(19) TZZ _Z_T

(11) EP 2 421 508 B1

(12) EUROPEAN PATENT SPECIFICATION

(45) Date of publication and mention (51) Int Cl.: of the grant of the patent: A61K 9/14 (2006.01) 14.12.2016 Bulletin 2016/50 (86) International application number: (21) Application number: 10716464.2 PCT/DK2010/000056

(22) Date of filing: 26.04.2010 (87) International publication number: WO 2010/121620 (28.10.2010 Gazette 2010/43)

(54) PARTICULATE MATERIAL FOR CONTROLLED RELEASE OF ACTIVE INGREDIENTS PARTIKELFÖRMIGES MATERIAL ZUR VERZÖGERTEN WIRKSTOFFFREISETZUNG MATIÈRE PARTICULAIRE POUR LA LIBÉRATION CONTRÔLÉE DE PRINCIPES ACTIFS

(84) Designated Contracting States: • ANDERSEN, Jette, Bæk AT BE BG CH CY CZ DE DK EE ES FI FR GB GR DK-7100 Vejle (DK) HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO SE SI SK SM TR (74) Representative: Plougmann Vingtoft a/s Rued Langgaards Vej 8 (30) Priority: 24.04.2009 US 172474 P 2300 Copenhagen S (DK)

(43) Date of publication of application: (56) References cited: 29.02.2012 Bulletin 2012/09 EP-A1- 1 974 807 EP-A1- 2 168 572 WO-A1-2008/055006 WO-A2-2005/072125 (73) Proprietor: Omya International AG GB-A- 1 572 718 US-A- 1 171 392 4665 Oftringen (CH) US-A- 5 633 027

(72) Inventors: Remarks: • PEDERSEN, Kurt, Møller Thefile contains technical information submitted after DK-7323 Give (DK) the application was filed and not included in this specification

Note: Within nine months of the publication of the mention of the grant of the European patent in the European Patent Bulletin, any person may give notice to the European Patent Office of opposition to that patent, in accordance with the Implementing Regulations. Notice of opposition shall not be deemed to have been filed until the opposition fee has been paid. (Art. 99(1) European Patent Convention). EP 2 421 508 B1

Printed by Jouve, 75001 PARIS (FR) 1 EP 2 421 508 B1 2

Description of the chewing gum, the particulate material comprising a combination of one or more active ingredients, exclud- FIELD OF THE INVENTION ing nicotine, and an inorganic mineral filler comprising natural carbonate and/or precipitated calcium [0001] The present invention relates to the field of5 carbonate, where the inorganic mineral filler is obtainable chewing gum for controlled release of active ingredients, by pre-treatment with one or more medium-strong to + such as a flavoring agent. In particular, the present in- strong sources of H3O ions and/or pre-treatment with vention relates to a chewing gum comprising a chewing an inorganic salt, and pre-treatment with gaseous CO2, gum core with at least one sub-layer, wherein a particu- wherein the active ingredient is reversibly absorbed into late material for controlled release of active ingredients 10 and/or adsorbed onto the inorganic mineral filler, wherein is added to said at least one sub-layer or both the sub- the BET specific surface area of the inorganic mineral layer and the core of the chewing gum, the particulate filler is above 15 m2/g, the BET specific surface area material comprising a combination of one or more active measured in accordance with ISO 9277 and wherein the ingredients, excluding nicotine, and an inorganic mineral at least one sub-layer is between the chewing gum core filler comprising natural and/or pre- 15 and an outer coating cipitated calcium carbonate, where the inorganic mineral [0006] WO2008/055006 discloses a long flavor dura- filler is obtainable by pre-treatment with one or more me- tion releasing structure comprising: i) a thermoplastic cel- + dium-strong to strong sources of H3O ions and/or pre- lulose material, a non-cellulosic thermoplastic polymer, treatment with an inorganic salt, and pre-treatment with and a porous flavor reservoir material; and ii) a flavoring 20 gaseous CO2, wherein the active ingredient is reversibly agent incorporated into the structure. The porous flavor absorbedinto and/or adsorbedonto the inorganic mineral reservoir material is selected from silica, , titanium filler, wherein the BET specific surface area of the inor- dioxide, calcium carbonate, , maltodextrin and ganic mineral filler is above 15 m2/g, the BET specific mixtures thereof. D4 further relates to a chewing gum surface area measured in accordance with ISO 9277 and composition with a long flavor duration releasing struc- whereinthe atleast onesub-layer isbetween thechewing 25 ture. gum core and an outer coating. [0007] The inorganic mineral filler of the present inven- tion provides a surprisingly high loading capacity of active BACKGROUND OF THE INVENTION ingredients, such as flavoring agents. The high loading capacity may be a benefit in a number of applications. [0002] It is a general understanding that controlled re- 30 One advantage is that a higher content of active ingre- lease of active ingredients may be a critical parameter in dients may be applied. Another advantage is that active terms of the ability to deliver an active ingredient in the ingredients may be effectively separated from other in- mostsuitable manner. This appliesto confectionery prod- gredients in the formulation, whereby unfavorably inter- ucts where a controlled release of active ingredients, action between the ingredients may be avoided. Yet an- such as nutraceuticals or oral care agents, is critical to 35 other advantage is that a high loading capacity implies a give the desired effect. This applies also to pharmaceu- better stability of active ingredient. tical products where active pharmaceutical ingredients [0008] In addition, the active ingredient is reversibly may be harmfull or even lethal in a high dose. In addition absorbedinto and/oradsorbed onto theinorganic mineral it may be beneficial that the release of active ingredients filler, which is highly advantageous in order for a control- is controlled in order to achieve an improved experience 40 led release of active ingredients. of the product, such as a better taste of the product or a [0009] The particulate material of the present invention masking effect. may give an immediate release of active ingredients or [0003] Although various solutions have been provided may be designed to sustain the release for longer peri- in the past, the solutions imply several drawbacks, which ods. In particular the present invention may provide sus- have been difficult or sometimes impossible to solve. 45 tained release of active ingredients in a much better way compared to the prior art. The porous nature of inorganic SUMMARY OF THE INVENTION mineral filler, such as natural calcium carbonate, offers a much better stability of the active ingredients, and is [0004] The present inventors have surprisingly found tasteless, stabile and biocompatible. It exhibits good that inorganic mineral filler, such as natural calcium car- 50 compactability in drug mixtures. bonate, is a highly suitable carrier of active ingredients, [0010] Compared to other carrier materials, natural such as a flavoring agent, without the drawbacks of the calcium carbonate may in particular be useful. The prior art. present invention is particularly suitable for delivery of a [0005] In one aspect the present invention pertains to flavoring agent. The present invention is suitable for con- a chewing gum comprising a chewing gum core with at 55 trolled release in chewing gum. least one sub-layer, wherein a particulate material for [0011] As disclosed herein chewing gum is used as controlled release of active ingredients is added to said the delievery dehicle. at least one sub-layer or both the sub-layer and the core [0012] Accordingly, there is provided a particulate ma-

2 3 EP 2 421 508 B1 4 terial for controlled release of active ingredients, the par- [0020] The present invention concerns a particulate ticulate material comprising a combination of one or more material for controlled release of active ingredients, the active ingredients, excluding nicotine, and an inorganic particulate material comprising a combination of one or mineral filler, wherein the active ingredient is reversibly more active ingredients, excluding nicotine, and an inor- absorbedinto and/or adsorbedonto the inorganic mineral 5 ganic mineral filler, wherein the active ingredient is re- filler, and wherein the BET specific surface area of the versibly absorbed into and/or adsorbed onto the inorgan- inorganic mineral filler is above 15 m 2/g, the BET specific ic mineral filler, and wherein the BET specific surface surface area measured in accordance with ISO 9277. area of the inorganic mineral filler is above 15 m 2/g, the BET specific surface area measured in accordance with DETAILED DESCRIPTION 10 ISO 9277. [0021] The active ingredient according to the present [0013] The present invention provides for a particulate invention may be any active ingredient which is absorbed material, where an active ingredient is absorbed into into or adsorbed onto the particulate material, excluding and/or adsorped onto an inorganic mineral filler, such as nicotine. Suitable APIs are preferably selected among natural calcium carbonate. Thereby the active ingredient, 15 the below listed compounds. such as a flavoring agent, is stabilised. The release of [0022] Teeth whitening actives may be included in the the active ingredient from the active ingredient-carbonate present invention. The actives suitable for whitening are mixture may be immediate or may be controlled so that selected from the group consisting of oxalates, perox- the active ingredient is delivered at a pre-determed time. ides, metal chlorites, perforates, percarbonates, peroxy- [0014] The term "compressed chewing gum" is used 20 acids, and mixtures thereof Suitable com- in thisdocument to indicatea chewing gum manufactured pounds include , , by compressing granules and optionally other ingredi- peroxide, carbamide peroxide, urea peroxide, ents at a certain pressure to obtain a chewing gum. The sodium percarbonate and mixtures thereof. Optionally, term "tabletting" used in this document is synonymous the peroxide is hydrogen peroxide. Suitable metal chior- with compressing, whereas the term tabletting in prior art 25 ites include calcium chlorite, barium chlorite, sometimes indicate the process of making standard chlorite, lithium chlorite, sodium chlorite and potassium chewing gum pieces (tablets) by punching or the like. chlorite. Additional whitening actives may be hypochior- [0015] According to the present invention, the particu- ite and chlorine dioxide. A preferred chlorite is sodium late material according to the present invention is chem- chlorite. The effectiveness of whitening actives can, op- ically and physically stable. In the present context the 30 tionally, be enhanced by means of a catalyst, i.e. a two- term "stable" means that the inorganic mineral filler com- component peroxide-catalyst system. Useful whitening binedwith the active ingredient ischemically and/or phys- agent catalysts or catalytic agents can be found in U.S. ically stable for at least about 22 weeks such as, e.g., at Patent Number 6,440,396 to McLaughlin. least 14 weeks when stored open at a temperature of 40 [0023] When incorporating peroxide actives, the par- °C and a relative humidity of 50%. 35 ticulate material of present invention can, optionally, con- [0016] It is especially of importance that the active in- tain peroxide active stabilizers. Peroxide active stabiliz- gredient does not migrate out of the inorganic mineral ers suitable for use herein include, but are not limited to, filler as such a migration will lead to a marked loss in the polyethylene glycols such as PEG 40 or PEG 600; zinc content of active ingredient in the material. A particulate salts such as zinc citrate; polyoxyalkylene block-poly- material according to the present invention is also phys- 40 mers (e.g. Pluronics); aminocarboxylic acids or salts ically stable. Thus, within a time period of 22 weeks or thereof; glycerols; dyes such as Blue #1 or Green #3; more no visible changes had been observed and the dis- phos- phates such as phosphoric acid, sodium phos- solution profile did not change. phate or sodium acid pyrophosphate; stannous salts [0017] With reference to this invention, the term "chew- such as stannous chloride; sodium stannate; citric acid; ing gum" means all chewable gum products. The term 45 etidronic acid; carbomers or carboxypolymethylenes "API" intends to mean active pharmaceutical ingredient. such as those of the Carbopol® series, butylated hydrox- [0018] The terms "buccal" and "buccally" and equiva- ytoluene (BHT), ethylenediaminetetraacetic acid (EDTA) lents are herein intended to pertain to all of or any part and mixtures thereof. of the tissue of the oral cavity. [0024] Anti-tartar agents useful herein include phos- [0019] The term "surface area" and equivalents are 50 phates. Phosphates include pyrophosphates, polyphos- deemed according to the following method: The specific phates, polyphosphonates and mixtures thereof. Pyro- surface area of the powders was obtained from a BET phosphates are among the best known phosphates for analysis of N2 adsorption isotherms (ASAP 2010, Micro- use in dental care products. Pyrophosphate ions deliv- mekics, USA). From the same set of measurements, the ered to the teeth derive from pyrophosphate salts. The total pore volume of the powders was obtained by the 55 pyrophosphate salts useful in the present compositions ASAP 2010 V4 software. The weight of the samples in include the dialkali metal pyrophosphate salts, tetra-al- these measurements was chosen so as to produce a kali metal pyrophosphate salts, and mixtures thereof. total sur face of 5-10 m2. Disodium dihydrogen pyrophosphate (Na2H2P2O7), tet-

3 5 EP 2 421 508 B1 6 rasodium pyrophosphate (Na4P2O7), and tetrapotassi- diphenhydramine, dextromethorphan, bromhexine and um pyrophosphate (K4P207) in their non-hydrated as chiorpheniramine, gastrointestinal agents such as famo- well as hydrated forms are preferred. Anticalculus phos- tidine, loperamide and sirnethicone, anti-fungals such as phates include potassium and sodium pyrophosphates; miconazole nitrate, antibiotics and analgesics such as sodium tripolyphosphate; diphosphonates, such as5 ketoprofen and fluribuprofen. ethane-1-hydroxy-1,I-diphosphonate; 1 -azacyclohep- [0030] The particulate material may comprise a flavor- tane- 1,1 - diphosphonate; and linear alkyl diphospho- ing agent. One particular embodiment comprises embed- nates;linear carboxylic acids and sodium and zinc citrate. ding in a sub-layer between the chewing gum core and [0025] Agents that may be used in place of or in com- an outer coating to prolong the flavoring sensation. bination with the above pyrophosphate salt include ma- 10 [0031] In order to reduce manufacturing costs and in terials such as synthetic anionic polymers including poly- order to facilitate product approval for similar chewing acrylates and copolymers of maleic anhydride or acid gums by health authorities it is often desirable to use the and methyl vinyl ether, e.g. Gantrez, as described, for same core with differently flavored coatings. Thereby the example, in U. S. Patent Number 4,627,977, to Gaffar et flavor of the core needs to be dominated by the flavor of al. , as well as e.g. polyamino propane sulfonic acid15 the coating(s). This effect is obtained by the present in- (AMPS), zinc citrate trihydrate, polyphosphates, e.g. vention where the flavor of the at least the sub-layer may tripolyphosphate and hexametaphosphate, diphospho- dominate over the flavor of the core. nates, e.g. EHDP and AMP, polypeptides, such as pol- [0032] An example of such domination is when a fruit yaspartic and polyglutamic acids, and mixtures thereof. flavor in the sub-layer dominates over a mint flavor of the [0026] Antimicrobial agents can also be present in the 20 core. The mechanism behind this flavor domination is particulate material of the present invention as oral that the flavor in the polymer coating has a slow release agents and/or systemic actives. Such agents may in- therefrom. Further, upon chewing, part of the sub-layer clude, but are not urn- ited to, 5-chloro-2-(2, 4-dichlo- gets embedded in the core, from where the sub-layer rophenoxy)- phenol, commonly referred to as triclosan, flavor is subsequently slowly released. Sub-layers also chiorhexidine, alexidine, hexetidine, sanguinarine, ben- 25 allows for addition of a large percentage of flavor as com- zalkonium chloride, salicylamide, domiphen bromide, ce- pared to a hard coating. tylpyridiurn chloride (CPC), tetradecyl pyridiniurn chlo- [0033] For flavored API-containing chewing gums the ride (TPC); N-tetradecyl-4- ethyl pyridinium chloride invention provides a solution to the combined problem (TDEPC); octenidine; delmopinol, octapinol, and other of obtaining a long lasting effect of the flavoring agent(s), piperidino derivatives, niacin preparations; zinc/stan-30 obtaining domination of flavoring agents in the coating(s) nous ion agents;antibiotics suchas AUGMENTIN, amox- over flavoring agent(s) in the core, avoiding problems of ycillin, , doxycyline, minocycline, and metro- chemical or pharmaceutical incompatibility between an nidazole; and analogs, derivatives and salts of the above API in the core and flavoring agent(s) in the coating(s), antimicrobial agents and mixtures thereof. and/or increasing the control of the release of the drug. [0027] Anti-inflammatory agents can also be present 35 Known techniques for flavoring chewing gums imply that in the particulate material of the present invention as oral flavoring agents are added to a gum core and optionally agents and/or systemic actives. Such agents may in- to a hard coating on the core. Anyhow, such flavoring clude, but are not limited to, non- steroidal anti- inflam- does not solve the preceding problem. matory agents or NSAIDs, such as propionic acid deriv- [0034] According to the present invention said com- atives; acetic acid derivatives; fenamic acid derivatives; 40 bined problem may be solved by providing a chewing biphenylcarboxylic acid derivatives; and oxicams. All of gum core with at least one sub-layer, whereby the flavor- these NSAIDs are fully described in U.S. Patent Number ing agent(s) is/are added to at least the sub-layer. The 4,985,459 to Sunshine et al.. Examples of useful NSAIDs API may be in the core and/or in one or more of the coat- include acetylsalicylic acid, ibuprofen, naproxen, benox- ings. aprofen, flurbiprofen, fenoprofen, fenbufen, ketoprofen, 45 [0035] Also useful herein are tooth desensitizing indoprofen, pirprofen, carprofen, oxaprozin, pranopro- agents. Tooth desensitizing agents that may be used in fen, microprofen, tioxaprofen, suprofen, alminoprofen, ti- the present invention include potassium nitrate, citric ac- aprofenic acid, fluprofen, bucloxic acid and mixtures id, citric acid salts, strontium chloride, and the like, as thereof. well as other desensitizing agents known in the art. One [0028] Also useful are the steroidal anti-inflammatory 50 particular embodiment includes a desensitizing agent in drugs such as hydrocortisone and the like, and COX-2 combination with a tooth whitening agent. The amount inhibitors such as meloxicam, celecoxib, rofecoxib, val- of desensitizing agent included within the dental whiten- decoxib, etoricoxib or mixtures thereof. Mixtures of any ing compositions of the present invention may vary ac- of the above anti-inflammatories may be used. cording to the concentration of the potassium nitrates, [0029] Other materials that can be used with the55 the desired strength and intended treatment times. Ac- present invention include commonly known mouth and cordingly, if included at all, the other desensitizing agents throat products. These products include, but are not lim- will preferably be included in an amount in a range from ited to, upper respiratory agents such as phenylephrine, about 0.1% to about 10% by weight of the dental desen-

