The present invention relates to the field of slow release oral delivery systems, such as chewing gums. In particular the invention pertains to reducing phosphorus level in users in need thereof.

Background

Phosphorus intake occurs with food, and it is well-known that the amount of phosphorus in food varies a lot. Meat, for example, is rich in phosphorus whereas low-protein food may be lower in phosphorus-content. However, a complete avoidance of all kinds of phosphorus-rich food may result in malnutrition.

EP 1 827 386 describes the use of phosphorous binding agents, such as chitosan, to lower phosphorous-levels in patients suffering from hyperphosphatemia.

Chitosan has been seen to be highly suitable to reduce phosphorus-levels as chitosan is not digestible and passes through the digestive tract without being absorbed and therefore does not add any calories. As such chitosan may advantageously be used as a non-pharmaceutical food supplement e.g. in a population that is particularly exposed to risk of phosphorus-related diseases.

A problem related to this prior art is that rather large amounts of chitosan need to be used in order to obtain a satisfying lowering of the phosphorus level.

It is therefore an object of the present invention to establish an improved method of lowering phosphorus-levels in users in need thereof.

Summary of the present invention

The invention relates to the non-medical use of a combination of a phosphorus compound binding agent and an organic acid in a slow release oral delivery system comprising at least one delivery vehicle and/or excipient, wherein said phosphorus compound binding agent is chitosan, for reducing the level of free phosphorus compounds in the digestive juice. According to the present invention, it has surprisingly been found that the phosphorus-binding ability of chitosan may be improved by combining chitosan with an organic acid in a slow release oral delivery system.

Hereby, by using the present oral delivery system as a food supplement, already known advantageous results of lowering phosphorus-levels in the digestive juice of users may be obtained to an even higher degree.

Lowering of phosphorus-levels in the digestive juice of users may be pleasant for a variety of users, e.g. people suffering from hyperphosphatemia.

In order to bind as much phosphorus as possible, oral delivery systems according to embodiments of the present invention are characterized by continuous slow release characteristics of the chitosan and the organic acid. Moreover, the composition may preferably be retained in the mouth for as long time as necessary to draw close to exhaustion of the phosphorus binding agent.

According to an embodiment of the present invention, said use is non-therapeutic. In an embodiment of the invention, said organic acid is ascorbic acid.

According to a preferred embodiment of the present invention, the benefits of chitosan may be boosted by using ascorbic acid as the organic acid. Both D-Ascorbic acid and L-ascorbic acid may be used, and according to the present invention it has been shown that these are preferable among the organic acids for enhancing chitosan's ability to reduce the level of free phosphorus in the digestive juice. Consequently, the combination of chitosan and ascorbic acid may result in even lower phosphorus levels.

In an embodiment of the invention n the reduction of the level of free phosphorous compounds is increased by between ,5 and 50%, such as 15 - 40 % when compared to the same oral delivery system without organic acid.

It has surprisingly been discovered that the combination of chitosan and an organic acid enhance the binding capacity of chitosan with respect to free phosphorous compounds when used in a slow release oral delivery system.

For example, the amount of phosphate in the saliva may be reduced much more effectively by combining chitosan and an organic acid in an oral delivery system when compared to the same delivery system without organic acid added.

In an embodiment of the invention, the dosage of said combination of a phosphorus compound binding agent and an organic acid is in an amount sufficient to reducing the level of free phosphorus compounds in the digestive juice with at least 10%, such as 20% or 30%.

Such reducing of level of free phosphorus compounds in the digestive juice may e.g. be measured with respect to physiological level, or as % by weight.

In an embodiment of the invention, said oral delivery system comprises a chewing gum.

According to embodiments of the present invention, the oral delivery system is suitable for being retained for a long time in the mouth of the user. A preferred embodiment is chewing gum, since it can be retained in the mouth for an extended period, even hours. Furthermore, it allows the user to control the permanence of the chitosan in the mouth.

Finally, by letting the oral delivery system comprise a chewing gum, further advantages are obtained. Phosphate sequestration may occur in the mouth, in particular from saliva, the major source of recirculating phosphorus. Therefore, once the chitosan has absorbed amounts of phosphorus compounds, the chewing gum can be discarded and a new chewing gum can be taken. This avoids swallowing the composition and engaging the gastrointestinal tract with the presence of a composition loaded with phosphorus, so that the user has not to worry about a possible release of phosphorus in the gastrointestinal tract or the effective elimination of the composition.

