallowed are reduced. One such product is a chewing gum or the like, which comprises a chewable inner core and a calcium-containing coating wherein the coating ingredients dissolves in the saliva except in the event where the calcium source is water-insoluble. Advantageously, chewing gum stimulates the production of saliva resulting in better conditions for swallowing the active substances and other excipients without the need of concurrent intake of water.

However, chewing gum formulations with high load of active substances, in particular substances with poor water solubility, may be problematic to prepare without risking poor mouth feeling due to release of particles into the buccal cavity and/or low moisturising effect. Furthermore, it is problematic to achieve the proper crunching effect of the coating surface in view of the limited amount of other excipients besides the source of calcium.

Calcium has been used in chewing gum formulations. By example in the form of a pH- adjusting agent in respect of making the saliva slightly alkaline, which may increase buccal/lingual absorption of ingredients into the blood stream.

Prior art:

WO 00/35298 relates to chewing gum formulations wherein the active agent level in the ^• composition is from about 25 μg to 250 mg per gram chewing gum product.

EP 0 263 224 A2 relates to a chewing gum which contains a coating with sweeteners and mineral compounds. It is disclosed that the coating may contain from 5%-60% by weight mineral compounds. It is also disclosed that mineral compound concentrations greater than about 60% by weight are not useable since they result in a dry, chalky, gritty product and result in a flaked or peeled product.

EP 0 228 999 A2 discloses a coated chewing gum wherein calcium carbonate is used as a drying agent in the coating. The document discloses unsuccessful attempts to prepare coated chewing gums wherein the coating contains a high load of calcium carbonate. The chewing gums having the highest calcium carbonate concentrations were found to be flaky and brittle and had an unsatisfactory overall quality. SUMMARY OF THE INVENTION

The present invention relates in its broadest sense to a composition comprising an inner core and a very high load of one or more minerals, e.g. elemental calcium, present in a coating that is partly of fully surrounding the inner core. Thereby it is possible to provide a therapeutically relevant dose of one or more minerals, say elemental calcium, upon administering the composition orally.

DETAILED DESCRIPTION OF THE INVENTION

As mentioned, the requirements of high load of one or more minerals, such as elemental calcium, in products having therapeutically effect in preventing diseases, such as osteoporosis, is critical for the formulation of such products. Particularly with respect to incorporating sufficient amounts of other excipients without increasing the size of a unit dosage to an unacceptable extent and to meet the requirement of pleasant mouth feeling, such as a moist feeling in the mouth, and proper crunch properties of the product.

The present inventors have found that it is possible to provide compositions in the form of distinct dosage units for oral administration, wherein a very high load of one or more minerals, e.g. elemental calcium, in a coating, i.e. one or more coating layers, which partly or fully surrounds the inner core of the composition. Despite the very high load of one or more minerals the composition of the invention has maintained a pleasant mouth feeling and robustness of the coating, i.e. the coating does not flake or peel off during process and further handling of the composition.

As described below, the inner core may in principle be made of any material provided that the inner core does not immediately disintegrate into a number of smaller particles, which need to be swallowed together with water. The exact nature of the coating may also be selected from a broad range of ingredients, which are mainly water-soluble. The load of the one or more minerals, e.g. elemental calcium, enclosed in the coating may preferably be more than 25% by weight of the coating. Calcium carbonate is a widely used calcium source because of its comprehensive properties. In using calcium carbonate as the source of calcium, the coating comprises at least 63% by weight of the coating.

Thus, the invention provides in its first aspect a composition comprising a source of elemental calcium, the composition comprises two or more distinct fractions, namely i) an inner core, preferably an inner core comprising a continuous material such as a chewing gum core, a chewable tablet, a lozenge, a candy or a caramel and N) a coating wherein elemental calcium is enclosed in an amount of at least 25% by weight of the coating.

An additional aspect of the present invention relates to a composition comprising i) an inner core, preferably an inner core comprising a continuous material such as a chewing gum core, a chewable tablet, a lozenge, a candy or a caramel and ii) a coating wherein a one or more minerals, e.g. a source of elemental calcium, are present in an amount of at least 63% by weight of the coating.

Yet another aspect of the present invention relates to a composition comprising i) an inner core, preferably an inner core comprising a continuous material such as a chewing gum core, a lozenge, a candy or a caramel, and ii) a coating wherein a water-insoluble, particulate, inorganic material is present in an amount of at least 63% by weight of the coating.

The coating may comprise the water-insoluble, particulate, inorganic material in an amount ranging between 63-90% by weight of the coating, preferably ranging between 70-90%, more preferably ranging between 75-90%, such as between 75-85%, most preferably ranging between 78-85% by weight of the coating.

As said elemental calcium is needed in a relatively high daily dosage. Therefore, interestingly the invention provides a chewing gum comprising a high load of calcium carbonate. Hence, in a particular aspect the invention encompasses a composition comprising a source of elemental calcium, the composition comprises i) an inner core comprising a chewing gum core; and ii) a coating, wherein the coating comprises calcium carbonate in an amount of at least 63% by weight of the coating.

The composition may be further formulated in the form of individual dosage units intended for oral administration. Each dosage unit consists of the compositions mentioned herein in a unit weight between 1-6 g, preferably 2-4 g, such as 2.5-3.5 and 3 g. Thus, a particular aspect of the invention relates to a composition in the form of a dosage unit having a unit weight of about 2.5-3.5 g, the dosage unit comprises an inner core and a coating, wherein the coating comprises a dose of 100 mg to 2000 mg of elemental calcium, e.g. a dose of calcium carbonate of 250 mg to 5000 mg.

The one or more minerals preferably comprise one or more inorganic compounds such as e.g. inorganic salts. Even more preferred, a mineral may be a water-insoluble, inorganic compound. The mineral may e.g. be on particulate form such as a dry powder, when the mineral is applied to the composition according to the present invention. In a preferred embodiment of the present invention, the one or more minerals comprises elemental calcium, e.g. in the form of calcium carbonate. The composition may comprise several minerals, e.g. 2, 3, 4, 5, 6, 7, 8, 9, 10 or even more minerals. In a preferred embodiment, the composition comprises minerals comprising both elemental calcium and elemental magnesium, such as e.g. calcium carbonate and magnesium carbonate.

The coating of the composition may comprise the one or more minerals in an amount ranging between 60-90% by weight of the coating, preferably ranging between 63-90% such as 65-90%, 69-90%, 71-90%, or 73-90%, or e.g. ranging between 60-90%, such as between 60-85%, 60-80%, 60-75%, 63-85%, 63-80%, 63-75%, 65-85%, 65-80%, 65- 75% by weight of the coating.

The coating may e.g. comprise the one or more minerals in an amount ranging between 70-90% by weight of the coating, preferably ranging between 72-90% such as 74-90%, 76-90%, or 78-90% by weight of the coating.

As used herein, the term "source of elemental calcium" or "calcium source" is meant to define any biological or synthetically source of elemental calcium. The source of elemental calcium may releases free ionised calcium upon being contacted with aqueous solution such as saliva from the buccal cavity and/or it may release free ionised calcium upon contact with the acidic environment of the stomach. Ionic calcium is mainly presented in the form of calcium(II) ions. Thus, intentionally the calcium is not covalently bound. Typically sources of calcium encompass calcium salts such as calcium carbonate, calcium citrate, calcium gluconate, calcium glycerophosphate, calcium lactate, calcium tartrate, calcium malate, calcium malate-citrate, calcium levulinate, calcium phosphate, monobasic calcium phosphate, calcium hypophosphate, calcium succinate, calcium gluceptate, calcium sulfate, calcium chloride, calcium chelates, calcium amino acid chelate, anhydrous forms and/or hydrates thereof. Table 1 summarises the properties for useful calcium compounds and also presents useful magnesium compound, which use will be described in further detail below.