4 7 EP 2 421 508 B1 8 sitizing composition, more preferably in a range from mineral filler below 15 m2/g, the BET specific surface about 1 to about 7% by weight of the wet sub-coatcom- area measured in accordance with ISO 9277. position. [0043] As disclosed herein, the inorganic mineral filler [0036] An individual enzyme or a combination of sev- comprises a natural calcium carbonate, such as a mar- eral compatible enzymes can also be included in the 5 ble, a calcite, a chalk or a carbonate containing dolomite; chewing gum composition of the present invention. and/or a precipitated calcium carbonate (PCC). [0037] Antioxidants are generally recognized as useful [0044] As disclosed herein the inorganic mineral filler in compositions such as those of the present invention. is obtainable by pre-treatment with one or more medium- + Antioxidants that may be included in the coating compo- strong to strong sources of H3O ions and/or pre-treat- sitions of the present invention include, but are not limited 10 ment with an inorganic salt, such as a magnesium sul- to, Vitamin E, ascorbic acid, uric acid, carote- noids, Vi- phate in combination with sulphate and/or zinc tamin A, flavonoids and polyphenols, herbal antioxidants, sulphate, and pre-treatment with gaseous CO2, and for melatonin, aminoindoles, lipoic acids and mixtures there- precipitated calcium carbonate preferably at a CO2 gas of. flow rate of below 30 litres per minute at standard tem- [0038] It may be desirable to add pH adjusting agents, 15 perature and pressure per kilogram calcium hydroxide or buffers, such as , sodium phos- during precipitation. phate, sodium hydroxide, ammonium hydroxide, sodium [0045] Accordingly, the natural carbonate acoording to stannate, citric acid, hydrochloric acid, sodium citrate, the present invention, such as for example natural calci- and combinations thereof to the core and/or to any of the um carbonate or dolomite, is treated in combination by 20 + coatings. The pH adjusting agents are added in sufficient one or more medium-strong to strong providers of H 3O amounts so as to adjust the pH of oral cavity to a suitable ions and gaseous CO2. value, e.g. from about 4.5 to about 11, preferably from [0046] Various natural carbonates may be suitable ob- about 5.5 to about 8.5. tainable from chalk, in particular chalk from Champagne, [0039] The particulate material according to the calcite or marble, and mixtures thereof with talc, kaolin present invention pertains to a BET specific surface area 25 and/or dolomite, and/or hydroxides of aluminium, and/or of the inorganic mineral filler is between 15 m 2/g and 200 titanium oxide, and similar oxides and m2/g, the BET specific surface area measured in accord- hydroxides known in the industry concerned. ance with ISO 9277. [0047] The invention particularly concerns the treat- [0040] The particulate material according to the ment, by a combination of one or more medium-strong 30 + present invention pertains to an average grain diameter to strong H 3O ion-providers in an active gaseous medi- of the inorganic mineral filler is between 50 and 0.1 mi- um, of inorganic mineral filler, containing natural carbon- crons. ate such as natural calcium carbonate, and/or in combi- In a particular embodiment of the invention, the inorganic nation with other minerals. mineral filler has the following characteristics: a mean [0048] The acid used will be any medium-strong or 35 + grain diameter, measured by the sedimentation method strong acid or any mixture of such acids, generating H 3O on a Sedigraph 5100™ instrument, between 50 and 0.1 ions under the processing conditions. microns and a BET specific surface area, measured in [0049] In one embodiment it is preferred, that the accordance with ISO 9277, ranging from 15 m2/g to 200 strong acid will be chosen among the acids with a pKa m2/g. value lower than or equal to zero at 22° C. and more [0041] In an even more particular manner they are40 particularly chosen from sulphuric acid, hydrochloric acid characterised by the fact that inorganic mineral filler has or mixtures thereof. the following characteristics: a mean grain diameter, [0050] In another embodiment it is preferred, that the measured by the sedimentation method on a Sedigraph medium-strong acid will be chosen among the acids with 5100™ instrument, between 25 and 0.5 microns and a pKa value between 0 and 2.5 inclusive at 22° C. and even more particularly between 7 and 0.7 microns and 45 more particularly chosen from H2SO4, HSO4-, H3PO4 a BET specific surface area, measured in accordance and oxalic acid or mixtures thereof. We can quote as a with ISO 9277, ranging from 20 m2/g to 80 m2/g and particular example a pKal of H3PO4 equal to 2.161 even more particularly between 30 and 60 m2/g. (Römpp Chemie, Edition Thieme). The particulate material according to one embodiment [0051] In one embodiment of the invention it is pre- of the invention, wherein the weight of the dried inorganic 50 ferred, that the medium-strong acid or acids can be mixed mineral filler is increased by at least 1 % at a relative with the strong acid or acids. humidity of 95 % at 25 degree Celcius compared to a [0052] According to the invention, the molar quantity + relative humidity of 0 %, such as 2%, 3%, 4%, 5%, 6%, of medium-strong to strong providers of H 3O ions rela- 7%, 8%, 9%, 10 % or 12%. tive to the number of moles of CaCO3 is in total between [0042] The particulate material according to 55 the 0.1 and 2 and preferably between 0.25 and 1. present invention, wherein the powder flow of the partic- [0053] According to the invention, the process is char- ulate material is higher than the powder flow of particulate acterised by the fact that the said filler is treated by a material with a BET specific surface area of inorganic combination of one or more medium-strong to strong pro-

5 9 EP 2 421 508 B1 10

+ viders of H3O ions and gaseous CO2. phosphate, glycerophosphate or citrate of an alkali metal, [0054] The particulate material according to the such as potassium or sodium, or ammonium; sodium hy- present invention may further comprise a modifying droxide, potassium hydroxide, , and mix- agent, such as a water-soluble natural or synthetic pol- tures thereof. ymer. 5 [0061] Further embodiments may use trisodium or Polymers suitable as modifying agent are preferably se- tripotassium citrate, and mixtures thereof. lected from, but not limited to, the group consisting of [0062] Still further embodiments may comprise differ- hydroxypropyl cellulose, hydroxypropylmethyl cellulose, ent phosphate systems, such as , hydroxyethyl cellulose, polyvinyl pyrrolidone, car- disodium hydrogen phosphate; and tripotassium phos- boxymethyl cellulose, polyvinyl alcohol, sodium alginate, 10 phate, dipo- tassium hydrogen phosphate, and calcium , pullulan, tragacanth gum, guar gum, hydroxide, sodium glycinate; and mixtures thereof. acacia gum, arabic gum, polyacrylic acid, methylmeth- [0063] Alkali metal carbonates, glycinates and phos- acrylate copolymer, carboxyvinyl polymer, amylose, high phates are preferred buffering agents. amylose starch, hydroxypropylated high amylose starch, [0064] The amount of the buffering agent or agents in dextrin, pectin, chitin, chitosan, gelatin, zein, gluten, soy 15 the liquid pharmaceutical formulation is preferably suffi- proteinisolate, wheyprotein- isolate, caseinand mixtures cient in the specific embodiments to raise the pH of the thereof Suitable polymers also include water- insoluble saliva to above 7, as specified above and, to maintain polymers selected from the group consisting of hydro- the pH of the saliva in the oral cavity above 7, e g pH 7 genated vegetable oils, hydrogenated caster oil, polyvi- - 11. Otherwise expressed the liquid pharmaceutical for- nyl chloride, shellac, polyurethane, cellulose derivatives, 20 mulation should be alkalised by buffering and/or pH reg- gum rosins, wood rosens, waxes, acrylate and methacr- ulation in such a way that upon administration to a subject ylate polymers, copolymers of acrylic and methacrylic the pH of the liquid of the oral cavity of the subject is acid esters and mixtures thereof. transiently increased by about 0.3 - 4 pH units, preferably [0055] The particulate material according to the by about 0.5 - 2.5 pH units. The amount of buffering present invention is used in a chewing gum, such as a 25 agent(s) required to achieve such an increase in pH is compressed chewing gum.. readily calculated by a person skilled in the art. [0056] The chewing gum comprise a chewing gum [0065] Optional additives comprise one or more stabi- core. The chewing gum core may comprise a continuous lizing additives, such as those selec ted from the group mass of pre-heated chewing gum ingredients, including consisting of antioxidants including vitamin E, i e toco- gum base. The chewing gum may also comprise a com- 30 pheroles, vitamin C, i e ascorbic acid and its salts, sodium pressed mixture of chewing gum granules, including gum pyrosulfite, butylhydroxytoluene, butylated hyd roxy- base. anisole; and preservatives including parabenes, benza- [0057] As disclosed herein the particulate material is lkonium chloride, chlorbutanol, benzyl alcohol, beta-phe- contained in the chewing gum core. In another embodi- nylethyl alcohol, cetylpyridinium chloride, citric acid, tar- ment of the invention the particulate material is part of a 35 taric acid, lactic acid, malic acid, acetic acid, benzoic acid, sub-coat between the chewing gum core and an outer andsorbic acid and their salts; and chelating agents,such coating. In yet another embodiment the chewing gum as EDTA; and galates, such as propyl galate. comprise a combination of the above. [0066] Further optional additives comprise one or more [0058] According to the present disclosure, the partic- additives selected from the group consisting of: - enhanc- ulate material is used in chewing gum. A chewing gum 40 ers, such as ozone; - vitamins, such as vitamins B. C and product according to the present invention may be a med- E; - minerals, such as fluorides, especially sodium fluo- icated chewing gum. Medicated chewing gums are here- ride, sodium monofluoro phosphate and stannous fluo- in intended to mean solid or semisolid, single-dose prep- ride; - anti- odours, such as zinc and cyclodextrins; - pro- arations with a base consisting mainly of gum that are pellants, such as 1,1, 2,2- tekafluoroethane (HFC-134a), intended to be chewed but not swallowed, whereby the 45 optionally being liquefied, and 1,1,1,2, 3,3, 3-heptafluor- chewing gum acts as a drug delivery system. Such gums orpropane (HFC-227), optionally being liquefied; - sweet- contain one or more active substances, which are re- eners including one or more synthetic sweetening agents leased upon chewing. After dissolution or dispersion of and/or natural sugars, such as those selected from the the active substance in the saliva systemic delivery of groups consisting of e g saccharin and its sodium and the drug takes place through kansmucosal uptake50 calcium salts, aspartame, acesulfame and its potassium throughout the oral cavity. salt, thaumatin, glycyrrhizin, sucralose, dihydrochal- [0059] Optional addition of buffering agents in any of cone, alitame, miraculin, monellin and stevside. the delievery systems above may be buffering agents, optionally added mainly, but not exclusively, in formula- - polyhydric alcohols such as , xylitol, mannitol tions ofthe presentinvention intended for buccal delivery. 55 and glycerol; - monosaccharides including glucose [0060] Forbuffering may be usedone or more buffering (also called dextrose), fructose (also called laevu- agents selected from the group consisting of carbonates lose) and galactose; - disaccharides including sac- including bicarbonate or sesquicarbonate7 glycinate, charose (also called sucrose), lactose (also called

6 11 EP 2 421 508 B1 12

milk sugar) and maltose (also called malt sugar); - b) of between 1 hour and 10 hours and preferably mixtures of sugars including liquid glucose syrup e between 1 hour and 5 hours without addition of a g starch hydrolysates con- taining a mixture of chiefly base, or immediately after the end of stages a) and dextrose, maltose, dextrins and water, invert sugar b) with the addition of a base, stage c) being the final syrup e g sucrose inverted by invertase containing 5 stage in the process. a mixture of dextrose, laevulose and water, high sug- ar content syrups such as treacle, honey and malt [0072] In a preferred manner also, the gaseous CO2 extract; and mixtures thereof; - flavoring and/or aro- comes from an external CO2 supply or from the recircu- matizing agents, such as those selected from the lation of CO2 or from the continuous addition of the same 10 + group consisting of essential oils obtained by distil- medium-strong to strong provider of H3O ions as used lations, solvent extractions or cold expressions of in stage a) of the treatment or from another medium- + fresh or dried flowers, buds, leaves, stems, fruit, strong to strong provider of H 3O ions or from an excess seeds, peel, bark, or root e g oil of pepper- mint, pressure of CO2, preferably an excess pressure of be- spearmint, eucalyptus, wintergreen, niaouli, clove, tween 0.05 and 5 bars. In this regard, it should be noted cardamom, cinnamon, bitter almond, coriander, car- 15 that the processing tank, filled with fillers having a specific away, ginger, juniper, orange, bitter orange, lemon, gravity of the order of 1 to 2, may reach a height of for grapefruit, mandarine, bergamot, thyme, fennel and example 20 metres and hence create an excess pressure rosemary; - natural flavors and aroma agents includ- of CO2 which can reach several bars and in particular ing either diluted solutions of essential oils or con- up to approximately 5 bars at the bottom of the tank or centrates of flavor components with natural origin 20 in a closed tank. from e g fruits, berries, nuts, spices, mints, tobacco, [0073] In a preferred mode of implementation, stages cocoa, coffee, tea, vanilla, liquorice, caramel, toffee, a) and b) may be repeated several times. honey, wine, liquors and brews; - synthetic flavors [0074] Similarly, in a preferred mode of implementa- and aroma agents consisting of mixtures of chemi- tion, the pH measured at 20° C. ranges from 3 to 7.5 cals com- prising , alcohols, alde-25 during stages a) and b) of processing and the processing hydes, esters, ketones, ethers and oxides blended temperature is between 50° C. and 90° C. and preferably to match the natural flavor of e g fruits, berries, nuts, between 45° C. and 60° C. spices, mints, tobacco, cocoa, coffee, tea, vanilla, [0075] In another preferred mode of implementation, liquorice, caramel, toffee, honey, wine, liquors or between 1 hour and 10 hours and more particularly be- brews; - and mixtures thereof. 30 tween 1 hour and 5 hours after the end of processing, the pH is greater than 7.5 at ambient temperature without [0067] According to the present disclosure the partic- the addition of any base whatever. If any base is added, ulate material is contained in a sub-layer between the the pH then rises immediately. It should moreover be chewing gum core and an outer coating. noted that after several days no resistance to acids is [0068] According to the present invention, flavoring 35 observed. agents may be incorporated in the core or in the sub- [0076] The process in one embodiment is character- layer between the core and an outer coating. Advantages ised by the fact that the concentration of gaseous CO2 of the invention include long lasting effect of flavoring in the suspension is, in terms of volume, such that the agent(s), domination of flavoring agents in the coating(s) ratio (volume of suspension:volume of gaseous CO2) is over flavoring agent(s) in the core, the avoidance of prob- 40 between 1:0.05 and 1:20 with the said ratio being be- lems of chemical or pharmaceutical incompatibility be- tween 1:1 and 1:20 in stage a) and between 1:0.05 and tween a drug in the core and flavoring agent(s) in the 1:1 in stage b). coating(s), and increased control of the release of the [0077] In a highly preferable manner, the concentration drug and of non-active excipients. of gaseous CO2 in the suspension is, in terms of volume, [0069] According to the present disclosure the partic- 45 such that the ratio (volume of suspension:volume of gas- ulate material is contained in the chewing gum core. eous CO2) is between 1:0.05 and 1:5 with the said ratio [0070] In one embodiment the particulate material is being between 1:0.5 and 1:10 in stage a) and between contained in an outer coating. 1:0.05 and 1:1 in stage b). [0071] In a preferred manner the process is character- [0078] The gaseous CO2 may be introduced in liquid ised by: 50 or anhydride form. [0079] In a manner which is also preferred, the duration a) Treatment with one or more medium-strong to of stage b) of the treatment is from 0 to 10 hours and + strong providers of H3O ions preferably from 2 to 6 hours. b) Treatment with gaseous CO2, whether this treat- [0080] The treatment process is implemented in the ment be an integral part of stage a), be carried out 55 aqueous (slurry) phase at low, medium-high or high con- in parallel withstage a) or be carried outafter stagea) centrations of dry matter, but can also be implemented c) The raising of pH beyond 7.5, measured at 20° for mixtures of slurries at those differing concentrations. C., in a time interval after the end of stages a) and In a preferential manner, the dry matter content by weight