In an embodiment of the invention, said chewing gum is a compressed chewing gum. In an even more preferred embodiment, the chewing gum is a compressed chewing gum. In a compressed chewing gum, typically, gum base granules are mixed with further chewing gum ingredients, such as sweeteners and flavor. This final mix of granules is then compressed under high pressure into a chewing gum tablet.

The result is that an initial chew of a compressed chewing gum results in an initial disintegration of the chewing gum followed by a gathering of the water-insoluble ingredients over time upon chewing. Hereby, a larger amount of the chitosan and the organic acid may be initially quickly released inside the mouth cavity, thereby facilitating initial quick larger uptake possibilities for phosphorus compounds in the mouth of the user. However, the advantages described above related to chewing gum in general still applies, since the end product may still be discarded as any kind of chewing gum.

In an embodiment of the invention, said at least one delivery vehicle and/or excipient is selected from the group consisting of lactose anhydrous or monohydrate, povidone, microcystalline cellulose, hydroxypropylcellulose, sodium

croscaramellose, magnesium stearate, El 71 , El 72, mannitol, sodium laurylsulphate, ipromellose, methacrylic acid copolymer, macrogol, magnesium stearate, gelatine, saccharose, starch, sorbitol, flavours, sodium saccharine, colloidal silica, titanium dioxide, maltitol syrup, gum arabic, glycerol, aspartame, hydrogenated vegetal oil, sorbitol, citric acid, pectin, caramel, sucrose and methylcellulose. In an embodiment of the invention, said use is for reducing the level of free phosphorus compounds in at least one selected from the group consisting of saliva, gastric juice, pancreatic juice, bile, and intestinal juice. In an embodiment of the invention, said chitosan has a molecular weight of above 30.000 Da, preferably above 50.000 Da.

According to further embodiments of the invention, said chitosan has a molecular weight of between 3.000 and 30.000 Da.

In an embodiment of the invention, said chitosan has a degree of deacetylation above 85%, preferably above 90%, most preferably above 95%.

In an embodiment of the invention, said chitosan has fat binding affinity.

In an embodiment of the invention, said oral delivery system comprises said chitosan and said organic acid in a ratio between 1 :4 and 40: 1 by weight, preferably between 1 : 1 and 10: 1 by weight. In an embodiment of the invention, the total amount of said chitosan taken by a user on a single day is between 0.1 and 20 g, preferably between 0.2 and 10 g.

In an advantageous embodiment of the invention at least a part of said chitosan is retained in the chewing gum after chewing.

By retaining chitosan in the chewing gum after the chewing process, free phosphorous compounds my be bound by the chitosan still in the chewing gum and disposal of the chewing gum after chewing will remove the chitosan-bound phosphorous compounds from the body. Thereby, a passage of the chitosan-bound phosphorous compounds retained in the chewing gum through the gastrointestinal tract is avoided. In a further advantageous embodiment of the invention, the chitosan is retained in the gum base of the chewing gum.

In another embodiment of the invention the synergy between chitosan and organic acid in binding free phosphorous compounds is utilized while both chitosan and organic acid are encapsulated in a gum base of a chewing gum.

In this way, a delivery system that may effectively bind phosphorous compounds within a gum base of a chewing gum has been obtained.

Moreover, the invention relates to a method of reducing the level of free phosphorus compounds in the digestive juice by the use of a combination of a phosphorus compound binding agent and an organic acid in a slow release oral delivery system comprising at least one delivery vehicle and/or excipient, wherein said phosphorus compound binding agent is chitosan.

In various embodiments of the method, the above-mentioned use embodiments may be used as well. Moreover, the invention relates to a compressed chewing gum tablet comprising chewing gum granules, wherein said chewing gum granules comprises gum base, wherein said chewing gum tablet comprises a gum base content of at least 5%, preferably at least 10% by weight of the tablet,

wherein said chewing gum tablet comprises chitosan in an amount of at least 1%, preferably at least 3% by weight of the tablet,

wherein said chitosan has a molecular weight of above 30.000 Da, preferably above 50.000 Da,

wherein said chitosan has a degree of deacetylation above 85%, preferably above 90%, most preferably above 95%,

wherein said chewing gum tablet comprises ascorbic acid in an amount of at least 0.1%), preferably at least 0.5% by weight of the tablet. Detailed description

In the present context, the term "digestive juice" is generally used to indicate the various juices found within the human digestive tract, e.g. saliva, gastric juice, pancreatic juice, bile, and intestinal juice.