In a preferred embodiment the source of elemental calcium is a water-insoluble compound. In the present context a material or compound is considered water-insoluble if its solubility is at most 0.1 g material or compound per 100 g water at 25°C. Table 1 Physical and chemical properties of useful calcium and magnesium sources.

In preferred embodiments of the invention, the calcium source is calcium carbonate, calcium citrate or calcium malate-citrate of which calcium carbonate is more preferred because of the high amount of calcium per weight unit of calcium salt.

As said, the coating comprises elemental calcium in an amount of at least 25%, such as at least 28%, 30% and 32% by weight of the coating. The amount of elemental calcium ranges between 25-36% by weight of the coating, preferably between 28-35%, more preferably between 30-35% by weight of the coating.

Given that the elemental calcium is calcium carbonate, the coating comprises calcium carbonate in an amount ranging between 60-90% by weight of the coating, preferably ranging between 63-90% such as 65-90%, 69-90%, 71-90%, or 73-90%, or e.g. ranging between 60-90%, such as between 60-85%, 60-80%, 60-75%, 63-85%, 63-80%, 63- 75%, 65-85%, 65-80%, 65-75% by weight of the coating.

The coating may e.g. comprise calcium carbonate in an amount ranging between 70-90% by weight of the coating, preferably ranging between 72-90% such as 74-90%, 76-90%, or 78-90% by weight of the coating.

Calcium carbonate exists in several physical forms which each may affect the properties of the composition in terms of pleasant mouth feeling, ease of production and the maximum load of calcium in the coating.

In an embodiment, the calcium carbonate is micronised, either crystalline or amorphous. Calcium carbonate may also be defined in terms of its density. The specific gravity of the calcium carbonate may range between 2.5 -3 g/cm³ such as e.g. 2.6-2.9 g/cm³. For example, the specific gravity of the calcium carbonate may about 2.7 g/cm³. The bulk density of calcium carbonate powder may range between 0.3 - 1.5 g/cm³, such as e.g. 0.6-1.2 g/cm³. For example, the bulk density of the calcium carbonate powder may about 1 g/cm³.

In an embodiment, the calcium carbonate has a mean diameter in the range of 0.1-200 micrometer, such as e.g. 0.1-50 micrometer, 1-50 micrometer, 1-150 micrometer, 5-100 micrometer, or 10-75 micrometer.

In an embodiment, at least 10% by weight of the calcium carbonate has a particle diameter of at most 2 μm, such as at least 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 95%, such as at least 99% by weight of the calcium carbonate. The particle diameter may e.g. be measured by laser granulometry or by image analysis. Using the latter, the diameter of a particle is measured as the longest dimension of the particle. In an embodiment, the calcium carbonate has a sieving residue at 45 μm of at most 500 mg per 100 g calcium carbonate powder, such as a sieving residue at 45 μm of at most 500 mg, 250 mg, 100 mg, 50 mg, 25 mg, 10 mg, 5 mg, 1 mg, or 0.1 mg per 100 g calcium carbonate powder.

As said, according to the invention the calcium may be enclosed in the coating. However, additional amounts of elemental calcium may be comprised in the inner core, such as about 0.5% to 10% of the amount of elemental calcium in the coating may in addition be added to the inner core.

In a preferred embodiment of the invention, the composition comprises an inner core comprising a water-insoluble gum base and a coating, the coating comprises from about 65-90% of calcium carbonate and 10 to 30% of a sugar alcohol by weight of the coating, the sugar alcohol constitutes 5%-25% of the composition in total.

Magnesium is essential for the functioning of a number of critical enzymes including enzymes involved with ATP-dependent phosphorylation, protein synthesis, and carbohydrate metabolism. Magnesium deficiency also causes apathy, depression, delirium, and convulsions. Thus, the composition may furthermore comprise a magnesium compound such as organic and inorganic salts of magnesium wherein the anionic portion of the salt is acetate, carbonate hydroxide, chloride, citrate, dibasic citrate, hydroxide, lactate, oxide, phosphate monobasic, phosphate dibasic, trisilicate, sulfate as well as co- precipitated gel of aluminum hydroxide and magnesium carbonate, aluminum magnesium silicate, aluminum magnesium hydroxide, or mixtures thereof. Table 2 shows the useful daily dosage of elemental magnesium.

Table 2 - Magnesium Recommended Daily Allowance (RDA) and Estimated Average Requirement (EAR) (In terms of elemental magnesium)

*Adequate intake (AI)

5 Thus, elemental magnesium may be present in the composition, e.g. the chewing gum, in an amount in the range of 25-500 mg, such as 25-50 mg, 50-100 mg, 100-150 mg, or 150-400 mg.

Lithium has been found useful in the treatment of manic-depressive illness, as a mood 0 stabilizer, and as an antidepressive. Thus, the composition may furthermore comprise organic and inorganic salts of lithium wherein the anion is e.g. chloride, carbonate, citrate, sulfate, bromide, or mixtures thereof.

Sodium in the form of salts (sodium chloride) plays the major role in control of distribution 5 of water in the body. Salt deficiency results in a diminution in extracellular space, and induces profound changes in the circulatory system. Salt deficiency leads to symptoms such as mental depression with drowsiness, apathy, anorexia, nausea and vertigo. Thus, the composition may furthermore comprise organic and inorganic salts of sodium wherein the anionic portion of the salt is acetate, ascorbate, bicarbonate, carbonate, chloride, 0 citrate, hypophosphite, lactate, phosphate monobasic, phosphate dibasic, phosphate tribasic, sulfate, tartarate, or mixtures thereof.

Potassium is the important cationic constituent of the intracellular fluid. Potassium deficiency may result in kidney damage and vacuolization of the collection tubules. 5 Potassium deficiency is characterized by mental changes (hallucinations, loquacity) an animated facial expression and limpness of the extremities. The muscles become soft and weak. Thus, the composition may furthermore comprise inorganic and organic salts of potassium wherein the anionic portion of the salt is acetate, bicarbonate, bitartrate, bromide, carbonate, chloride, citrate, gluconate, phosphate monobasic, phosphate dibasic, phosphate tribasic, sulfate, tartrate, or mixtures thereof.

Iron plays an important role in oxygen and electron transport. Symptoms of iron deficiency are fatigability, weakness and lassitude. Other symptoms of anemia include pallor, dyspnea on exertion, palpitation and a feeling of exhaustion. Thus, the composition may furthermore comprise organic and inorganic salts of iron and chelates of iron such as reduced iron, ferrous sulfate, iron ammonium citrate, ferrous carbonate, ferrous chloride, ferrous fumarate, ferroglycine sulfate, ferronascin, ferrous carbonate mass, ferrous carbonate saccharated, ferrous citrate, ferrous gluconate, ferrous lactate, ferrous sulfate, ferrous succinate, iron chelates, iron chelate with magnesium trisilicate, or mixtures thereof.

Zinc activates a number of enzymes concerned in protein metabolism as well as some enolases and lecithinases. There is evidence to suggest that zinc deficiency may cause dwarfism and hypogonadism. Thus, the composition may furthermore comprise inorganic and organic salts of zinc wherein the anionic portion of the salt is e.g. carbonate, chloride, citrate, or mixtures thereof.

The composition may furthermore comprise phosphorous e.g. in the form of salts wherein the anionic portion is a phosphate and the cationic portion is sodium, potassium, magnesium, iron, calcium, lithium, zinc, or mixtures thereof.