7 13 EP 2 421 508 B1 14 is between 1% and 80%. copolymers e.g. having styrene-butadiene ratios of about [0081] Without wishing to be bound by any theory, the 1:3 to 3:1, polyvinyl acetate (PVA), e.g. having a GPC applicant believes that the gaseous CO2 plays the part, average molecular weight in the range of 2,000 to 90,000 among others, of a pH regulator and a regulator of ad- such as the range of 3,000 to 80,000 including the range sorption/desorption. 5 of 30,000 to 50,000, where the higher molecular weight [0082] In one embodiment the amount of gum base polyvinyl acetates are typically used in bubble gum base, according to the invention is about 15 - 80 % by weight polyisoprene, polyethylene, vinyl acetate-vinyl laurate of the total gum core, and preferably at least about 40 % copolymer e.g. having a vinyl laurate content of about 5 by weight. to 50% by weight such as 10 to 45% by weight of the [0083] The gum base may be of any conventional na- 10 copolymer, and combinations hereof. ture known in the art. For example it may comprise a gum [0089] The elastomers (rubbers) employed in the gum base of natural or synthetic origin readily available from base may vary depending upon various factors such as a commercial source. Natural gum bases include e. g. the type of gum base desired, the texture of gum com- chicle, jelutong-, lechi de caspi-, soh-, siak-, katiau-, position desired and the other components used in the sorwa-, balata-, pendare-, malaya-, and peach gums, 15 composition to make the final chewing gum product. The natural cautchouc and natural resins such as dammar elastomer may be any water-insoluble polymer known in and mastix. Synthetic gum bases are a mixture of: - elas- the art, and includes those gum polymers utilized for tomers (polymers, masticating substances), - plasticizer chewing gums and bubble gums. Illustrative examples (resin, elastomers, solvent, hydrophobic resin), - filler of suitable polymers in gum bases include both natural (texturizer, water- insoluble adjuvant), - softener (fat), - 20 and synthetic elastomers. For example, those polymers emulsifier, - wax, - antioxidant, and - anti-tacking agents which are suitable in gum base compositions include, (vinyl polymer, hydrophilic resin). without limitation, natural substances (of vegetable ori- [0084] Other examples of gum bases are gums includ- gin) such as chicle gum, natural rubber, crown gum, nis- ing agar, alginate, arabic gum, carob gum, carrageenan, pero, rosidinha, jelutong, perillo, niger gutta, tunu, balata, ghatti gum, guar gum, karaya gum, pectin, tragacanth 25 guttapercha, lechi capsi, sorva, gutta kay, and the like, gum, locust beam gum, gellan gum and xanthan gum. and mixtures thereof. Examples of synthetic elastomers [0085] Examples of gelling agents comprise gum ara- include, without limitation, styrene-butadiene copoly- bic, starch, gelatine, agar, and pectin. mers (SBR), polyisobutylene, isobutylene-isoprene co- [0086] In an embodiment of the invention, said natural polymers, polyethylene, polyvinyl acetate and the like, resin comprises terpene resins, e.g. derived from alpha- 30 and mixtures thereof. pinene, beta-pinene, and/or d-limonene, natural terpene [0090] It is common in the industry to combine in a gum resins, glycerol esters of gum rosins, tall oil rosins, wood base a synthetic elastomer having a high molecular rosins or other derivatives thereof such as glycerol esters weight and a synthetic elastomer having a low molecular of partially hydrogenated rosins, glycerol esters of po- weight. Examples of such combinations are polyisobuty- lymerized rosins, glycerol esters of partially dimerised 35 lene and styrene-butadiene, polyisobutylene and rosins, pentaerythritol esters of partially hydrogenated polyisoprene, polyisobutylene and isobutylene-isoprene rosins, methyl esters of rosins, partially hydrogenated copolymer (butyl rubber) and a combination of methyl esters of rosins or pentaerythritol esters of rosins polyisobutylene, styrene-butadiene copolymer and iso- and combinations thereof. butylene isoprene copolymer, and all of the above indi- [0087] Materials to be used for the above-mentioned 40 vidual synthetic polymers in admixture with polyvinyl ac- encapsulation methods might e.g. include Gelatine, etate, vinyl acetate-vinyl laurate copolymers, respective- Wheat protein, Soya protein, Sodium caseinate, Ca- ly and mixtures thereof. seine, Gum arabic, Mod. starch, Hydrolyzed starches [0091] Examples of natural resins are: Natural rosin (maltodextrines), Alginates, Pectin, Carregeenan, Xan- esters, often referred to as ester gums including as ex- than gum, Locus bean gum, Chitosan, Bees wax, Can- 45 amples glycerol esters of partially hydrogenated rosins, delilla wax, Carnauba wax, Hydrogenated vegetable oils, glycerol esters of polymerised rosins, glycerol esters of Zein and/or Sucrose. partially dimerized rosins, glycerol esters of tally oil ros- [0088] Examples of generally synthetic resins include ins, pentaerythritol esters of partially hydrogenated ros- polyvinyl acetate, vinyl acetate-vinyl laurate copolymers ins, methyl esters of rosins, partially hydrogenated me- and mixtures thereof. Examples of non-biodegradable 50 thyl esters of rosins, pentaerythritol esters of rosins, syn- synthetic elastomers include, but are not limited to, syn- thetic resins such as terpene resins derived from alpha- thetic elastomers listed in Food and Drug Administration, pinene, beta-pinene, and/or d-limonene, and natural ter- CFR, Title 21, Section 172,615, the Masticatory Sub- pene resins. stances, Synthetic) such as polyisobutylene. e.g. having [0092] The chewing gum may be provided with an out- a gel permeation chromatography (GPC) average mo- 55 er coating. lecular weight in the range of about 10,000 to 1,000,000 [0093] The applicable hard coating may be selected including the range of 50,000 to 80,000, isobutylene-iso- from the group comprising of sugar coating and a sug- prene copolymer (butyl elastomer), styrene-butadiene arless coating and a combination thereof. The hard coat-

8 15 EP 2 421 508 B1 16 ing may e.g. comprise 50 to 100% by weight of a polyol coating agent applied in a hard coating process is a sug- selected from the group consisting of sorbitol, maltitol, arless coating agent, e.g. a polyol including as examples mannitol, xylitol, erythritol, and Isomalt and vari- sorbitol, maltitol, mannitol, xylitol, erythritol, lactitol and ations thereof. In an embodiment of the invention, the isomalt or e.g. a mono- di-saccharide including as exam- outer coating is an edible film comprising at least one 5 ple trehalose. component selected from the group consisting of an ed- [0099] Or alternatively a sugar-free soft coating e.g. ible film-forming agent and a wax. The film-forming agent comprising alternately applying to the centers a syrup of may e.g. be selected from the group comprising cellulose a polyol or a mono- di-saccharide, including as examples derivative, a modified starch, a dextrin, gelatine, shellac, sorbitol, maltitol, mannitol, xylitol, erythritol, lactitol, iso- gum arabic, zein, a vegetable gum, a synthetic polymer 10 malt and trehalose. and any combination thereof. In an embodiment of the [0100] In further useful embodiments, a film coating is invention, the outer coating comprises at least one addi- provided by film-forming agents such as a cellulose de- tive component selected from the group comprising of a rivative, a modified starch, a dextrin, gelatine, zein, shel- binding agent, a moisture-absorbing component, a film- lec, gum arabic, a vegetable gum, a synthetic polymer, forming agent, a dispersing agent, an antisticking com- 15 etc. or a combination thereof. ponent, a bulking agent, a flavoring agent, a coloring [0101] In an embodiment of the invention, the outer agent, a pharmaceutically or cosmetically active compo- coating comprises at least one additive component se- nent, a lipid component, a wax component, a sugar, an lected from the group comprising a binding agent, a mois- acid and an agent capable of accelerating the after-chew- ture-absorbing component, a film-forming agent, a dis- ing degradation of the degradable polymer. 20 persing agent, an antisticking component, a bulking [0094] Generally, the ingredients may be mixed by first agent, a flavoring agent, a coloring agent, a pharmaceu- melting the gum base and adding it to the running mixer. tically or cosmetically active component, a lipid compo- Colors, active agents and/or emulsifiers may also be add- nent, a wax component, a sugar, and an acid. ed at this time. A softener such as glycerin may also be [0102] A coated chewing gum center may have any added at this time, along with syrup and a portion of the 25 form, shape or dimension that permits the chewing gum bulking agent/sweetener. Further portions of the bulking center to be coated using any conventional coating proc- agent/sweetener may then be added to the mixer. A fla- ess. voring agent is typically added with the final portion of [0103] It should however be noted that application of the bulking agent/sweetener. A high-intensity sweetener different coating should be done with care as com- is preferably added after the final portion of bulking agent 30 pressed chewing gum tablets may be very affected by and flavor has been added. direct contact with moisture or water. [0095] The entire mixing procedure typically takes from [0104] The composition of gum base formulations can five to fifteen minutes, but longer mixing times may some- vary substantially depending on the particular product to times be required. Those skilled in the art will recognize be prepared and on the desired masticatory and other that many variations of the above-described procedure 35 sensorycharacteristics ofthe final product. However, typ- may be followed. Including the one-step method de- ical ranges of the above gum base components are: 5 to scribed in US patent application 2004/0115305. Chewing 80% by weight of elastomeric compounds, 5 to 80% by gums are formed by extrusion, compression, rolling and weight of elastomer plasticizers, 0 to 40% by weight of may be centre filled with liquids and/or solids in any form. waxes, 5 to 35% by weight of softener, 0 to 50% by weight [0096] The chewing gum may also be provided with an 40 of filler, and 0 to 5% by weight of miscellaneous ingredi- outer coating, which may be a hard coating, a soft coat- ents such as antioxidants, colorants, etc. The gum base ing, a film coating, or a coating of any type that is known may comprise about 5 to about 95% by weight of the in the art, or a combination of such coatings. The coating chewing gum, more commonly; the gum base comprises may typically constitute 0.1 to 75% by weight of a coated 10 to about 60% by weight of the gum. chewing gum piece. 45 [0105] Elastomers provide the rubbery, cohesive na- [0097] One preferred outer coating type is a hard coat- ture to the gum, which varies depending on this ingredi- ing, which term is including sugar coatings and sugar- ent’s chemical structure and how it may be compounded free (or sugarless) coatings and combinations thereof. with other ingredients. Elastomers suitable for use in the The object of hard coating is to obtain a sweet, crunchy gum base and gum of the present invention may include layer, which is appreciated by the consumer and to pro- 50 natural or synthetic types. tect the gum centers. In a typical process of providing [0106] Elastomer plasticizers vary the firmness of the the chewing gum centers with a protective sugar coating gum base. Their specificity on elastomer inter-molecular the gum centers are successively treated in suitable coat- chain breaking (plasticizing) along with their varying sof- ing equipment with aqueous solutions of crystallizable tening points cause varying degrees of finished gum firm- sugar such as sucrose or dextrose, which, depending on 55 ness and compatibility when used in gum base. This may the stage of coating reached, may contain other function- be important when one wants to provide more elastomer- al ingredients, e.g. fillers, colors, etc. ic chain exposure to the alkanic chains of the waxes. [0098] In one presently preferred embodiment, the [0107] If desired, conventional elastomers or resins

9 17 EP 2 421 508 B1 18 may be supplemented or substituted by biodegradable digestible dextrins (e.g. Fibersol®). However, other low- polymers. calorie bulking agents can be used. [0108] In addition to a water insoluble gum base por- [0115] The chewing gum may contain aroma agents tion, a typical chewing gum includes a water soluble bulk and flavoring agents including natural and synthetic fla- portion and one or more flavoring agents. The water- 5 vorings e.g. in the form of natural vegetable components, soluble portion may include bulk sweeteners, high-inten- essential oils, essences, extracts, powders, including ac- sity sweeteners, flavoring agents, softeners, emulsifiers, ids and other substances capable of affecting the taste colors, acidulants, buffering agents, fillers, antioxidants, profile. Examples of liquid and powdered flavorings in- and other components that provide desired attributes. clude coconut, coffee, chocolate, vanilla, grape fruit, or- [0109] Combinationsof sugar and/ornon-sugar sweet- 10 ange, lime, menthol, liquorice, caramel aroma, honey eners can be used in the chewing gum formulation proc- aroma, peanut, walnut, cashew, hazelnut, almonds, essed in accordance with the invention. Additionally, the pineapple, strawberry, raspberry, tropical fruits, cherries, softener may also provide additional sweetness such as cinnamon, peppermint, wintergreen, spearmint, eucalyp- aqueous sugar or alditol solutions. tus, and mint, fruit essence such as from apple, pear, [0110] Useful sugar sweeteners are saccharide-con- 15 peach, strawberry, apricot, raspberry, cherry, pineapple, taining components commonly known in the chewing andplum essence.The essentialoils include peppermint, gum art including, but not limited to, sucrose, dextrose, spearmint, menthol, eucalyptus, clove oil, bay oil, anise, maltose, dextrins, trehalose, D-tagatose, dried invert thyme, cedar leaf oil, nutmeg, and oils of the fruits men- sugar, fructose, levulose, galactose, corn syrup solids, tioned above. and the like, alone or in combination. 20 [0116] The chewing gum flavor may be a natural fla- [0111] Sorbitol can be used as a non-sugar sweetener. voring agent, which is freeze-dried, preferably in the form Other useful non-sugar sweeteners include, but are not of a powder, slices or pieces or combinations thereof. limited to, other sugar alcohols such as mannitol, xylitol, The particle size may be less than 3 mm, less than 2 mm hydrogenated starch hydrolysates, maltitol, isomaltol, or more preferred less than 1 mm, calculated as the long- erythritol, lactitol and the like, alone or in combination. 25 est dimension of the particle. The natural flavoring agent [0112] High-intensity artificial sweetening agents can may be in a form where the particle size is from about 3 also be used alone or in combination with the above mm to 2 mm, such as from 4m m to 1 mm. Preferred sweeteners. Preferred high-intensity sweeteners in- natural flavoring agents include seeds from fruit e.g. from clude, but are not limited to sucralose, aspartame, salts strawberry, blackberry and raspberry. of acesulfame, alitame, neotame, twinsweet, saccharin 30 [0117] Various synthetic flavors, such as mixed fruit and its salts, cyclamic acid and its salts, glycyrrhizin, di- flavors may also be used in the present chewing gum hydrochalcones, thaumatin, monellin, stevioside and the centers. As indicated above, the aroma agent may be like, alone or in combination. In order to provide longer used in quantities smaller than those conventionally lasting sweetness and flavor perception, it may be desir- used. The aroma agents and/or flavors may be used in able to encapsulate or otherwise control the release of 35 the amount from 0.01 to about 30% by weight of the final at least a portion of the artificial sweetener. Techniques product depending on the desired intensity of the aroma such as wet granulation, wax granulation, spray drying, and/or flavor used. Preferably, the content of aroma/fla- spray chilling, fluid bed coating, coascervation, encap- vor is in the range of 0.2 to 3% by weight of the total sulation in yeast cells and fiber extrusion may be used composition. to achieve the desired release characteristics. Encapsu- 40 [0118] In an embodiment of the invention, the flavoring lation of sweetening agents can also be provided using agents comprise natural and synthetic flavorings in the another chewing gum component such as a resinous form of natural vegetable components, essential oils, es- compound. sences,extracts, powders,including acids andother sub- [0113] Usage level of the high-intensity artificial sweet- stances capable of affecting the taste profile. ener will vary considerably and will depend on factors 45 In one embodiment of the invention, the flavor may be suchas potency ofthe sweetener, rate ofrelease, desired used as taste masking in chewing gum comprising active sweetness of the product, level and type of flavor used ingredients, which by themselves have undesired taste and cost considerations. Thus, the active level of high- or which alter the taste of the formulation. potency artificial sweetener may vary from about 0 to [0119] Further chewing gum ingredients, which may about 8% by weight, preferably 0.001 to about 5% by 50 be included in the chewing gum according to the present weight. When carriers used for encapsulation are includ- invention, include surfactants and/or solubilisers, espe- ed, the usage level of the encapsulated sweetener will cially when pharmaceutically or biologically active ingre- be proportionately higher. dients are present. As examples of types of surfactants [0114] If a low-calorie gum is desired, a low-caloric to be used as solubilisers in a chewing gum composition bulking agent can be used. Examples of low caloric bulk- 55 according to the invention, reference is made to H.P. Fie- ing agents include polydextrose, Raftilose, Raftilin, fruc- dler, Lexikon der Hilfstoffe für Pharmacie, Kosmetik und tooligosaccharides (NutraFlora®), palatinose oligosac- Angrenzende Gebiete, pages 63-64 (1981) and the lists charides; guar gum hydrolysates (e.g. Sun Fiber ®) or in- of approved food emulsifiers of the individual countries.

