US 2009016.9677A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2009/0169677 A1 Wittorff et al. (43) Pub. Date: Jul. 2, 2009

(54) CHEWING GUM COMPRISINGA Publication Classification HYDROPHOBC ENZYME FORMULATION (51) Int. Cl. (76) Inventors: Helle Wittorff, Vejle Øst A23G 4/12 (2006.01) (DK); Jesper Neergaard, Å:rhus (DK) (52) U.S. Cl...... 426/5: 426/3 Correspondence Address: FROST BROWN TODD, LLC (57) ABSTRACT 2200 PNCCENTER, 201 E. FIFTH STREET A chewing gum comprising at least one biodegradable poly CINCINNATI, OH 45202 (US) mer, sweetener in an amount from about 0.5% to about 95% of said chewing gum, one or more flavoring agents, filler in an (21) Appl. No.: 12/304,656 amount from about 0 to 50% by weight of said chewing gum, further chewing gum ingredients and at least one enzyme, (22) PCT Fled: Jun. 16, 2006 wherein said at least one enzyme is comprised in a hydropho bic enzyme formulation. According to the invention, it has (86) PCT NO.: PCT/DKO6/OO349 been established that an enzymatically activated degradation may by obtained when applying a hydrophobic enzyme for S371 (c)(1), mulation even though the hydrophobic enzyme formulation, (2), (4) Date: Dec. 12, 2008 e.g. when applying a dispersion of Substantially hydrophilic (30) Foreign Application Priority Data enzymes in a hydrophobic medium such as oil, might be Suspected to have a negative influence on the functionality of Jul. 6, 2006 (US) ...... 60818829 the enzymes at the active sites of the applied enzyme. Patent Application Publication Jul. 2, 2009 US 2009/016.9677 A1

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CHEWING GUM COMPRISINGA during the chewing process as it migrates into the saliva and HYDROPHOBC ENZYME FORMULATION further on to the stomach of the consumer. SUMMARY OF THE INVENTION FIELD OF THE INVENTION 0009. The invention relates to a chewing gum comprising 0001. The invention relates to a chewing gum according to at least one biodegradable polymer, Sweetener in an amount claim 1. from about 0.5% to about 95% of said chewing gum, one or more flavoring agents, fillers in an amount from about 0 to 50% by weight of said chewing gum, further chewing gum BACKGROUND ingredients and at least one enzyme, wherein said at least one enzyme is comprised in a hydrophobic enzyme formulation. 0002. It is generally recognized that chewing gum that is 0010. According to the invention, it has been established dropped in indoor or outdoor environments gives rise to con that an enzymatically activated degradation may by obtained siderable nuisances and inconveniences due to the fact that when applying a hydrophobic enzyme formulation even the dropped gum Sticks firmly to e.g. Street and pavement though the hydrophobic enzyme formulation, e.g. when Surfaces and to shoes and clothes of people being present or applying a dispersion of Substantially hydrophilic enzymes in moving in the environments. Adding Substantially to Such a hydrophobic medium Such as oil, might be suspected to nuisances and inconveniences is the fact that currently avail have a negative influence on the functionality of the enzymes able chewing gum products are based on the use of elasto at the active sites of the applied enzyme. meric and resinous polymers of natural or synthetic origin 0011. This effect has also surprisingly been obtained even that are Substantially non-degradable in the environment. during degradation tests where the desired degradation was 0003 City authorities and others being responsible for obtained through hydrolysis. 0012. According to the invention, several different cleanliness of indoor and outdoor environments therefore examples of hydrophobic enzyme formulations have been have to exercise considerable efforts to remove dropped provided. chewing gum, Such efforts, however, being both costly and 0013. A further advantageous feature of the invention is without satisfactory results. that the predegradation may be minimized due to the fact that 0004 Attempts have been made to reduce the nuisances the enzyme(s) in the chewing gum may be relatively well associated with the Widespread use of chewing gum, e.g. by isolated from moisture prior to chewing. improving cleaning methods to make them more effective 0014. In an embodiment of the invention said hydrophobic with regard to removal of dropped chewing gum remnants or enzyme formulation comprises at least one hydrophobic by incorporating anti-sticking agents into chewing gum for enzyme. mulations. However, none of these precautions have contrib 0015. In an embodiment of the invention said hydrophobic uted significantly to Solving the pollution problem. enzyme formulation comprises at least one enzyme at least partly encapsulated by a hydrophobic encapsulation. 0005. The past two decades have seen an increasing 0016. In an embodiment of the invention said hydrophobic amount of interest paid to synthetic polyesters for a variety of enzyme formulation comprises at least one enzyme dispersed applications ranging from biomedical devices to gum bases. in an anhydrous dispersion medium. Many of these polymers are readily hydrolyzed to their mono 0017. According to en embodiment of the invention, the meric hydroxy-acids, which are easily removed by metabolic dispersion media may preferably comprise a hydrophobic pathways. Biodegradable polymers are e.g. anticipated as dispersion medium. It should however be noted that hydro alternatives to traditional non- or low-degradable plastics phobic formulation also may be obtained e.g. by means of an Such as poly(styrene), poly(isobutylene), and poly(methyl initial step of dissolving the enzyme(s) in a hydrophilic methacrylate). medium, e.g. water, and then, Subsequently dispersing this 0006 Thus, it has recently been disclosed, e.g. in U.S. Pat. pre-solution into a hydrophobic medium, Evidently, several No. 5,672.367, that chewing gum may be made from certain other applicable methods and formulations may be applied synthetic polymers having in their polymerchains chemically for the purpose of obtaining a hydrophobically invoked bind unstable bonds that can be broken under the influence of light ing of enzyme(s) to at least one of the gum base polymers. or hydrolytically into water-soluble and non-toxic compo 0018. In an embodiment of the invention said hydrophobic nents. The claimed chewing gum comprises at least one enzyme formulation comprises at least one enzyme dispersed degradable polyester polymer obtained by the polymerization in a hydrophobic medium. of cyclic esters, e.g. based on lactides, glycolides, trimethyl 0019. An applicable anhydrous medium may e.g. com prise oil or other suitable lipophilic solvents. ene carbonate and e-caprolactone. It is mentioned in this 0020. In an embodiment of the invention said hydrophobic patent application that chewing gum made from Such poly enzyme formulation comprises at least one enzyme adsorbed mers that are referred to as biodegradable are degradable in to a hydrophobic carrier. the environment. 0021. In an embodiment of the invention said hydrophobic 0007. A problem related to the prior art is, however, that enzyme formulation comprises at least one hydrophilic even biodegradable chewing gum may under certain circum enzyme. stances inherit unsatisfying degradability rates. 0022. In an embodiment of the invention said hydrophobic 0008. A chewing gum comprising enzyme in order to enzyme formulation comprises at least one modified enzyme. increase degradability rates for the chewing gum is known 0023 The at least one modified enzyme may be modified e.g. from WO 2005/063037. A problem related to this is that in many different ways. Examples, which are meant to be a rather high percentage of the employed enzyme is lost exemplifying and not limiting are: chemically modified, US 2009/O 169677 A1 Jul. 2, 2009

genetically modified, phosphorylated, a Zymogen, a proen 0033. In an embodiment of the invention said release con Zyme (a non-activated enzyme which upon cleavage of a trol is provided by encapsulating said enzyme within a hydro certain C-terminal or N-terminal peptide sequence will be phobic material. activated), etc. 0034 Methods of encapsulating Substances, e.g. enzyme, 0024. In an embodiment of the invention said chewing within hydrophobic materials are well described in the prior gum comprises at least one biodegradable polymer, Sweet art, as the present problem has been known for a long time. ener in an amount from about 0.5% to about 95% of said However the use of these methods in a chewing gum has never chewing gum, been seen. As examples we will mention EP 0 238 216 and one or more flavoring agents, filler in an amount from about 0 U.S. Pat. No. 5,846,927, hereby incorporated by reference, to 50% by weight of said chewing gum, further chewing gum wherein the encapsulating is employed in another context, but ingredients and at least one enzyme, wherein said at least one nevertheless they are applicable in chewing gums as well, enzyme is release controlled by a hydrophobic enzyme for when applying non-toxic hydrophobic materials. mulation. 0035. In an embodiment of the invention said release con 0025. The use of hydrophilic enzymes in prior art has trol is provided by encapsulating said enzyme within a hydro proven to result in a relative large migration of enzyme from phobic polymer. the chewing gum into the saliva during chewing due to the 0036. In an embodiment of the invention said release con hydrophilicity of the enzyme. trol is provided by encapsulating said enzyme within a wax. 0026. One aspect of the invention is that the use of a 0037. In an embodiment of the invention said release con hydrophobic enzyme formulation in the chewing gum trol is provided by encapsulating said enzyme within a fat. enzymes may result in a reduced release of enzymes from a 0038. In an embodiment of the invention said release con chewing gum during chewing and at the same time obtain a trol is provided by keeping said enzyme withina hydrophobic reasonable degradation of the chewing gum during and of dispersion. course Subsequent to the chewing process even in spite of the 0039. In an embodiment of the invention said hydrophobic fact that a hydrophobic formulation could have denatured or dispersion is an oil dispersion. at least reduced the effect of the enzyme for several different 0040. By keeping said enzyme as a dispersion within a CaSOS. hydrophobic solution, which typically would be an oil dis 0027. It has thus been established that the chewing of a persion, a hydrophobic enzyme formulation is obtained. This chewing gum, comprising enzymatically catalyzable gum method for obtaining a hydrophobic enzyme formulation is base polymers and furthermore comprising the hydrophobic advantageous due to the very straightforward procedure of formulated enzymes according to the provisions of the inven mixing of enzyme with the oil dispersion. tion, may result in the an improved degradation, even with 0041 U.S. Pat. No. 4,849,357, hereafter incorporated by respect to enzymes, e.g. Trypsin, already known to be suitable reference, describes one method for modifying a hydrophilic for triggering of degradation in a biodegradable chewing enzyme to impart hydrophobic characteristics. In this method gun. the enzyme is mixed with one or more water-insoluble fatty 0028. This feature may among other facts relate to the fact acid metal salts in the presence of an organic solvent whereby, that enzymes of the chewing gum are attached or bonded to upon removal of the organic solvent, the fatty acid acts as a the gum base by using hydrophobic enzymes or increasing hydrophobic carrier for the enzyme. the resulting hydrophobicity of the enzymes relevant. Hence 0042. In an embodiment of the invention said release con even when applying a relative high initial amount of enzyme trol is provided by adding to said enzyme a part making it within the chewing gum it may be necessary to ensure a hydrophobic. Sufficient remaining concentration of enzyme after chewing 0043. Another method known to the person skilled in the in order to degrade the chewing gum. This initial amount of art is to bond polyethylene glycol on the surface of the enzyme may be avoided or at least reduced by the use of at enzyme with a covalent bond. least one enzyme being release controlled by being incorpo 0044) Further methods of making at least a part of said rated in a hydrophobic formulation according to the inven enzyme hydrophobic are present and the methods described tion. herein are meantas non-limitative examples of suitable meth 0029 Biodegradable polymers in prior art are typically ods. more hydrophilic than conventional polymers, yet still hydro 0045. In an embodiment of the invention said hydrophobic phobic. Hence by applying a hydrophobic enzyme it is enzyme formulation is obtained by employing a predomi achieved that the enzyme is more strongly connected to the nantly hydrophobic enzyme. gum base than for equivalent hydrophilic enzymes. 0046 According to the invention a hydrophobic enzyme 0030 Hydrophobic enzyme formulation designates that formulation may advantageously be found by employing an the applied enzyme is formulated hydrophobically in the enzyme which by itselfhas the desired characteristics, e.g. the sense that the enzyme is associated to hydrophobic parts employed enzyme is a hydrophobic enzyme. mechanically of chemically. 0047. In an embodiment of the invention said at least one 0031 When obtaining even a minor increased hydropho enzyme is activated when, during chewing, contact is made bicity by means of release-controlling a hydrophilic enzyme between said enzyme, said at least one biodegradable poly by a hydrophobic enzyme formulation, an advantageous fea mer and water. ture by the present invention is obtained. 0048. According to an embodiment of the invention said 0032. According to the invention an object is to employ a enzyme is, by means of any of the above methods, kept hydrophobic enzyme formulation and in Some cases even adequately separated from said at least one biodegradable obtain a resulting improved degradation of the at least one polymer prior to chewing to keep degradation of said chewing biodegradable gum base polymer. gum in hold until chewing. US 2009/O 169677 A1 Jul. 2, 2009

0049. In an embodiment of the invention said at least one 0066. According to an embodiment of the invention the enzyme is activated when, during chewing, contact is made employed enzyme has optimal activity around the typical between said enzyme, said at least one biodegradable poly temperatures of human saliva, i.e. 32°C. to 35°C., whereby mer, water and at least one second enzyme present in the oral a beginning degradation of the chewing gum has the best cavity. possible conditions during the time when chewing the chew 0050. In an embodiment of the invention the water content ing gum. of said chewing gum is below 5% by weight of said chewing 0067. In an embodiment of the invention at least two gun. enzymes having different temperature optimums are applied 0051 Prior to chewing of the chewing gum it is important at the same time. to keep the water content low in any of the separate ingredi 0068 According to an embodiment of the invention a ents in the chewing gum to prevent the chewing gum from number of enzymes with different temperature optimums degrading e.g. a hydrolytically degradation catalyzed by may be applied, e.g. one enzyme having an optimum at the hydrolase enzymes. typical temperature of human saliva and another enzyme 0.052. In an embodiment of the invention the water content having an optimum at e.g. an average outdoor temperature for of said chewing gum is below 2% by weight of said chewing the location for selling. gun. 0069. In an embodiment of the invention said at least one 0053 According to the invention preferably the water con enzyme is selected from the group consisting of oxidoreduc tent as a whole of all ingredients present should be low in tases, transferases, hydrolases, lyases, isomerases and order to minimize the risk of water establishing contact to a ligases. hydrophilic enzyme within said hydrophobic enzyme formu 0070. In an embodiment of the invention said chewing lation prior to chewing. gum comprises a buffering system. 0054. In an embodiment of the invention said at least one 0071. According to an embodiment of the invention a buff biodegradable polymer comprises synthetic biodegradable ering system may provide a predefined pH-value in the chew polymers and/or natural biodegradable polymers. ing gum in order to obtain and maintain the desired condi 0055. In an embodiment of the invention said at least one tions. biodegradable polymer comprises a polyester. 0072. In an embodiment of the invention said buffering 0056. In an embodiment of the invention at least one of system provides a pH-value above 5.5. said synthetic biodegradable polymers is selected from the group consisting of cellulose derivatives such as cellulose (0073 Preferably it should be ensured that the pH-value ether, cellulose ester or cellulose co-esters, aliphatic polyes within the mouth of the consumer during chewing is kept ters such as poly lactic acid, polyhydroxybutyric acid, hydro above 5.5 due to risk of damaging the teeth. phobic proteins such as Zein and any combination thereof. 0074. In an embodiment of the invention said chewing 0057. In an embodiment of the invention at least one of gum is centerfilled. said biodegradable polymers is selected from the group con 0075. In an embodiment of the invention said chewing sisting of polypeptides Such as collagen and gelatin: gum is formed by compression. polyamino acids Such as poly-L-glutamic acid and poly-L- 0076. In an embodiment of the invention said fillers com lysine; polysaccharides Such as alginic acid, chitin or any prise hydrophilic fillers. combination thereof. 0077. Typically gum bases are inherently hydrophobic 0.058. In an embodiment of the invention said at least one and it may be difficult to contact gum base-incorporated enzyme is immobilized by an enzyme carrier. enzyme with water. This problem may be solved by means of 0059. According to the invention an enzyme carrier may enhancing the hydration of the gum base when the chewing aid to immobilize said at least one enzyme, whereby an even gum is chewed. Such means could e.g. be incorporation of lesser amount of enzyme is lost during chewing. hydrophilic or hygroscopic fillers, emulsifiers, or Sweeteners 0060. In an embodiment of the invention the amount of etc. which promote the absorption of water into the gum base. said enzyme carrier in the chewing gum Subsequent to chew 0078. In an embodiment of the invention said hydrophilic ing in about five minutes is above 10% of the initial amount of fillers are selected from the group consisting of ground lime said enzyme carrier. stone, calcium carbonate, magnesium silicate, starch, alumi 0061. In an embodiment of the invention the amount of num silicate, talc, mono-, di- and tri-calcium phosphate, cel said at least one enzyme in the chewing gum Subsequent to lulose polymers and combinations thereof. chewing in about five minutes is above 10% of the initial 0079. In an embodiment of the invention said chewing amount of said at least one enzyme. gum comprises filler in an amount of about 1 to about 50% by 0062. In an embodiment of the invention the chewing of weight of the chewing gum, more typically about 10 to about said chewing gum facilitates said at least one enzyme to 40% by weight of the chewing gum. initiate the degradation of said at least one biodegradable 0080. In an embodiment of the invention said chewing polymer gum comprises active ingredients. 0063. In an embodiment of the invention said at least one I0081. Some suitable active ingredients are disclosed in the enzyme has a temperature optimum in an interval between 0° detailed description. C. and 80°C., preferably between 15° C. and 55° C. 0082 In an embodiment of the invention said Sweetener 0064. In an embodiment of the invention said at least one comprises bulk Sweeteners. enzyme has a temperature optimum in an interval between I0083) Suitable bulk sweeteners include both sugar and 30° C. and 37° C., preferably 32° C. and 35° C. non-Sugar Sweetening components. Bulk Sweeteners typi 0065. In an embodiment of the invention the temperature cally constitute from about 5 to about 95% by weight of the range between 32°C. and 35°C. is within the range of optimal chewing gum, more typically about 20 to about 80% by activity of the enzyme. weight such as 30 to 60% by weight of the chewing gum. US 2009/O 169677 A1 Jul. 2, 2009