In a preferred embodiment of the present invention, the one or more minerals are present in the coating of the composition.

The inner core may be selected from a chewing gum core, a chewable tablet, a lozenge, a candy or a caramel.

The inner core may e.g. be a chewable tablet, which is to be ingested after being chewed. The tablet to be chewed may e.g. be a compressed centre. The compressed centre may comprise one or more components selected from the group consisting of a filler, a bulk sweetener, a high intensity sweetener, a flavour, a lubricant and a binder.

In a preferred embodiment the compressed centre comprises a filler, a bulk sweetener, a flavour, a lubricant and a binder. The filler may e.g. be selected from the group consisting of calcium sulphate, dibasic calcium phosphate, starch, calcium carbonate, microcrystalline cellulose, or modified starch.

The bulk sweetener may e.g. be selected from the group consisting of saccharose, sorbitol, xylitol, mannitol and maltitol.

The high intensity sweetener may e.g. be selected from the group consisting of saccharin, saccharin sodium, saccharin calcium, aspartame, twinsweet, cyclamate, acesulfame-K, sucralose, neotame, alitame, neohesperidin DC, stevia, glycyrrhizin, thaumatin.

The flavour may e.g. be selected from the group consisting of a natural flavour, a nature identical flavour and a synthetic flavour.

The lubricant may e.g. be selected from the group consisting of magnesium stearate, calcium stearate, zinc stearate, hydrogenated vegetable oils, talc, and polyethylene glycol.

The binder may e.g. be selected from the group consisting of starch, pregelatinized starch, polyvinylpyrrolidone, methylcellulose, sodium carboxymethylcellulose, ethylcellulose, and polyvinyl alcohol.

The chewable tablet may be made by direct compression or include granulation and binders.

In a preferred embodiment of the present invention, the inner core comprises a chewing gum core. When the inner core comprises a chewing gum core, the composition of the present invention may be considered a coated chewing gum. The chewing gum core may comprise a water-insoluble gum base and optionally also a water-soluble portion and/or one or more flavouring agents. The water-insoluble gum base and the water-soluble portion will normally be mixed, e.g. via a kneading process or via compression of granulates.

Typically, the water-soluble portion is released with a portion of the flavouring agent over a period of time during chewing. The water-insoluble gum base is preferably retained in the mouth throughout the chew.

In a preferred embodiment of the present invention, the chewing gum core comprises a water-insoluble gum base and a water-soluble portion. The water-insoluble gum base may e.g. comprise one or more components selected from the group consisting of an elastomer, an elastomer solvent, a softening agent, an emulsifier and a filler. 5

The water-insoluble gum base may be a hydrophobic water-insoluble gum base or a hydrophilic water-insoluble gum base.

A hydrophobic water-insoluble gum base may e.g. comprise a hydrophobic polymer. 10 Preferably the hydrophobic polymer is elastic and/or rubbery at 37°C, such as for example an elastomer.

In an embodiment of the invention, the hydrophobic polymer comprises at least 10% by weight of the water-insoluble gum base of the chewing gum core, such as at least 20%, 15 30%, 40%, 50%, 60%, 70% 80% or 90%, such as at least 95% by weight of the water- insoluble gum base of the chewing gum core.

The hydrophobic water-insoluble gum base may comprise hydrophobic polymer in range of 1-100% by weight of the water-insoluble gum base, such as in the range of 1-15%, 15%- 20 20%, 20%-30%, 30%-40%, 40%-50%, 50%-60%, 60%-70%, 70%-80% or 80%-90%, such as in the range of 90%-100%. In a preferred embodiment of the present invention, the hydrophobic water-insoluble gum base comprises hydrophobic polymer in range of 1- 50% by weight of the water-insoluble gum base, such as e.g. 15- 30% by weight.

25 Thus, the hydrophobic polymer may e.g. comprise an elastomer selected from the group of consisting of a styrene-butadiene rubber, a polyisobutulene rubber, a isobutylene-isoprene copolymer elastomers, a polyvinylacetate, styrene butadiene rubber and a natural gum. The natural gum could for example be jelutong, lechi caspi, perillo, massaranduba balata, massaranduba chocolate, nispero, rosindinha, chicle, gutta hang kang, or mixtures thereof.

30 The elastomer can also be a mixture of such natural and synthetic elastomers. These elastomer mixtures can then be used with excellent results as the chewing gum core in the production of chewing gum.

Elastomer used in chewing gum core may be categorized as hard elastomers or soft 35 elastomers. Hard elastomers, which are most commonly butyl rubber and styrene butadiene rubber, generally have a high molecular weight, typically a Flory molecular weight over 200,000. A typical butyl rubber used in chewing gum core may have a Flory molecular weight of about 400,000. Hard elastomers are those which require high shear, dispersive mixing to be utilized in chewing gum core. Hard elastomers generally do not flow at room temperature, even over an extended period of time, and are not pumpable even when heated to temperatures just below which substantial degradation occurs.

Soft elastomers have a lower molecular weight, typically a Flory molecular weight under 100,000. Polyisobutylene and polybutadiene are typically soft elastomers. A typical polyisobutylene used in chewing gum core has a Flory molecular weight of about 53,000. Soft elastomers are generally pumpable at temperatures normally used to make chewing gum core, and will flow at room temperature, though often very slowly.

In addition to Flory molecular weight, sometimes a Stodinger molecular weight is specified. Stodinger molecular weights are generally 1/3 to 1/5 of Flory molecular weights. For example, the polyisobutylene having a Flory molecular weight of 53,000 has a Stodinger molecular weight of about 12,000. Sometimes number average or weight average molecular weights are reported, or the measurement method is not reported. In such instances, the above recitation of the functionality of the elastomer and how they are mixed in producing the chewing gum core can generally be used to classify the elastomer as hard or soft.

As said, a hydrophobic water-insoluble gum base may also comprise one or more additives selected from the group consisting of an elastomer solvent, a softening agent, an emulsifier and a filler.

In a preferred embodiment the chewing gum core comprises an elastomer solvent, a softening agent, an emulsifier and a filler.

The elastomer solvent may constitute from about 0 to about 75 percent by weight of the hydrophobic water-insoluble gum base, preferably 5 to 45 percent by weight and most preferably 10 to 30 percent by weight. Elastomer solvents may include natural rosin esters such as glycerol ester of wood rosin, glycerol ester of partially hydrogenated rosin, glycerol ester of polymerized rosin, glycerol ester of partially dimerized rosin, glycerol ester of rosin, pentaerythritol esters of partially hydrogenated rosin, methyl and partially hydrogenated methyl esters of rosin, pentaerythritol ester of rosin, resin ester of glycerol abietate or mixtures thereof. Elastomer solvents may also include synthetics such as terpene resins derived from alpha-pinene, beta-pinene and/or d-limonene.

Softening agents of hydrophobic water-insoluble gum bases may include oils, fats, waxes and emulsifiers. Oils and fats, sometimes referred to as plasticizers, may include tallow, lard, hydrogenated and partially hydrogenated vegetable oils, such as soybean oil, cotton seed oil, palm oil, palm kernel oil, coconut oil, sunflower oil and corn oil, cocoa butter, and lipids made from triglycerides of fatty acids. Commonly employed waxes may include polywax, paraffin, microcrystalline and natural waxes such as candelilla, beeswax and carnauba. Paraffin waxes may be considered to be plasticizers. Microcrystalline waxes, especially those with a high degree of crystallinity, may be considered as bodying agents or textural modifiers.