10 19 EP 2 421 508 B1 20

Anionic, cationic, amphoteric or non-ionic solubilisers D: Dermatologicals can be used. Suitable solubilisers include lecithin, poly- G: Genito urinary system and sex hormones oxyethylene stearate, polyoxyethylene sorbitan fatty acid H: Systemic hormonal preparations, excl. sex hor- esters, fatty acid salts, mono and diacetyl tartaric acid mones and insulins esters of mono and diglycerides of edible fatty acids, citric 5 J: Antiinfectives for systemic use acid esters of mono and diglycerides of edible fatty acids, L: Antineoplastic and immunomodulating agents saccharose esters of fatty acids, polyglycerol esters of M: Musculo-skeletal system fatty acids, polyglycerol esters of interesterified N: Nervous system acid (E476), sodium stearoyllatylate, sodium lauryl sul- P: Antiparasitic products, insecticides and repellents fate and sorbitan esters of fatty acids and polyoxyethyl- 10 R: Respiratory system ated hydrogenated castor oil (e.g. the product sold under S: Sensory organs the trade name CREMOPHOR), block copolymers of eth- V: Various ylene oxide and propylene oxide (e.g. products sold un- der trade names PLURONIC and POLOXAMER), poly- [0124] Further subdivision is done into a second, third, oxyethylene fatty alcohol ethers, polyoxyethylene sorb- 15 fourth and fifth sub-group, which is based on the thera- itan fatty acid esters, sorbitan esters of fatty acids and peutic main group, the therapeutic/pharmacological sub- polyoxyethylene steraric acid esters. group, the chemical/therapeutic/pharmacological sub- [0120] Particularly suitable solubilisers are polyox- group, and the chemical substance subgroup respective- yethylene stearates, such as for instance polyoxyethyl- ly. In this sense each active ingredient has been given a ene(8)stearate and polyoxyethylene(40)stearate, the20 unique ATC identification code indicating where the ac- polyoxyethylene sorbitan fatty acid esters sold under the tive ingredient may be useful. trade name TWEEN, for instance TWEEN 20 (monolau- [0125] However, as some active ingredients are useful rate), TWEEN 80 (monooleate), TWEEN 40 (monopalmi- in more than one area, some of the active ingredients tate), TWEEN 60 (monostearate) or TWEEN 65 (tristea- mentioned in this document belong to two or more of the rate), mono and diacetyl tartaric acid esters of mono and 25 mentioned groups, e.g. phenylephrine, which has an diglycerides of edible fatty acids, citric acid esters of mo- ATC identification code in both C, R, and S, i.e. both no and diglycerides of edible fatty acids, sodium stearoyl- C01CA06, R01AA04, R01AB01, R01BA03, S01FB01, latylate, sodium laurylsulfate, polyoxyethylated hydro- and S01GA05 are ATC identification codes identifying genated castor oil, blockcopolymers of ethylene oxide phenylephrine. and propyleneoxide and polyoxyethylene fatty alcohol 30 [0126] The following list discloses examples of active ether. The solubiliser may either be a single compound ingredients which can be classified according to the ATC or a combination of several compounds. In the presence classification mentioned above and which are active in- of an active ingredient, the chewing gum may preferably gredients which may be used in a chewing gum granule also comprise a carrier known in the art. or a compressed chewing gum according to the inven- [0121] Active ingredients may advantageously be ap- 35 tion: plied in a chewing gum according to the invention. Active ingredients generally refer to those ingredients that are Ephedrine, , Pseudoephedrine, Sildena- included in a delivery system and/or compressible chew- fil, Xylocaine, Benzalconium chloride, Caffeine, Phe- ing gum composition for the desired end benefit they pro- nylephrine, Amfepramone, Orlistat, Sibutramine, vide to the user. In some embodiments, active ingredi- 40 Acetaminophen, Aspirin, Aluminum amino acetate, ents can include medicaments, nutrients, nutraceuticals, Aluminum amino acetate in combination with Mag- herbals, nutritional supplements, pharmaceuticals, nesium oxide, Aluminum oxide hydrate in combina- drugs, and the like and combinations thereof. Moreover, tion with Magnesiumoxide, Calcium carbonate in in the present context, active ingredients may refer to combination with , Calcium- flavor components, high intensity sweeteners or other 45 carbonate, Dihydroxy Aluminum sodium carbonate, taste establishing components. Magnesiumoxide, Glitazones, Metformin, Chlorpro- [0122] Active ingredients may be classified according mazine, Dimenhydrinat, Domperidone, Meclozine, to The Anatomical Therapeutic Chemical (ATC) classifi- Metoclopramide, Odansetron, Prednisolone, Pro- cation system, which is a system for classification of me- methazine, Acrivastine, Cetirizine, Cinnarizine, dicinal products according to their primary constituent 50 Clemastine, Cyclizine, Desloratadine, Dexchlorphe- and to the organ or system on which they act and their niramine, Dimenhydrinate, Ebastine, Fexofenadine, chemical, pharmacological and therapeutic properties. Ibuprofen, Levolevoproricin, Loratadine, Meclozine, [0123] The first level of the ATC is split into 14 main Mizolastine, Promethazine, Miconazole, Vitamin groups based on the anatomical group: B12, Folic acid, Ferro compounds, vitamin C, Chlo- 55 rhexidine diacetate,Fluoride, Decapeptide KSL, Alu- A: Alimentary tract and minum fluoride, Aminochelated calcium, Ammonium B: Blood and blood forming organs fluoride, Ammonium fluorosilicate, Ammonium C: Cardiovascular system monofluorphosphate, Calcium fluoride, Calcium glu-

11 21 EP 2 421 508 B1 22 conate, Calcium glycerophosphate, Calcium lactate, racycline, Trimethoprim, Vancomycin, Acarbose, Calcium monofluorphosphate, Calciumcarbonate, Glibenclamide, Gliclazide, Glimepiride, Glipizide, In- Carbamide, Cetyl pyridinium chloride, Chlorhexi- sulin,Repaglinide, Tolbutamide, Oseltamivir, Aciclo- dine, Chlorhexidine digluconate, Chlorhexidine vir, Famciclovir, Penciclovir, Valganciclovir, Amlopi- Chloride, Chlorhexidine diacetate, CPP Caseine 5 dine, Diltiazem, Felodipine, Nifedipine, Verapamil, Phospho Peptide, Hexetedine, Octadecentyl Am- Finasteride, Minoxidil, Cocaine, Buphrenorphin, monium fluoride, Potasium fluorosilicate, Potassium Clonidine, Methadone, Naltrexone, Calciumantago- Chloride, Potassium monofluorphosphate, Sodium nists, Clonidine, Ergotamine,β -blockers, Ace- bi carbonate, Sodium carbonate, Sodium fluoride, clofenac, Celecoxib, Dexiprofen, Etodolac, Indomet- Sodium fluorosilicate, Sodium monofluorphosphate, 10 acin, Ketoprofen, Ketorolac, Lornoxicam, Meloxi- Sodium tri polyphosphate, Stannous fluoride, Stear- cam, Nabumetone, Oiroxicam, Parecoxib, Phenylb- yl Trihydroxyethyl Propylenediamine Dihydrofluo- utazone,Piroxicam, Tiaprofenic acid, Tolfenamic ac- ride, Strontium chloride, Tetra potassium pyrophos- id, Aripiprazole, Chlorpromazine, Chlorprothixene, phate, Tetra sodium pyrophosphate, Tripotassium Clozapine, Flupentixol, Fluphenazine, Haloperidol, orthophosphate, Trisodium orthophosphate, Alginic 15 Lithium carbonate, Lithium citrate, Melperone, Pen- acid, Aluminum hydroxide, Sodium bicarbonate, fluridol, Periciazine, Perphenazine, Pimozide, Sildenafil, Tadalafil, Vardenafil, Yohimbine, Cimeti- Pipamperone, Prochlorperazine, Risperidone, dine, Nizatidine, Ranitidine, Acetylsalicylic acid, Thioridizin, Fluconazole, Itraconazole, Ketocona- Clopidogrel, Acetylcysteine, Bromhexine, Codeine, zole, Voriconazole, Opium, Benzodiazepines, Hy- Dextromethorphan, Diphenhydramine, Noscapine, 20 droxine, Meprobamate, Phenothiazine, Aluminiu- Phenylpropanolamine, vitamin D, Simvastatin, Bisa- maminoacetate, Esomeprazole, Famotidine, Mag- codyl,Lactitol, , Magnesium oxide, Sodium nesium oxide, Nizatide, Omeprazole, Pantoprazole, picosulfate, Senna glycosides, Benzocaine, Lido- Fluconazole, Itraconazole, Ketoconazole, Metroni- caine, Tetracaine, Almotriptan, Eletriptan, Nar- dazole, Amphetamine, Atenolol, Bisoprolol fuma- atriptan, Rizatriptan, Sumatriptan, Zolmitriptan, Cal- 25 rate, Metoprolol, Metropolol, Pindolol, Propranolol, cium, Chromium, Copper, Iodine, Iron, Magnesium, Auranofin, and Bendazac. Manganese, Molybdenium, Phosphor, Selenium, Zinc, Chloramine, Hydrogenperoxide, Metronida- [0127] Further examples of useful active ingredients zole, Triamcinolonacetonide, Benzethonium Chl., include active ingredients selected from the therapeutical Cetyl pyrid. Chl., Chlorhexidine, Fluoride, Lidocaine, 30 groups comprising: Analgesic, Anaestetic, Antipyretic, Amphotericin, Miconazole, Nystatin, Fish oil, Ginkgo Anti allergic, Anti-arrytmic, Appetite suppressant, Anti- Biloba, Ginseng, Ginger, Purple coneflower, Saw fungal, Anti-inflammatory, Broncho dilator, Cardiovascu- Palmetto, Cetirizine, Levocetirizine, Loratadine, Di- lar drugs, Coronary dilator, Cerebral dilator, Peripheral clofenac, Flurbiprofen, Acrivastine Pseudoephe- vasodilator, Anti-infective, Psychotropic, Anti- manic, drine, Loratadine Pseudoephedrine, Glucosamine, 35 Stimulant, Antihistamine, , Decongestrant, Gas- hyaluronic acid, Decapeptide KSL-W, Decapeptide tro-intestinal sedative, Sexual dysfunction agent, Desin- KSL, Resveratrol, Misoprostol, Bupropion, On- fectants, Anti-diarrheal, Anti-anginal substance, Vasodi- dansetron HCl, Esomeprazole, Lansoprazole, Ome- lator, Anti-hypertensive agent, Vasoconstrictor, Migraine prazole, Pantoprazole, Rabeprazole, Bacteria and treating agent, Antibiotic, Tranquilizer, Ntipsychotic, Anti- the like, Loperamide, Simethicone, Acetylsalicylic 40 tumor drug, Anticoagulant, Antithrombotic agent, Hyp- acid and others, Sucralfate, Vitamin A, Vitamin B1, notic, Sedative, Anti-emetic, Anti-, auseant, Anticonvul- Vitamin B12, Vitamin B2, Vitamin B6, Biotin, Vitamin sant, Neuromuscular agent, Hyper and hypoglycaemic, C, Vitamin D, Vitamin E, Folinic acid, Vitamin K, Ni- Thyroid and antithyroid, Diuretic, Antispasmodic, Uterine acin, Q10, Clotrimazole, Fluconazole, Itraconazole, relaxant, Anti-obesity agent, Anoretic, Spasnolytics, An- Ketoconazole, Terbinafine, Allopurinol, Probenecid, 45 abolic agent, Erythropoietic agent, Anti-asthmatic, Ex- Atorvastatin, Fluvastatin, Lovastatin, Nicotinic acid, pectorant, Cough suppressant, Mucolytic, Anti-uricemic Pravastatin, Rosuvastatin, Simvastatin, Pilocarpine, agent, Dental vehicle, Breath freshener, , Anti- Naproxen, Alendronate, Etidronate, Raloxifene, diuretc, Anti-flatulent, Betablokker, Teeth Whitener, En- Risedronate, Benzodiazepines, Disulfiram, Naltrex- zyme, Co-enzyme, Protein, Energy booster, Fiber, Pro- one, Buprenorphine, Codeine, Dextropropoxy-50 biotics, Prebiotics, Antimicrobial agent, NSAID, Anti-tus- phene, Fentanyl, Hydromorphone, Ketobemidone, sives, Decongestrants, Anti-histamines, Expectorants, Ketoprofen, Methadone, Morphine, Naproxen, Nico- Anti-diarrheals, Hydrogen antagonists, Proton pump in- morphine, Oxycodone, Pethidine, Tramadol, Amox- hibitors, General nonselective CNS depressants, Gen- icillin, Ampicillin, Azithromycin, Ciprofloxacin, Clari- eral nonselective CNS stimulants, Selectively CNS func- thromycin, Doxycyclin, Erythromycin, Fusidic acid, 55 tion modyfying drugs, Antiparkinsonism, Narcotic-anal- Lymecycline, Metronidazole, Moxifloxacin,getics, Analgetic-antipyretics, Psychopharmacological Ofloxacin, Oxytetracycline, Phenoxymethylpenicil- drugs, and Sexual dysfunction agents. lin, Rifamycins, Roxithromycin, Sulfamethizole, Tet- [0128] Examples of useful active ingredients include:

12 23 EP 2 421 508 B1 24

Casein glyco-macro-peptide (CGMP), Triclosan, Cetyl migrainepreparations, motion sickness treatments, mus- pyridinium chloride, Domiphen bromide, Quarternary cle relaxants, obesity management agents, osteoporosis ammonium salts, Zinc components, Sanguinarine, Flu- preparations, oxytocics, parasympatholytics, parasym- orides, Alexidine, Octonidine, EDTA, Aspirin, Acetami- pathomimetics, prostaglandins, psychotherapeutic nophen, Ibuprofen, Ketoprofen, Diflunisal, Fenoprofen 5 agents, respiratoryagents, sedatives, smoking cessation calcium, Naproxen, Tolmetin sodium, Indomethacin, aids such as bromocriptine, sympatholytics, tremor prep- Benzonatate, Caramiphen edisylate, Menthol, Dex- arations, urinary tract agents, vasodilators, , tromethorphan hydrobromide, Theobromine hydrochlo- , ion exchange resins, anti-pyretics, appetite ride, Chlophendianol Hydrochloride, Pseudoephedrine suppressants, expectorants, anti-anxiety agents, antiul- Hydrochloride, Phenylephrine, Phenylpropanolamine, 10 cer agents, anti-inflammatory substances, coronary di- Pseudoephedrine sulphate, Brompheniramine maleate, lators, cerebral dilators, peripheral vasodilators, psycho- Chlorpheniramine- maleate, Carbinoxamine maleate, tropics, stimulants, anti-hypertensive drugs, vasocon- Clemastine fumarate, Dexchlorpheniramine maleate, strictors, migraine treatments, antibiotics, tranquilizers, Dephenhydramine hydrochloride, Diphenpyralide hydro- anti-psychotics, anti-tumor drugs, anti-coagulants, anti- chloride, Azatadine maleate, Diphenhydramine citrate, 15 thrombotic drugs, hypnotics, anti-emetics, antinause- Doxylamine succinate, Promethazine hydrochloride, Py- ants, anti-convulsants, neuromuscular drugs, hyper- and rilamine maleate, Tripellenamine citrate, Triprolidine hy- hypo-glycemic agents, thyroid and anti-thyroid prepara- drochloride, Acrivastine, Loratadine, Brompheniramine, tions, diuretics, anti-spasmodics, terine relaxants, anti- Dexbrompheniamine, Guaifenesin, Ipecac, Potassium obesity drugs, erythropoietic drugs, anti-asthmatics, iodide, Terpin hydrate, Loperamide, Famotidine, Raniti- 20 cough suppressants, mucolytics, DNA and genetic mod- dine, Omeprazole, Lansoprazole, Aliphatic alcohols, ifying drugs, and combinations thereof. Barbiturates, Caffeine, Strychnine, Picrotoxin, Penty- [0130] Examples of active ingredients contemplated enetetrazol, Phenyhydantoin, Phenobarbital, Primidone, for use in the present invention can include antacids, H2- Carbamazapine, Etoxsuximide, Methsuximide, Phen- antagonists, and analgesics. For example, antacid dos- suximide, Trimethadione, Diazepam, Benzodiazepines, 25 ages can be prepared using the ingredients calcium car- Phenacemide, Pheneturide, Acetazolamide, Sulthiame, bonate alone or in combination with magnesium hydrox- Bromide, Levodopa, Amantadine, Morphine, Heroin, Hy- ide, and/or aluminum hydroxide. Moreover, antacids can dromorphone, Metopon, Oxymorphone, Levophanol, be used in combination with H2-antagonists. Codeine, Hydrocodone, Xycodone, Nalorphine,[0131] Analgesics include opiates and opiate deriva- Naloxone, Naltrexone, Salicylates, Phenylbutazone, In- 30 tives, such as Oxycontin™, ibuprofen, aspirin, acetami- domethacin, Phenacetin, Chlorpromazine, Methotrime- nophen, and combinations thereof that may optionally prazine, Haloperidol, Clozapine, Reserpine, Imipramine, include caffeine. Tranylcypromine, Phenelzine, Lithium, Sildenafil citrate, [0132] Other drug active ingredients for use in embod- Tadalafil, and Vardenafil CL. iments can include anti-diarrheals such as Immodium™ [0129] Examples of useful active ingredients include 35 AD, anti-histamines, anti-tussives, decongestants, vita- active ingredients selected from the groups of ace-inhib- mins, and breath fresheners. Also contemplated for use itors, antianginal drugs, anti- arrhythmias, anti-asthmat- herein are anxiolytics such as Xanax™; anti-psychotics ics, anti-cholesterolemics, analgesics, anesthetics, anti- such as Clozaril™ and Haldol™; non-steroidal antiin- convulsants, anti-depressants, antidiabetic agents, anti- flammatories (NSAID’s) such as ibuprofen, naproxen so- preparations, antidotes, anti-histamines, anti- 40 dium, Voltaren™ and Lodine™, anti-histamines such as hypertensive drugs, anti-inflammatory agents, anti-lipid Claritin™, Hismanal™, Relafen™, and Tavist™; an- agents, anti- manics, antinauseants, anti-stroke agents, tiemetics such as Kytril™ and Cesamet™; bronchodila- anti-thyroid preparations, anti-tumor drugs, anti- viral tors such as Bentolin™, Proventil™; anti-depressants agents, acne drugs, alkaloids, amino acid preparations, such as Prozac™, Zoloft™, and Paxil™; anti-migraines anti-tussives, anti- uricemic drugs, anti- viral drugs, an- 45 such as Imigra™, ACE-inhibitors such as Vasotec™, Ca- abolic preparations, systemic and non-systemic anti-in- poten™ and Zestril™; anti-Alzheimer’s agents, such as fective agents, anti-neoplasties, antiparkinsonian Nicergoline™; and CaH-antagonists such as Procar- agents, anti-rheumatic agents, appetite stimulants, bio- dia™, Adalat™, and Calan™. logical response modifiers, blood modifiers, bone metab- [0133] The popular H2-antagonists which are contem- olism regulators, cardiovascular agents, central nervous 50 plated for use in the present invention include cimetidine, system stimulates, cholinesterase inhibitors, contracep- ranitidine hydrochloride, famotidine, nizatidien, ebroti- tives, decongestants, dietary supplements, dopamine re- dine, mifentidine, roxatidine, pisatidine and aceroxati- ceptor agonists, endometriosis management agents, en- dine. zymes, erectile dysfunction therapies such as sildenafil [0134] Active antacid ingredients can include, but are citrate, which is currently marketed as Viagra™, fertility 55 not limited to, the following: aluminum hydroxide, dihy- agents, gastrointestinal agents, homeopathic remedies, droxyaluminum aminoacetate, aminoacetic acid, alumi- hormones, hypercalcemia and hypocalcemia manage- num phosphate, dihydroxyaluminum sodium carbonate, ment agents, immunomodulators, immunosuppressives, bicarbonate, bismuth aluminate, bismuth carbonate, bis-

13 25 EP 2 421 508 B1 26 muth subcarbonate, bismuth subgallate, bismuth subni- tem, the type or amount of coating on the delivery system, trate, bismuth subsilysilate, calcium carbonate, calcium the type or amount of coating on an ingredient prior to phosphate, citrate ion (acid or salt), amino acetic acid, the ingredient being encapsulated, etc. hydrate magnesium aluminate sulfate, magaldrate, mag- [0136] In some embodiments, the release profiles of nesium alumino silicate, , magne- 5 one or more components of an effervescing system are sium glycinate, magnesium hydroxide, magnesium ox- managed for a compressible gum. The effervescent sys- ide, magnesium trisilicate, milk solids, aluminum mono- tem may include one or more edible acids and one or ordibasic calcium phosphate, tricalcium phosphate, po- more edible alkaline materials. The edible acid(s) and tassium bicarbonate, , sodium bicarbo- the edible alkaline material(s) may react together to gen- nate, magnesium aluminosilicates, tartaric acids and 10 erate effervescence. In some embodiments, the alkaline salts. A variety of nutritional supplements may also be material(s) may be selected from, but is not limited to, used as active ingredients including virtually any vitamin alkali metal carbonates, alkali metal bicarbonates, alka- or mineral. For example, vitamin A, vitamin C, vitamin D, line earth metal carbonates, alkaline earth metal bicar- vitamin E, vitamin K, vitamin B6, vitamin B12, thiamine, bonates, and combinations thereof. The edible acid(s) riboflavin, biotin, folic acid, niacin, pantothenic acid, so- 15 may be selected from, but is not limited to, citric acid, dium, potassium, calcium, magnesium, phosphorus, sul- phosphoric acid, tartaric acid, malic acid, ascorbic acid, fur, chlorine, iron, copper, iodine, zinc, selenium, man- and combinations thereof. In some embodiments, an ef- ganese, choline, chromium, molybdenum, fluorine, co- fervescing system may include one or more other ingre- balt and combinations thereof, may be used. Examples dients such as, for example, carbon dioxide, oral care of nutritional supplements that can be used as active in- 20 ingredients, flavorants, etc. gredients are set forth in U.S. Patent Application Publi- [0137] For examples of use of an effervescing system cation Nos. 2003/0157213 A1, 2003/0206993 and in a chewing gum, refer to U.S. Provisional Patent No. 2003/0099741 A1. Various herbals may also be used as 60/618,222 filed October 13, 2004, and entitled "Effer- active ingredients such as those with various medicinal vescent Pressed Gum Tablet Compositions".. Other ex- or dietary supplement properties. Herbals are generally 25 amples can be found in U.S. Patent No. 6,235,318. Typ- aromatic or parts and or extracts thereof that ically, encapsulation of the one or more ingredients in an can be used medicinally or for flavoring. Suitable herbals effervescing system will result in a delay in the release can be used singly or in various mixtures. Commonly of the predominant amount of the one or more ingredients used herbs include Echinacea, Goldenseal, Calendula, during consumption of a compressible chewing gum that Rosemary, Thyme, Kava Kava, Aloe, Blood Root, Grape- 30 includes the encapsulated one or more ingredients (e.g., fruit Seed Extract, Black Cohosh, Ginseng, Guarana, as part of a delivery system added as an ingredient to Cranberry, Ginko Biloba, St. John’s Wort, Evening Prim- the compressible chewing gum composition). The re- rose Oil, Yohimbe Bark, Green Tea, Ma Huang, Maca, lease profile of the one or more ingredients can be man- Bilberry, Lutein, and combinations thereof. aged for a compressible gum by managing various char- [0135] Especially when hydrophilic, encapsulation of 35 acteristics of the ingredient, delivery system containing the active will result in a delay in the release of the pre- the ingredient, and/or the compressible chewing gum dominant amount of the active during consumption of a containing the delivery system and/or how the delivery compressible chewing gum that includes the encapsu- system is made. For example, characteristics might in- lated active (e.g., as part of a delivery system added as clude one or more of the following: tensile strength of the an ingredient to the compressible chewing gum), in some 40 delivery system, water solubility of the ingredient, water embodiments, the release profile of the ingredient (e.g., solubility of the encapsulating material, water solubility the active) can be managed for a compressible gum by ofthe deliverysystem, ratio ofingredient to encapsulating managing various characteristics of the ingredient, de- materialin the delivery system,average or maximum par- livery system containing the ingredient, and/or the com- ticle size of ingredient, average or maximum particle size pressible chewing gum containing the delivery system 45 of ground delivery system, the amount of the ingredient and/or how the delivery system is made. For example, or the delivery system in the compressible chewing gum, characteristics might include one or more of the following: ratio of different polymers used to encapsulate one or tensile strength of the delivery system, water solubility of more ingredients, hydrophobicity of one or more poly- the ingredient, water solubility of the encapsulating ma- mers used to encapsulate one or more ingredients, hy- terial, water solubility of the delivery system, ratio of in- 50 drophobicity of the delivery system, the type or amount gredient to encapsulating material in the delivery system, of coating on the delivery system, the type or amount of average or maximum particle size of ingredient, average coating on an ingredient prior to the ingredient being en- or maximum particle size of ground delivery system, the capsulated, etc. amount of the ingredient or the delivery system in the [0138] In some embodiments, the release profiles of compressible chewing gum, ratio of different polymers 55 one or more appetite suppressors are managed for a used to encapsulate one or more ingredients, hydropho- compressible gum. Appetite suppressors can be ingre- bicity of one or more polymers used to encapsulate one dients such as fiber and protein that function to depress or more ingredients, hydrophobicity of the delivery sys- the desire to consume food. Appetite suppressors can

14 27 EP 2 421 508 B1 28 also include benzphetamine, diethylpropion, mazindol, [0141] In addition to essential oils and chemicals de- phendimetrazine, phentermine, hoodia (P57), Olibra™, rived from them, in some embodiments, breath freshen- ephedra, caffeine and combinations thereof. Appetite ers can include but are not limited to zinc citrate, zinc suppressors are also known by the following trade acetate, zinc fluoride, zinc ammonium sulfate, zinc bro- names: Adipex™, Adipost™, Bontril™ PDM, Bontril™ 5 mide, zinc iodide, zinc chloride, zinc nitrate, zinc flurosil- Slow Release, Didrex™, Fastin™, Ionamin™, Mazan- icate, zinc gluconate, zinc tartarate, zinc succinate, zinc or™, Melfiat™, Obenix™, Phendiet™, Phendiet-105™, formate, zinc chromate, zinc phenol sulfonate, zinc Phentercot™, Phentride™, Plegine™, Prelu-2™, Pro- dithionate, zinc sulfate, siliver nitrate, zinc salicylate, zinc Fast™, PT 105™, Sanorex™, Tenuate™, Sanorex™, glycerophosphate, copper nitrate, chlorophyll, copper Tenuate™, Tenuate Dospan™, Tepanil Ten-Tab™,10 chlorophyll, chlorophyllin, hydrogenated cottonseed oil, Teramine™, and Zantryl™. These and other suitable ap- chlorine dioxide, beta cyclodextrin, zeolite, silica-based petite suppressors are further described in the following materials, carbon-based materials, enzymes such as lac- U.S. patents: U.S. 6,838,431 to Portman, U.S. 6,716,815 case, and combinations thereof. In some embodiments, to Portman, U.S. 6,558,690 to Portman, U.S. 6,468,962 the release profiles of probiotics can be managed for a to Portman, U.S. 6,436,899 to Portman. 15 compressible gum including, but not limited to lactic acid [0139] Typically, encapsulation of the appetite sup- producing microorganisms such as Bacillus coagulans, pressor will result in a delay in the release of the predom- Bacillus subtilis, Bacillus laterosporus, Bacillus laevol- inant amount of the appetite suppressor during consump- acticus, Sporolactobacillus inulinus, Lactobacillus acido- tion of a compressible chewing gum that includes the philus, Lactobacillus curvatus, Lactobacillus plantarum, encapsulated appetite suppressor (e.g., as part of a de- 20 Lactobacillus jenseni, Lactobacillus casei, Lactobacillus livery system added as an ingredient to the compressible fermentum, Lactococcus lactis, Pedioccocus acidilacti, chewing gum). In some embodiments, the release profile Pedioccocus pentosaceus, Pedioccocus urinae, Leu- of the ingredient (e.g., the appetite suppressor) can be conostoc mesenteroides, Bacillus coagulans, Bacillus managed for a compressible gum by managing various subtilis, Bacillus laterosporus, Bacillus laevolacticus, characteristics of the ingredient, delivery system contain- 25 Sporolactobacillus inulinus and mixtures thereof Breath ing the ingredient, and/or the compressible chewing gum fresheners are also known by the following trade names: containing the delivery system and/or how the delivery Retsyn™, Actizol™, and Nutrazin™. Examples of malo- system is made. For example, characteristics might in- dor-controlling compositions are also included in U.S. clude one or more of the following: tensile strength of the Patent No. 5,300,305 to Stapler et al. and in U.S. Patent delivery system, water solubility of the ingredient, water 30 Application Publication Nos. 2003/0215417 and solubility of the encapsulating material, water solubility 2004/0081713. of the delivery system, ratio of ingredient to encapsulating [0142] Typically, encapsulation of the breath-freshen- material in the delivery system, average or maximum par- ing ingredient will result in a delay in the release of the ticle size of ingredient, average or maximum particle size predominant amount of the active during consumption of of ground delivery system, the amount of the ingredient 35 a compressible chewing gum that includes the encapsu- or the delivery system in the compressible chewing gum, lated breath-freshening ingredient (e.g., as part of a de- ratio of different polymers used to encapsulate one or livery system added as an ingredient to the compressible more ingredients, hydrophobicity of one or more poly- chewing gum composition). In some embodiments, the mers used to encapsulate one or more ingredients, hy- release profile of the ingredient (e.g., the breath-fresh- drophobicity of the delivery system, the type or amount 40 ening ingredient) can be managed for a compressible of coating on the delivery system, the type or amount of gum by managing various characteristics of the ingredi- coating on an ingredient prior to the ingredient being en- ent, delivery system containing the ingredient, and/or the capsulated, etc. compressible chewing gum containing the delivery sys- [0140] In some embodiments, the release profiles of tem and/or how the delivery system is made. For exam- one or more breath fresheners are managed for a com- 45 ple, characteristics might include one or more of the fol- pressible gum. Breath fresheners can include essential lowing: tensile strength of the delivery system, water sol- oils as well as various aldehydes, alcohols, and similar ubility of the ingredient, water solubility of the encapsu- materials. In some embodiments, essential oils can in- lating material, water solubility of the delivery system, clude oils of spearmint, peppermint, wintergreen, sassa- ratio of ingredient to encapsulating material in the deliv- fras, chlorophyll, citral, geraniol, cardamom, clove, sage, 50 ery system, average or maximum particle size of ingre- carvacrol, eucalyptus, cardamom, magnolia bark extract, dient, average or maximum particle size of ground deliv- marjoram, cinnamon, lemon, lime, grapefruit, and or- ery system, the amount of the ingredient or the delivery ange. In some embodiments, aldehydes such as cinnam- system in the compressible chewing gum, ratio of differ- ic aldehyde and salicylaldehyde can be used. Addition- ent polymers used to encapsulate one or more ingredi- ally, chemicals such as menthol, carvone, iso-garrigol, 55 ents, hydrophobicity of one or more polymers used to andanethole can functionas breath fresheners.Of these, encapsulate one or more ingredients, hydrophobicity of the most commonly employed are oils of peppermint, the delivery system, the type or amount of coating on the spearmint and chlorophyll. delivery system, the type or amount of coating on an in-