0084. In an embodiment of the invention said Sweetener control of release during chewing is obtained through adding comprises high-intensity Sweeteners. of hydrophobic enzyme formulation to the chewing gum. 0085 Suitable high intensity sweeteners include those 0104 Moreover the invention relates to the use of a hydro mentioned in the detailed description. In different embodi phobic enzyme formulation for the purpose of delaying or ments according to the present invention, the chewing gum minimizing release of enzyme from a chewing gum during typically comprises high intensity Sweeteners in an amount of chewing about 0 to about 1.2%, preferably about 0.1 to about 0.6% by weight of the chewing gum. THE DRAWINGS I0086. In an embodiment of the invention said chewing gum comprises flavor. 0105. The invention will now be described with reference 0087. In an embodiment of the invention said chewing to the drawings of which gum comprises at least one coloring agent. 0106 FIG. 1a and FIG. 1b illustrate the degradation pro 0088. In an embodiment of the invention said chewing cess when applying a hydrophobic enzyme formulation gum comprises a coating. according to an embodiment of the invention. 0089. In an embodiment of the invention said chewing gum comprises softeners. DETAILED DESCRIPTION 0090 Advantageously the softeners present are hydro philic and hence capable of absorbing moisture from the 0107. In the prior art enzymes have been incorporated in chewing gum. chewing gum for the purpose of obtaining an accelerated degradation of biodegradable gum base polymers. This tech 0091 Softeners may according to the invention be added nique has proved to be very promising. A problem related to both in the chewing gum and the gum base. the prior art enzymes is however that the enzymes tend to be 0092. In an embodiment of the invention said softeners are released from the chewing gum faster than desired. Such too selected from the group consisting of glycerol monostearate, fast release of enzymes results in at least two drawbacks glycerol triacetate, lecithin, mono-, and diglycerides, short relevant for the cost efficiency and application of the final and medium chain triglycerides, acetylated monoglycerides, chewing gum, namely that Substantial amount of enzymes and combinations thereof. ends in the mouth of the user, thereby reducing the number of 0093. In an embodiment of the invention at least one of applicable enzymes with respect to legalization and moreover said at least one biodegradable polymer comprises at least one that a release of Such as a Substantial amount of the chewing biodegradable elastomer. gum incorporated enzymes results in that the enzymes, con 0094. In an embodiment of the invention at least one of sequently, looses influence on the degradation process, as a said at least one biodegradable polymer comprises at least one Substantial part of the degradation process takes effect after biodegradable elastomer plasticizer. Such release. 0.095. In an embodiment of the invention at least one of 0108. According to the invention it has been established said at least one biodegradable polymer comprises at least one that prior art enzymes are Substantially hydrophilic and that synthetic polymer. this hydrophilicity results in that the enzymes releases from 0096. In an embodiment of the invention at least one of the chewing gum too fast during chewing. said at least one biodegradable polymer comprises at least one 0109. It has however been established that such release polyester polymer obtained by polymerization of at least one may be reduced by applying a hydrophobic formulation of the cyclic ester. enzyme(s) to be used in the chewing gum and the present 0097. In an embodiment of the invention at least one of invention relates to chewing gum comprising biodegradable said at least one biodegradable polymer comprises at least one polymers, chewing gum ingredients and a release-controlling polyester polymer obtained by polymerization of at least one hydrophobic enzyme formulation. By these means a chewing alcohol orderivative thereofand at least one acid orderivative gum may be provided, wherein the polymers constitute Sub thereof. strates for the hydrophobic enzyme formulation and conse 0098. In an embodiment of the invention at least one of quently are at least partly degraded. said at least one biodegradable polymer comprises at least one 0110. As explained in the application, different methods polyester obtained by polymerization of at least one com may be applied for obtaining release-control of enzymes by pound selected from the group of cyclic esters, alcohols or using a hydrophobic enzyme formulation. These methods derivatives thereof and carboxylic acids or derivatives may both involve a modification of enzymes or enzyme prod thereof. ucts used in the chewing gum or, evidently, choosing enzymes 0099. In an embodiment of the invention said at least one which are hydrophobic or at least more hydrophobic than the biodegradable polyester is produced by condensation. usually applied enzymes. 0100. In an embodiment of the invention said at least one 0111 Hence, as disclosed below, an enzyme formulation biodegradable polyester is produced by ring-opening. may relate both to the chemical nature of the enzymes perse 0101. In an embodiment of the invention said hydrophobic orrelate to a more physical nature of enzyme e.g. when mixed enzyme formulation is at least partly comprised in the chew with carriers, encapsulation, etc. Hence when it is stated that ing gum. a hydrophobic enzyme formulation is capable of degrading or 0102. In an embodiment of the invention said hydrophobic facilitating degradation of the degradable polymers it is the enzyme formulation is at least partly comprised in a coating enzyme, which is naturally a part of the hydrophobic enzyme provided to the chewing gum. formulation, which is capable of degrading the degradable 0103 Moreover the invention relates to a method of polymers. release controlling at least one enzyme in a chewing gum 0112. As explained below, it is well-known that enzymes comprising at least one biodegradable polymer, whereby the may enhance degradation of gum base polymers. US 2009/O 169677 A1 Jul. 2, 2009