Emulsifiers, which also sometimes have plasticizing properties, include glycerol monostearate, lecithin, mono and diglycerides of fatty acids, glycerol mono and distearate, triacetin, acetylated monoglyceride, and glycerol triacetate.

The filler of the hydrophobic water-insoluble gum base may e.g. be calcium carbonate, magnesium carbonate, talc, dicalcium phosphate or the like. The filler may e.g. comprise about 5% to about 60% by weight of the chewing gum core, such as e.g. 15-35% or 15- 20% by weight of the chewing gum core.

It should be noted that the emulsifier and/or the filler need not be hydrophobic. The filler is typically an inorganic material with low water solubility. Typically, emulsifiers comprise both a polar part and a non-polar part of their molecular structure, which may render them partly soluble in both polar and non-polar media.

In another embodiment of the present invention, the chewing gum core comprises a hydrophilic water-insoluble gum base, which comprises a hydrophilic polymer. Preferably, the hydrophilic polymer is water-insoluble.

The hydrophilic polymer may e.g. comprise polyvinyl acetate of various molecular weights, short and/or medium chain polyesters or polyamides, or short and medium side chain poly (vinyl esters) (e.g. polyvinyl butyrates, polyvinyl propionates). The hydrophilic water- insoluble gum base is typically essentially free of hydrophobic polymers such as natural and synthetic rubber elastomers, particularly butyl elastomers, polyisobutylene and styrene butadiene rubber elastomers. The water-insoluble gum base may be essentially free of elastomer solvents, such as terpene resins, ester gums and rosin esters. The hydrophilic water-insoluble gum base may comprise hydrophilic softeners/emulsifiers, but will be essentially free of hydrophobic softeners such as waxes. Thus, the hydrophilic water-insoluble gum base may e.g. be wax-free. The hydrophilic water-insoluble gum base can constitute about 5% to about 95% by weight of the chewing gum core, more commonly about 10% to about 50% of the gum or about 25% to 35% by weight of the chewing gum core. In a particular embodiment, the chewing gum core of the present invention comprises about 20% to about 90% by weight hydrophilic polymers, about 4% to about 50% by weight filler, about 5% to about 35% by weight hydrophilic softeners/emulsifiers, and optional minor amounts (about 1% or less by weight) of miscellaneous ingredients such as colorants, antioxidants, etc.

Fillers/texturizers may include magnesium and calcium carbonate, ground limestone, silicate types such as magnesium and aluminum silicate, clay, alumina, talc, titanium oxide, mono-, di- and tri-calcium phosphate, cellulose polymers, such as oat fiber, and combinations thereof.

Hydrophilic softeners/emulsifiers may include glycerol monostearate, glycerol triacetate, lecithin, mono-, and diglycerides, and short and medium chain triglycerides, acetylated monoglycerides, and combinations thereof.

Colorants and whiteners may include FD&C-type dyes and lakes, fruit and vegetable extracts, titanium dioxide, and combinations thereof.

Softeners are added to the chewing gum in order to optimize the chewability and mouth feel of the gum. The softeners, which are also known as plasticizers and plasticizing agents, generally constitute between approximately 0.5% to about 15% by weight of the chewing gum. The softeners may include glycerine, lecithin, and combinations thereof. Aqueous sweetener solutions such as those containing sorbitol, hydrogenated starch hydrolysates, corn syrup and combinations thereof, may also be used as softeners and binding agents in chewing gum.

For example a chewing gum core having a hydrophilic water-insoluble gum base may comprise: a) about 20% to about 90% hydrophilic polymers; b) about 5% to about 35% hydrophilic softeners/emulsifiers; and c) about 4% to about 50% filler; d) the chewing gum core being essentially free of hydrophobic polymers, hydrophobic elastomer solvents, waxes and hydrophobic softeners.

In an interesting embodiment of the present invention, the water-insoluble gum base is not completely water insoluble but it looses a small fraction of its weight matter when chewed according to the standard described in The European Pharmacopoeia, 3rd Edition, 2001, published by the European Directorate of the Quality of Medicines within the Council of Europe, Strasbourg. The standard method employs a chewing apparatus. The chewing apparatus comprises a chewing chamber of approximately 40 mL in the chewing gum core is artificially chewed by two horisontal pistons, which operate together at constant speed. At the end of a chew, 5 the pistons can rotate around their own axis in opposite directions to each other. In this way, the chewing gum core is subjected to maximum chewing. A third vertical piston, simulating the tongue, operates alternately with the two horisontal pistons and makes sure that the chewing gum core stays in the right place during the chews. The pistons are driven by compressed air and all the materials in contact with the chewing gum core is 10 made of stainless steel.

In order to make a measurement using the apparatus, the temperature of the chewing chamber is adjusted to 36-37 degrees C, and 20 mL phosphate buffer of pH 7.4 is added to the chewing chamber. The chewing machine is started and runs for 2 minutes without

15 any chewing gum core in there. Remove all the buffer by pipette and replace it by 20 mL fresh buffer. The buffer, which was removed, may be analysed as a control for the cleaning procedure of the chewing machine. A piece of chewing gum core having a weight of about 1 g (should weigh precisely before it is chewed) is put into the chewing chamber and the chewing machine is started. The chewing machine is allowed to run for 1 hour with a

20 temperature of 36-37 degrees C in the chewing chamber. After the chewing has ended the non-dissolved residues of the chewing gum core are recovered from the chewing chamber and the remaining dry matter of chewing gum core is determined. Following this test procedure, the remaining dry matter of chewing gum core should at least be 15% by weight of the original dry matter that was placed in the chewing chamber, such as at least

25 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 95% such as at least 99%.

Alternatively, following the above test procedure, the remaining dry matter of chewing gum core should be in the range of 10%-20% by weight of the original dry matter that was placed in the chewing chamber, such as in the range of 20%-30%, 30%-40%, 40%-

30 50%, 50%-60%, 60%-70%, 70%-80% or 80%-90%, such as in the range of 90%- 100% by weight of the original dry matter that was placed in the chewing chamber. In a preferred embodiment of the present invention, the remaining dry matter of chewing gum core should be in the range of 10%-20% by weight of the original dry matter that was placed in the chewing chamber.

35

The water-soluble portion of the chewing gum core may comprise one or more components selected from the group consisting of a softener, a bulk sweetener, a high intensity sweetener, and a flavouring agent. In a preferred embodiment of the present invention, the water-soluble portion of the chewing gum core comprises a softener, a bulk sweetener, and a flavouring agent and in a further embodiment the water-soluble portion furthermore comprises a high intensity sweetener. When reference is made to a sweetener this may e.g. be a bulk sweetener or a high intensity sweetener.

Bulk sweeteners may constitute between 5-95% by weight of the chewing gum core, more typically 20-80% by weight of the chewing gum core and most commonly 30-60% by weight of the chewing gum core. Bulk sweeteners may include both sugar and sugarless sweeteners. Sugar sweeteners may include saccharide containing components including but not limited to sucrose, dextrose, maltose, dextrin, dried invert sugar, fructose, levulose, galactose, corn syrup solids, and the like, alone or in combination. Sugarless sweeteners include components with sweetening characteristics but are devoid of the commonly known sugars. Sugarless sweeteners include but are not limited to sugar alcohols such as sorbitol, mannitol, xylitol, hydrogenated starch hydrolysates, maltitol, and the like, alone or in combination.