15 29 EP 2 421 508 B1 30 gredient prior to the ingredient being encapsulated, etc. dental care ingredients can include antibacterial agents [0143] In some embodiments, the release profiles of such as, but not limited.to, triclosan, chlorhexidine, zinc one or more dental care ingredients may be managed citrate, silver nitrate, copper, limonene, and cetyl pyrid- for a compressible gum. Such dental care ingredients inium chloride. In some embodiments, additional anti- (also known as oral care ingredients) may include but 5 caries agents can include fluoride ions or fluorine-provid- are not limited to tooth whiteners, stain removers, oral ing components such as inorganic fluoride salts. In some cleaning, bleaching agents, desensitizing agents, dental embodiments, soluble alkali metal salts, for example, so- remineralization agents, antibacterial agents, anticaries dium fluoride, potassium fluoride, sodium fluorosilicate, agents, plaque acid buffering agents, surfactants and an- ammonium fluorosilicate, sodium monofluorophosphate, ticalculus agents. Non-limiting examples of such ingre- 10 as well as tin fluorides, such as stannous fluoride and dients can include, hydrolytic agents including proteolytic stannous chloride can be included. In some embodi- enzymes, abrasives such as hydrated silica, calcium car- ments, a fluorine-containing compound having a benefi- bonate, sodium bicarbonate and alumina, other active cial effect on the care and hygiene of the oral cavity, e.g., stain-removing components such as surface-active diminution of enamel solubility in acid and protection of agents, including, but not limited to anionic surfactants 15 the teeth against decay may also be included as an in- such as sodium stearate, sodium palminate, sulfated gredient. Examples thereof include sodium fluoride, stan- butyl oleate, sodium oleate, salts of fumaric acid, glycer- nous fluoride, potassium fluoride, potassium stannous ol, hydroxylated lecithin, sodium lauryl sulfate and che- fluoride (SnF.sub.2 -KF), sodium hexafluorostannate, lators such as polyphosphates, which are typically em- stannous chlorofluoride, sodium fluorozirconate, and so- ployed as tartar control ingredients. In some embodi- 20 dium monofluorophosphate. In some embodiments, urea ments, dental care ingredients can also include tetraso- is included. Further examples are included in the follow- dium pyrophosphate and sodium tri-polyphosphate, so- ing U.S. patents and U.S. published patent applications: dium bicarbonate, sodium acid pyrophosphate, sodium U.S. Patent Nos. 5,227,154 to Reynolds, 5,378,131 to tripolyphosphate, xylitol, sodium hexametaphosphate. In Greenberg, 6,846,500 to Luo et al, 6,733,818 to Luo et some embodiments, such as carbamide per- 25 al., 6,696,044 to Luo et al., 6,685,916 to Holme et al., oxide, calcium peroxide, , sodium 6,485,739 to Luo et al., 6,479,071 to Holme et al., peroxide, hydrogen peroxide, and peroxydiphospate are 6,471,945 to Luo et al., U.S. Patent Publication Nos. included. In some embodiments, potassium nitrate and 20050025721. to Holme et al., 2005008732 to Gebrese- potassium citrate are included. Other examples can in- lassie et al., and 20040136928 to Holme et al. clude casein glycomacropeptide, calcium casein pep- 30 [0144] Typically, encapsulation of the active will result tone-calcium phosphate, casein phosphopeptides, ca- in a delay in the release of the predominant amount of sein phosphopeptide- amorphous calcium phosphate theactive duringconsumption of acompressible chewing (CPP-ACP), and amorphous calcium phosphate. Still gum that includes the encapsulated active (e.g., as part other examples can include papaine, krillase, pepsin, of a delivery system added as an ingredient to the com- trypsin, lysozyme, dextranase, mutanase, glycoamyla- 35 pressible chewing gum composition). In some embodi- se, amylase, glucose oxidase, and combinations thereof. ments, the release profile of the ingredient (e.g., the den- Further examples can include surfactants such as sodi- tal care active) can be managed for a compressible gum um stearate, sodium ricinoleate, and sodium lauryl sul- by managing various characteristics of the ingredient, fate surfactants for use in some embodiments to achieve delivery system containing the ingredient, and/or the increased prophylactic action and to render the dental 40 compressible chewing gum containing the delivery sys- care ingredients more cosmetically acceptable. Sur- tem and/or how the delivery system is made. For exam- factants can preferably be detersive materials which im- ple, characteristics might include one or more of the fol- part to the composition detersive and foaming properties. lowing: tensile strength of the delivery system, water sol- Suitable examples of surfactants are water-soluble salts ubility of the ingredient, water solubility of the encapsu- of higher fatty acid monoglyceride monosulfates, such 45 lating material, water solubility of the delivery system, as the sodium salt of the monosulfated monoglyceride ratio of ingredient to encapsulating material in the deliv- of hydgrogenated coconut oil fatty acids, higher alkyl sul- ery system, average or maximum particle size of ingre- fates such as sodium lauryl sulfate, alkyl aryl sulfonates dient, average or maximum particle size of ground deliv- such as sodium dodecyl benzene sulfonate, higher alkyl ery system, the amount of the ingredient or the delivery sulfoacetates, sodium lauryl sulfoacetate, higher fatty ac- 50 system in the compressible chewing gum, ratio of differ- id esters of 1,2-dihydroxy propane sulfonate, and the ent polymers used to encapsulate one or more ingredi- substantially saturated higher aliphatic acyl amides of ents, hydrophobicity of one or more polymers used to lower aliphatic amino carboxylic acid compounds, such encapsulate one or more ingredients, hydrophobicity of as those having 12 to 16 carbons in the fatty acid, alkyl the delivery system, the type or amount of coating on the or acyl radicals, and the like. Examples of the last men- 55 delivery system, the type or amount of coating on an in- tioned amides are N-lauroyl sarcosine, and the sodium, gredient prior to the ingredient being encapsulated, etc. potassium, and ethanolamine salts of N-lauroyl, N-myr- [0145] In some embodiments, the release profiles of istoyl, or N-palmitoyl sarcosine. In addition to surfactants, one or more flavor potentiators can be managed for a

16 31 EP 2 421 508 B1 32 compressible gum. Flavor potentiators can consist of ma- coating on an ingredient prior to the ingredient being en- terials that may intensify, supplement, modify or enhance capsulated, etc. the taste and/or aroma perception of an original material [0147] In some embodiments, the release profiles of without introducing a characteristic taste and/or aroma one or more acids may be managed for a compressible perception of their own. In some embodiments, potenti- 5 gum. Acids can include, but are not limited to acetic acid, ators designed to intensify, supplement, modify, or en- adipic acid, ascorbic acid, butyric acid, citric acid, formic hancethe perceptionof flavor, sweetness,tartness, uma- acid, fumaric acid, glyconic acid, lactic acid, phosphoric mi, kokumi, saltiness and combinations thereof can be acid, malic acid, oxalic acid, succinic acid, tartaric acid included. In some embodiments, sweetness may be po- and combinations thereof. tentiated by the inclusion of monoammonium glycyrrhiz- 10 [0148] Typically, encapsulation of a food acid will result inate, licorice glycyrrhizinates, citrus aurantium, maltol, in a delay in the release of the predominant amount of ethyl maltol, vanilla, vanillin, and combinations thereof. theactive duringconsumption of acompressible chewing In some embodiments, sugar acids, sodium chloride, po- gum that includes the encapsulated food acid (e.g., as tassium chloride, sodium acid sulfate, and combinations part of a delivery system added as an ingredient to the thereof may be included for flavor potentiation. In other 15 compressible chewing gum). In some embodiments, the examples, glutamates such as monosodium glutamate release profile of the ingredient (e.g., the food acid) can (MSG), monopotassium glutamate, hydrolyzed vegeta- be managed for a compressible gum by managing vari- ble protein, hydrolyzed animal protein, yeast extract, and ouscharacteristics of the ingredient,delivery system con- combinationsthereof are included.Further examples can taining the ingredient, and/or the compressible chewing include glutathione, and nucleotides such as inosine20 gum containing the delivery system and/or how the de- monophosphate (IMP), disodium inosinate, xanthosine livery system is made. For example, characteristics might monophosphate, guanylate monophosphate (GMP), and include one or more of the following: tensile strength of combinations thereof. For bitterness blocking or taste the delivery system, water solubility of the ingredient, wa- masking, ingredients that interact with bitterness recep- ter solubility of the encapsulating material, water solubil- tors to suppress bitterness or off tastes may be included. 25 ity of the delivery system, ratio of ingredient to encapsu- In some embodiments, adenosine monophosphate lating material in the delivery system, average or maxi- (AMP) can be included for bitterness suppression. Bit- mum particle size of ingredient, average or maximum terness modification can also be accomplished by using particle size of ground delivery system, the amount of sweetness or flavors with complementary bitter notes the ingredient or the delivery system in the compressible such as chocolate. Further examples of flavor potentiator 30 chewing gum, ratio of different polymers used to encap- compositions that impart kokumi are also included in U.S. sulate one or more ingredients, hydrophobicity of one or Patent No. 5,679,397 to Kuroda et al.. more polymers used to encapsulate one or more ingre- [0146] Typically, encapsulation of a flavor potentiator dients, hydrophobicity of the delivery system, the type or will result in a delay in the release of the predominant amount of coating on the delivery system, the type or amount of the flavor potentiator during consumption of a 35 amount of coating on an ingredient prior to the ingredient compressible chewing gum that includes the encapsu- being encapsulated, etc. lated flavor potentiator (e.g., as part of a delivery system [0149] In some embodiments, the release profiles of added as an ingredient to the compressible chewing gum one or more micronutrients can be managed for a com- composition). In some embodiments, the release profile pressible gum. Micronutrients can include materials that of the ingredient (e.g., the flavor potentiator) can be man- 40 have an impact on the nutritional wellbeing of an organ- aged for a compressible gum by managing various char- ism even though the quantity required by the organism acteristics of the ingredient, delivery system containing to have the desired effect is small relative to macronutri- the ingredient, and/or the compressible chewing gum ents such as protein, carbohydrate, and fat. Micronutri- containing the delivery system and/or how the delivery ents can include, but are not limited to vitamins, minerals, system is made. For example, characteristics might in- 45 enzymes, phytochemicals, antioxidants, and combina- clude one or more of the following: tensile strength of the tions thereof. In some embodiments, vitamins can in- delivery system, water solubility of the ingredient, water clude fat soluble vitamins such as vitamin A, vitamin D, solubility of the encapsulating material, water solubility vitamin E, and vitamin K and combinations thereof, in of the delivery system, ratio of ingredient to encapsulating some embodiments, vitamins can include water soluble material in the delivery system, average or maximum par- 50 vitamins such as vitamin C (ascorbic acid), the B vitamins ticle size of ingredient, average or maximum particle size (thiamine or B1, riboflavoin or B2, niacin or B3, pyridoxine of ground delivery system, the amount of the ingredient or B6, folic acid or B9, cyanocobalimin or B12, pantothen- or the delivery system in the compressible chewing gum, ic acid, biotin), and combinations thereof. ratio of different polymers used to encapsulate one or [0150] In some embodiments, minerals can include but more ingredients, hydrophobicity of one or more poly- 55 are not limited to sodium, magnesium, chromium, iodine, mers used to encapsulate one or more ingredients, hy- iron, manganese, calcium, copper, fluoride, potassium, drophobicity of the delivery system, the type or amount phosphorous, molybdenum, selenium, zinc, and combi- of coating on the delivery system, the type or amount of nations thereof.