0113. It is typically noted that the polymers of interest disintegrated to lumps or particles, which are no longer rec with respect to degradation relates to the typical gum base ognizable as being chewing gum remnants. The degradation polymers, such as resins or elastomers. Such polymers may or disintegration of Such degradable polymers may be both be synthetic or natural although synthetic polymers may effected or induced by physical factors such as temperature, be preferred in certain contexts. light, moisture, etc., by chemical factors such as oxidative 0114. According to the invention it has been noted that the conditions, pH, hydrolysis, etc. or by biological factors such release of enzyme may be reduced by a hydrophobic formu as microorganisms and/or enzymes. The degradation prod lation of the enzyme, e.g. by means of a simple encapsulation ucts may be larger oligomers, trimers, dimers and monomers. in fat, and it has moreover been Surprisingly noted that the use I0123 Preferably, the ultimate degradation products are of a hydrophobic formulation of the enzyme does not neces Small inorganic compounds such as carbon dioxide, nitrogen sarily result in a reduced effective degradation even in a oxides, methane, ammonia, water, etc. context where the desired degradation is established at least 0.124. In some useful embodiments all of the polymer partly by hydrolysis and where the applied enzyme(s) is/are components of the gum base are environmentally or biologi applied for the purpose of improving Such hydrolysis. cally degradable polymers. It is typically noted that the poly 0115 This particular effect will be explained and illus mers of interest with respect to degradation relates to the trated by the below examples. typical gum base polymers. Such as resins or elastomers. Such 0116. Initially, a short explanation will be given with polymers may both be synthetic or natural. respect to the intended effect of enzymes in chewing gum. 0.125. Two further aspects of the invention will now 0117 Evidently, enzymes used for enhancement of deg shortly be summarized. A first aspect according to an embodi radation relates to chewing gum where the gum base poly ment of the invention is to address the possibility of increas mers, i.e. elastomer and resins are biodegradable, and where ing the degradability of a biodegradable chewing gum applied the enzymes result in increased polymer degradation with in a chewing gum having a polymer matrix solely or partly respect to rate and extent of degradation as compared to comprising biodegradable polymers. A second quite different non-enzymatic degradation. aspect is rather to facilitate use of conventional polymers or 0118. It is realized that use of enzymes for the purpose of biodegradable polymers, which without any catalyzing chewing gum polymer degradation may advantageously enzyme is less suitable for the application with respect to, for facilitate the possibility to include polymers that under nor example, degradation rate. mal circumstances are regarded as having a limited biode I0126. In short, those and further aspects are obtained by gradability and therefore to some extent are avoided in bio applying hydrophobically formulated enzymes in chewing degradable chewing gum compositions. The favorable gum as degradation triggers and catalysts. In others words, influence on the desired texture that these polymers may have according to the invention, at least one biodegradable poly may due to the use of enzymes be obtained without compro mer of a chewing gum forms a Substrate paired with a suitable mising the chewing gum degradability. hydrophobically formulated enzyme. Several different crite 0119. In an embodiment of the invention, degradation of a ria must be considered when determining which enzymes biodegradable polymer is improved and/or accelerated when should be paired with which polymers, by which processes, applied under environmental conditions under which biodeg what type of hydrophobic formulation results in the desired radation would not occur untriggered. chewing gum, the intended degradation, etc. 0120 If chewing gum is disposed in dirt in outdoor envi I0127. In the present context the term enzyme is used in ronments, there are a lot of chemical, physical and biological the same sense as it is used within the arts of biochemistry and factors, whereby degradation of biodegradable polymers is molecular biology. Enzymes are biological catalysts, typi facilitated. But falling on for example pavements or indoors cally proteins, but non-proteins with enzymatic properties the chewing gum may not meet the required circumstances have been discovered. Enzymes originate from living organ for degradation. In that case even biodegradable chewing isms where they act as catalysts and thereby regulate the rate gum may be of inconvenience. A solution according to the at which chemical reactions proceed without themselves present invention facilitates acceleration of the degradation in being altered in the process. The biological processes that environments, where the conditions are only slightly degrad occur within all living organisms are chemical processes, and ing. The presence of enzymes makes the degradation process enzymes regulate most of them. Without enzymes, many of progress faster than if the only influences are physical- and/or these reactions would not take place at a perceptible rate. chemical factors in the Surroundings. Enzymes catalyze all aspects of cell metabolism. This 0121 According to a preferred definition of biodegrad includes the conservation and transformation of chemical ability according to the invention, biodegradability is a prop energy, the construction of cellular macromolecules from erty of certain organic molecules whereby, when exposed to Smaller precursors and the digestion of food, in which large the natural environment or placed within a living organism, nutrient molecules such as proteins, carbohydrates, and fats they react through an enzymatic or microbial process, often in are broken down into Smaller molecules. combination with a chemical process Such as hydrolysis, to I0128 Generally enzymes have valuable industrial and form simpler compounds, and ultimately carbon dioxide, medical applications. The fermenting of wine, leavening of nitrogen oxides, methane, water and the like. bread, curdling of cheese, and brewing of beer have been 0122. In the present context the term biodegradable poly practiced from earliest times, but not until the 19th century mers’ means environmentally or biologically degradable were these reactions understood to be the result of the cata polymer compounds and refers to chewing gum base compo lytic activity of enzymes. Since then, enzymes have assumed nents which, after dumping the chewing gum, are capable of an increasing importance in industrial processes that involve undergoing a physical, chemical and/or biological degrada organic chemical reactions. The investigations and develop tion whereby the dumped chewing gum waste becomes more ing of enzymes are still on going and new applications of readily removable from the site of dumping or is eventually enzymes are discovered. Synthetic polymers are often US 2009/O 169677 A1 Jul. 2, 2009 regarded as hardly degradable by enzymes and theories inactive by varying pH, temperature, solvent, etc. Yet some explaining this phenomenon have been proposed suggesting enzymes require co-enzymes or other co-factors to be present that enzymes tend to attack chain ends and that chain ends of in order to be effective, in some cases forming association man-made polymers tend to be deep in the polymer matrix. complexes in which a co-enzyme acts as a donor or acceptor However, experiments according to the present invention Sur for a specific group. Some times enzymes may be specified as prisingly showed that the effect of adding enzymes in chew endo-enzymes or exo-enzymes, thereby referring to their ing gum apparently was that the polymers of the chewing gum mode of action. According to this terminology exo-enzymes experienced more degradation. may successively attack chain ends of polymer molecules and 0129. Enzymes are proteins which catalyze a wide variety thereby for instance liberate terminal residues or single units, of chemical reactions, many of great commercial importance. whereas endo-enzymes may attack mid-chain and act on inte Enzymes are generally classified according to the type of rior bonds within the polymer molecules, thereby cleaving reaction which they catalyze, e.g., hydrolases are enzymes larger molecules to Smaller molecules. Generally enzymes that catalyze the addition of the elements of water across the may be attainable as liquids or powders and eventually be bond that is cleaved, e.g., an ester or peptide linkage. Com encapsulated in various materials. mercially-important hydrolases include proteases which are I0133. Today, several thousand different enzymes have employed in laundry detergents, polysaccharidases which been discovered and more are continuously being discovered, control Slime in industrial process waters, and lipases which thus the number of known enzymes is still increasing. For this are employed to transesterify fats and oils. Cellulases and reason the Nomenclature Committee of the International ligninolases can be employed in wood fiber production and Union of Biochemistry and Molecular Biology (NC bleaching. IUBMB) has established a rational naming and numbering 0130. The majority of enzymes to be used in chewing system. In the present context enzyme names are used in gums is hydrophilic by nature and hence has a tendency accordance with the recommendations devised by towards migrating into the saliva during chewing. Hence by NC-IUBMB. using a hydrophobic enzyme formulation according to the 0.134 Different methods are available for establishing a invention to be able to release-control the amount of enzyme hydrophobic enzyme formulation in order to release control migrating into the saliva an advantageous improvement is the enzyme(s) added to the chewing gum. obtained. In this context it should be noted that even a slight I0135) In the following, four non-limiting methods appli reduction of release of enzymes from the chewing gum during cable within the scope of the invention will be mentioned. chewing is advantageous with respect to e.g. cost efficiency with respect to the enzymes perse. Encapsulation 0131 AS catalysts enzymes generally may increase the 0.136. One way to obtain the desired result may be where rate of attainment of equilibrium between reactants and prod the release control is provided by encapsulating the enzyme ucts of chemical reactions. According to the present invention within a hydrophobic material, e.g. a hydrophobic polymer. these reactants comprise polymers and different degrading Methods for encapsulating Substances, e.g. enzymes, within molecules such as water, oxygen or other reactive Substances, hydrophobic materials are well described in prior art; how which may come into the vicinity of the polymers, whereas ever the use of these methods in a chewing gum has never the products comprise oligomers, trimers, dimers, monomers been seen. Some examples can be seen in EP 0238 216 and and Smaller degradation products. When reactions are U.S. Pat. No. 5,846,927, hereby incorporated by reference, enzyme catalyzed, at least one of the reactants forms a Sub wherein the encapsulating is employed in another context, but strate for at least one enzyme, which means that a temporary nevertheless they are applicable in chewing gums as well, binding emerges between reactants i.e. enzyme Substrates when applying non-toxic hydrophobic materials. and enzymes. In different ways this binding makes the reac tion proceed faster, for instance by bringing the reactants into Oil Dispersion conformations or positions that favor reaction. An increase in reaction rate due to enzymatic influence i.e. catalysis gener 0.137 Another method is where said release control is ally occurs because of a lowering of an activation energy provided keeping the enzyme within an oil dispersion. Here barrier for the reaction to take place. However, enzymes do the enzyme is mixed into a dispersion within a hydrophobic not change the difference in free energy level between initial solution, which typically would be an oil dispersion, whereby and final states of the reactants and products, as the presence a hydrophobic enzyme formulation is obtained. This method of a catalyst has no effect on the position of equilibrium. for obtaining a hydrophobic enzyme formulation is very When a catalytic process has been completed, the at least one straightforward, as the mixing may be carried out very fast enzyme releases the product or products and returns to its and without the use of dedicated equipment. original state, ready for another Substrate. I0138 U.S. Pat. No. 4,849,357, hereafter incorporated by 0132) The temporary binding of one or more molecules of reference, describes another method for modifying a hydro Substrate happens in regions of the enzymes called the active philic enzyme to impart hydrophobic characteristics. In this sites and may for example comprise hydrogen bonds, ionic method the enzyme is mixed with one or more water-in interactions, hydrophobic interactions or weak covalent soluble fatty acid metal salts in the presence of an organic bonds. In the complex tertiary structure of enzymes, an active Solvent whereby, upon removal of the organic solvent, the site may assume the shape of a pocket or cleft, which fit fatty acid acts as a hydrophobic carrier for the enzyme. particular Substrates or parts of Substrates. Some enzymes Amending the Enzyme have a very specific mode of action, whereas others have a wide specificity and may catalyze a series of different sub 0.139. Yet another method is where said release control is strates. Basically molecular conformation is important to the provided by adding to said enzyme a part making it hydro specificity of enzymes, and they may be rendered active or phobic. A method known to the person skilled in the art is to US 2009/O 169677 A1 Jul. 2, 2009 bond polyethylene glycol on the surface of the enzyme with a ways appears to be quite Suitable for the purpose and in some covalent bond. Another method with a covalent bond onto the processes temperature control or cooling may in fact be surface of an enzyme is mentioned in U.S. Pat. No. 5,134,072, avoided. wherein a polyurethane-modified enzyme is produced by 0.148 If a continuous mixing method is applied, again, the reaction of an enzyme in aqueous Solution with an aqueous active cooling and heating should be carefully controlled to solution of a water-soluble polyurethane pre-polymer/bisfu avoid the above-described destruction or damaging of the lite adduct, and wherein the reaction forms a covalent bond applied enzyme(s). between the enzyme and the pre-polymer/bisulfite adduct. In 0149 Turning now to one of several principal embodi this method the pre-polymer/bisulfite adduct could be substi ments of the invention, a chewing gum will be described in tuted to a choice between many other hydrophobic molecules, e.g. a hydrophobic protein. more general terms. 0140 Yet another method is to use an enzyme resulting as 0150. First of all, the chewing gum comprises a polymer a fusion proteinbetween an enzyme Suitable for degrading the composition, which is partly or Solely based on biodegradable gum base polymers and a hydrophobic protein. In amending polymers. These polymers are, as it is the case with conven the enzyme a large number of active sites is preferred, tional non-degradable chewing gum, the components of the whereby a higher degree of control of parameters relevant for chewing gum providing the texture and “masticatory’ prop the process of degradation may become present. This could erties of a chewing gum. Lists of Suitable and preferred poly e.g. be temperature and pH, which by adjusting appropriately mers according to the invention are described below (at the may facilitate the degradation of the gum base polymers even end of the description). better according an embodiment of the invention the inven 0151. Moreover, the chewing gum comprises further addi tion. tives applied for obtaining the desired fine-tuning of the above-mentioned chewing gum. Such additives may e.g. A Hydrophobic Enzyme comprise softeners, emulsifiers, etc. Lists of such Suitable and preferred additives are described below (at the end of the 0141. A further method is where said hydrophobic description). enzyme formulation is obtained by employing a predomi 0152 Moreover, the chewing gum comprises further nantly hydrophobic enzyme. By using a predominantly ingredients applied for obtaining the desired taste and prop hydrophobic enzyme the object of binding the enzyme to the erties of the above-mentioned chewing gum. Such ingredi gum base may be achieved. ents may e.g. comprise Sweeteners, flavors, acids, etc. Lists of 0142 Evidently, it should be noted that a hydrophobic such suitable and preferred ingredients are described below formulation of an enzyme may of course also be obtained by (at the end of the description). a hydrophobic modification of the usually applied carrier or immobilizer. 0153. It should be stressed that the above-mentioned addi 0143. The general principles in manufacturing an embodi tives and ingredients may interact in function. As an example, ment according to the invention will now be described flavors may e.g. be applied as or act as Softeners in the com together with a general description of the obtained product. plete system. A strict distinction between additives and ingre 0144. An enzyme containing biodegradable chewing gum dients may typically not be established. may be prepared by either a conventional two-step batch 0154 Furthermore, a coating may be applied for complete process, a less used but quite promising one-step process or or partial encapsulation of the obtained chewing gum center. e.g. a continuous mixing performed e.g. by means of an In the present context coating and center are regarded as a extruder and the fourth preferred embodiment is to prepare whole, thus using the term “chewing gum' includes both the the chewing gum by use of compression techniques. chewing gum body and an optional coating. Examples of 0145 The two-step process comprises separate manufac different coatings are described below (at the end of the turing of gum base and Subsequently mixing of gum base with description). further chewing gum ingredients. Several other methods may 0155 Advantages according to the invention are that a be applied as well. Examples of two-step processes are well partial disintegration or non-tack improvement of the chew described in the prior art. An example of a one-step process is ing gum lump may be obtained. A further explanation of the disclosed in WO 02/076229 A1, hereby included by refer advantages is given in two separate examples. One example is ence. Examples of continuous mixing methods are disclosed when enzymatic influences result in a partial disintegration in U.S. Pat. No. 6,017,565A, U.S. Pat. No. 5,976,581 A and and a crumbly structure of the lump thereby releasing the U.S. Pat. No. 4,968,511 A, hereby included by reference. lump forming ingredients from the Surface. Another example Examples of processes to produce compressed chewing gum deals with a situation in which the chewing gum lump are disclosed in U.S. Pat. No. 4,405,647, U.S. Pat. No. 4,753, changes its structure due to enzymatic influence and where 805, WO 8603967, EP 513978, U.S. Pat. No. 5,866,179, experiments have shown that the chewing gum lump when WO/97/21424, EP 0 890 358, DE 19751330, U.S. Pat. No. some conditions are fulfilled releases from surfaces to which 6,322,828, PCT/DK03/00070, PCT/DK03/00465, hereby the lump is attached. In other words, this non-tack property included by reference. may be obtained even without any visual disintegration of the 0146 If a two-step process is applied, care should be lump. taken, e.g. in avoiding too much heating of the applied 0156. It is a further advantage according to the invention enzymes. This may e.g. be done by mixing the applied that completely dissolving may be obtained, which means enzyme(s) into the chewing gum in the second step, i.e. in the that the polymer residues may enter the cycle in nature. Incor step where the gum base is mixed with the chewing gum poration of enzymatic influences results in completely bio ingredients. degradable chewing gum polymers. 0147 If a one-step process is applied, the same problem 0157. In accordance with the general principles in manu should be observed, although the one-step process in some facturing an embodiment according to the invention, Suitable US 2009/O 169677 A1 Jul. 2, 2009 examples of polymers, enzymes and chewing gum ingredi example, the dimethyl ester of terephthalic acid may be used ents will be outlined in the following. instead ofterephthalic acid itself. In this case, methanol rather 0158 Suitable examples of environmentally or biologi than water is condensed, and the former can be driven off cally degradable chewing gum base polymers, which may be more easily than water. Usually, the reaction is carried out in applied in accordance with the gum base of the present inven the bulk (no solvent) and high temperatures and vacuum are tion, include degradable polyesters, poly(ester-carbonates), used to remove the by-product and drive the reaction to polycarbonates, polyester amides, polypeptides, homopoly completion. In addition to an ester or anhydride, a halide of mers of amino acids such as polylysine, and proteins includ the carboxylic acid may also be used under certain circum ing derivatives thereof Such as e.g. protein hydrolysates StanceS. including a Zein hydrolysate. Particularly useful compounds 0162. Additionally for preparation of polyesters of this of this type include polyester polymers obtained by the poly type the preferred polyfunctional carboxylic acids or deriva merization of one or more cyclic esters such as lactide, gly tives thereof are usually either saturated or unsaturated ali collide, trimethylene carbonate, Ö-Valerolactone, B-propiolac phatic or aromatic and contain 2 to 100 carbon atoms and tone and e-caprolactone, and polyesters obtained by more preferably 4 to 18 carbon atoms. In the polymerization polycondensation of a mixture of open-chain polyacids and of this type of polyester some applicable examples of car polyols, for example, adipic acid and di(ethylene glycol). boxylic acids, which may be employed as Such or as deriva Hydroxy carboxylic acids such as 6-hydroxycaproic acid tives thereof, includes aliphatic polyfunctional carboxylic may also be used to form polyesters or they may be used in acids such as oxalic, malonic, citric, succinic, malic, tartaric, conjunction with mixtures of polyacids and polyols. Such fumaric, maleic, glutaric, glutamic, adipic, glucaric, pimelic, degradable polymers may be homopolymers, copolymers or Suberic, azelaic, sebacic, dodecanedioic acid, etc. and cyclic terpolymers, including graft- and block-polymers. aliphatic polyfunctional carboxylic acids such as cyclopro 0159. The particularly useful biodegradable polyester panedicarboxylic acid, cyclobutanedicarboxylic acid, cyclo compounds produced from cyclic esters may be obtained by hexane dicarboxylic acid, etc. and aromatic polyfunctional ring-opening polymerization of one or more cyclic esters, carboxylic acids such as terephthalic, isophthalic, phthalic, which includes glycolides, lactides, lactones and carbonates. trimelitic, pyromellitic and naphthalene 1,4-, 2.3-, 2,6-dicar The polymerization process may take place in the presence of boxylic acids and the like. at least one appropriate catalyst Such as metal catalysts, of 0163 For the purpose of illustration and not limitation, which stannous Octoate is a non-limiting example and the Some examples of carboxylic acid derivatives include polymerization process may be initiated by initiators such as hydroxy acids such as 3-hydroxy propionic acid and 6-hy polyols, polyamines or other molecules with multiple droxycaproic acid and anhydrides, halides or esters of acids, hydroxyl or other reactive groups and mixtures thereof. for example dimethyl or diethyl esters, corresponding to the 0160 Accordingly, the particularly useful biodegradable already mentioned acids, which means esters such as dim polyesters produced through reaction of at least one alcohol ethyl or diethyl oxalate, malonate, Succinate, fumarate, male orderivative thereof and at least one acid orderivative thereof ate, glutarate, adipate, pimelate, Suberate, aZelate, sebacate, may generally be prepared by step-growth polymerization of dodecanedioate, terephthalate, isophthalate, phthalate, etc. di-, tri- or higher-functional alcohols or esters thereof with Generally speaking, methyl esters are sometimes more pre di-, tri- or higher-functional aliphatic or aromatic carboxylic ferred than ethyl esters due to the fact that higher boiling acids or esters thereof. Likewise, also hydroxy acids or anhy alcohols are more difficult to remove than lower boiling alco drides and halides of polyfunctional carboxylic acids may be hols. used as monomers. The polymerization may involve direct 0164. Furthermore, the usually preferred polyfunctional polyesterification or transesterification and may be catalyzed. alcohols contain 2 to 100 carbonatoms as for instance polyg Use of branched monomers suppresses the crystallinity of the lycols and polyglycerols. In the polymerization process of polyester polymers. Mixing of dissimilar monomer units this type of polyester some applicable examples of alcohols, along the chain also Suppresses crystallinity. To control the which may be employed as such or as derivatives thereof, reaction and the molecular weight of the resulting polymer includes polyols such as ethylene glycol, 1,2-propanediol. the polymer chains may be ended by addition of monofunc 1,3-propanediol. 1,3-butanediol, 1,4-butanediol, 1.6-hex tional alcohols or acids and/or to utilize a stoichiometric anediol, diethylene glycol, 1.4-cyclohexanediol, 1.4-cyclo imbalance between acid groups and alcohol groups or deriva hexanedimethanol, neopentyl glycol, glycerol, trimethylol tives of either. Also the adding of long chain aliphatic car propane, pentaerythritol, Sorbitol, mannitol, etc. For the boxylic acids or aromatic monocarboxylic acids may be used purpose of illustration and not limitation, Some examples of to control the degree of branching in the polymer and con alcoholderivatives include triacetin, glycerol palmitate, glyc versely multifunctional monomers are sometimes used to erol sebacate, glycerol adipate, tripropionin, etc. create branching. Moreover, following the polymerization 0.165 Additionally, with regard to polymerization of poly monofunctional compounds may be used to endcap the free esters of this type the chain-stoppers sometimes used are hydroxyl and carboxyl groups. monofunctional compounds. They are preferably either 0161 Furthermore, polyfunctional carboxylic acids are in monohydroxy alcohols containing 1-20 carbon atoms or general high-melting solids that have very limited solubility monocarboxylic acids containing 2-26 carbon atoms. Gen in the polycondensation reaction medium. Often esters or eral examples are medium or long-chain fatty alcohols or anhydrides of the polyfunctional carboxylic acids are used to acids, and specific examples include monohydroxy alcohols overcome this limitation. Polycondensations involving car Such as methanol, ethanol, butanol, hexanol, octanol, etc. and boxylic acids or anhydrides produce water as the condensate, lauryl alcohol, myristyl alcohol, cetyl alcohol, Stearyl alco which requires high temperatures to be driven off. Thus, hol, Stearic alcohol, etc. and monocarboxylic acids such as polycondensations involving transesterification of the ester of acetic, lauric, myristic, palmitic, Stearic, arachidic, cerotic, a polyfunctional acid are often the preferred process. For dodecylenic, palmitoleic, oleic, linoleic, linolenic, erucic, US 2009/O 169677 A1 Jul. 2, 2009 benzoic, naphthoic acids and Substituted naptholic acids, drogenase, allyl-alcohol dehydrogenase, 4-hydroxybutyrate 1-methyl-2 naphthoic acid and 2-isopropyl-1-naphthoic acid, dehydrogenase, octanol dehydrogenase, aryl-alcohol dehy etc. Moreover an acid catalyst or a transesterification catalyst drogenase, cyclopentanol dehydrogenase, long-chain-3-hy is typically used in the polymerization of polyesters of this droxyacyl-CoA dehydrogenase, L-lactate dehydrogenase, type and non-limiting examples of those are the metal cata D-lactate dehydrogenase, butanal dehydrogenase, terephtha lysts such as acetates of manganese, Zinc, calcium, cobalt or late 12-cis-dihydrodiol dehydrogenase, Succinate dehydro magnesium, and antimony(III) oxide, germanium oxide or genase, glutamate dehydrogenase, glycine dehydrogenase, halide and tetraalkoxygermanium, titanium alkoxide, Zinc or hydrogen dehydrogenase, 4-cresol dehydrogenase, phospho aluminum salts. nate dehydrogenase and the like. 0166 Suitable enzymes in accordance with the general 0171 Specific examples of reductases belonging to the principles in manufacturing an embodiment within the scope group of oxidoreductases comprise enzymes such as diethyl of the present invention may be identified as belonging to six 2-methyl-3-oxoSuccinate reductase, tropinone reductase, classes according to their function: Oxidoreductases, trans long-chain-fatty-acyl-CoA reductase, carboxylate reductase, ferases, hydrolases, lyases, isomerases and ligases. Oxi D-proline reductase, glycine reductase and the like. doreductases catalyze oxidation-reduction reactions, and the 0172 Other preferred enzymes according to the invention Substrate oxidized is regarded as hydrogen or electron donor. are lyases, which may belong to either of the following Transferases catalyze transfer of functional groups from one groups: carbon-carbon lyases, carbon-oxygen lyases, carbon molecule to another. Hydrolases catalyze hydrolytic cleavage nitrogen lyases, carbon-sulfur lyases, carbon-halide lyases, of various bonds. Lyases catalyze cleavage of various bonds phosphorus-oxygen lyases and other lyases. by other means than by hydrolysis or oxidation, meaning for 0173 Among carbon-carbon lyases are carboxy-lyases, example that they catalyze removal of a group from or addi aldehyde-lyases, oxo-acid-lyases and others. Some specific tion of a group to a double bond, or other cleavages involving examples belonging to those groups are oxalate decarboxy electron rearrangement. Isomerases catalyze intramolecular lase, acetolactate decarboxylase, aspartate 4-decarboxylase, rearrangement, meaning changes within one molecule. lysine decarboxylase, aromatic-L-amino-acid decarboxy Ligases catalyze reactions in which two molecules are joined. lase, methylmalonyl-CoA decarboxylase, carnitine decar 0167 Some preferred enzymes according to the invention boxylase, indole-3-glycerol-phosphate synthase, gallate are oxidoreductases, which may act on different groups of decarboxylase, branched-chain-2-oxoacid, decarboxylase, donors, such as the CH-OH group, the aldehyde or oxo tartrate decarboxylase, arylmalonate decarboxylase, fruc group, the CH-CH group, the CH-NH group, the tose-bisphosphate aldolase, 2-dehydro-3-deoxy-phospho CH-NH group, NADH or NADPH, nitrogenous com gluconate aldolase, trimethylamine-oxide aldolase, propioin pounds, a Sulfur group, a heme group, diphenols and related synthase, lactate aldolase, Vanillin synthase, isocitrate lyase, Substances, hydrogen, single donors with incorporation of hydroxymethylglutaryl-CoA lyase, 3-hydroxyaspartate aldo molecular oxygen, paired donors with incorporation or lase, tryptophanase, deoxyribodipyrimidine photo-lyase, reduction of molecular oxygen or others. Oxidoreductases octadecanal decarbonylase and the like. may also be acting on CH groups or X-H and Y-H to form 0.174 Among carbon-oxygen lyases are hydro-lyases, an X Ybond. Typically enzymes belonging to the group of lyases acting on polysaccharides, phosphates and others. oxidoreductases may be referred to as oxidases, oxygenases, Some specific examples are carbonate dehydratase, fumarate hydrogenases, dehydrogenases, reductases or the like. hydratase, aconitate hydratase, citrate dehydratase, arabinon 0168 Specific examples of oxidoreductases comprise oxi ate dehydratase, galactonate dehydratase, altronate dehy dases such as malate oxidase, glucose oxidase, hexose oxi dratase, mannonate dehydratase, dihydroxy-acid dehy dase, aryl-alcohol oxidase, alcohol oxidase, long-chain-alco dratase, 3-dehydroquinate dehydratase, propanediol hol oxidase, glycerol-3-phosphate oxidase, polyvinyl dehydratase, glycerol dehydratase, maleate hydratase, oleate alcohol oxidase, D-arabinono-1,4-lactone oxidase, hydratase, pectate lyase, poly(B-D-mannuronate) lyase, oli D-mannitol oxidase, Xylitol oxidase, oxalate oxidase, carbon gogalacturonide lyase, poly(C-L-guluronate) lyase, Xanthan monoxide oxidase, 4-hydroxyphenylpyruvate oxidase, dihy lyase, ethanolamine-phosphate phospho-lyase, carboxym drouracil oxidase, ethanolamine oxidase, L-aspartate oxi ethyloxysuccinate lyase and others. dase, sarcosine oxidase, urate oxidase, methanethiol oxidase, 0.175. Among carbon-nitrogen lyases are ammonia 3-hydroxyanthranilate oxidase, laccase, catalase, fatty-acid lyases, lyases acting on amides, amidines, etc., amine-lyases peroxidase, peroxidase, diarylpropane peroxidase, ferroxi and others. Specific examples of those groups of lyases are dase, pteridine oxidase, columbamine oxidase and the like. aspartate ammonia-lyase, phenylalanine ammonia-lyase, 0169. Further specific examples of oxidoreductases com ethanolamine ammonia-lyase, glucosaminate ammonia prise oxygenases Such as catechol 1.2-dioxygenase, gentisate lyase, argininosuccinate lyase, adenyloSuccinate lyase, ure 1.2-dioxygenase, homogentisate 1,2-dioxygenase, lipoxyge idoglycolate lyase, 3-ketovalidoxylamine C-N-lyase nase, ascorbate 2,3-dioxygenase, 3-carboxyethylcatechol 0176 Among carbon-sulfur lyases are some specific 2,3-dioxygenase, indole 2,3-dioxygenase, caffeate 3,4-di examples Such as dimethylpropiothetin dethiomethylase, oxygenase, arachidonate 5-lipoxygenase, biphenyl-2,3-diol alliin lyase, lactoylglutathione lyase and cysteine lyase. 1.2-dioxygenase, linoleate 11-lipoxygenase, acetylacetone 0177 Among carbon-halide lyases are some specific cleaving enzyme, lactate 2-monooxygenase, phenylalanine examples such as 3-chloro-D-alanine dehydrochlorinase or 2-monooxygenase, inositol oxygenase and the like. dichloromethane dehalogenase. 0170 Further specific examples of oxidoreductases com 0.178 Among phosphorus-oxygen lyases are some spe prise dehydrogenases such as alcohol dehydrogenase, glyc cific examples Such as adenylate cyclase, cytidylate cyclase, erol dehydrogenase, propanediol-phosphate dehydrogenase, glycosylphosphatidylinositol diacylglycerol-lyase. L-lactate dehydrogenase, D-lactate dehydrogenase, glycerate 0179. In the most preferred embodiments of the invention, dehydrogenase, glucose 1-dehydrogenase, galactose 1-dehy the applied enzymes are hydrolases comprising glycosylases, US 2009/O 169677 A1 Jul. 2, 2009 enzymes acting on acid anhydrides and enzymes acting on phatase, inositol-1 (or 4)-monophosphatase, 4-phytase, phos specific bonds such as ester bonds, ether bonds, carbon-ni phatidylglycerophosphatase, ADPphosphoglycerate phos trogen bonds, peptide bonds, carbon-carbon bonds, halide phatase, N-acylneuraminate-9-phosphatase, nucleotidase, bonds, phosphorus-nitrogen bonds, Sulfur-nitrogen bonds, polynucleotide 3'-phosphatase, glycogen-synthase-Dphos carbon-phosphorus bonds, Sulfur-Sulfur bonds or carbon-sul phatase, pyruvate dehydrogenase (lipo-amide)-phos fur bonds. phatase, acetyl-CoA carboxylase-phosphatase, 3-deoxy 0180 Among the glycosylases the preferred enzymes are manno-octuloSonate-8-phosphatase, polynucleotide glycosidases, which are capable of hydrolysing O- and S-gly 5'-phosphatase, Sugar-terminal-phosphatase, alkylacetylg cosyl compounds or N-glycosyl compounds. Some examples lycerophosphatase, 2-deoxyglucose-6-phosphatase, gluco of glycosylases are C.-amylase, B-amylase, glucan 1,4-O-glu sylglycerol 3-phosphatase, 5-phytase, phosphodiesterase I. cosidase, cellulase, endo-1.3(4)-3-glucanase, inulinase, glycerophosphocholine phospho-diesterase, phospholipase endo-1,4-B-Xylanase, oligo-1,6-glucosidase, dextranase, C, phospholipase D, phosphoinositide phospholipase C, sph chitinase, polygalacturonase, lysozyme, levanase, quercitri ingomyelin phosphodiesterase, glycerophosphocholine cho nase, galacturan 1,4-O-galacturonidase, isoamylase, glucan linephosphodiesterase, alkylglycerophosphoethanolamine 1,6-O-glucosidase, glucan endo-1,2-3-glucosidase, licheni phosphodiesterase, glycerophosphoinositol glycerophos nase, agarase, exo-poly-O-galacturonosidase, K-carragee phodiesterase, arylsulfatase, steryl-sulfatase, glycosulfatase, nase, steryl-3-glucosidase, strictosidine B-glucosidase, man choline-Sulfatase, cellulose-polysulfatase, monomethyl-sul nosyl-oligosaccharide glucosidase, lactase, oligoxyloglucan fatase, D-lactate-2-sulfatase, glucuronate-2-sulfatase, pre B-glycosidase, polymannuronate hydrolase, chitosanase, nyl-diphosphatase, aryldialkylphosphatase, diisopropyl poly(ADP-ribose) glycohydrolase, purine nucleosidase, fluorophosphatase, oligonucleotidase, poly(A)-specific inosine nucleosidase, uridine nucleosidase, adenosine nucle ribonuclease, yeast ribonuclease, deoxyribonuclease (pyri osidase and others. midine dimer), Physarum polycephalum ribonuclease, ribon 0181 Among enzymes acting on acid anhydrides are for culease alpha, Aspergillus nuclease S, Serratia marcescens instance those acting on phosphorus- or Sulfonyl-containing nuclease and more. anhydrides. Some examples of enzymes acting on acid anhy 0183 The most preferred enzymes acting on ester bonds drides are inorganic diphosphatase, trimetaphosphatase, are carboxylic ester hydrolases such as carboxylesterase, ary adenosine-triphosphatase, apyrase, nucleoside-diphos lesterase, triacylglycerol lipase, phospholipase A, lyso phatase, acylphosphatase, nucleotide diphosphatase, phospholipase, acetylesterase, acetylcholinesterase, cho endopolyphosphatase, exopolyphosphatase, nucleoside linesterase, tropinesterase, pectinesterase, sterol esterase, phospho-acylhydrolase, triphosphatase, CDP-diacylglyc chlorophyllase, L-arabinonolactonase, gluconolactonase, erol-diphosphatase, undecaprenyl-diphosphatase, dolichyl uronolactonase, tannase, retinyl-palmitate esterase, hydroxy diphosphatase, oligosaccharide-diphosphodolichol diphos butyrate-dimer, hydrolase, acylglycerol lipase, 3-oxoadipate phatase, heterotrimeric G-protein GTPase, small monomeric enol-lactonase, 1.4-lactonase, galactolipase, 4-pyridoxolac GTPase, dynamin GTPase, tubulin GTPase, diphosphoinosi tonase, acylcarnitine hydrolase, aminoacyl-tRNA hydrolase, tol-polyphosphate diphosphatase, H-exporting ATPase, D-arabinonolactonase, 6-phosphogluconolactonase, phos monosaccharide-transporting ATPase, maltose-transporting pholipase A, 6-acetylglucose deacetylase, lipoprotein lipase, ATPase, glycerol-3-phosphate-transporting ATPase, oli dihydrocoumarin hydrolase, limonin-D-ring-lactonase, Ste gopeptide-transporting ATPase, polyamine-transporting roid-lactonase, triacetate-lactonase, actinomycin lactonase, ATPase, peptide-transporting ATPase, fatty-acyl-CoA-trans orsellinate-depside, hydrolase, cephalosporin-C deacetylase, porting ATPase, protein-secreting ATPase and others. chlorogenate hydrolase, C.-amino-acid, esterase, 4-methylox 0182 Most preferred enzymes of the present invention are aloacetate esterase, carboxymethylenebutenolidase, deoxyli those acting on ester bonds, among which are carboxylic ester monate A-ring-lactonase, 1-alkyl-2-acetylglycerophospho hydrolases, thiolester hydrolases, phosphoric ester hydro choline esterase, fusarinine-C ornithinesterase, Sinapine lases, Sulfuric ester hydrolases and ribonucleases. Some esterase, wax-ester hydrolase, phorbol-diester hydrolase, examples of enzymes acting on ester bonds are acetyl-CoA phosphatidylinositol deacylase, Sialate O-acetylesterase, hydrolase, palmitoyl-CoA hydrolase. Succinyl-CoA hydro acetoxybutynylbithiophene deacetylase, acetylsalicylate lase, 3-hydroxyisobutyryl-CoA hydrolase, hydroxymethyl deacetylase, methylumbelliferyl-acetate deacetylase, 2-py glutaryl-CoA hydrolase, hydroxyacylglutathione hydrolase, rone-4,6-dicarboxylate lactonase, N-acetylgalactosami glutathione thiolesterase, formyl-CoA hydrolase, noglycan deacetylase, juvenile-hormone esterase, bis(2-eth acetoacetyl-CoA hydrolase, S-formylglutathione hydrolase, ylhexyl)phthalate esterase, protein-glutamate, S-Succinyl-glutathione hydrolase, oleoyl-acyl-carrier-pro methylesterase, 11-cis-retinyl-palmitate hydrolase, all-trans teinhydrolase, ubiquitin thiolesterase, citrate-(pro-3S)- retinyl-palmitate hydrolase, L-rhamnono-1.4-lactonase, lyasethiolesterase, (S)-methylmalonyl-CoA hydrolase, 5-(3,4-diacetoxybut-1-ynyl)-2,2'-bithiophene deacetylase, ADP-dependent short-chain-acyl-CoA hydrolase, ADP-de fatty-acyl-ethyl-ester synthase, Xylono-1.4-lactonase, cetrax pendent medium-chain-acyl-CoA hydrolase, acyl-CoA ate benzylesterase, acetylalkylglycerol acetylhydrolase, hydrolase, dodecanoyl-acyl-carrier proteinhydrolase, acetylxylan esterase, feruloyl esterase, cutinase, poly(3-hy palmitoyl-(protein) hydrolase, 4-hydroxybenzoyl-CoA droxybutyrate) depolymerase, poly(3-hydroxyoctanoate), thioesterase, 2-(2-hydroxy-phenyl)benzenesulfonate hydro depolymerase acyloxyacyl hydrolase, acyloxyacyl hydro lase, alkaline phosphatase, acid phosphatase, phospho-serine lase, polyneuridine-aldehyde esterase and others. phosphatase, phosphatidate phosphatase, 5'-nucleotidase, 0.184 Accordingly, enzymes acting on ether bonds 3'-nucleotidase, 3'(2),5'-bisphosphate nucleotidase, include trialkylsulfonium hydrolases and ether hydrolases. 3-phytase, glucose-6-phosphatase, glycerol-2-phosphatase, Enzymes acting on ether bonds may act on both thioether phosphoglycerate phosphatase, glycerol-1-phosphatase, bonds and on the oxygen equivalent. Specific enzyme mannitol-1-phosphatase, Sugar-phosphatase. Sucrose-phos examples belonging to these groups are adenosylhomocys US 2009/O 169677 A1 Jul. 2, 2009 teinase, adenosylmethionine hydrolase, isochorismatase, kexin, Subtilisin, oryzin, endopeptidase K, thermomycolin, alkenylglycerophosphocholine hydrolase, epoxide hydro thermitase, endopeptidase So, t-plasminogen activator, pro lase, trans-epoxy Succinate hydrolase, alkenylglycerophos tein C (activated), pancreatic endopeptidase E, pancreatic phoethanolamine hydrolase, leukotriene-A hydrolase, hep elastase II, IgA-specific serine endopeptidase, u-plasmino oXilin-epoxide hydrolase and limonene-1,2-epoxide gen activator, Venombin A, furin, myeloblastin, semenoge hydrolase. lase, granzyme A, granzyme B. Streptogrisin A, Streptogrisin 0185. Among enzymes acting on carbon-nitrogen bonds B. glutamyl endopeptidase II, oligopeptidase B, omptin, are linear amides, cyclic amides, linear amidines, cyclic togavirin, flavivirin, endopeptidase Clp, proprotein conver amidines, nitriles and other compounds. Specific examples tase 1, proprotein convertase 2, lactocepin, assemblin, hepa belonging to these groups are asparaginase, glutaminase, civirin, spermosin, pseudomonalisin, Xanthomonalisin, ()-amidase, amidase, urease, B-ureidopropionase, arylforma C-terminal processing peptidase, physarolisin, cathepsin B, midase, biotinidase, aryl-acylamidase, amino-acylase, aspar papain, ficain, chymopapain, asclepain, clostripain, Strepto toacylase, acetylornithine deacetylase, acyl-lysine deacylase, pain, actinidain, cathepsin L, cathepsin H. cathepsin T. glycyl Succinyl-diaminopimelate desuccinylase, pantothenase, endopeptidase, cancer procoagulant, cathepsin S, picornain ceramidase, choloylglycine hydrolase, N-acetylglu 3C, picornain 2A, caricain, ananain, stem bromelain, fruit cosamine-6-phosphate deacetylase, N-acetylmuramoyl-L- bromelain, legumain, histolysain, caspase-1, gingipain R, alanine amidase, 2-(acetamidomethylene)Succinate hydro cathepsin K, adenain, bleomycin hydrolase, cathepsin F. lase, 5-aminopentanamidase, formylmethionine cathepsin O. cathepsin V, nuclear-inclusion-a endopeptidase, deformylase, hippurate hydrolase, N-acetylglucosamine helper-component proteinase, L-peptidase, gingipain K, sta deacetylase, D-glutaminase, N-methyl-2-oxoglutaramate phopain, separase, V-cath endopeptidase, cruzipain, calpain hydrolase, glutamin-(asparagin-)ase, alkylamidase, acylag 1, calpain-2, pepsin A, pepsin B, gastricsin, chymosin, cathe matine amidase, chitin deacetylase, peptidyl-glutaminase, psin D, nepenthesin, renin, Pro-opiomelanocortin converting N-carbamoyl-sarcosine amidase, N-(long-chain-acyl)etha enzyme, aspergillopepsin I, aspergillopepsin II, penicillopep nolamine deacylase, mimosinase, acetyl-putrescine deacety sin, rhizopuspepsin, endothiapepsin, mucorpepsin, can lase, 4-acetamidobutyrate deacetylase, theanine hydrolase, didapepsin, saccharopepsin, rhodotorulapepsin, acrocylin 2-(hydroxymethyl)-3-(acetamidomethylene)Succinate dropepsin, polyporopepsin, pycnoporopepsin, hydrolase, 4-methyleneglutaminase, N-formylglutamate Scytalidopepsin A, Scytalidopepsin B, cathepsin E, barrier deformylase, glycosphingolipid deacylase, aculeacin-A pepsin, signal peptidase II, plasmepsin I, plasmepsin II, deacylase, peptide deformylase, dihydropyrimidinase, dihy phytepsin, yapsin 1, thermopsin, prepilin peptidase, nodavi droorotase, carboxymethyl-hydantoinase, creatininase, rus endopeptidase, memapsin 1, memapsin 2, atrolysin A, L-lysine-lactamase, arginase, guanidinoacetase, creatinase, microbial collagenase, leucolysin, stromelysin 1, meprin A, procollagen C-endopeptidase, astacin, pseudolysin, thermol allantoicase, cytosine deaminase, riboflavinase, thiaminase, ysin, bacillolysin, aureolysin, coccolysin, mycolysin, gelati 1-aminocyclo-propane-1-carboxylate deamin and more. nase B, leishmanolysin, Saccharolysin, gametolysin, Serral 0186. Some preferred enzymes of the present invention ysin, horrilysin, ruberlysin, bothropasin, oligopeptidase A, belong to the group of enzymes acting on peptide bonds, endothelin-converting enzyme, AD-AM10 endopeptidase which group is also referred to as peptidases. Peptidases can and others. be further divided into exopeptidases that act only near a terminus of a polypeptide chain and endopeptidases that act 0187 Suitable enzymes acting on carbon-carbon bonds, internally in polypeptide chains. Enzymes acting on peptide which may be found in ketonic Substances include, but are not bonds include enzymes selected from the group of aminopep limited to oxaloacetase, fumarylacetoacetase, kynureninase, tidases, dipeptidases, di- or tripeptidyl-peptidases, peptidyl phloretin hydrolase, acylpyruvate hydrolase, acetylpyruvate dipeptidases, serine-type carboxypeptidases, metallocarbox hydrolase, B-diketone hydrolase, 2,6-dioxo-6-phenylhexa-3- ypeptidases, cysteine-type carboxypeptidases, omega enoate hydrolase, 2-hydroxymuconate-semialdehyde hydro peptidases, serine endopeptidases, cysteine endopeptidases, lase and cyclohexane-1,3-dione hydrolase. aspartic endopeptidases, metalloendopeptidases and threo 0188 Examples of enzymes within the group acting on nine endopeptidases. Some specific examples of enzymes halide bonds are alkylhalidase, 2-haloacid dehalogenase, belonging to these groups are cystinyl aminopeptidase, trip haloacetate dehalogenase, thyroxine deiodinase, haloalkane eptide aminopeptidase, prolyl aminopeptidase, arginyl ami dehalogenase, 4-chlorobenzoate dehalogenase, 4-chloroben nopeptidase, glutamyl aminopeptidase, cytosol alanyl ami Zoyl-CoA dehalogenase, atrazine chlorohydrolase and the nopeptidase, lysyl aminopeptidase, Met-X dipeptidase, non like. Stereospecific dipeptidase, cytosol nonspecific dipeptidase, 0189 Further examples according to the present invention membrane dipeptidase, dipeptidase E, dipeptidyl-peptidase I. of enzymes acting on specific bonds are phosphoamidase, dipeptidyl-dipeptidase, tripeptidyl-peptidase I, tripeptidyl N-sulfoglucosamine Sulfohydrolase, cyclamate Sulfohydro peptidase II, X-Pro dipeptidyl-peptidase, peptidyl-dipepti lase, phosphonoacetaldehyde hydrolase, phosphonoacetate dase A, lysosomal Pro-X carboxypeptidase, carboxypepti hydrolase, trithionate hydrolase, UDPsulfoquinovose syn dase C, acylaminoacyl-peptidase, peptidyl-glycinamidase, thase, lipase from Rhizopus arrhizus from Sigma and the like. B-aspartyl-peptidase, ubiquitinyl hydrolase 1, chymotrypsin, 0190. Further suitable enzymes known for hydrolyzing chymotrypsin C, metridin, trypsin, thrombin, plasmin, poly(lactic acid) includes pronase, proteinase K, bromelain, enteropeptidase, acrosin, C.-Lytic endopeptidase, glutamyl ficin, esterase, trypsin and the like. endopeptidase, cathepsin G, cucumisin, prolyl oligopepti 0191). According to the present invention enzymes added dase, brachyurin, plasma kallikrein, tissue kallikrein, pancre in biodegradable chewing gum may be of one type alone or atic elastase, leukocyte elastase, chymase, cerevisin, hypo different types in combination. dermin C, lysyl endopeptidase, endopeptidase La, Y-renin, 0.192 Some enzymes require co-factors to be effective. Venombin AB, leucyl endopeptidase, tryptase, Scutelarin, Examples of such co-factors are 5,10-methenyltetrahydro US 2009/O 169677 A1 Jul. 2, 2009