The chewing gum core may comprise one or more high intensity sweeteners which are commonly used together with sugarless sweeteners. When used, high intensity sweeteners typically constitute between 0.001-5% by weight of the chewing gum core, preferably between 0.01-1% by weight of the chewing gum core. Typically, high intensity sweeteners are at least 20 times sweeter than sucrose. These may include but are not limited to sucralose, aspartame, N-substituted APM derivatives such as neotame, salts of acesulfame, alitame, saccharin and its salts, cyclamic acid and its salts, glycyrrhizinate, dihydrochalcones, thaumatin, monellin, and the like, alone or in combination. In order to provide longer lasting sweetness and flavour perception, it may be desirable to encapsulate or otherwise control the release of at least a portion of the high intensity and/or sugarless sweetener.

Combinations of sugar and/or sugarless sweeteners may be used in chewing gum core. The sweetener may also function in the chewing gum in whole or in part as a water-soluble bulking agent. Additionally, a softener may provide additional sweetness such as with aqueous sugar or alditol solutions.

Flavour may be present in the chewing gum in an amount within the range of about 0.1- 15% by weight of the chewing gum, preferably between about 0.2-5% by weight of the chewing gum core, most preferably between about 0.5-3% by weight of the chewing gum core. Flavouring agents may include essential oils, synthetic flavours or mixtures thereof including but not limited to oils derived from plants and fruits such as citrus oils, fruit essences, peppermint oil, spearmint oil, other mint oils, clove oil, oil of wintergreen, anise and the like. Artificial flavouring agents and components may also be used in the flavour ingredient of the invention. Natural and artificial flavouring agents may be combined in any sensoπally acceptable fashion.

For example, useful flavours may be selected from the group consisting of peppermint, periwinkle, eucalyptus, spearmint, anethol, menthol, powdered anise, and fruit flavours such as orange, lemon, mango, pineapple, lime, strawberry, cherry, black currant, blueberry, raspberry, wild berry, cranberry, apple, pear, banana, prune, and plum flavour, etc.

The flavour may also be a plant extract which may be applied instead of or together with one or more of the above-mentioned flavour(s) are preferably selected among extracts of liquorice, coffee, tea, herbs such as sage, thyme, basil, bergamot, balm, valerian, camomile, lavender, aloe vera, and spices such as pepper, cinnamon, capsicum, paprika, tarragon, fennel, mustard, dill, caraway, parsley, tomato, etc.

A humectant, such as aqueous sorbitol or glycerine, may be added to the chewing gum core in manufacturing chewing gum.

Softeners may be added to the chewing gum core in order to optimize the chewabihty and mouth feel of the chewing gum. The softeners, which are also known as plasticizers or plasticizing agents, generally constitute between about 0.5-15% by weight of the chewing gum core. The softeners may include glycerine, lecithin, and combinations thereof.

Aqueous sweetener solutions such as those containing sorbitol, hydrogenated starch hydrolysates, corn syrup and combinations thereof, may also be used as softeners and binding agents in a chewing gum core.

Optional ingredients such as colours, emulsifiers, pharmaceutical agents and additional flavouring agents may also be included in chewing gum core. TiO₂ may e.g. be used to provide a white colour.

By the term "coating" is meant one layer or the sum of several layers. The coating may be placed directly onto the inner core or onto one or more of other layers that may surround the inner core. The coating may comprise from 50% to 90% by weight of the entire composition, preferably from 55% to 80%, more preferably from 60% to 75% by weight of the composition. As said, the coating comprises as its main constituent one or more minerals, such as a source of calcium, which in the case of calcium carbonate is water-insoluble. The source of calcium and/or the one or more minerals may be fully enclosed in the coating or it may be partly enclosed in the coating. Some of the source of calcium or the one or more minerals may only be partly enclosed by the coating, thus e.g. having air contact.

The coating may fully surround the inner core or it may only partly surround the inner core. It is however preferred that at least 30% of the outer surface of the inner core is covered by the coating such as at least 50%, 75%, 90%, 95%, 99%, or 100% of the outer surface of the inner core is covered with the coating.

Besides the source of calcium or the one or more minerals, the coating may comprise additionally components, preferably water-soluble ingredients. For example, the coating may comprise one or more components selected from the group consisting of a bulk sweetener, a high intensity sweetener, a binder, a colour and an emulsifier.

In a preferred embodiment of the present invention, the coating comprises a bulk sweetener, a binder, an emulsifier and one or more minerals such as calcium carbonate. The coating may furthermore comprise a high intensity sweetener.

In another preferred embodiment of the present invention, the coating comprises a bulk sweetener, a high intensity sweetener, a binder, a colour and an emulsifier.

Bulk sweeteners may include both sugar and sugarless sweeteners and components. Sugar sweeteners may include saccharide containing components including but not limited to sucrose, dextrose, maltose, dextrin, dried invert sugar, fructose, levulose, galactose, corn syrup solids, and the like, alone or in combination. Sugarless sweeteners include components with sweetening characteristics but are devoid of the commonly known sugars. Sugarless sweeteners include but are not limited to sugar alcohols such as sorbitol, mannitol, xylitol, hydrogenated starch hydrolysates, maltitol, isomalt and the like, alone or in combination. In a preferred embodiment, at least 50% by weight of the bulk sweetener is a sugar alcohol, such as at least 60%, 70%, 80%, 90%, or 95%, such as at least 99% of the bulk sweetener. In a particular embodiment, essentially all the bulk sweetener is a sugar alcohol.

In a preferred embodiment of the invention, the coating comprises sugarless sweeteners, such as the polyols. Typically examples of polyols are mannitol, sorbitol, xylitol and maltitol. In an especially preferred embodiment of the invention, the coating comprises sorbitol. In an embodiment of the present invention, the coating comprises at most 20% by weight xylitol, such as e.g. at most 15%, 10%, 7,5%, 5%, 2%, or at most 1%, such as at most 0.5% by weight xylitol. In an embodiment, the coating does not comprise xylitol.

In an embodiment of the present invention, the coating comprises at most 40% by weight sugar alcohol, such as e.g. at most 35%, 30%, 25%, 20%, 15%, or at most 10%, such as at most 5% by weight sugar alcohol. In an embodiment, the coating does not comprise xylitol.

In a particular embodiment, at least 50% by weight of the bulk sweetener is sorbitol, such as at least 60%, 70%, 80%, 90%, or 95%, such as at least 99% of the bulk sweetener. In a particular embodiment, essentially all the bulk sweetener is sorbitol.

In a particular embodiment, at least 50% by weight of the bulk sweetener is mannitol, such as at least 60%, 70%, 80%, 90%, or 95%, such as at least 99% of the bulk sweetener. In a particular embodiment, essentially all the bulk sweetener is mannitol.

In an interesting embodiment, at least 50% by weight of the bulk sweetener is xylitol, such as at least 60%, 70%, 80%, 90%, or 95%, such as at least 99% of the bulk sweetener. In a particular embodiment, essentially all the bulk sweetener is xylitol.

In a preferred embodiment, at least 50% by weight of the bulk sweetener is maltitol, such as at least 60%, 70%, 80%, 90%, or 95%, such as at least 99% of the bulk sweetener. In a particular embodiment, essentially all the bulk sweetener is maltitol.

High intensity sweeteners may also be present in the coating and are commonly used with sugarless sweeteners. When used, high intensity sweeteners typically constitute between 0.001-5% by weight of the coating, preferably between 0.01-1% by weight of the coating. Typically, high intensity sweeteners are at least 20 times sweeter than sucrose. These may include but are not limited to sucralose, aspartame, salts of acesulfame such as acesulfame-K, alitame, saccharin and its salts such as saccharin sodium and saccharin calcium, cyclamic acid and its salts, neotame, alitame, neohesperidin DC, stevia, glycyrrhizin, dihydrochalcones, thaumatin, monellin, twinsweet and the like, alone or in combination. Combinations of sugar and/or sugarless sweeteners may also be used in the coating.