The term "binding affinity" herein means that a material is capable for binding to another material. Chitosan having fat-binding affinity thus means that chitosan is capable of binding fat. In the present context, chitosan is called a phosphorus compound binding agent because it can bind phosphorus in a stable manner throughout the transit of the chitosan along the gastrointestinal tract. Examples of phosphorus binding are any kind of chemical bond, such as ionic bond, covalent bond, Van der Waals interactions, chelating phenomenon.

In the present context, the term "phosphorus compound" is intended any substance containing phosphorus, for example phosphate.

For the purposes of the present invention, oral delivery system is intended as any system which can be administered by oral route to a subject. Also for the purposes of the present invention, slow release oral delivery system is intended a system which releases in a continuous manner the chitosan in the gastrointestinal tract, oral environment included. The oral delivery systems for the continuous slow release of chitosan cover any composition which, when retained in the mouth for a sufficient period of time, continuously releases chitosan in a slow manner. Examples of oral delivery systems are pills, lozenges, tablets, capsules, powdery compositions, solutions, suspensions, emulsions, preferably in the form of gel. According to the present invention, also some formulations pertaining to alimentary field are considered oral delivery systems, such as for example, confectionery, such as candies, gummy candies, chewing gum.

Chewing gum is a preferred oral delivery system according to embodiments of the present invention. However, other oral delivery systems which can be retained for a long time in the mouth of a user may be used as well. Examples of such systems are a chewable tablet, a sachet, a mouthwash, a gummy candy, a sucking tablet or candies. An advantage related to chewing gum is that saliva is a major source of recirculating phosphorus from the body and once the oral delivery system has bound a lot of phosphorus, it can be discarded from the mouth and possibly a new chewing gum can be taken. This avoids swallowing the composition and engaging the gastrointestinal tract with the presence of a composition loaded with phosphorus, so that the user has not to worry about a possible release of phosphorus in the gastrointestinal tract or the effective elimination of the composition.

The desired amount of chitosan in the oral delivery systems of the invention may vary. However, e.g. in a chewing gum, an amount should be sufficient to have an effect but at the same time avoid that the chewing gum is unpleasant to chew.

Preferred chitosan to be used according to embodiments of the present invention is low- and medium- viscosity chitosan (FLUKA cat. 50494 and cat. 28191). Both chitosan and the organic acid, such as ascorbic acid, can be added to the oral delivery system by any suitable method known to the skilled person in the art. For a chewing gum, these may be mixed with the gum base or added as part of the water- soluble chewing gum ingredients, or even a part of these may be part of an optional coating. The composition of gum base formulations can vary substantially depending on the particular product to be prepared and on the desired masticatory and other sensory characteristics of the final product. However, typical ranges (% by weight) of the above ingredients in the gum base matrix are: 5 to 80% by weight elastomeric compounds, 5 to 80% by weight elastomer plasticizers, 0 to 40% by weight of waxes, 5 to 35% by weight softener, 0 to 50% by weight filler, and 0 to 5% by weight of miscellaneous ingredients such as antioxidants, colourants, etc. The gum base may comprise about 5 to about 95 percent, by weight, of the chewing gum, more commonly the gum base comprises 10 to about 60 percent, by weight, of the gum.

Elastomers provide the rubbery, cohesive nature to the gum, which varies depending on this ingredient's chemical structure and how it may be compounded with other ingredients. Elastomers suitable for use in the gum base and gum of the present invention may include natural or synthetic types.

Elastomer plasticizers vary the firmness of the gum base. Their specificity on elastomer inter-molecular chain breaking (plasticizing) along with their varying softening points cause varying degrees of finished gum firmness and compatibility when used in base. This may be important when one wants to provide more elastomeric chain exposure to the alkane chains of the waxes.

The elastomers (rubbers) employed in the gum base may vary depending upon various factors such as the type of gum base desired, the texture of gum composition desired and the other components used in the composition to make the final chewing gum product. Illustrative examples of suitable polymers in gum bases include both natural and synthetic elastomers. For example, those polymers which are suitable in gum base compositions include, without limitation, natural substances (of vegetable origin) such as chicle gum, natural rubber, crown gum, nispero, rosidinha, jelutong, perillo, niger gutta, tunu, balata, guttapercha, lechi capsi, sorva, gutta kay, and the like, and mixtures thereof. Moreover, methyl vinyl ether-maleic anhydride copolymers may be added. Examples of synthetic elastomers include, without limitation, styrene-butadiene copolymers (SBR), polyisobutylene, isobutylene- isoprene copolymers, polyisoprene, polyethylene, polyvinyl acetate, vinyl acetate- vinyl laureate copolymer and the like, and mixtures thereof. Natural resins may be used according to the invention and may be natural rosin esters, often referred to as ester gums including as examples glycerol esters of partially hydrogenated rosins, glycerol esters of polymerised rosins, glycerol esters of partially dimerized rosins, glycerol esters of tally oil rosins, pentaerythritol esters of partially hydrogenated rosins, methyl esters of rosins, partially hydrogenated methyl esters of rosins, pentaerythritol esters of rosins, synthetic resins such as terpene resins derived from alpha-pinene, beta-pinene, and/or d-limonene, and natural terpene resins.