folate, ammonia, ascorbate, ATP bicarbonate, bile salts, partially hydrogenated vegetable oils or completely or par biotin, bis(molybdopterin guanine dinucleotide)molybde tially hydrogenated animal fats. num cofactor, cadmium, calcium, cobalamin, cobalt, coen 0199. In an embodiment of the invention, the chewing Zyme F430, coenzyme-A, copper, dipyrromethane, dithio gum comprises filler. threitol, divalent cation, FAD, flavin, flavoprotein, FMN, 0200. A chewing gum base formulation may, if desired, glutathione, heme, heme-thiolate, iron, iron(2+), iron-molyb include one or more fillers/texturisers including as examples, denum, iron-Sulfur, lipoyl group, magnesium, manganese, magnesium and calcium carbonate, Sodium Sulphate, ground metalions, molybdenum, molybdopterin, monovalent cation, limestone, silicate compounds such as magnesium and alu NAD, NAD(P)H, nickel, potassium, PQQ, protoheme IX, minum silicate, kaolin and clay, aluminum oxide, silicium pyridoxal-phosphate, pyruvate, selenium, Siroheme, Sodium, oxide, talc, titanium oxide, mono-, di- and tri-calcium phos tetrahydropteridine, thiamine diphosphate, topaquinone, phates, cellulose polymers, such as wood, and combinations tryptophan tryptophylduinone (TTO), tungsten, Vanadium thereof. and zinc. 0201 In addition to a water insoluble gum base portion, a 0193 In accordance with the general principles in manu typical chewing gum includes a water Soluble bulk portion facturing a chewing gum within the scope of the invention, and one or more flavoring agents. The water-soluble portion variations of different suitable ingredients are listed and may include bulk Sweeteners, high intensity Sweeteners, fla explained below. Voring agents, softeners, emulsifiers, colors, acidulants, fill 0194 The chewing gum according to the invention may ers, antioxidants, and other components that provide desired comprise coloring agents. According to an embodiment of the attributes. invention, the chewing gum may comprise color agents and 0202 Combinations of sugar and/or non-Sugar Sweeteners whiteners such as FD&C-type dyes and lakes, fruit and veg can be used in the chewing gum formulation processed in etable extracts, titanium dioxide and combinations thereof. accordance with the invention. Additionally, the Softener may 0.195. Further useful chewing gum base components also provide additional Sweetness such as aqueous Sugar or include antioxidants, e.g. butylated hydroxytoluene (BHT), alditol solutions. butyl hydroxyanisol (BHA), propylgallate and tocopherols, 0203 Useful sugar Sweeteners are saccharide-containing and preservatives. components commonly known in the chewing gum art 0196. A gum base formulation may, in accordance with including, but not limited to. Sucrose, dextrose, maltose, dex the present invention, comprise one or more softening agents trins, trehalose, D-tagatose, dried invert Sugar, fructose, levu e.g. sucrose esters including those disclosed in WOO0/25598, lose, galactose, corn Syrup Solids, and the like, alone or in which is incorporated herein by reference, tallow, hydroge combination. nated tallow, hydrogenated and partially hydrogenated veg 0204] Sorbitol can be used as a non-sugarsweetener. Other etable oils, cocoa butter, degreased cocoa powder, glycerol useful non-Sugar Sweeteners include, but are not limited to, monostearate, glyceryl triacetate, lecithin, mono-, di- and other Sugar alcohols such as mannitol, Xylitol, hydrogenated triglycerides, acetylated monoglycerides, fatty acids (e.g. starch hydrolysates, maltitol, isomaltol, erythritol, lactitol Stearic, palmitic, oleic and linoleic acids) and combinations and the like, alone or in combination. thereof. As used herein the term “softener” designates an 0205 High-intensity artificial sweetening agents can also ingredient, which softens the gum base or chewing gum for be used alone or in combination with the above Sweeteners. mulation and encompasses waxes, fats, oils, emulsifiers, Sur Preferred high-intensity sweeteners include, but are not lim factants and solubilisers. ited to Sucralose, aspartame, salts of acesulfame, alitame, 0197) To soften the gum base further and to provide it with neotame, twinsweet, saccharin and its salts, cyclamic acid water-binding properties, which confer to the gum base a and its salts, glycyrrhizin, dihydrochalcones, thaumatin, pleasant Smooth Surface and reduce its adhesive properties, monellin, Stevioside and the like, alone or in combination. In one or more emulsifiers is/are usually added to the composi order to provide longer lasting Sweetness and flavor percep tion, typically in an amount of 0 to 18% by weight, preferably tion, it may be desirable to encapsulate or otherwise control 0 to 12% by weight of the gum base. Mono- and diglycerides the release of at least a portion of the artificial sweetener. of edible fatty acids, lactic acid esters and acetic acid esters of Techniques such as wet granulation, wax granulation, spray mono- and diglycerides of edible fatty acids, acetylated mono drying, spray chilling, fluid bed coating, coascervation, and diglycerides, Sugar esters of edible fatty acids, Na-, K-, encapsulation in yeast cells and fiber extrusion may be used to Mg- and Ca-stearates, lecithin, hydroxylated lecithin and the achieve the desired release characteristics. Encapsulation of like are examples of conventionally used emulsifiers which Sweetening agents can also be provided using another chew can be added to the chewing gum base. In case of the presence ing gum component Such as a resinous compound. of a biologically or pharmaceutically active ingredient as 0206. Usage level of the high intensity artificial Sweetener defined below, the formulation may comprise certain specific will vary considerably and will depend on factors such as emulsifiers and/or solubilisers in order to disperse and release potency of the Sweetener, rate of release, desired sweetness of the active ingredient. the product, level and type of flavor used and cost consider 0198 Waxes and fats are conventionally used for the ations. Thus, the active level of high potency artificial sweet adjustment of the consistency and for softening of the chew ener may vary from about 0 to about 8% by weight, preferably ing gum base when preparing chewing gum bases. In connec 0.001 to about 5% by weight. When carriers used for encap tion with the present invention, any conventionally used and Sulation are included, the usage level of the encapsulated Suitable type of wax and fat may be used, such as for instance sweetener will be proportionately higher. rice bran wax, polyethylene wax, petroleum wax (refined 0207. If a low-calorie gum is desired, a low-caloric bulk paraffin and microcrystalline wax), paraffin, beeswax, car ing agent can be used. Examples of low caloric bulking agents nauba wax, candelilla wax, cocoa butter, degreased cocoa include polydextrose, Raftilose, Raftilin, fructooligosaccha powder and any suitable oil or fat, as e.g. completely or rides (NutraFloraR), palatinose oligosaccharides; guar gum US 2009/O 169677 A1 Jul. 2, 2009 hydrolysates (e.g. Sun Fiber(R) or indigestible dextrins (e.g. lauryl Sulfate and Sorbitan esters of fatty acids and polyoxy FibersolR). However, other low-calorie bulking agents can be ethylated hydrogenated castor oil (e.g. the product sold under used. the trade name CREMOPHOR), block copolymers of ethyl 0208. The chewing gum according to the present invention ene oxide and propylene oxide (e.g. products sold under trade may contain aroma agents and flavoring agents including names PLURONIC and POLOXAMER), polyoxyethylene natural and synthetic flavorings e.g. in the form of natural fatty alcohol ethers, polyoxyethylene sorbitan fatty acid Vegetable components, essential oils, essences, extracts, pow esters, Sorbitan esters of fatty acids and polyoxyethylene ders, including acids and other Substances capable of affect Stearic acid esters. ing the taste profile. Examples of liquid and powdered flavor 0214 Particularly suitable solubilisers are polyoxyethyl ings include coconut, coffee, chocolate, Vanilla, grape fruit, ene Stearates, such as for instance polyoxyethylene(8)Stearate orange, lime, menthol, liquorice, caramel aroma, honey and polyoxyethylene(40)stearate, the polyoxyethylene sorbi aroma, peanut, walnut, cashew, hazelnut, almonds, pine tan fatty acid esters sold under the trade name TWEEN, for apple, Strawberry, raspberry, tropical fruits, cherries, cinna instance TWEEN 20 (monolaurate), TWEEN 80 (mo mon, peppermint, wintergreen, spearmint, eucalyptus, and nooleate), TWEEN 40 (monopalmitate), TWEEN 60 mint, fruit essence Such as from apple, pear, peach, Straw (monostearate) or TWEEN 65 (tristearate), mono and berry, apricot, raspberry, cherry, pineapple, and plum diacetyl tartaric acid esters of mono and diglycerides of essence. The essential oils include peppermint, spearmint, edible fatty acids, citric acid esters of mono and diglycerides menthol, eucalyptus, clove oil, bay oil, anise, thyme, cedar of edible fatty acids, sodium stearoylatylate, sodium lauryl leaf oil, nutmeg, and oils of the fruits mentioned above. Sulfate, polyoxyethylated hydrogenated castor oil, blockco 0209. The chewing gum flavor may be a natural flavoring polymers of ethylene oxide and propyleneoxide and polyoxy agent, which is freeze-dried, preferably in the form of a pow ethylene fatty alcohol ether. The solubiliser may either be a der, slices or pieces or combinations thereof. The particle size single compound or a combination of several compounds. In may be less than 3 mm, less than 2 mm or more preferred less the presence of an active ingredient, the chewing gum may than 1 mm, calculated as the longest dimension of the particle. preferably also comprise a carrier known in the art. The natural flavoring agent may in a form where the particle 0215. In one embodiment the chewing gum according to size is from about 3 um to 2 mm, Such as from 4 um to 1 mm. the invention comprises a pharmaceutically, cosmetically or Preferred natural flavoring agents include seeds from fruit biologically active Substance. Examples of Such active Sub e.g. from strawberry, blackberry and raspberry. stances, a comprehensive list of which is found e.g. in WO 0210 Various synthetic flavors, such as mixed fruit flavors 00/25598, which is incorporated herein by reference, include may also be used in the present chewing gum centers. As drugs, dietary Supplements, antiseptic agents, pH-adjusting indicated above, the aroma agent may be used in quantities agents, anti-Smoking agents and Substances for the care or Smaller than those conventionally used. The aroma agents treatment of the oral cavity and teeth Such as hydrogen per and/or flavors may be used in the amount from 0.01 to about oxide and compounds capable of releasing urea during chew 30% by weight of the final product depending on the desired 1ng. intensity of the aroma and/or flavor used. Preferably, the 0216 Examples of active agents in the form of antiseptics content of aroma/flavor is in the range of 0.2 to 3% by weight are for instance salts and compounds of guanidine and bigu of the total composition. anidine (for instance chlorhexidine diacetate) and the follow 0211. In an embodiment of the invention, the flavoring ing types of Substances with limited water-solubility: quater agents comprise natural and synthetic flavorings in the form nary ammonium compounds (for instance ceramine, of natural vegetable components, essential oils, essences, chloroxylenol, crystal violet, chloramine), aldehydes (for extracts, powders, including acids and other substances instance paraformaldehyde), compounds of dequaline, capable of affecting the taste profile. polynoxyline, phenols (for instance thymol, para chlorophe 0212. In one embodiment of the invention, the flavor may nol, cresol) hexachlorophene, Salicylic anilide compounds, be used as taste masking in chewing gum comprising active triclosan, halogenes (iodine, iodophores, chloroamine, ingredients, which by themselves have undesired taste or dichlorocyanuric acid salts), alcohols (3.4 dichlorobenzyl which alter the taste of the formulation. alcohol, benzyl alcohol, phenoxyethanol, phenylethanol), cf. 0213 Further chewing gum ingredients, which may be furthermore Martindale, The Extra Pharmacopoeia, 28th edi included in the chewing gum according to the present inven tion, page 547-578; metal salts, complexes and compounds tion, include Surfactants and/or solubilisers, especially when with limited water-solubility, such as aluminum salts, (for pharmaceutically or biologically active ingredients are instance aluminum potassium sulfate AlK (SO) 2, 12H2O) present. As examples of types of Surfactants to be used as and furthermore salts, complexes and compounds of boron, solubilisers in a chewing gum composition according to the barium, strontium, iron, calcium, zinc, (Zinc acetate, Zinc invention, reference is made to H. P. Fiedler, Lexikon der chloride, Zinc gluconate), copper (copper chloride, copper Hilfstoffe für Pharmacie, Kosmetik und Angrenzende Gebi Sulfate), lead, silver, magnesium, sodium, potassium, lithium, ete, pages 63-64 (1981) and the lists of approved food emul molybdenum, Vanadium should be included; other composi sifiers of the individual countries. Anionic, cationic, ampho tions for the care of mouth and teeth: for instance; salts, teric or non-ionic solubilisers can be used. Suitable complexes and compounds containing fluorine (such as solubilisers include lecithin, polyoxyethylene Stearate, poly Sodium fluoride, Sodium monofluorophosphate, amino fluo oxyethylene Sorbitan fatty acid esters, fatty acid salts, mono rides, Stannous fluoride), phosphates, carbonates and sele and diacetyl tartaric acid esters of mono and diglycerides of 1. edible fatty acids, citric acid esters of mono and diglycerides 0217. Further active substances can be found in J. Dent. of edible fatty acids, saccharose esters of fatty acids, polyg Res. Vol. 28 No. 2, pages 160-171, 1949. lycerol esters offatty acids, polyglycerol esters of interesteri 0218. Examples of active substances in the form of agents fied castor oil acid (E476), sodium stearoylatylate, sodium adjusting the pH in the oral cavity include: amacopoeiacids, US 2009/O 169677 A1 Jul. 2, 2009