, Optionally, the coating also comprises a binder such as gum arabic, gelatine, polyvinylpyrrolidone, starches or cellulose. In an embodiment, the coating comprises approximately 0.5-5% by weight binder, about 5-30% by weight sweetener and approximately 65% to about 90% by weight mineral. For example, in a preferred embodiment, the coating comprises about 15-25% by weight sweetener, about 3-5% by weight binder and 75-80% by weight calcium source, such as calcium carbonate.

In an embodiment of the present invention, the average thickness of the coating of a coated chewing gum is within the range of 50-5000 micrometer, such as e.g. 100-2000 micrometer, 200-1000 micrometer, and 250-750 micrometer.

In an embodiment of the present invention, the weight of the coating of the composition, e.g. a chewing gum, may be within the range of 0.2-4 g, such as 0.8-3 g or 1.5-2.5 g.

In an embodiment of preparing the coated chewing gum, first a coating suspension is distributed on the chewing gum cores. Typically, the coating suspension comprises water, sweetener and a binder. The solids typically account for 40-65% of the weight of the coating suspension. After the application of the coating suspension, a portion of the powder is sprinkled on top of the chewing gum cores and sticks to the sticky layer of coating suspension. The chewing gum cores are dried and a further amount of coating suspension is applied and powder is supplied again. This process is continued until the necessary amount of coating suspension and powder have been applied to the exterior of the chewing gum cores, e.g., 5 to 50 coating layers or more are applied.

It may be preferred that the powder is dry when it is applied to the sticky layer of coating suspension on the chewing gum cores. The water content in the powder may e.g. be at most 10% such as e.g. at most 5%, 1% or 0.1% by weight of the powder.

The coating suspension may also comprise suspended particles of the calcium source, e.g. calcium carbonate. Thus, elemental calcium may both be provided via the coating suspension and via the application of dry powder. If provided in the coating suspension the percentage of dry matter may be kept at the same level by lowering the concentration of the sweetener. As an embodiment of this invention, further active agents such as one or more vitamins and/or minerals different from calcium may be added to the composition either as part of the inner core or the coating or both. Vitamins include vitamin A, beta carotene, B vitamins (B-I, B-2, B-6 or B-12), vitamin C, D, E or K, niacinamide, pantothenic acid, folic acid or biotin. Minerals include iron, lithium, magnesium, iodine, copper, phosphorous, zinc, manganese, potassium, sodium, chromium, molybdenum, selenium, zinc, tin, silicon, vanadium and boron.

Particularly, the further active ingredient is vitamin D or an analogue thereof, such as vitamin D₂, ergocalciferol, vitamin D₃, cholecalciferol, or a mixture thereof or active forms thereof. Preferably, the further active ingredient is vitamin D₃ including the active form thereof in that vitamin D₃ enhances the absorption of calcium from the intestinal tract.

Preferably, the vitamins and minerals are included in such levels as to provide a significant dietary supplement. Typically, a dosage unit of the invention, such as a piece of chewing gum, comprises vitamin D₃ in range of 1-20 microgram, such as 3-5 microgram and 8-12 microgram. The ratio of calcium in elemental form to Vitamin D, expressed in mg of elemental calcium per IU of vitamin D may be in the range 1-5, such as e.g. 2-3. The dosage unit could for example comprise 500mg elemental Ca and 200 IU vitamin D. One microgram vitamin D corresponds to approximately 40 IU (International Units).

Due to problems with achieving homogenous compositions of vitamins and minerals added in relatively small amounts, the vitamin may be added in the form of a pre-mix. The vitamin may be encapsulated or spray-dried. The vitamin may be entrapped onto the surface of an inert carrier. In an embodiment the inert carrier may be the source of elemental calcium, e.g. calcium carbonate.

In a preferred embodiment, the coating comprises a vitamin such as vitamin D₃. When located in the coating, Vitamin D₃ is preferably used in an encapsulated form.

In an embodiment, the composition further comprises active ingredients of relevance in reducing the risk of osteoporosis, such as estrogens, including the so-called phytoestrogens, parathyroidea hormone and analogues thereof, and/or vitamin K.

The process for the preparation of the composition may be performed as described below: The conventional chewing gum components are mixed in kneading kettles (mixers) with strong horizontally placed Z-shaped arms, which processes the raw materials and produces a homogeneous gum mass. The kneading kettles are heated to a temperature of 30-80⁰C, typically approx. 45°C. The mixing process starts with gum base quantities that have been weighed out, and the processing of these lasts for 1-20 minutes, typically approx. 10 minutes. Then one or more sweetener(s) in powder form or in liquid form is/are added. The dosage of sweeteners and the following processing last from 1 to 20 minutes, typically approx. 7 minutes.

Then the flavours and the remaining components are added and kneaded for a further 1 to 10 minutes, typically approx. 5 minutes. The admixture of flavours and the remaining components may also take place in the beginning of the kneading process, i.e. before the admixture of the sweeteners. It is also possible to add flavours in two or more portions during the kneading process.

When the kneading is completed, the kneading kettle is tipped, and the gum mass is taken out into carts, onto trays or the like.

The next process is the forming of the chewing gum core. Before the forming can take place, the chewing gum mass, however, must be cooled. When taken out, the chewing gum mass has a temperature of 50-70⁰C, and in order to form the chewing gum core, the temperature must be reduced to 30-45⁰C. The cooling of the chewing gum core either takes place by storing the chewing gum mass in carts or on trays for quite a long time or by transporting a thin chewing gum carpet through a cooling tunnel.

The forming of the chewing gum cores may take place by extrusion through a specially formed nozzle, or the chewing gum core may be formed after extrusion by means of rollers, punching machines, tentering wheels, and the like.

The chewing gum core may be formed into cores of suitable shape, e.g. rectangular pellets/tablets, sticks, balls, cubes, cylinders, and many other shapes.

In order to prevent the chewing gum core from sticking to the rollers and other tools, the chewing gum core is frequently powdered with a powder, which may consist of i.a. icing sugar, talc, corn flour, and the like.

The formed chewing gum cores can be cooled immediately to room temperature in a cooling tunnel or the cooling may take place on trays at a store for semi manufactured products at a controlled temperature and moisture.

The formed and cooled chewing gum core is then treated by means coating and polishing processes before the packing. The coating of the chewing gum cores may take place in a tilted, round or horizon-tally placed cylindrical coating kettle that rotate during the whole process. The coating kettle may be made from copper, stainless steel or fiberglass-reinforced polyester, and are often equipped with a piping system that supplies and exhausts air and doses the coating suspension.

The coating process may take place as described below. It should be noted that even though the process mentions a source of elemental calcium such as calcium carbonate, other mineral sources may be incorporated into the coating of by the same coating process, which has proved to be especially useful for obtaining high loads of water- insoluble mineral compounds in the coating:

The coating suspension is heated up to a temperature in the range of 35-75°C depending on the sweetener, preferable for sorbitol in the range of 37-45°C, such as about 40⁰C. Air for drying the layers of coating suspension on the chewing gum cores is typically heated up to at least 35°C such as about 40⁰C.

The coating suspension typically comprises a bulk sweetener, preferably a polyol, water and optionally also a binder. The coating suspension typically comprises 30-70% by weight bulk sweetener, e.g. polyol, preferably 40-60% by weight and even more preferably 50- 60% by weight such as 54-56% by weight.

The coating suspension typically comprises 20-70% by weight water, preferably 30-50% by weight and even more preferably 35-45% by weight such as 38-42% by weight.