17 33 EP 2 421 508 B1 34

[0151] In some embodiments micronutrients can in- butyric acid, citric acid, formic acid, fumaric acid, glyconic clude but are not limited to L- carnitine, choline, coen- acid, lactic acid, phosphoric acid, malic acid, oxalic acid, zyme Q10, alpha-lipoic acid, omega-3 -fatty acids, pep- succinic acid, tartaric acid and combinations thereof sin, phytase, trypsin, lipases, proteases, cellulases, and Mouth moisteners can also include hydrocolloid materi- combinations thereof. 5 als that hydrate and may adhere to oral surface to provide [0152] Antioxidants can include materials that scav- a sensation of mouth moistening. Hydrocolloid materials enge free radicals. In some embodiments, antioxidants can include naturally occurring materials such as plant can include but are not limited to ascorbic acid, citric acid, exudates, seed gums, and seaweed extracts or they can rosemary oil, vitamin A, vitamin E, vitamin E phosphate, be chemically modified materials such as cellulose, tocopherols, di-alpha-tocopheryl phosphate, tocot-10 starch, or natural gum derivatives. In some embodi- rienols,alpha lipoic acid, dihydrolipoicacid, xanthophylls, ments, hydrocolloid materials can include pectin, gum beta cryptoxanthin, lycopene, lutein, zeaxanthin, astax- arabic, acacia gum, alginates, agar, carageenans, guar anthin, beta-carotene, carotenes, mixed carotenoids, gum, xanthan gum, locust bean gum, gelatin, gellan gum, polyphenols, flavonoids, and combinations thereof. galactomannans, tragacanth gum, karaya gum, curdlan, [0153] In some embodiments, phytochemicals can in- 15 konjac, chitosan, xyloglucan, beta glucan, furcellaran, cludebut are not limited to cartotenoids,chlorophyll, chlo- gum ghatti, tamarin, bacterial gums, and combinations rophyllin, fiber, flavanoids, anthocyanins, cyaniding, del- thereof. Additionally, in some embodiments, modified phinidin, malvidin, pelargonidin, peonidin, petunidin, fla- natural gums such as propylene glycol alginate, car- vanols, catechin, epicatechin, epigallocatechin, epigal- boxymethyl locust bean gum, low methoxyl pectin, and locatechingallate, theaflavins, thearubigins, proanthocy- 20 their combinations can be included. In some embodi- anins, flavonols, quercetin, kaempferol, myricetin, ments, modified celluloses can be included such as mi- isorhamnetin,flavononeshesperetin, naringenin, eriodic- crocrystalline cellulose, carboxymethlcellulose (CMC), tyol, tangeretin, flavones, apigenin, luteolin, lignans, phy- methylcellulose (MC), hydroxypropylniethylcellulose toestrogens, resveratrol, isoflavones, daidzein, genis- (HPCM), and hydroxypropylcellulose (MPC), and com- tein,glycitein, soy isoflavones, and combinations thereof. 25 binations thereof. Similarly, humectants which can pro- [0154] Typically,encapsulation ofthe micronutrientwill vide a perception of mouth hydration can be included. result in a delay in the release of the predominant amount Such humectants can include, but are not limited to glyc- of the active during consumption of a compressible chew- erol, sorbitol, polyethylene glycol, erythritol, and xylitol. ing gum that includes the encapsulated micronutrient Additionally, in some embodiments, fats can provide a (e.g., as part of a delivery system added as an ingredient 30 perception of mouth moistening. Such fats can include to the compressible chewing gum). In some embodi- medium chain triglycerides, vegetable oils, fish oils, min- ments, the release profile of the ingredient (e.g., the mi- eral oils, and combinations thereof. Typically, encapsu- cronutrient) can be managed for a compressible gum by lation of a mouth moistening agent will result in a delay managing various characteristics of the ingredient, de- in the release of the predominant amount of the active livery system containing the ingredient, and/or the com- 35 during consumption of a compressible chewing gum that pressible chewing gum containing the delivery system includes the encapsulated mouth moistening agent (e.g., and/or how the delivery system is made. For example, as part of a delivery system added as an ingredient to characteristics might include one or more of the following: the compressible chewing gum). In some embodiments, tensile strength of the delivery system, water solubility of the release profile of the ingredient (e.g., the mouth mois- the ingredient, water solubility of the encapsulating ma- 40 tening agent) can be managed for a compressible gum terial, water solubility of the delivery system, ratio of in- by managing various characteristics of the ingredient, gredient to encapsulating material in the delivery system, delivery system containing the ingredient, and/or the average or maximum particle size of ingredient, average compressible chewing gum containing the delivery sys- or maximum particle size of ground delivery system, the tem and/or how the delivery system is made. For exam- amount of the ingredient or the delivery system in the 45 ple, characteristics might include one or more of the fol- compressible chewing gum, ratio of different polymers lowing: tensile strength of the delivery system, water sol- used to encapsulate one or more ingredients, hydropho- ubility of the ingredient, water solubility of the encapsu- bicity of one or more polymers used to encapsulate one lating material, water solubility of the delivery system, or more ingredients, hydrophobicity of the delivery sys- ratio of ingredient to encapsulating material in the deliv- tem, the type or amount of coating on the delivery system, 50 ery system, average or maximum particle size of ingre- the type or amount of coating on an ingredient prior to dient, average or maximum particle size of ground deliv- the ingredient being encapsulated, etc. ery system, the amount of the ingredient or the delivery [0155] In some embodiments, the release profiles of system in the compressible chewing gum, ratio of differ- one or more mouth moisteners can be managed for a ent polymers used to encapsulate one or more ingredi- compressible gum. Mouth moisteners can include, but 55 ents, hydrophobicity of one or more polymers used to are not limited to, saliva stimulators such as acids and encapsulate one or more ingredients, hydrophobicity of salts and combinations thereof. In some embodiments, the delivery system, the type or amount of coating on the acids can include acetic acid, adipic acid, ascorbic acid, delivery system, the type or amount of coating on an in-

18 35 EP 2 421 508 B1 36 gredient prior to the ingredient being encapsulated, etc. nabumetone, naproxen, piroxicam, caffeine and mix- [0156] In some embodiments, the release profiles of tures thereof. In some embodiments, local anesthetics one or more ingredients that soothe the throat can be can include, but are not limited to, lidocaine, benzocaine, managed for a compressible gum. Throat soothing in- phenol, dyclonine, benzonotate and mixtures thereof. In gredients can include analgesics, anesthetics, demul- 5 some embodiments nasal decongestants and ingredi- cents, antiseptic, and combinations thereof. In some em- ents that provide the perception of nasal clearing can be bodiments, analgesics/anesthetics can include menthol, included. In some embodiments, nasal decongestants phenol, hexylresorcinol, benzocaine, dyclonine hydro- can include but are not limited to phenylpropanolamine, chloride, benzyl alcohol, salicyl alcohol, and combina- pseudoephedrine, ephedrine, phenylephrine, oxymeta- tions thereof. In some embodiments, demulcents can in- 10 zoline, and combinations thereof. In some embodiments clude but are not limited to slippery elm bark, pectin, gel- ingredients that provide a perception of nasal clearing atin, and combinations thereof. In some embodiments, can include but are not limited to menthol, camphor, bor- antiseptic ingredients can include cetylpyridinium chlo- neol, ephedrine, eucalyptus oil, peppermint oil, methyl ride, domiphen bromide, dequalinium chloride, and com- salicylate, bornyl acetate, lavender oil, wasabi extracts, binations thereof. 15 horseradish extracts, and combinations thereof. In some [0157] In some embodiments, antitussive ingredients embodiments, a perception of nasal clearing can be pro- such as chlophedianol hydrochloride, codeine, codeine vided by odoriferous essential oils, extracts from woods, phosphate, codeine sulfate, dextromethorphan, dex- gums, flowers and other botanicals, resins, animal se- tromethorphan hydrobromide, diphenhydramine citrate, cretions, and synthetic aromatic materials. and diphenhydramine hydrochloride, and combinations 20 [0161] Typically, encapsulation of a throat care agent thereof can be included. will result in a delay in the release of the predominant [0158] In some embodiments, throat soothing agents amount of the active during consumption of a compress- such as honey, propolis, aloe vera, glycerine, menthol ible chewing gum that includes the encapsulated throat and combinations thereof can be included. In still other care agent (e.g. as part of a delivery system added as embodiments, cough suppressants can be included.25 an ingredient to the compressible chewing gum). In some Such cough suppressants can fall into two groups: those embodiments, the release profile of the ingredient (e.g. that alter the texture or production of phlegm such as the dental care active) can be managed for a compress- mucolytics and expectorants; and those that suppress ible gum by managing various characteristics of the in- the coughing reflex such as codeine (narcotic cough sup- gredient, delivery system containing the ingredient, pressants), antihistamines, dextromethorphan and iso- 30 and/or the compressible chewing gum containing the de- proterenol (non-narcotic cough suppressants). In some livery system and/or how the delivery system is made. embodiments, ingredients from either or both groups can For example, characteristics might include one or more be included. of the following: tensile strength of the delivery system, [0159] In still other embodiments, antitussives can in- water solubility of the ingredient, water solubility of the clude, but are not limited to, the group consisting of co- 35 encapsulating material, water solubility of the delivery deine, dextromethorphan, dextrorphan, diphenhy- system, ratio of ingredient to encapsulating material in dramine, hydrocodone, noscapine, oxycodone, pentox- the delivery system, average or maximum particle size yverine and combinations thereof. In some embodi- of ingredient, average or maximum particle size of ground ments, antihistamines can include, but are not limited to, delivery system, the amount of the ingredient or the de- acrivastine, azatadine, brompheniramine, chlo[phi]he- 40 livery system in the compressible chewing gum, ratio of niramine, clemastine, cyproheptadine, dexbromphe- different polymers used to encapsulate one or more in- niramine, dimenhydrinate, diphenhydramine, doxy- gredients, hydrophobicity of one or more polymers used lamine, hydroxyzine, meclizine, phenindamine, phenyl- to encapsulate one or more ingredients, hydrophobicity toloxamine, promethazine, pyrilamine, tripelennamine, of the delivery system, the type or amount of coating on triprolidine and combinations thereof. In some embodi- 45 the delivery system, the type or amount of coating on an ments, non-sedating antihistamines can include, but are ingredient prior to the ingredient being encapsulated, etc. not limited to, astemizole, cetirizine, ebastine, fexofena- [0162] In some embodiments, one or more colors can dine, loratidine, terfenadine, and combinations thereof. be included. As classified by the United States Food, [0160] In some embodiments, expectorants can in- Drug, and Cosmetic Act (21 C.F.R. 73), colors can in- clude, but are not limited to, ammonium chloride, guaife- 50 clude exempt from certification colors (sometimes re- nesin, ipecac fluid extract, potassium iodide and combi- ferred to as natural even though they can be synthetically nations thereof. In some embodiments, mucolytics can manufactured) and certified colors (sometimes referred include, but are not limited to, acetylcycsteine, ambroxol, to as artificial), or combinations thereof. In some embod- bromhexine and combinations thereof. In some embod- iments, exempt from certification or natural colors can iments, analgesic, antipyretic and anti-inflammatory55 include, but are not limited to annatto extract, (E 160b), agents can include, but are not limited to, acetami- bixin, norbixin, astaxanthin, dehydrated beets (beet pow- nophen, aspirin, diclofenac, diflunisal, etodolac, fenopro- der), beetroot red/betanin (E 162), ultramarine blue, can- fen, flurbiprofen, ibuprofen, ketoprofen, ketorolac, thaxanthin (E161g), cryptoxanthin (E161c), rubixanthin

19 37 EP 2 421 508 B1 38

(E161d), violanxanthin (E161e), rhodoxanthin (E161f), ingredient prior to the ingredient being encapsulated, etc. caramel (E150(a-d)), β-apo-8’-carotenal (E160e), β-car- [0164] In some embodiments, a delivery system or otene, (E160a), alpha carotene, gamma carotene, ethyl compressible chewing gum may include two or more in- ester of beta-apo-8 carotenal (E160f), fiavoxanthin gredients for which managed release from the compress- (E161a), lutein (E161b), cochineal extract (E120); car- 5 ible chewing gum during consumption of the compress- mine (E132), carmoisine/azorubine (E122), sodium cop- ible chewing gum is desired. In some embodiments, the per chlorophyllin (E141), chlorophyll (E140), toasted par- ingredients may be encapsulated or otherwise included tially defatted cooked cottonseed flour, ferrous gluco- separately in different delivery systems. Alternatively, in nate, ferrous lactate, grape color extract, grape skin ex- some embodiments the ingredients may be encapsulat- tract (enocianina), anthocyanins (E163), haematococ- 10 ed or otherwise included in the same delivery system. cus algae meal, synthetic iron oxide, iron oxides and hy- As another possibility, one or more of the ingredients may droxides (E172), fruit juice, vegetable juice, dried algae be free (e.g. unencapsulated) while one or more other meal, tagetes (Aztec marigold) meal and extract, carrot ingredients may be encapsulated. A compressible chew- oil, corn endosperm oil, paprika, paprika oleoresin, phaf- ing gum may include a group of ingredients for which fia yeast, riboflavin (E101), saffron, titanium dioxide, tur- 15 managed release of the group during consumption of the meric (E100), turmeric oleoresin, amaranth (E123), cap- compressible chewing gum is desired. Groups of two or santhin/capsorbin (E160c), lycopene (E160d), and com- more ingredients for which managed release from a com- binations thereof. pressible chewing gum during consumption of the com- [0163] In some embodiments, certified colors can in- pressible chewing gum may be desired include, but are clude, but are not limited to, FD&C blue #1, FD&C blue 20 not limited to: color and flavor, multiple flavors, multiple #2, FD&C green #3, FD&C red #3, FD&C red #40, FD&C colors, cooling agent and flavor, warming agent and fla- yellow #5 and FD&C yellow #6, tartrazine (E102), quin- vor, cooling agent and warming agent, cooling agent and oline yellow (E104), sunset yellow (E110), ponceau high-intensity sweetener, warming agent and high-inten- (E124), erythrosine (E127), patent blue V (E131), titani- sity sweetener, multiple cooling agents (e.g., WS-3 and um dioxide (E171), aluminum (E173), silver (E174), gold 25 WS-23, WS-3 and menthyl succinate), menthol and one (E175), pigment rubine/lithol rubine BK (E180), calcium or more cooling agents, menthol and one or more warm- carbonate(E170), carbon black (E153), blackPN/brilliant ing agents, multiple warming agents, high-intensity black BN (E151), green S/acid brilliant green BS (E142), sweetener(s) and tooth whitening active(s), high-intensi- and combinations thereof. In some embodiments, certi- ty sweetener(s) and breath-freshening active(s), an in- fied colors can include FD&C aluminum lakes. These 30 gredient with some bitterness and a bitterness suppres- consist of the aluminum salts of FD&C dyes extended on sor for the ingredient, multiple high-intensity sweeteners an insoluble substrate of alumina hydrate. Additionally, (e.g., ace-k and aspartame), multiple tooth whitening ac- in some embodiments, certified colors can be included tives (e.g., an abrasive ingredient and an antimicrobial as calcium salts. Typically, encapsulation of a color will ingredient, a peroxide and a nitrate, a warming agent and result in a delay in the release of the predominant amount 35 a polyol, a cooling agent and a polyol, multiple polyols, of the active during consumption of a compressible chew- a warming agent and micronutrient, a cooling agent and ing gum that includes the encapsulated color (e.g., as a micronutrient,a warming agent and a mouth moistening part of a delivery system added as an ingredient to the agent, a cooling agent and a mouth moistening agent, a compressible chewing gum). In some embodiments, the warming agent and a throat care agent, a cooling agent release profile of the ingredient (e.g., the color) can be 40 and a throat care agent, a warming agent and a food managed by managing various characteristics of the in- acid, a cooling agent and food acid, a warming agent and gredient, delivery system containing the ingredient, an emulsifier/surfactant, a cooling agent and an emulsi- and/or the compressible chewing gum containing the de- fier/surfactant, a warming agent and a color, a cooling livery system and/or how the delivery system is made. agent and a color, a warming agent and a flavor poten- For example, characteristics might include one or more 45 tiator, a cooling agent and a flavor potentiator, a warming of the following: tensile strength of the delivery system, agent with sweetness potentiator, a cooling agent with a water solubility of the ingredient, water solubility of the sweetness potentiator, a warming agent and an appetite encapsulating material, water solubility of the delivery suppressant, a cooling agent and an appetite suppres- system, ratio of ingredient to encapsulating material in sant, a high-intensity sweetener and a flavor, a cooling the delivery system, average or maximum particle size 50 agent and a teeth-whitening agent, a warming agent and of ingredient,average ormaximum particle size of ground a teeth-whitening agent, a warming agent and breath- delivery system, the amount of the ingredient or the de- freshening agent, a cooling agent and a breath-freshen- livery system in the compressible chewing gum, ratio of ing agent, a cooling agent and an effervescing system, different polymers used to encapsulate one or more in- a warming agent and an effervescing system, a warming gredients, hydrophobicity of one or more polymers used 55 agent and an antimicrobial agent, a cooling agent and to encapsulate one or more ingredients, hydrophobicity an antimicrobial agent, multiple anticalcums ingredients, of the delivery system, the type or amount of coating on multiple remineralization ingredients, multiple sur- the delivery system, the type or amount of coating on an factants, remineralization ingredients with demineraliza-