Such as adipinic acid. Succinic acid, fumaric acid, or salts progesterone, acetylsalicylic acid, dimenhydrinate, cyclizine, thereof or salts of citric acid, tartaric acid, malic acid, acetic metronidazole, Sodium hydrogen-carbonate, the active com acid, lactic acid, phosphoric acid and glutaric acid and accept ponents from ginkgo, the active components from propolis, able bases, such as carbonates, hydrogen carbonates, phos the active components from ginseng, methadone, oil of pep phates, Sulphates or oxides of sodium, potassium, ammo permint, salicylamide, hydrocortisone or astemizole. nium, magnesium or calcium, especially magnesium and 0222 Examples of active agents in the form of dietary calcium. Supplements are for instance salts and compounds having the 0219 Active ingredients may comprise the below-men nutritive effect of vitamin B2 (riboflavin), B12, folic acid, tioned compounds or derivates thereof but are not limited niacine, biotine, poorly soluble glycerophosphates, amino thereto: Acetaminophen, Acetylsalicylsyre Buprenorphine acids, the vitamins A, D, E and K, minerals in the form of Bromhexin Celcoxib Codeine, Diphenhydramin, Diclofenac, salts, complexes and compounds containing calcium, phos Etoricoxib, Ibuprofen, Indometacin, Ketoprofen, Lumira phorus, magnesium, iron, Zinc, copper, iodine, manganese, coxib, Morphine, Naproxen, Oxycodon, Parecoxib, Piroxi chromium, selenium, molybdenum, potassium, Sodium or cam, Pseudoefedrin, Rofecoxib, Tenoxicam, Tramadol, Val cobalt. decoxib, Calciumcarbonat, Magaldrate, Disulfiram, 0223 Furthermore, reference is made to lists of nutrients Bupropion, Nicotine, Azithromycin, Clarithromycin, Clotri accepted by the authorities in different countries such as for mazole, Erythromycin, Tetracycline, Granisetron, instance US code of Federal Regulations, Title 21, Section Ondansetron, Prometazin, Tropisetron, Brompheniramine, 1825O13.1825997 and 1828O13-182.8997. Ceterizin, leco-Ceterizin, Chlorcyclizine, Chlorpheniramin, 0224 Examples of active agents in the form of compounds Chlolpheniramin, Difenhydramine, Doxylamine, Fenofena for the care or treatment of the oral cavity and the teeth are for din, Guaifenesin, Loratidin, des-Loratidin, Phenyltoloxam instance bound hydrogen peroxide and compounds capable ine, Promethazin, Pyridamine, Terfenadin, Troxerutin, Meth of releasing urea during chewing. yldopa, Methylphenidate, Benzalcon. Chloride, Benzeth. 0225. Examples of active agents in the form of anti-smok Chloride, Cetylpyrid. Chloride, Chlorhexidine, Ecabet-so ing agents include for instance: nicotine, tobacco powder or dium, Haloperidol, Allopurinol, Colchinine. Theophylline, silver salts, for instance silver acetate, silver carbonate and Propanolol, Prednisolone, Prednisone, Fluoride, Urea, silver nitrate. Miconazole, Actot, Glibenclamide, Glipizide, Metformin, 0226 Further examples of active agents are medicines of Miglitol, Repaglinide, RosiglitaZone, Apomorfin, Cialis, any type. Sildenafil. Vardenafil. Diphenoxylate, Simethicone, Cimeti 0227 Examples of active agents in the form of medicines dine, Famotidine, Ranitidine, Ratinidine, cetrizin, Lorata include caffeine, Salicylic acid, salicylamide and related Sub dine, Aspirin, Benzocaine, Dextrometorphan, Ephedrine, stances (acetylsalicylic acid, choline Salicylate, magnesium Phenylpropanolamine, Pseudoephedrine, Cisapride, Domp salicylate, Sodium salicylate), paracetamol, salts of pentaZo eridone, Metoclopramide, Acyclovir, Dioctylsulfosucc., Phe cine (pentazocine hydrochloride and pentazocinelactate), nolphtalein, Almotriptan, Eletriptan, Ergotamine, Migea, buprenorphine hydrochloride, codeine hydrochloride and Naratriptan, Rizatriptan, Sumatriptan, Zolmitriptan, Alumi codeine phosphate, morphine and morphine salts (hydrochlo num salts, Calcium salts, Ferro salts, Silver salts, Zinc-salts, ride, sulfate, tartrate), methadone hydrochloride, ketobemi Amphotericin B, Chlorhexidine, Miconazole, Triamcino done and salts of ketobemidone (hydrochloride), beta-block lonacetonid, Melatonine, Phenobarbitol, Caffeine, Benzodi ers, (propranolol), calcium antagonists, Verapamil azepine, Hydroxyzine, Meprobamate, Phenothiazine, hydrochloride, nifedipine as well as suitable substances and Buclizine, Brometazine, Cinnarizine, Cyclizine, Difenhy salts thereof mentioned in Pharm. Int., Nov. 85, pages 267 dramine, Dimenhydrinate, Buflomedil, Amphetamine, Caf 271, Barney H. Hunter and Robert L. Talbert, nitroglycerine, feine, Ephedrine, Orlistat, Phenylephedrine, Phenylpropano erythrity1 tetranitrate, Strychnine and salts thereof, lidocaine, lamin, Pseudoephedrine, Sibutramin, Ketoconazole, tetracaine hydrochloride, etorphine hydrochloride, atropine, Nitroglycerin, Nystatin, Progesterone, Testosterone, Vitamin insulin, enzymes, polypeptides (oxytocin, gonadorelin, (LH. B12, Vitamin C, VitaminA, Vitamin D. Vitamin E. Pilocarpin, RH), desmopressin acetate (DDAVP), isoxSuprine hydro Aluminumaminoacetat, Cimetidine, Esomeprazole, Famoti chloride, ergotamine compounds, chloroquine (phosphate, dine, Lansoprazole, Magnesiumoxide, Nizatide and or Sulfate), isosorbide, demoxytocin, heparin. Ratinidine. 0228. Other active ingredients include beta-lupeol, Leti 0220. The active agents to be used in connection with the gen, Sildenafil citrate and derivatives thereof. present invention may be any Substance desired to be released 0229 Dental products include Carbami, CPP Caseine from the chewing gum. If an accelerated rate of release is Phospho Peptide; Chlorhexidine, Chlorhexidine diacetate, desired, corresponding to the effect obtained for the flavor, Chlorhexidine Chloride, Chlorhexidine digluconate, Hexete the primary substances are those with limited water solubility, dine, Strontium chloride, Potassium Chloride, Sodium bicar typically below 10 g/100 ml including substances which are bonate, Sodium carbonate, Fluor containing ingredients, entirely water insoluble. Examples are medicines, dietary Fluorides, Sodium fluoride, Aluminum fluoride, Ammonium Supplements, oral compositions, anti-Smoking agents, highly fluoride, Calcium fluoride, Stannous fluoride. Other fluor potent Sweeteners, pH adjusting agents, etc. containing ingredients Ammonium fluorosilicate, Potassium 0221) Further examples of active ingredients include fluorosilicate, Sodium fluorosilicate, Ammonium monofluo paracetamol, benzocaine, cinnarizine, menthol, carvone, cof rphosphate, Calcium monofluorphosphate, Potassium feine, chlorhexidine-di-acetate, cyclizine hydrochloride, 1.8- monofluorphosphate, Sodium monofluorphosphate, Octade cineol, nandrolone, miconazole, myStatine, aspartame, centyl Ammonium fluoride, Stearyl Trihydroxyethyl Propy Sodium fluoride, nicotine, Saccharin, cetylpyridinium chlo lenediamine Dihydrofluoride, Vitamins include A, B1, B2, ride, other quaternary ammonium compounds, vitamin E, B6, B12, Folic acid, niacin, Pantothensyre, biotine, C, D, E, vitamin A, vitamin D, glibenclamide or derivatives thereof, K. US 2009/O 169677 A1 Jul. 2, 2009