Optionally, the coating suspension may also comprise 0.5-10% by weight binder, preferably 2-8% by weight and even more preferably 3-6% by weight such as about 5% by weight. Preferably one or more binders of the coating are selected from the group consisting of gum arabic, gelatine, polyvinylpyrrolidone, starches, and cellulose. Gum arabic is particularly preferred as binder in the coating suspension.

In a preferred embodiment of the invention the coating suspension comprises 54-56% by weight polyol, e.g. sorbitol, 35-45% by weight water and 3-6% by weight binder.

The coating suspension may furthermore comprise various additives such as emulsifiers, flavours and colorants, e.g. the emulsifiers, flavours and colorants described herein. The chewing gum cores are put into movement in the rotating coating kettles. The coating suspension is added in small portions that disperse evenly over the surfaces of the cores after some time to smooth out. Then the powder source of elemental calcium and optionally also vitamin D₃ is applied by sprinkling it freely over the tablets. The cores are stirred well to assure an even distribution of the powder and to smooth out the surface. Then the cores are dried by means of air. The operation is repeated up to 90 times, preferably approx. 30-40 times, until the correct amount of elemental calcium is added and the cores have the preferred measure and the preferred weight.

Flavours might be added to the chewing gum tablets in addition to a small dosage of coating suspension. The addition of flavour might also be followed by addition of the powder source of elemental calcium as described. Preferable the flavour is added in different coating layers from the vitamin D₃ to avoid possible interactions.

Furthermore, between the dosages of the coating suspension and the addition of one or more active substance(s) in solid form, one or more active substance(s) in liquid form may be added.

In order to achieve a neat and smooth surface of the chewing gum tablets the coating can be finished by applying several small dosages of coating suspension without additional powder dosing and letting the tablets dry up without addition of airflow in between.

In order to achieve a shining surface of the chewing gum tablets with the completed coating, these may subsequently be subjected to a polishing. The polishing also takes place in rotating coating kettles in which a polishing suspension or a polishing powder is added to the coated cores in one or more portion(s). The polishing suspension often consists of wax, emulsifier, coating agent, gum arabic, water, etc. The polishing powder often consists of wax only, or of wax mixed with emulsifier, gum arabic or talc, etc.

Thus, an aspect of the present invention relates to a process for the manufacturing of a composition, e.g. a coated chewing gum, comprising an inner core and a coating, wherein one or more minerals, e.g. elemental calcium, are present in an amount of at least 25% by weight of the coating, the process comprises the steps of:

i) providing a inner core comprising a chewing gum core,

ii) providing a coating suspension comprising a polyol and, optionally, also a binder,

iii) providing one or more minerals, e.g. a source of elemental calcium, in powder form, iv) applying a layer of the coating suspension onto the inner core,

v) applying some of the powdered mineral, e.g. the source of elemental calcium, to the inner cores,

vi) repeating step iv) and v)

Typically the process also comprises a step of drying the layer of the suspension on the inner core. Such a step is preferably included as the last part of step iv) and/or in step v).

In step iv) the applied volume of coating suspension during one repetition of the step is typically in the range of 5-40 microL per inner core, preferably 10-30 microL, and even more preferred in the range of 15-25 microL.

The amount of polyol which is applied during one repetition of step iv) is typically in the range of 1-20 microgram per inner core, preferably 5-15 microgram, and even more preferred in the range of 7-13 microgram per inner core.

In step v) the applied amount of powdered mineral, e.g. a source of calcium such as calcium carbonate, is typically in the range of 10-200 mg per inner core for one repetition of the step, preferably 25-100 mg, and even more preferred in the range of 40-60 mg.

In a third aspect the invention relates to the use of a source of elemental calcium and optionally a vitamin D for the preparation of a medicament for the treatment of osteoporosis in a human, wherein said elemental calcium and vitamin D is provided in the form of a chewing gum that comprises i) an inner core comprising a chewing gum core; and ii) a coating comprising elemental calcium in an amount of at least 25% by weight of the coating; and wherein vitamin D is present in the inner core and/or in the coating. That is to say that the invention relates to a method for treating osteoporosis comprising administering to a human an effective amount of elemental calcium and vitamin D provided in the form of a chewing gum that comprises i) an inner core comprising a chewing gum core; and ii) a coating comprising elemental calcium in an amount of at least 25% by weight of the coating; and wherein vitamin D is present in the inner core and/or the coating.

The chewing gum may be a composition as described herein.

It is to be understood that the medicament is meant to be in the form of a chewing gum, which applies to the composition as defined herein. In a further aspect, the compositions defined herein may be used in the prevention of bone demineralisation in a human, e.g. in the event wherein the composition as defined herein is used as a nutritional and/or dietary supplement or as a pharmaceutical product for preventing, relieving or treating symptoms associated with osteoporosis and/or bone- mineralisation in a mammal, such as in a female as well as a male. The mammal may e.g. be human.

Another aspect of the present invention relates to method for preventing, relieving or treating symptoms associated with osteoporosis and/or bone-mineralisation in a mammal, such as in a female as well as a male, wherein said method comprises the step of administering the compositions defined herein to the mammal. The mammal may e.g. be human.

It must be emphasised that the present invention also envisions the combination of the described aspects and embodiments. For example, this could be a composition comprising a chewing gum core having a hydrophobic water-insoluble gum base, said composition comprising a coating which includes sorbitol, calcium carbonate, vitamin D₃, vitamin K and a magnesium compound.

EXAMPLES

EXAMPLE 1

CHEWING GUM CORES

Chewing gum cores with a composition as described below were prepared by mixing the below ingredients into the gum base in a kneading kettle. A conventional hydrophobic gum base was used.

Composition of chewing gum cores:

Gum base 700 g

Calcium carbonate 200 g

Sorbitol powder 1011 g

Maltitol syrup 20 g High intensity sweetener 9 g

Mint flavour 60 g

Total weight 2000 g The kneading kettles were heated to a temperature of approx. 45°C. The mixing process started with processing the gum base for approx. 10 minutes. Then the sweeteners in powder and liquid form were added followed by mixing for approx. 10 minutes.

After that the flavour and calcium carbonate were added and kneaded for a approx. 5 minutes.

The next, the gum base mixture was cooled to a temperature of about 35°C and subsequently, the chewing gum cores having a weight of about 1 g per piece were formed using a punching machine.

EXAMPLE 2

THE COATING PROCESS INCLUDING DRY CHARGING

About 2 kg of the chewing gum cores of Example 1 (about 2000 pieces of 1 g each) were transferred into a coating kettle.

A Sorbitol suspension having ingredients as mentioned below was prepared by mixing the ingredients into the water at a temperature of 4O⁰C.

Sorbitol suspension:

Sorbitol syrup (70%) 2378 g

Water 535 g Titanium dioxide 16 g

Polysorbate 80 4 g

Gum Arabic 134 g

Flavour powder: Mint flavour powder 12 g

Powder A:

Calcium carbonate 2000 g

Powder B (D^ pre-blend):

Calcium carbonate 500 g

D₃ encapsulated (850,000 IU) 0.474 g The Sorbitol suspension and the powders were applied to chewing gum cores in several dosage cycles. Initially in a dosage cycle, sorbitol suspension was applied to the chewing gum cores by spraying. When the suspension was evenly distributed on the chewing gum cores by rotation of the coating kettle, a dry charge of powder, that is, Powder A, B or mint flavour, was applied by sprinkling. When the powder was evenly distributed on the chewing gum cores an airflow for drying the suspension on the chewing gum cores was started and the chewing gum cores were dried until they stopped sticking together. Then the airflow was stopped and the surfaces of the cores were evened out. Finally, the airflow was applied again and the chewing gum cores were dried to be ready for the next dosage cycle. Typically, in a dosage cycle 20-40 mL Sorbitol suspension and about 100 g Powder A or B were used.