In an embodiment of the invention, the resin comprises terpene resins, e.g. derived from alpha-pinene, beta-pinene, and/or d-limonene, natural terpene resins, glycerol esters of gum rosins, tall oil rosins, wood rosins or other derivatives thereof such as glycerol esters of partially hydrogenated rosins, glycerol esters of polymerized rosins, glycerol esters of partially dimerised rosins, pentaerythritol esters of partially hydrogenated rosins, methyl esters of rosins, partially hydrogenated methyl esters of rosins or pentaerythritol esters of rosins and combinations thereof.

Gum bases are typically prepared by adding an amount of the elastomer, elastomer plasticizer and filler, and on occasion a vinyl polymer, to a heated (10°C - 120°C) sigma blade mixer with a front to rear speed ratio of from about 1.2: 1 to about 2: 1, the higher ratio typically being used for gum base which requires more rigorous compounding of its elastomers.

In an embodiment of the invention, said chewing gum comprises said gum base matrix and one or more chewing gum ingredients. In an embodiment of the invention, said chewing gum ingredients are selected from the group consisting of bulk sweeteners, flavors, dry-binders, tabletting aids, anti- caking agents, emulsifiers, antioxidants, enhancers, absorption enhancers, buffers, high intensity sweeteners, softeners, colors, or any combination thereof.

In addition to the above water-insoluble gum base composition, the bulk portion comprises a generally water-soluble part comprising a range of chewing gum additives. In the present context, the term "chewing gum additive" is used to designate any component, which in a conventional chewing gum manufacturing process is added to the bulk portion. The major proportion of such conventionally used additives is water soluble, but water-insoluble components, such as e.g. water- insoluble flavoring compounds, can also be included.

In the present context, chewing gum additives include bulk sweeteners, high intensity sweeteners, flavoring agents, softeners, emulsifiers, coloring agents, binding agents, acidulants, fillers, antioxidants and other components such as pharmaceutically or biologically active substances, conferring desired properties to the finished chewing gum product. Suitable bulk sweeteners include both sugar and non-sugar sweetening components. Bulk sweeteners typically constitute from about 5 to about 95% by weight of the chewing gum, more typically about 20 to about 80% by weight such as 30 to 70% or 30 to 60% by weight of the gum. Useful sugar sweeteners are saccharide-containing components commonly known in the chewing gum art including, but not limited to, sucrose, dextrose, maltose, dextrins, trehalose, D-tagatose, dried invert sugar, fructose, levulose, galactose, corn syrup solids, and the like, alone or in combination. Sorbitol can be used as a non-sugar sweetener. Other useful non-sugar sweeteners include, but are not limited to, other sugar alcohols such as mannitol, xylitol, hydrogenated starch hydrolysates, maltitol, isomalt, erythritol, lactitol, inulin and the like, alone or in combination.

High intensity artificial sweetening agents can also be used alone or in combination with the above sweeteners. Preferred high intensity sweeteners include, but are not limited to sucralose, aspartame, salts of acesulfame, alitame, saccharin and its salts, cyclamic acid and its salts, glycyrrhizin, dihydrochalcones, thaumatin, monellin, stevioside and the like, alone or in combination. Usage level of the artificial sweetener will vary considerably and will depend on factors such as potency of the sweetener, rate of release, desired sweetness of the product, level and type of flavor used and cost considerations. Thus, the active level of artificial sweetener may vary from about 0.001 to about 8% by weight (preferably from about 0.02 to about 8% by weight). When carriers used for encapsulation are included, the usage level of the encapsulated sweetener will be proportionately higher. Combinations of sugar and/or non-sugar sweeteners can be used in the chewing gum composition processed in accordance with the invention. Additionally, the softener may also provide additional sweetness such as with aqueous sugar or alditol solutions.