0230 Minerals include Calcium, phosphor, magnesium, in the range of 2,000 to 90,000 such as the range of 3,000 to iron, Zinc, Copper, lod, Mangan, Crom, Selene, Molybden. 80,000 including the range of 30,000 to 50,000, where the Other active ingredients include: Q10(a), enzymes. Natural higher molecular weight polyvinyl acetates are typically used drugs including Ginkgo Biloba, ginger, and fish oil. The in bubble gum base, polyisoprene, polyethylene, vinyl invention also relates to use of migraine drugs such as Sero acetate-vinyl laurate copolymer e.g. having a vinyl laurate tonin antagonists: Sumatriptan, Zolmitriptan, Naratriptan, content of about 5 to 50% by weight such as 10 to 45% by Rizatriptan, Eletriptan; nausea drugs such as Cyclizin, Cin weight of the copolymer, and combinations hereof. narizin, Dimenhydramin, Dilfenhydrinat; hay fever drugs Such as Cetrizin, Loratidin, pain relief drugs such as 0238. It is common in the industry to combine in a gum Buprenorfin, Tramadol, oral disease drugs such as Micona base a synthetic elastomer having a high molecular weight Zol, Amphotericin B, Triamcinolonaceton; and the drugs and a synthetic elastomer having a low molecular weight. Cisaprid, Domperidon, Metoclopramid. Examples of Such combinations of are polyisobutylene and 0231 Generally, it is preferred that the chewing gum and styrene-butadiene, polyisobutylene and polyisoprene, poly the gum bases prepared according to the invention are based isobutylene and isobutylene-isoprene co-polymer (butyl rub solely on biodegradable polymers. However, within the scope ber) and a combination of polyisobutylene, styrene-butadiene of the invention further conventional chewing gum elas copolymerandisobutylene isoprene copolymer, and all of the tomers or elastomer plasticizers may be applied. Thus, in an above individual synthetic polymers in admixture with poly embodiment of the invention, the at least one biodegradable vinyl acetate, vinyl acetate-vinyl laurate copolymers, respec polymer comprises from at least 5% to at least 90% of the tively and mixtures thereof. chewing gum polymers and where the rest of the polymers 0239 Examples of natural resins, which should preferably comprise polymers generally regarded as non-biodegradable, not be applied in the chewing gum according to the present Such as natural resins, synthetic resins and/or synthetic elas invention are: Natural rosin esters, often referred to as ester tOmerS. gums including as examples glycerol esters of partially 0232. In an embodiment of the invention, said natural resin hydrogenated rosins, glycerol esters of polymerised rosins, comprises terpene resins, e.g. derived from alpha-pinene, glycerolesters of partially dimerized rosins, glycerolesters of beta-pinene, and/or d-limonene, natural terpene resins, glyc tally oil rosins, pentaerythritol esters of partially hydroge erol esters of gum rosins, tall oil rosins, wood rosins or other nated rosins, methyl esters of rosins, partially hydrogenated derivatives thereof such as glycerol esters of partially hydro methyl esters of rosins, pentaerythritol esters of rosins, Syn genated rosins, glycerol esters of polymerized rosins, glyc thetic resins such as terpene resins derived from alpha erol esters of partially dimerised rosins, pentaerythritol esters pinene, beta-pinene, and/or d-limonene, and natural terpene of partially hydrogenated rosins, methyl esters of rosins, par resins. tially hydrogenated methyl esters of rosins or pentaerythritol 0240 The chewing gum according to the invention may be esters of rosins and combinations thereof. provided with an outer coating. The applicable hard coating 0233. In an embodiment of the invention, said synthetic may be selected from the group comprising of Sugar coating resin comprises polyvinyl acetate, vinyl acetate-vinyl laurate and a Sugarless coating and a combination thereof. The hard copolymers and mixtures thereof. coating may e.g. comprise 50 to 100% by weight of a polyol 0234. Materials to be used for the above-mentioned selected from the group consisting of sorbitol, maltitol, man encapsulation methods for Sweeteners might e.g. include nitol, xylitol, erythritol, lactitol and Isomalt and variations Gelatine. Wheat protein, Soya protein, Sodium caseinate, thereof. In an embodiment of the invention, the outer coating Caseine, Gum arabic, Mod. starch, Hydrolyzed starches is an edible film comprising at least one component selected (maltodextrines), Alginates, Pectin, Carregeenan, Xanthan from the group consisting of an edible film-forming agent and gum, Locus bean gum, Chitosan, Bees wax, Candelilla wax, a wax. The film-forming agent may e.g. be selected from the Carnauba wax, Hydrogenated vegetable oils, Zein and/or group comprising cellulose derivative, a modified Starch, a Sucrose. dextrin, gelatine, shellac, gum arabic, Zein, a vegetable gum, 0235 Generally, it is preferred that the chewing gum and a synthetic polymer and any combination thereof. In an the gum bases prepared according to the invention are based embodiment of the invention, the outer coating comprises at solely on biodegradable polymers. least one additive component selected from the group com 0236. However, within the scope of the invention, minor prising of a binding agent, a moisture-absorbing component, amounts of conventional synthetic chewing gum elastomers a film-forming agent, a dispersing agent, an antisticking com or elastomer plasticizers, examples of which are mentioned ponent, a bulking agent, a flavoring agent, a coloring agent, a below, may be applied. pharmaceutically or cosmetically active component, a lipid 0237 Examples of such generally non-biodegradable syn component, a wax component, a Sugar, an acid and an agent thetic resins include polyvinyl acetate, vinyl acetate-vinyl capable of accelerating the after-chewing degradation of the laurate copolymers and mixtures thereof. Examples of non degradable polymer. biodegradable synthetic elastomers include, but are not lim 0241 Generally, the ingredients may be mixed by first ited to, synthetic elastomers listed in Food and Drug Admin melting the gum base and adding it to the running mixer. istration, CFR, Title 21, Section 172,615, the Masticatory Colors, active agents and/or emulsifiers may also be added at Substances, Synthetic) Such as polyisobutylene. e.g. having a this time. A softener Such as glycerin may also be added at this gel permeation chromatography (GPC) average molecular time, along with syrup and a portion of the bulking agent/ weight in the range of about 10,000 to 1,000,000 including sweetener. Further portions of the bulking agent/sweetener the range of 50,000 to 80,000, isobutylene-isoprene copoly may then be added to the mixer. A flavoring agent is typically mer (butyl elastomer), styrene-butadiene copolymers e.g. added with the final portion of the bulking agent/sweetener. A having styrene-butadieneratios of about 1:3 to 3:1, polyvinyl high-intensity sweetener is preferably added after the final acetate (PVA), e.g. having a GPC average molecular weight portion of bulking agent and flavor has been added. US 2009/O 169677 A1 Jul. 2, 2009