The dosage cycles were repeated until about 1800 g of Powder A, 500 g of Powder B and the mint flavour powder had been used.

Another 5-8 dosage cycles, using only Sorbitol suspension, were then performed to even out and seal the surface of the coating of the chewing gum cores.

Finally, the coated chewing gum cores were polished in a rotating kettle using carnauba wax and 15 minutes rotation.

The resulting coated chewing gum had an average weight of 2530 mg of which 1567 mg was coating. Of the 1567 mg coating, CaCO₃ accounted for 1204 mg corresponding to 76% by weight CaCO₃ in the coating.

EXAMPLE 3

EVALUATION OF THE HIGH LOAD CALCIUM CARBONATE CHEWING GUM

Visual inspection

The coated chewing gums prepared according to Example 2 were inspected visually. The coated chewing gums were found to have uniform and robust coatings and did not display any tendency for peeling or flaking not even after 2 weeks storage at room temperature. All attempts to prepare high load calcium carbonate chewing gum reported in the prior art have been unsuccessful in obtaining a robust coatings for chewing gum having a calcium carbonate weight percent above 60% in the coating. Mouthfeel

The coated chewing gums prepared according to Example 2 were tested with respect to mouthfeel, that is, sensations that the consumer feels in her mouth when chewing the chewing gum. Surprisingly, the coated chewing gums of Example 2 were found to be crunchy despite the concentration of calcium carbonate used in the coating. All attempts to prepare high load calcium carbonate chewing gums reported in the prior art have been unsuccessful in obtaining a crunchy coatings for chewing gum having a calcium carbonate weight percent above 60% in the coating.

Claims

1. A composition comprising a source of elemental calcium, the composition comprises i) an inner core; and ii) a coating, said coating comprises elemental calcium in an amount of at least 25% by weight of the coating.

2. A composition comprising a source of elemental calcium, the composition comprises i) an inner core comprising a chewing gum core, the chewing gum core; and ii) a coating, said coating comprises elemental calcium in an amount of at least 25% by weight of the coating.

3. A composition comprising a source of elemental calcium, the composition comprises i) an inner core comprising a chewing gum core; and ii) a coating, said coating comprises calcium carbonate in an amount of at least 63% by weight of the coating.

4. The composition according to any of claims 1-3, wherein the coating constitutes from 50% to 85% by weight of the composition, preferably from 52% to 75%, more preferably from 55% to 70 % by weight of the composition.

5. The composition according to any of claims 1-4, wherein the inner core constitutes from 15% to 50% by weight of the composition, preferably from 20% to 45%, more preferably from 25% to 40% by weight of the composition.

6. The composition according to any of claims 1-5, wherein the coating comprises elemental calcium in an amount ranging between 25-36% by weight of the coating, preferably ranging between 28-35%, more preferably ranging between 30-35%.

7. The composition according to any of claims 1-6, wherein the inner core comprises a source of elemental calcium.

8. The composition according to any of claims 1-7, wherein the source of elemental calcium is a calcium salt selected from calcium carbonate, calcium lactate, calcium citrate, calcium gluconate, calcium maleate-citrate, calcium glycerophosphate, calcium phosphate and hydrates thereof.

9. The composition according to any of claims 1-8, wherein the source of elemental calcium is calcium carbonate or a hydrate thereof.

5 10. The composition according to any of claims 1-9, wherein when the source of elemental calcium is calcium carbonate, the coating comprises calcium carbonate in an amount ranging between 63-90% by weight of the coating, preferably ranging between 70- 90%, more preferably ranging between 75-90%, most preferably ranging between 78- 85% by weight of the coating.

10 11. The composition according to any of claims 1-10, wherein the source of elemental calcium, such as calcium carbonate, is micronised.

12. The composition according to any one of the preceding claims, further comprising a vitamin.

13. The composition according to claim 12, wherein the vitamin is included in the inner 15 core.

14. The composition according to claim 12 or 13, wherein the vitamin is included in the coating.

15. The composition according to claim 12, wherein the vitamin is included in the inner core and the coating.

20 16. The composition according to any of claims 12-15, wherein the vitamin is trapped or coated onto the surface of the source of elemental calcium.

17. The composition according to any of claims 12-16, wherein sad vitamin is a vitamin D or its analogues.

18. The composition according to claim 17, wherein said vitamin D is selected from

25 vitamin D2, ergocalciferol, vitamin D₃, cholecalciferol, or a mixture thereof or active forms thereof.

19. The composition according to claim 18, wherein said vitamin D is vitamin D₃ or its active form.

20. The composition according to any of claims 18-19, wherein the vitamin D₃ or its 30 active form is present in an amount in the range of 2-15 microgram in the composition.

21. The composition according to any of claims 1-20, wherein the composition further comprises one or more minerals.

22. The composition according to claim 21, wherein the one or more minerals comprises elemental magnesium.

5 23. The composition according to any of claims 1-22, wherein the coating comprises a polyol.

24. The composition according to claim 23, wherein the polyol is selected from mannitol, sorbitol, xylitol and maltitol.

25. The composition according to claim 24, wherein the polyol is sorbitol.

10 26. The composition according to any of claims 1-25, wherein the coating further comprises a binder.

27. The composition according to claim 26, wherein the binder is selected from the group consisting of gum arabic, gelatine, polyvinylpyrrolidone, starch, cellulose, and derivatives thereof.

15 28. The composition according to any of claims 1-27, wherein the composition is a chewing gum with a unit weight in the range of 2-4 g, preferably 2-3 g, such as 2.5 g.

29. A composition comprising a source of elemental calcium and a vitamin D, the composition comprises i) an inner core comprising a water insoluble gum base; and 20 ii) a coating comprising a binder, sorbitol, and calcium carbonate in an amount ranging between 65-90% by weight of the coating, the coating constitutes from 50% to 85% by weight of the composition.

25 30. A process for the manufacturing of a chewing gum comprising a chewing gum core and a coating surrounding the chewing gum core, wherein elemental calcium is present in an amount of at least 25% by weight of the coating, the process comprises the steps of:

i) providing a chewing gum core comprising a water-insoluble gum base,

30 ii) providing a suspension of a polyol and a binder,

ii) providing a source of elemental calcium in powder form, iv) coating a first layer of the suspension onto the chewing gum core

v) applying some of the powdered source of elemental calcium by dry charging, and

vi) repeating step iv) and v).

5 31. Use of a source of elemental calcium and a vitamin D for the preparation of a medicament for the treatment of osteoporosis in a human,

said elemental calcium and vitamin D is provided in the form of a chewing gum that comprises i) an inner core comprising a gum base; and ii) a coating comprising elemental calcium in an amount of at least 25% by weight of the coating; and wherein 10 vitamin D is present in the inner core and/or the coating.

32. The use according to claim 31, wherein the chewing gum is a composition as defined by any one of claims 1-29.

33. Use of the composition as defined by any one of claims 1-29 in the prevention of bone demineralisation in a human.

15 34. Use of the composition as defined by any one of claims 1-29 as a dietary supplement.

35. A method for treating osteoporosis comprising administering to a human an effective amount of elemental calcium and vitamin D provided in the form of a chewing gum that comprises i) an inner core comprising a gum base; and ii) a coating comprising

20 elemental calcium in an amount of at least 25% by weight of the coating; and wherein vitamin D is present in the inner core and/or the coating.

36. The method according to claim 35, wherein the chewing gum is a composition as defined by any one of claims 1-29.

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