In an embodiment of the invention, the chewing gum comprises one or more chewing gum ingredients selected from the group consisting of bulk sweeteners, flavors, dry-binders, tabletting aids, anti-caking agents, emulsifiers, antioxidants, enhancers, absorption enhancers, buffers, or any combination thereof.

Further useful chewing gum base include antioxidants, e.g. butylated hydroxytoluene (BHT), butyl hydroxyanisol (BHA), propylgallate and tocopherols, and preservatives. A gum base formulation may, in accordance with the present invention, comprise one or more softening agents e.g. sucrose esters, tallow, hydrogenated tallow, hydrogenated and partially hydrogenated vegetable oils, cocoa butter, degreased cocoa powder, glycerol monostearate, glyceryl triacetate, lecithin, mono-, di- and triglycerides, acetylated monoglycerides, lanolin, sodium stearate, potassium stearate, glyceryl lecithin, propylene glycol monostearate, glycerine, fatty acids (e.g. stearic, palmitic, oleic and linoleic acids) and combinations thereof. As used herein the term "softener" designates an ingredient, which softens the gum base or chewing gum composition and encompasses waxes, fats, oils, emulsifiers, surfactants and solubilisers. Softeners are typically used in an amount of 0 to 18% by weight, preferably 0 to 12% by weight of the gum base.

Useful emulsifiers can include, but are not limited to, glyceryl monostearate, propylene glycol monostearate, mono- and diglycerides of edible fatty acids, lactic acid esters and acetic acid esters of mono- and diglycerides of edible fatty acids, acetylated mono and diglycerides, sugar esters of edible fatty acids, Na-, K-, Mg- and Ca-stearates, lecithin, hydroxylated lecithin and the like and mixtures thereof are examples of conventionally used emulsifiers which can be added to the chewing gum base. In case of the presence of a biologically or pharmaceutically active ingredient as defined below, the formulation may comprise certain specific emulsifiers and/or solubilisers in order to disperse and release the active ingredient.

Waxes and fats are conventionally used for the adjustment of the texture and for softening of the chewing gum base when preparing chewing gum bases. In connection with the present invention, any conventionally used and suitable type of natural and synthetic wax and fat may be used, such as for instance rice bran wax, polyethylene wax, petroleum wax (refined paraffin and microcrystalline wax), sorbitan monostearate, tallow, propylene glycol, paraffin, beeswax, carnauba wax, candelilla wax, cocoa butter, degreased cocoa powder and any suitable oil or fat, as e.g. completely or partially hydrogenated vegetable oils or completely or partially hydrogenated animal fats. A chewing gum base may, if desired, include one or more fillers/texturisers including as examples, magnesium and calcium carbonate, sodium sulphate, ground limestone, silicate compounds such as magnesium and aluminum silicate, kaolin and clay, aluminum oxide, silicium oxide, talc, titanium oxide, mono-, di- and tri-calcium phosphates, cellulose polymers, such as wood, and combinations thereof.

In an embodiment of the invention, said chewing gum comprises a biodegradable gum base polymer. In an embodiment of the invention, the chewing gum is provided with an outer coating selected from the group consisting of hard coating, soft coating and edible film-coating or any combination thereof.

EXAMPLE 1

General binding properties of chitosan with or without ascorbic acid

The following example is carried out at a pH of 6.4.

About 250 mg sample is weighed into a conical flask and is added 50 ml phosphate solution with 120 ppm phosphate. The solution is stirred for 30 minutes. 2x1 ml is used for a SPE column (Oasis MCX 3cc). 1 ml is discarded; 2 ml is collected and analyzed for phosphate content by ion chromatography. In case no phosphate- binding occurs, the content of free phosphate is expected to be 120 ppm in the samples. The measured content is used to calculate how much phosphate is bound for each gram of sample. The results can be seen in table 1.

Sample Ascorbic acid Free phosphate (ppm) Bound phosphate (mg/g)

Water No 0 N/A

Phosphate No 1 18 N/A

solution Chitosan- No 85 7.0

product 1 Yes 48 14.4

Chitosan- No 59 12.2

product 2 Yes 52 13.6

Table 1

Conclusion

Chitosan-product 2 binds more phosphate than Chitosan-product 1. The addition of ascorbic acid increases the phosphate binding.

EXAMPLE 2

Reduction of level of free phosphorus compounds in the digestive juice for chewing gum comprising chitosan with and without ascorbic acid in the formulation.