0242. The entire mixing procedure typically takes from beraverage molecular weight (Mn) in g/mol. Furthermore, as five to fifteen minutes, but longer mixing times may some used herein the short form PD designates the polydispersity times be required. Those skilled in the art will recognize that of polymers, polydispersity being defined as Mw/Mn, where many variations of the above described procedure may be Mw is the weight average molecular weight of a polymer. A followed. Including the one-step method described in US well-established technique for characterization of biodegrad patent application 2004/01 15305 hereby incorporated as ref able polymers is gel permeation chromatography (GPC). erence. Chewing gums are formed by extrusion, compres 0252. The hydrophobicity and hydrofilicity of substances Sion, rolling and may be centre filled with liquids and/or are expressions defining whether the Substance is repelled or Solids in any form. attracted by water. A hydrophobic molecule tends to be elec 0243 The chewing gum according to the present invention trically neutral and non-polar, whereas a hydrophilic mol may also be provided with an outer coating, which may be a ecule tends to be a polar molecule and hence is attracted by hard coating, a soft coating, a film coating, or a coating of any the electric displacements found in the H-bindings of a water type that is known in the art, or a combination of Such coat molecule. ings. The coating may typically constitute 0.1 to 75 percent by 0253 Hydrophobicity is normally used on a relative scale, weight of a coated chewing gum piece. i.e. that one substance is more hydrophobic or hydrophilic 0244 One preferred outer coating type is a hard coating, than another Substance. A theoretical expression to be used which term is including Sugar coatings and Sugar-free (or for measuring and comparing the hydrophobicity of a Sub Sugarless) coatings and combinations thereof. The object of stance X directly is given by: hard coating is to obtain a Sweet, crunchy layer, which is appreciated by the consumer and to protect the gum centers. Log P-Log Ka-Log (LXIoctano/Alwater) In a typical process of providing the chewing gum centers whereby Log P can be found by measuring the solubility in with a protective Sugar coating the gum centers are succes water and octanol respectively for the Substance. sively treated in Suitable coating equipment with aqueous Solutions of crystallizable Sugar Such as Sucrose or dextrose, 0254 The gum base is the masticatory substance of the which, depending on the stage of coating reached, may con chewing gum, which imparts the chew characteristics to the tain other functional ingredients, e.g. fillers, colors, etc. final product. The gum base typically defines the release 0245. In one presently preferred embodiment, the coating profile of flavors and Sweeteners and plays a significant role in agent applied in a hard coating process is a Sugarless coating the gum product. agent, e.g. a polyol including as examples sorbitol, maltitol, 0255. The composition of gum base formulations can vary mannitol. Xylitol, erythritol, lactitol and isomalt or e.g. a Substantially depending on the particular product to be pre mono-di-saccharide including as example trehalose. pared and on the desired masticatory and other sensory char 0246 Or alternatively a Sugar free soft coating e.g. com acteristics of the final product. However, typical ranges (% by prising alternately applying to the centres a syrup of a polyol weight) of the above gum base components are: 5 to 80% by or a mono-di-saccharide, including as examples Sorbitol, weight elastomeric compounds, 5 to 80% by weight elas maltitol, mannitol, Xylitol, erythritol, lactitol, isomalt and tomer plasticizers, 0 to 40% by weight of waxes, 5 to 35% by trehalose. weight softener, 0 to 50% by weight filler, and 0 to 5% by 0247. In further useful embodiments a film coating is pro weight of miscellaneous ingredients such as antioxidants, vided by film-forming agents such as a cellulose derivative, a colorants, etc. The gum base may comprise about 5 to about modified Starch, a dextrin, gelatine, Zein, shellec, gum arabic, 95 percent, by weight, of the chewing gum, more commonly, a vegetable gum, a synthetic polymer, etc. or a combination the gum base comprises 10 to about 60 percent of the gum. thereof. 0256 Elastomers provide the rubbery, cohesive nature to 0248. In an embodiment of the invention, the outer coating the gum, which varies depending on this ingredient's chemi comprises at least one additive component selected from the cal structure and how it may be compounded with other group comprising of a binding agent, a moisture-absorbing ingredients. Elastomers Suitable for use in the gum base and component, a film-forming agent, a dispersing agent, an anti gum of the present invention may include natural or synthetic Sticking component, a bulking agent, a flavoring agent, a types. coloring agent, a pharmaceutically or cosmetically active 0257 Elastomer plasticizers vary the firmness of the gum component, a lipid component, a wax component, a Sugar, an base. Their specificity on elastomer inter-molecular chain acid breaking (plasticizing) along with their varying softening 0249. A coated chewing gum center according to the points cause varying degrees of finished gum firmness and invention may have any form, shape or dimension that per compatibility when used in base. This may be important when mits the chewing gum center to be coated using any conven one wants to provide more elastomeric chain exposure to the tional coating process. alkanic chains of the waxes. (0250) The glass transition temperature (T) may be deter 0258. The elastomer compounds may be of natural origin mined by for example DSC (DSC: differential scanning calo but are preferably of synthetic origin, preferably synthetic rimetry). The DSC may generally be applied for determining polyesters. According to the invention, the resin compounds and studying of the thermal transitions of a polymer and are preferably biodegradable polymers, and in preferred specifically, the technique may be applied for the determina embodiments, the resin compounds are biodegradable Syn tion of a second order transition of a material, i.e. a thermal thetic polyesters. Natural resins of any kind are avoided in the transition that involves a change in heat capacity, but does not chewing gum of the present invention. have a latent heat. The glass transition is a second-order 0259. According to an embodiment of the invention, the transition. polymerization process to obtain the biodegradable polymer, 0251 Unless otherwise indicated, as used herein with which is applied in the chewing gum of the present invention, regard to polymers, the term "molecular weight' means num may be initiated by an initiator Such as a polyfunctional US 2009/O 169677 A1 Jul. 2, 2009

alcohol, amine or other molecules or compounds with mul 0269. Further suitable examples of additional environ tiple hydroxyl or other reactive groups or mixtures thereof. mentally or biologically degradable chewing gum base poly 0260 According to an embodiment of the invention, mers, which may be applied in accordance with the gum base examples of suitable multifunctional initiators includebut are of the present invention, include degradable polyesters, poly not limited to glycerol, trimethylolpropane, pentaerythritol, carbonates, polyester amides, polypeptides, homopolymers dipentaerythritol, and ethoxylated or propoxylated of amino acids Such as polylysine, and proteins including polyamines. derivatives hereof such as e.g. protein hydrolysates including 0261) Furthermore, in a preferred embodiment of the a Zein hydrolysate. invention, the initiator may be di-functional, and examples of applicable di-functional initiators include di-functional alco 0270. The following non-limiting examples illustrate the hols, and non-limiting examples include 1.2-propane diol. manufacturing of chewing gums comprising enzyme in dif 1,3-butane diol, other alkane diols, ethylene glycol, generally ferent formulations including the evaluation of these. alcohols having two hydroxyl groups, and other di-functional compounds capable of initiating a ring-opening polymeriza Example 1 tion. 0262 According to an embodiment of the invention, the Preparation of Polyester Elastomer Obtained by fraction of initiators in the biodegradable polymer being Step-Growth Polymerization difunctional or higher functional may be regulated, whereby the degree of linearity and branching may be controlled. 0271 An elastomer sample is produced using a 500 mL 0263. In an embodiment of the invention, the difunctional resin kettle equipped with an overhead stirrer, nitrogen gas initiators comprise at least 50 mol % of the total content of inlet tube, thermometer, and distillation head for removal of initiator molecules applied. Hereby, a considerable linearity methanol. To the kettle are charged 83.50 g (0.43 mole) dim may be introduced in the biodegradable polymer according to ethyl terephthalate, 99.29 g (0.57 mole) dimethyl adipate, the present invention, and a certain desired crystallinity may 106.60 g (1.005 mole) di(ethylene glycol) and 0.6 g calcium be obtained. Hereby, the biodegradable polyester polymer acetate monohydrate. Under nitrogen, the mixture is slowly may gain very Suitable properties as elastomer plasticizer, and heated with stirring until all components become molten hence an advantageous biodegradable resin may be provided (120-140°C.). Heating and stirring are continued and metha in the chewing gum of the present invention. To increase the nol is continuously distilled. The temperature slowly rises in linearity to improve the crystallinity, plasticizing properties the range 150-200° C. until the evolution of methanol ceases. and robustness of the chewing gum in an embodiment of the Heating is discontinued and the content is allowed to cool to invention, the content of difunctional initiators may be raised about 100° C. The reactor lid is removed and the molten to e.g. 60%, 70%, 80%, 90%, or about 100% of the total polymer is carefully poured into a receiving vessel. content of moles initiator molecules applied. 0264. Accordingly, a Substantially linear polyester poly 0272 Characterization of the product indicates Mn-40, mer may according to an embodiment of the invention com 000 g/mol, Mw =190,000 g/mol and Tg -30°C. prise above e.g. 50 or 80 percent linear polymer chains. Gen erally, the biodegradable polymers used in the chewing gum Example 2 of the present invention may be homopolymers, copolymers or terpolymers, including graft- and block-polymers. Preparation of Polyester Resin Obtained by Ring 0265 Useful polymers, which may be applied as elas Opening Polymerization tomers in the chewing gum of the present invention, may generally be prepared by step-growth polymerization of di-, 0273 A resin sample is produced using a cylindrical glass, tri- or higher-functional alcohols oresters thereof with di-, tri jacketed 10 L pilot reactor equipped with glass stir shaft and or higher-functional aliphatic or aromatic carboxylic acids or Teflon stir blades and bottom outlet. Heating of the reactor esters thereof. Likewise, also hydroxy acids or anhydrides contents is accomplished by circulation of silicone oil, and halides of polyfunctional carboxylic acids may be used as thermo stated to 130° C., through the outer jacket. e-capro monomers. The polymerization may involve direct polyes lactone (358.87 g, 3.145 mol) and 1,2-propylene glycol (79. terification or transesterification and may be catalyzed. 87 g, 1.050 mol) are charged to the reactor together with 0266 The usually preferred polyfunctional alcohols con stannous octoate (1.79g. 4.42x10 mol) as the catalyst and tain 2 to 100 carbon atoms as for instance polyglycols and reacting in about 30 min. at 130°C. Then molten D.L-lactide polyglycerols. (4.877 kg, 33.84 mol) are added and reaction continued for 0267 In the polymerization of an elastomer for use in the about 2 hours. At the end of this period, the bottom outlet is chewing gum of the present invention, Some applicable opened, and molten polymer is allowed to drain into a Teflon examples of alcohols, which may be employed as such or as lined paint can. Characterization of the product indicates derivatives thereof, include polyols such as ethylene glycol, M-6,000 g/mol, M-7,000 g/mol and Tg 25-30°C. 1.2-propanediol. 1,3-propanediol. 1,3-butanediol. 1,4-bu tanediol, 1.6-hexanediol, diethylene glycol, 1,4-cyclohex Example 3 anediol. 1,4-cyclohexanedimethanol, neopentylglycol, glyc erol, trimethylolpropane, pentaerythritol, Sorbitol, mannitol, Preparation of Polyester Resin Obtained by Ring etc Opening Polymerization 0268 Generally, the elastomer polymers used in the chew ing gum of the present invention may be homopolymers, 0274. A polymerization similar to example 2 is performed copolymers or terpolymers, including graft- and block-poly to prepare a resin sample with a molar ratio of 50% D.L- CS. lactide and 50% glycolide. US 2009/O 169677 A1 Jul. 2, 2009