20 39 EP 2 421 508 B1 40 tion ingredients, acidic ingredients with acid buffering in- chewing gum, however, this list should not be considered gredients, anticalculus ingredients with antibacterial in- as exhaustive. gredients, remineralization ingredients with anticalculus [0168] Active ingredients to be applied in tablets ac- ingredients, anticalculus ingredients with remineraliza- cording to embodiments of the invention may be applied tion ingredients with antibacterial ingredients, surfactant 5 as such or be included or bonded in different ways, such ingredients with anticalculus ingredients, surfactant in- as being part of an inclusion complex e.g. as described gredients with antibacterial ingredients, surfactant ingre- in US 5,866,179. Further conventional methods of apply- dients with remineralization ingredients, surfactants with ing active ingredients may obviously be applied within anticalculus ingredients with antibacterial ingredients, the scope of the invention. multiple types of vitamins or minerals, multiple micronu- 10 [0169] The active ingredients may advantageously be trients, multiple acids, multiple antimicrobial ingredients, applied in a gum base-containing module or a tablet- multiple breath-freshening ingredients, breath-freshen- module substantially free of gum base depending on the ingingredients and antimicrobial ingredients, multipleap- applied type of active ingredient. If the active ingredient petite suppressors, acids and bases that react to effer- is of the pharmaceutical type, such ingredient may very vesce, a bittercompound with a high-intensity sweetener, 15 often advantageously be comprised in a tablet module a cooling agent and an appetite suppressant, a warming substantially free of gum base whereas taste relevant agent and an appetite suppressant, a high-intensity active ingredients advantageously may be added to the sweetener and an appetite suppressant, a high-intensity gum base-containing module and very often to both types sweetener with an acid, a probiotic ingredient and a preb- of modules. The taste relevant active ingredient may both iotic ingredient, a vitamin and a mineral, a metabolic en- 20 be added as separate particles which are mixed and com- hancement ingredient with a macronutrient, a metabolic pressed with gum base-containing particles in one mod- enhancement ingredient with a micronutrient, an enzyme ule and it may be incorporated into gum base-containing with a substrate, a high-intensity sweetener with a sweet- granules. ness potentiator, a cooling compound with a cooling po- [0170] In the present context, the terms granule and tentiator, a flavor with a flavor potentiator, a warming25 particle are used interchangeable in the sense that a compound with a warming potentiator, a flavor with salt, granule or particle for use in a compression process is a high-intensity sweetener with salt, an acid with salt, a regarded to be a relatively small object, which together cooling compound with salt, a warming compound with with other granules or particles may be compressed into salt, a flavor with a surfactant, an astringent compound a stable chewing gum tablet. The granules or particles with an ingredient to provide a sensation of hydration, 30 may be produced in several different ways. A gum base- etc. In some embodiments, the multiple ingredients may containing granule of particle may typically be produced be part of the same delivery system or may be part of substantially into the desired shape by means of an ex- different delivery systems. Different delivery systems trusion process or alternatively be produced on the basis may use the same or different encapsulating materials. of a gum base-containing mass which is subsequently [0165] Typically, encapsulation of the multiple ingredi- 35 separated into particles of a smaller size. ents will result in a delay in the release of the predominant [0171] According to the present invention the embod- amount of the multiple ingredients during consumption iments mentioned in the text above may be combined in of a compressible chewing gum that includes the encap- any order and in any sequence. Accordingly, the embod- sulated multiple ingredients (e.g. as part of a delivery imentsin thetext above should notbe read independently system added as an ingredient to the compressible chew- 40 of each other. ing gum). This may be particularly helpful in situations [0172] The following examples illustrate the present in- wherein separate encapsulation of the ingredients may vention. The examples are nonlimiting and are meant to cause them to release with different release profiles. For be examples of a particular way to carry out the invention. example, different high-intensity sweeteners may have different release profiles because they have different wa- 45 EXAMPLE 1 ter solubilities or differences in other characteristics. En- capsulating them together may cause them to release Preparation of gum base more simultaneously. [0166] In some embodiments, the release profile of the [0173] A gum base is prepared, which comprises the multiple ingredients can be managed for a compressible 50 following ingredients. gum by managing various characteristics of the multiple ingredients, the delivery system containing the multiple Ingredients Percent by weight ingredients, and/or the compressible chewing gum con- Elastomer 10 taining the delivery system and/or how the delivery sys- Natural resin 28 tem is made in a manner as previously discussed above. 55 Synthetic resin 22 [0167] The active ingredients mentioned above are meant as examples of active ingredients which could be Fat/wax/emulsifier 23 applicable in a chewing gum granule or compressed Fillers 17

21 41 EP 2 421 508 B1 42

[0174] It should be emphasized that several other gum EXAMPLE 7 base compositions may be applied within the scope of the invention. Preparation of nicotine-containing chewing gum [0175] The elastomer and filler are added to a mixing cores with flavor mixture kettle provided with mixing means like e.g. horizontally 5 placed Z-shaped arms. The kettle has been preheated [0184] Chewing gum cores are prepared by use of the for 15 minutes to a temperature of about 120°C. The rub- gum base in example 1 and according to a conventional ber is broken into small pieces and softened with me- mechanical mixing procedure during moderate use of chanical action in the kettle. heating as described below. [0176] The resin is slowly added to the elastomer until 10 the mixture becomes homogeneous. The remaining res- Gum base 57.4% in is then added to the kettle and mixed for 10-20 minutes. Filler 16.9% [0177] The softening ingredients are added and mixed Nicotine Polacrilex for 20-40 minutes until the whole mixture becomes ho- Nicotine 0.2% 15 mogeneous. Ion exchange resin 0.8% [0178] The mixture is then discharged into the pan and Buffer agents allowed to cool to room temperature from the discharged Sodiumhydrogencarbonate 1.0% temperature of 120 °C. Sodium carbonate 2.0% EXAMPLE 2 - premixture of one flavor and modified 20 Sorbitol powder 19.1% CaCO3 with 33% load Flavor mixture from example 2-4: 0,7% Liquid sweetener 1.5% [0179] 1 part by weight of cinnamon aldehyde is mixed Intense sweetener 0.4% with 2 parts by weight of natural CaCO3 modified to a surface area at apx- 40 m2/g and remain to be a non- 25 [0185] Gum base and filler are mixed in a mixing kettle stick material. provided with mixing means like e.g. horizontally placed Z-shaped arms. The kettle has been preheated to a tem- EXAMPLE 3 - premixture of one flavor and modified perature of up to approximately 50 °C. CaCO3 with 50% load 30 [0186] When the content is homogenous the other in- gredients are added according to a specified time sched- [0180] 1 part by weight of orange flavor is mixed with ule. Nicotine is added in the first half of the mixing process 1 parts by weight of natural CaCO3 modified to a surface and can be added as pure nicotine, as a nicotine salt or area at apx- 40 m2/g to form a free-flowing material. bound to an ion exchange resin, e.g. Amberlite IRP 64. [0187] The chewing gum cores may be formulated with EXAMPLE 4- premixture of 2 flavors, sucralose and 35 0.1 - 8 mg of nicotine per piece preferably 2 or 4 mg. The modified CaCO3 piecesevaluated above comprise2 mgnicotine complex. The flavormixture from example 2-4 or the like is added [0181] 1 part by weight of cinnamon aldehyde and © in the second half of the mixing process and can be added part of menthol is mixed with 2 parts by weight of natural in 1 or more steps. The stability of nicotine in the gum CaCO3 modified to a surface area at apx- 40 m2/g to 40 increased significant. form a free-flowing material. 2 parts of sucralose is added to the mixture and mixed. EXAMPLE 8 EXAMPLE 5 - premixture of 2 flavors, nicotin bound Preparation of nicotine-containing chewing gum to resin and modified CaCO3 45 cores with flavor and nicotine mixture [0182] 1 part by weight of cinnamon aldehyde and © [0188] The nicotine - mixture from example 5-6 and part of menthol is mixed with 2 parts by weight of natural flavor-mixture (from ex. 2-4) is added to the chewing gum CaCO3 modified to a surface area at apx- 40 m2/g to cores preparation as described in example 7. The stabil- form a free-flowing material. The nicotine and resin need- 50 ity of nicotine in the gum increased significant and the ed for one trial is added to the mixture and mixed. nicotine release was controlled. EXAMPLE 6 - premixture of nicotine and modified EXAMPLE 9 CaCO3 55 Coating with flavor mixture [0183] 1 part by weight of pure nicotin is mixed with 2 parts by weight of natural CaCO3 modified to a surface [0189] To a standard coating solution flavor-mixture area at apx- 40 m2/g to form a free-flowing material.

22 43 EP 2 421 508 B1 44

(from ex. 2-4) is added and the nicotine chewing gum 6. The chewing gum according to any of the preceding from ex. 7-8 are coated. The stability of the flavor and claims, wherein the inorganic mineral filler is obtain- the gum increased significant. able by pre-treatment with one or more medium- + strong to strong sources of H3O ions and/or pre- EXAMPLE 10 5 treatment with an inorganic salt, such as a magne- sium sulphate in combination with aluminium sul- Impregnation with flavor mixture phate and/or zinc sulphate, and pre-treatment with gaseous CO2, and for precipitated calcium carbon- [0190] Flavor-mixture (from ex. 2-4) is used to perform ate preferably at a CO2 gas flow rate of below 30 impregnation as described in PCT/DK2008/000196, and 10 litres per minute at standard temperature and pres- the nicotine chewing gum are then coated. The amount sure per kilogram calcium hydroxide during precipi- of flavor impregnated increased significant. tation.

Claims 15 Patentansprüche

1. A chewing gum comprising a chewing gum core with 1. Kaugummi, umfassend einen Kaugummikern mit at least one sub-layer, wherein a particulate material wenigstens einer Unterschicht, bei dem ein partiku- for controlled release of active ingredients is added läres Material für die kontrollierte Freisetzung von to said at least one sub-layer or both the sub-layer 20 Wirkstoffen zu der wenigstens einen Unterschicht and the core of the chewing gum, the particulate ma- oder sowohl der Unterschicht als auch dem Kern des terial comprising a combination of one or more active Kaugummis zugegeben ist, wobei das partikuläre ingredients, excluding nicotine, and an inorganic Material eine Kombination von einem oder mehreren mineral filler comprising natural calcium carbonate Wirkstoffen, ausgenommen Nikotin, und einem an- and/or precipitated calcium carbonate, where the in- 25 organischen Mineralfüllstoff, der natürliches Calci- organic mineral filler is obtainable by pre-treatment umcarbonat und/oder gefälltes Calciumcarbonat with one or more medium-strong to strong sources umfasst, umfasst, wobei der anorganische Mineral- + of H3O ions and/or pre-treatment with an inorganic füllstoff erhältlich ist durch Vorbehandlung mit einer salt, and pre-treatment with gaseous CO2, wherein oder mehreren mittelstarken bis starken Quellen von 30 + the active ingredient is reversibly absorbed into H3O -Ionen und/oder durch Vorbehandlung mit ei- and/or adsorbed onto the inorganic mineral filler, nem anorganischen Salz, und durch Vorbehandlung wherein the BET specific surface area of the inor- mit gasförmigem CO2, bei dem der Wirkstoff in den ganic mineral filler is above 15 m 2/g, the BET specific anorganischen Mineralfüllstoff reversibel absorbiert surface area measured in accordance with ISO 9277 und/oder auf den anorganischen Mineralfüllstoff re- and wherein the at least one sub-layer is between 35 versibel adsorbiert ist, bei dem die BET spezifische the chewing gum core and an outer coating Oberfläche des anorganischen Mineralfüllstoffs über 15 m2/g beträgt, wobei die BET spezifische 2. The chewing gum according to claim 1, wherein the Oberfläche in Übereinstimmung mit ISO 9277 ge- active ingredient is a flavoring agent. messen wurde, und bei dem die wenigstens eine 40 Unterschicht zwischen dem Kaugummikern und ei- 3. The chewing gum according to any of the preceding ner äusseren Beschichtung ist. claims, wherein the average grain diameter of the inorganic mineral filler is between 50 and 0.1 mi- 2. Kaugummi nach Anspruch 1, bei dem der Wirkstoff crons. ein Aromastoff ist. 45 4. The chewing gum according to any of the preceding 3. Kaugummi nach einem der vorhergehenden An- claims, wherein the weight of the dried inorganic min- sprüche, bei dem der mittlere Korndurchmesser des eral filler is increased by at least 1 % by weight at a anorganischen Mineralfüllstoffs zwischen 50 und 0,1 relative humidity of 95 % at 25 degree Celcius com- Mikrometern liegt. pared to a relative humidity of 0%. 50 4. Kaugummi nach einem der vorhergehenden An- 5. The chewing gum according to any of the preceding sprüche, bei dem das Gewicht des getrockneten an- claims, wherein the powder flow of the particulate organischen Mineralfüllstoffs um wenigstens 1 material is higher than the powder flow of particulate Gew.-% erhöht ist, bei einer relativen Feuchtigkeit material with a BET specific surface area of inorganic 55 von 95 % bei 25°C, verglichen mit einer relativen mineral filler below 15 m 2/g, the BET specific surface Feuchtigkeit von 0 %. area measured in accordance with ISO 9277. 5. Kaugummi nach einem der vorhergehenden An-

23 45 EP 2 421 508 B1 46

sprüche, bei dem die Pulverfliessfähigkeit des par- vendications précédentes, dans laquelle le poids de tikulären Materials höher ist als die Pulverfliessfä- la matière minérale inorganique sèche est augmenté higkeit von partikulärem Material mit einer BET spe- par au moins 1 % en poids à une humidité relative zifischen Oberfläche von anorganischem Mineral- de 95 % à 25 °C comparativement à une humidité füllstoff unter 15 m2/g, wobei die BET spezifische 5 relative de 0 %. Oberfläche in Übereinstimmung mit ISO 9277 ge- messen wurde. 5. Gomme à mâcher selon l’une quelconque des re- vendications précédentes, dans laquelle l’écoule- 6. Kaugummi nach einem der vorhergehenden An- ment de la poudre de la matière particulaire est su- sprüche, bei dem der anorganische Mineralfüllstoff 10 périeure à l’écoulement de la poudre de la matière erhältlich ist durch Vorbehandlung mit einer oder particulaire ayant une surface spécifique BET de la mehreren mittelstarken bis starken Quellen von charge minérale inorganique inférieure à 15 m 2/g, la + H3O -Ionen und/oder durch Vorbehandlung mit ei- surface spécifique BET étant mesurée conformé- nem anorganischen Salz, wie einem Magnesiumsul- ment à la norme ISO 9277. fat in Kombination mit Aluminiumsulfat und/oder15 Zinksulfat, und durch Vorbehandlung mit gasförmi- 6. Gomme à mâcher selon l’une quelconque des re-

gem CO2, und für gefälltes Calciumcarbonat bevor- vendications précédentes, dans laquelle la charge zugt bei einer CO2-Gasdurchflussmenge von unter minérale inorganique peut être obtenue par prétrai- 30 Litern pro Minute bei Standardtemperatur und tement avec une ou plusieurs sources moyenne- 20 + -druck pro Kilogramm Calciumhydroxid während der ment fortes à fortes d’ions H 3O et/ou prétraitement Ausfällung. avec un sel inorganique, tel qu’un sulfate de magné- sium en combinaison avec du sulfate d’aluminium et/ou du sulfate de zinc, et prétraitement avec du

Revendications CO2 gazeux, et pour du carbonate de calcium pré- 25 cipité de préférence à un débit de CO 2 gazeux infé- 1. Gomme à mâcher, comprenant un coeur de gomme rieur à 30 litres par minute à une température et une à mâcher avec au moins une sous-couche, dans la- pression standard par kilogramme d’hydroxyde de quelle une matière particulaire pour la libération con- calcium pendant la précipitation. trôlée des principes actifs est ajoutée à ladite sous- couche ou à la fois à la sous-couche et au coeur de 30 la gomme à mâcher, la matière particulaire compre- nant une combinaison d’un ou plusieurs principes actifs, à l’exclusion de la nicotine, et une charge mi- nérale inorganique comprenant du carbonate de cal- cium naturel et/ou du carbonate de calcium précipité, 35 où la charge minérale inorganique peut être obtenue par prétraitement avec une ou plusieurs sources + moyennement fortes à fortes d’ions H 3O et/ou pré- traitement avec un sel inorganique, et prétraitement 40 avec du CO2 gazeux, dans laquelle le principe actif est réversiblement absorbé et/ou adsorbé sur de la charge minérale inorganique, dans laquelle la sur- face spécifique BET de la charge minérale inorga- nique est supérieure à 15 m 2/g, la surface spécifique BET étant mesurée conformément à la norme ISO 45 9277 et dans laquelle la sous-couche se trouve com- prise entre le coeur de la gomme à mâcher et un revêtement extérieur.

2. Gomme à mâcher selon la revendication 1, dans la- 50 quelle le principe actif est un agent aromatisant.

3. Gomme à mâcher selon l’une quelconque des re- vendications précédentes, dans laquelle le diamètre de grain moyen de la charge minérale inorganique 55 est compris entre 50 et 0,1 mm.

4. Gomme à mâcher selon l’une quelconque des re-

24 EP 2 421 508 B1

REFERENCES CITED IN THE DESCRIPTION

This list of references cited by the applicant is for the reader’s convenience only. It does not form part of the European patent document. Even though great care has been taken in compiling the references, errors or omissions cannot be excluded and the EPO disclaims all liability in this regard.

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