The phosphate-binding abilities of three different chewing gums were tested. Chewing gum 1 (CGI) is a conventional chewing gum, Chewing gum 2 (CG2) is identical to CGI but comprises further 200 mg chitosan whereas chewing gum 3 (CG3) is identical to CG2 but comprises further 50 mg of ascorbic acid.

The tests were carried out on a chewing machine (European Pharmacopeia 4 th. ed. 2.9.25 Chewing gum medicated, drug release from) in a phosphate buffer with a pH of 6.4 to simulate saliva.

The remaining amount of free phosphate compounds in the solution for each of the chewing gums was measured over time at specified time intervals of 0, 5, and 10 minutes. Obviously 100% indicates the amount of free phosphate compounds upon start of each of the tests. A lowering in the amount of free phosphate compounds indicates that some phosphate compounds have been bound by the chitosan.

The results are seen from table 2. Time Amount of free phosphate compounds remaining

CGI (conventional CG2 (without CG3 (with

chewing gum) ascorbic acid) ascorbic acid)

0 min 100 % 100 % 100 %

5 min 100 % 96 % 93 %

10 min 99 % 92 % 87 %

Table 2

The effect of chitosan is clearly found when comparing CGI and CG2. Surprisingly, the ascorbic acid has a positive influence on the binding of the phosphate ions in the solution, such that CG3 binds even more phosphate ions than CG2.

This indicates that for people desiring a fast removal of phosphorus compounds from the digestive juice, a chewing gum comprising both chitosan and ascorbic acid is favorable.

EXAMPLE 3

Reduction of level of free phosphorus compounds in the digestive juice for compressed chewing gums. Example 2 was repeated, this time using compressed chewing gums. An even faster binding of phosphorous compounds was seen, however over time approximating the same total binding of phosphorous compounds.

EXAMPLE 4

Varying ratio between chitosan and ascorbic acid.

The phosphate-binding abilities of four different chewing gums, CG4, CG5, CG6, and CG7 were tested. The difference between these can be seen in table 3 here below. The chewing gums were tested for the ability of binding phosphorous compounds under the same conditions as described in example 2. Time Amount of free phosphate compounds remaining

(chitosan/ CG4 (200 CG5 (200 CG6 (200 CG7 (200

Ascorbic acid) mg, 5 mg) mg, 25 mg) mg, 75 mg) mg, 800 mg)

0 min 100 % 100 % 100 % 100 %

5 min 96 % 95 % 91 % 90 %

10 min 91 % 89 % 85 % 83 %

Table 3

The effect of varying the ratio between chitosan and ascorbic acid is clearly seen. Small amounts of ascorbic acid have no recognizable effect, whereas excess amounts of ascorbic acid only have a slightly better effect.

8. Use according to claims 1-6 for reducing the level of free phosphorus compounds in the saliva. 9. Use according to claims 1-8, wherein said chitosan has a molecular weight of above 30.000 Da, preferably above 50.000 Da.

10. Use according to claims 1-9, wherein said chitosan has a degree of deacetylation above 85%, preferably above 90%, most preferably above 95%.

11. Use according to claims 1-10, wherein said chitosan has fat binding affinity.

12. Use according to claims 1-1 1, wherein said oral delivery system comprises said chitosan and said organic acid in a ratio between 1 :4 and 40: 1 by weight, preferably between 1 : 1 and 10: 1 by weight.

13. Use according to claims 1-12, wherein the total amount of said chitosan taken by a user on a single day is between 0.1 and 20 g, preferably between 0.2 and 10 g. 14. Use according to claims 4 or 5, wherein at least part of said chitosan is retained in the chewing gum after chewing.

15. Method of reducing the level of free phosphorus compounds in the digestive juice by the use of a combination of a phosphorus compound binding agent and an organic acid in a slow release oral delivery system comprising at least one delivery vehicle and/or excipient, wherein said phosphorus compound binding agent is chitosan.

16. Method according to claim 15 in combination with any of the claims 2-12. 17. Compressed chewing gum tablet comprising chewing gum granules, wherein said chewing gum granules comprises gum base,

wherein said chewing gum tablet comprises a gum base content of at least 5%, preferably at least 10% by weight of the tablet,

wherein said chewing gum tablet comprises chitosan in an amount of at least 1%, preferably at least 3% by weight of the tablet,

wherein said chitosan has a molecular weight of above 30.000 Da, preferably above 50.000 Da,

wherein said chitosan has a degree of deacetylation above 85%, preferably above 90%, most preferably above 95%,

wherein said chewing gum tablet comprises ascorbic acid in an amount of at least 0.1%, preferably at least 0.5% by weight of the tablet.