(0275 Characterization of the product indicates Mn=6,000 exposed to an elevated temperature due to the short material g/mol, Mw-7,000 g/mol and Tg 36° C. residence time in the extruder. The extruderused is a Leistritz corotational twin screw mixing extruder (Leistritz ZSE Example 4 27HP-40D), which is equipped with gravitational (loss-in Preparation of Gum Bases weight) feeders. In this experiment the extruder is operated with a screw speed of 80-120 rpm. 0276. The process of preparing gum bases is carried out in 0282. Hydrogenated vegetable oil with a melting point of the following way: The gum base components are added to a 52°C. is added to the extruder inlet and passed through a mixing kettle provided with mixing means like e.g. horizon melting Zone (barrel temperature of 75° C.). Then, following tally placed Z-shaped arms. The kettle has been preheated for a cooling Zone (barrel temperature of 55°C.) Trypsin is added 15 minutes to a temperature of about 120-140°C. The mix to form a 30% mixture with the oil. After the Trypsin feeding ture is mixed for 30-120 minutes until the whole mixture point, a mixing Zone follows (barrel temperature of 55° C.) becomes homogeneous. The mixture is then discharged into before a cooling Zone (barrel temperature of 10° C.). The the pan and allowed to cool to room temperature from the product is discharged as a number of thin robes which are discharged temperature of 80-100° C. further cooled by air and cut with a rotational knife. 0283. The resulting product is enzyme partly encapsulated TABLE 1. in fat. gun base preparation 0284. Alternatively, the encapsulated enzyme may be obtained by means of a standard fluidized bed encapsulation Ingredients Amount (%) technique. Elastomer of example 1 15 0285. The resulting product is then used in chewing gum Resin of example 3 40 no. 101, formulation of which is seen in example 7. Emulsifier: 5 Fat: 2O Example 7 Filler: 2O Preparation of Chewing Gum Example 5 0286 The gum bases of example 4 are used in the prepa ration of different chewing gums with the basic formulations Preparation of Enzyme Formulations shown in table 3. The formulations are identical with the 0277. The object of this example is to compare dispersions exception that adding of enzyme Substitutes Sorbitol in made from: equivalent amounts. a hydrophobic enzyme formulation by using Sunflower oil 0287 Enzyme formulations 10-12 as defined in example 5 and are used with chewing gum no. 101 and enzyme formulations a hydrophilic enzyme formulation—by using water 13-17 as defined in example 5 are used with chewing gum no. 0278. The two enzyme dispersions are to be compared 102. Finally chewing gum no. 100 is used as reference with with the enzyme as obtained from the supplier. out any enzyme formulation. This gives a total of 9 different 0279 Three different enzymes are used: Neutrase (liquid), chewing gums. Bromelain (powder) and Trypsin (powder). These are mixed 0288 The chewing gum products are prepared as follows: to give different enzyme formulations as can be seen from 0289. The gum base is added to a mixing kettle provided table 2. with mixing means like e.g. horizontally placed Z-shaped arms. The kettle has been preheated for 15 minutes to a TABLE 2 temperature of about 40-60° C. or the chewing gum is made in one step, immediately after preparation of gum base in the enzyme formulations, given in 96 of same mixer where the gum base and kettle has a temperature the total chewing gun, see table 3. of less than 60° C. Formulation No. 0290. One half portion of the sorbitol is added together with the gum base and mixed for 3 minutes. Softeners are Ingredients 10 11 12 13 14 15 16 17 slowly added and mixed for 5 minutes. Then the remaining Neutrase 5 5 half portion of sorbitol is added and mixed for 3 minute. Bromelain 5 5 5 Peppermint and menthol are then added to the kettle and Trypsin 5 5 5 mixed for 1 minute. Then aspartame and acesulfame are Water 5 5 added to the kettle and mixed for 2 minutes. Xylitol is added Sunflower oil 5 5 5 and mixed for 3 minutes. Finally enzyme is added and mixing Total 5 5 5 10 10 10 1 0 10 continues for 1-1/2 minutes. After addition of enzyme, care should be taken not to exceed the temperature, which is tol erated by the applied type of enzyme. The resulting gum 0280. The mixing is carried out by means of an Ultra Turax mixture is then discharged and e.g. transferred to a pan at a high speed mixer mixing at room temperature (21°C.) for temperature of 40-48°C. The gum is then rolled and cut into about 2 minutes. cores, Sticks, balls, cubes, or any other desired shape, option Example 6 ally followed by coating and polishing processes prior to packaging or use. Evidently, within the scope of the inven Preparation of Encapsulated Enzyme tion, other processes and ingredients may be applied in the 0281 Encapsulation of the enzyme is made by means of process of manufacturing the chewing gum, for instance the an extrusion process where the enzyme is only shortly one-step method may be a lenient alternative. US 2009/O 169677 A1 Jul. 2, 2009 19

were left for degradation in air at a temperature of 40°C. and TABLE 3 the remaining 2 of each were put into test tubes containing water. The chewing gums were separately exposed to the Chewing gun formulations with different enzyme concentrations. following steps: 0298 1. Placed in a mastication device containing 20 ml Chew. Gum No. phosphate buffer solution (ammonium-di-hydrogen Ingredients 1OO 101 102 phosphate 0.012 Madjusted to pH 7.4 with a 2 MNaOH Enzyme formulation O.O S.O 1O.O Solution). Sorbitol 48.6 43.6 38.6 0299 2. Chewed for 8 minutes with a chewing fre Gum base 40.O 40.O 40.O quency of 60 chews/min. Maltitol syrup 3.0 3.0 3.0 Peppermint flavor 1.5 1.5 1.5 0300 3. Removed from solution and formed into a Menthol crystals O.S O.S O.S spherical ball. Aspartame O.2 O.2 O.2 0301 4. Placed in the center of a Petri dish—or placed Acesulfame K O.2 O.2 O.2 in a closed glass containing 5 ml (0.012 M) phosphate Xylitol 6.O 6.O 6.O buffer solution adjusted to pH 5.6. All made with peppermint flavor. Ingredient concentrations are given in per 0302) 5. The Petri dish placed at 40° C.—or the glass cent by weight. containing buffer solution placed at 40°C. 0303 6. Evaluated for degradation. Continuous Mixing of Chewing Gum: Example 10 0291 Alternatively an extruder apparatus, e.g. a Leistritz co-rotational twin screw mixing extruder, could be used for Evaluation the continuous mixing of chewing gum. 0304. An evaluation of the chewing gums of example 7 0292. The extruder is divided into 10 barrels/heating Zones was carried out immediately after manufacture of the gum and the screw design is optimized by proper combination of pieces and then after 9 and 16 days. various screw elements including conveying elements, 0305 The initial evaluation of the chewing gum pieces reverse conveying elements, kneading discs and blocks, and was that hydrophobic formulation was possible and may be mixing elements. For a further detailed description see e.g. combined with conventional or slightly modified processes. U.S. Pat. No. 6,630,182 column 4. The mixing speed is (0306 A visual evaluation after 9 and 16 days revealed no 80-120 rpm and gravitational (loss in weight) feeders are clear difference in degradation of the gum base polymers of used. the chewing. 0293 The 10 barrels have individual purposes as listed 0307. In order to supplement the visual evaluation a GPC below: analysis was carried out on the Trypsin based enzyme formu Barrel 1. Adding gum base and half the sorbitol, T-25°C. lations as this particular enzyme is known to have an advan Barrel 2+3. Mixing and kneading, T-40°C. tageous effect on degradation, even when applying trypsin Barrel 4. Adding rest of sorbitol using a side feeder, T-40°C. perse. Barrel 5. Mixing, T-40°C. Example 11 0294 Barrel 6. Adding maltitol syrup and flavor, T-40°C. Barrel 7. Adding Xylitol, aspartame, acesulfame in addition to GPC Analysis menthol using a side feeder, T-40°C. 0308 GPC (gel permeation chromatography) measure Barrel 8. Adding enzyme, T-40°C. ments were carried out on samples taken after 0, 9 and 16 days to estimate the degradation of the chewing gums of example Barrel 9+10. Mixing, T-40°C. 7. In GPC the average Mw of the compound in question is 0295 Following the mixing process the chewing gum measured, which is seen in FIG.1a. product is discharged to be rolled, scored, etc. 0309 The abbreviations stand for: TP: Trypsin in powder form, Example 8 TW: Trypsin mixed with water TO: Trypsin dispersed in Sunflower oil Preparation of Chewing Gum from Encapsulated Enzyme STD: Standard 0296. The encapsulated enzyme formulation of example 6 0310. The average Mw is decreasing over time for all four is used in the chewing gum formulation no. 101 of example 7 graphs, hence in order to be able to see the changes more and the chewing gum is made by means of an extruder accord clearly FIG.1b is added showing the same data as in FIG.1a. ing to the process outlined in example 7. Alternatively, this wherein all data are indexed according to the evolution from preparation may also be made by using the mixing kettle also the initial value. The abbreviations are also the same. as described in example 7. 0311. Initially, it is noted that a certain degradation is obtained even when no enzyme is added to the chewing gum Example 9 (STD). 0312 Moreover, it is realized that degradation over time is Chewing Gum Treatment improved when adding trypsinto the chewing gumina hydro 0297 All the manufactured chewing gums of example 7 phobic formulation (TO), i.e. when Suspending trypsin in oil were put into a mastication device (CFJansson) and 6 of each prior to adding of the formulation to the chewing gum. US 2009/O 169677 A1 Jul. 2, 2009 20

0313 Furthermore, and most important, it is noted that 22. A chewing gum according to claim 1, wherein said at enzymes may be added hydrophobically formulated to chew least one biodegradable polymer comprises synthetic biode ing gum and thereby obtaining a minimized or delayed gradable polymers and/or natural biodegradable polymers. release of enzymes from the chewing gum without necessar 23. A chewing gum according to claim 1, wherein said at ily denaturing and compromising the effect of the enzyme. least one biodegradable polymer comprises a polyester. 24. A chewing gum according to claim 1, wherein at least 1. A chewing gum comprising at least one biodegradable one of said synthetic biodegradable polymers is selected from polymer, a Sweetener in an amount from about 0.5% to about the group consisting of cellulose derivatives such as cellulose 95% of said chewing gum, one or more flavoring agents, ether, cellulose ester or cellulose co-esters, aliphatic polyes fillers in an amount from about 0 to 50% by weight of said ters such as poly lactic acid, polyhydroxybutyric acid, hydro chewing gum, further chewing gum ingredients and at least phobic proteins such as Zein and any combination thereof. one enzyme, wherein said at least one enzyme comprises a 25. A chewing gum according to claim 1, wherein at least hydrophobic enzyme formulation. one of said biodegradable polymers is a polypeptide selected 2. A chewing gum according to claim 1, wherein said from the group consisting of collagen and gelatin; polyamino hydrophobic enzyme formulation comprises at least one acids such as poly-L-glutamic acid and poly-L-lysine; hydrophobic enzyme and/or at least one enzyme which is at polysaccharides such as alginic acid, chitin or any combina least partly encapsulated by a hydrophobic encapsulation. tion thereof. 3. (canceled) 26. A chewing gum according to claim 1, wherein said at 4. A chewing gum according to claim 1, wherein said least one enzyme is immobilized by an enzyme carrier, hydrophobic enzyme formulation comprises at least one wherein the amount of said enzyme carrier in the chewing enzyme dispersed in eitheran anhydrous dispersion medium, gum Subsequent to chewing in about five minutes is above a hydrophobic medium, or adsorbed to a hydrophobic carrier. 10% of the initial amount of said enzyme carrier. 5. (canceled) 27. (canceled) 6. (canceled) 28. A chewing gum according to claim 1, wherein the 7. A chewing gum according to claim 1, wherein said amount of said at least one enzyme in the chewing gum hydrophobic enzyme formulation comprises at least one subsequent to chewing in about five minutes is above 10% of hydrophilic enzyme and/or at least one modified enzyme. the initial amount of said at least one enzyme. 8. (canceled) 29. A chewing gum according to claim 1, wherein chewing 9. A chewing gum according to claim 1 comprising at least of said chewing gum facilitates said at least one enzyme to one biodegradable polymer, a Sweetener in an amount from initiate the degradation of said at least one biodegradable about 0.5% to about 95% of said chewing gum, one or more polymer. flavoring agents, filler in an amount from about 0 to 50% by 30. A chewing gum according to claim 1, wherein said at weight of said chewing gum, further chewing gum ingredi least one enzyme has a temperature optimum in an interval ents and at least one enzyme, wherein said at least one enzyme between 0° C. and 80° C. is release controlled by a hydrophobic enzyme formulation. 31. (canceled) 10. A chewing gum according to claim 9, wherein said 32. (canceled) release control is provided by encapsulating said enzyme 33. A chewing gum according to claim 1, wherein at least within a hydrophobic material, and/or within a hydrophobic two enzymes having different temperature optimums are polymer, and/or within a wax, and/or within a fat. applied at the same time. 11. (canceled) 34. A chewing gum according to claim 1, wherein said at 12. (canceled) least one enzyme is selected from the group consisting of 13. (canceled) oxidoreductases, transferases, hydrolases, lyases, isomerases 14. A chewing gum according to claim 9, wherein said and ligases. release control is provided by keeping said enzyme within a 35. A chewing gum according to claim 1, wherein said hydrophobic dispersion. chewing gum comprises a buffering system, wherein said 15. A chewing gum according to claim 14, wherein said buffering system provides a pH-value above 5.5. hydrophobic dispersion is an oil dispersion. 36. (canceled) 16. A chewing gum according to claim 1, wherein said 37. (canceled) release control is provided by adding to said enzyme a part 38. A chewing gum according to claim 1, wherein said making it hydrophobic. chewing gum is formed by compression. 17. A chewing gum according to claim 1, wherein said 39. A chewing gum according to claim 1, wherein said hydrophobic enzyme formulation is obtained by employing a fillers comprise hydrophilic fillers selected from the group predominantly hydrophobic enzyme. consisting of ground limestone, calcium carbonate, magne 18. A chewing gum according to claim 1, wherein said at sium silicate, starch, aluminum silicate, talc, mono-, di- and least one enzyme is activated when, during chewing, contact tri-calcium phosphate, cellulose polymers and combinations is made between said enzyme, said at least one biodegradable thereof. polymer and water or, between said enzyme, said at least one 40. (canceled) biodegradable polymer, water and at least one second enzyme 41. A chewing gum according to claim 1, wherein said present in the oral cavity. chewing gum comprises filler in an amount of about 1 to 19. (canceled) about 50% by weight of the chewing gum. 20. A chewing gum according to claim 1, wherein the water 42. (canceled) content of said chewing gum is below 5%, by weight, of said 43. A chewing gum according to claim 1, wherein said chewing gum. Sweetener comprises bulk Sweeteners and/or high-intensity 21. (canceled) SWeetenerS. US 2009/O 169677 A1 Jul. 2, 2009

44. (canceled) 55. A chewing gum according to claim 1, wherein the at 45. (canceled) least one biodegradable polymer comprises at least one poly 46. (canceled) ester obtained by polymerization of at least one compound 47. A chewing gum according to claim 1, wherein said selected from the group of cyclic esters, alcohols or deriva chewing gum comprises a coating. tives thereof and carboxylic acids or derivatives thereof. 48. A chewing gum according to claim 1, wherein said chewing gum comprises softeners selected from the group 56. A chewing gum according to claim 1, wherein said at consisting of glycerol monostearate, glycerol triacetate, leci least one biodegradable polyester is produced by condensa thin, mono-, and diglycerides, short and medium chain trig tion and/or by ring-opening. lycerides, acetylated monoglycerides, and combinations 57. (canceled) thereof. 58. A chewing gum according to claim 1, wherein said 49. (canceled) hydrophobic enzyme formulation is at least partly comprised 50. A chewing gum according to claim 1, wherein at least in the chewing gum and/or in a coating provided to the chew one of said at least one biodegradable polymer comprises at ing gum. least one biodegradable elastomer and/or at least one of said at least one biodegradable polymer comprises at least one 59. (canceled) biodegradable elastomer plasticizer. 60. Method of release controlling at least one enzyme in a 51. (canceled) chewing gum comprising at least one biodegradable polymer, 52. A chewing gum according to claim 1, wherein at least according to any of the preceding claims, whereby the control one of said at least one biodegradable polymer comprises at of release during chewing is obtained through addition of the least one synthetic polymer. hydrophobic enzyme formulation to the chewing gum. 53. (canceled) 61. Use of a hydrophobic enzyme formulation according to 54. A chewing gum according to claim 1, wherein the at any of the preceding claims, for the purpose of delaying or least one biodegradable polymer comprises at least one poly minimizing release of the enzyme from a chewing gum dur ester polymer obtained by polymerization of at least one ing chewing. alcohol orderivative thereofand at least one acid orderivative thereof.