Link:  Pharm/Biotech Resources

Title:  Method of controlling release of antimicrobial agents in chewing gum

United States Patent:  6,955,827

Issued:  October 18, 2005

Inventors:  Barabolak; Roman M. (Palos Park, IL); Zibell; Steven E. (Tinley Park, IL); Witkewitz; David L. (Bridgeview, IL); Greenberg; Michael J. (Northbrook, IL)

Assignee:  Wm. Wrigley Jr. Company (Chicago, IL)

Appl. No.:  619849

Filed:  July 14, 2003

A method for producing a chewing gum with a controlled release of an antimicrobial agent, as well as the chewing gum so produced, is obtained by physically modifying the release properties of the antimicrobial agent by coating and drying. The antimicrobial agent is coated by encapsulation, partially coated by agglomeration, entrapped by absorption, or treated by multiple steps of encapsulation, agglomeration, and absorption. The coated antimicrobial agent is preferably then co-dried and particle sized to produce a release-modified antimicrobial agent for use in chewing gum. When incorporated into the chewing gum, these particles are adapted to produce a fast release or a delayed release when the gum is chewed. The preferred antimicrobial agent is chlorhexidine digluconate.

SUMMARY OF THE INVENTION

The present invention is a method of producing chewing gum with antimicrobial agents which have been physically modified to control their release. The present invention also relates to the chewing gum so produced. These agents may be added to sucrose type gum formulations, replacing a small quantity of sucrose. The formulation may be a low or high moisture formulation containing low or high amounts of moisture containing syrup. These agents may also be used in low or non-sugar gum formulations, replacing a small quantity of sorbitol, mannitol, other polyols or carbohydrates. Non-sugar formulations may include low or high moisture sugar free chewing gums.

Antimicrobial agents may be combined or co-dried with bulk sweeteners typically used in chewing gum, such as sucrose, dextrose, fructose and maltodextrins, as well as sugar alcohols such as sorbitol, mannitol, xylitol, maltitol, lactitol, hydrogenated isomaltulose and hydrogenated starch hydrolyzates.

The modified release rate noted above may be a fast release or a delayed release. The modified release of antimicrobial agents is obtained by encapsulation, partial encapsulation or partial coating, entrapment or absorption with high or low water soluble materials or water insoluble materials. The procedures for modifying the antimicrobial agents include spray drying, spray chilling, fluid bed coating, coacervation, extrusion and other agglomerating and standard encapsulating techniques. Antimicrobial agents may also be absorbed onto an inert or water-insoluble material. Antimicrobial agents may be modified in a multiple step process comprising any of the processes, or a combination of the processes noted. Prior to encapsulation, antimicrobial agents may also be combined with bulk sweeteners including sucrose, dextrose, fructose, maltodextrin or other bulk sweeteners, as well as sugar alcohols such as sorbitol, mannitol, xylitol, maltitol, lactitol, hydrogenated isomaltulose and hydrogenated starch hydrolyzates.

Prior to encapsulation, antimicrobial agents may be combined with high-intensity sweeteners, including but not limited to thaumatin, aspartame, alitame, acesulfame K, saccharin acid and its salts, glycyrrhizin, cyclamate and its salts, stevioside and dihydrochalcones. Co-encapsulation of antimicrobial agents along with a high-intensity sweetener may improve the taste quality of the antimicrobial agent and control the sweetener release with the agent. This can improve the quality of the gum product and increase consumer acceptability.

Preferable antimicrobial agents include 1) TRICLOSAN (2,4,4-trichloro-2-hydroxydiphenyl ether), 2) cetylpyridinium chloride, 3) hexylresorcinol, and 4) chlorhexidine digluconate.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

In the context of this invention, chewing gum refers to chewing gum, bubble gum and the like. Moreover, all percentages are based on weight percentages unless otherwise specified. Further, although some terms are referred to in the singular, it is understood that coated products often contain multiple layers of coating. Therefore a phrase that refers to "the coating," refers to one or more layers of coating. Finally, all references cited herein are incorporated by reference.

As discussed previously, there are a wide variety of antimicrobial agents which can be used in oral compositions. Some of the preferred antimicrobial agents are 1) TRICLOSAN (2,4,4-trichloro-2-hydroxydiphenyl ether), 2) cetylpyridinium chloride, 3) hexylresorcinol, and 4) chlorhexidine digluconate. Among these, the most preferred is chlorhexidine digluconate.

Most of the antimicrobial agents vary in their water solubility. Some solubilities are:

Triclosan—about 0.05% at 25° C.

Hexylresorcinol—about 0.05% at 25° C.

Chlorhexidine digluconate—50% at 25° C.

Cetylpyridinium chloride—33% at 25° C.

In some instances, the water soluble agents which release readily from chewing gum may be modified by encapsulation to give an even faster release from chewing gum. However, in most instances the water soluble agents would be encapsulated or entrapped to give a delayed release from gum.

Other antimicrobial agents that are not very water soluble may release slowly and may not be as effective. As a result, encapsulation for fast release may be desired for these antimicrobial agents. Other agents may have a moderate release and these may be entrapped to give a much longer delayed release.

Levels of antimicrobial agents will vary according to their effectiveness. Generally, antimicrobial agents will be used in gum at about 0.01% to about 5% and preferably about 0.05% to about 2%. Most preferably, levels of 0.1% to about 1.0% should be used in chewing gum.

Water soluble antimicrobial agents can be added to chewing gum as a powder, as an aqueous dispersion, or dispersed in glycerin, propylene glycol, corn syrup, hydrogenated starch hydrolyzate, or any other compatible aqueous dispersion. Water insoluble agents can be added to chewing gum as a powder or with flavors, emulsifiers or organic softeners.

For aqueous dispersions, an emulsifier can also be mixed in the solution with the antimicrobial agents and the mixture added to a chewing gum. A flavor can also be added to the antimicrobial agents/ emulsifier mixture. The emulsion formed can be added to chewing gum. Antimicrobial agents in powder form may also be mixed into a molten chewing gum base during base manufacture or prior to manufacture of the gum. Antimicrobial agents may also be mixed with base ingredients during base manufacture.

As stated previously, antimicrobial agents release at various rates from chewing gum during the early stages of mastication of the gum because of their varying solubility in water. Physical modifications of the antimicrobial agent by encapsulation with highly water soluble substrates will increase their release in chewing gum by increasing the solubility or dissolution rate. Any standard technique which gives partial or full encapsulation can be used. These techniques include, but are not limited to, spray drying, spray chilling, fluid-bed coating and coacervation. These encapsulation techniques may be used individually in a single step process or in any combination in a multiple step process. The preferred technique for fast release of antimicrobial agents is spray drying.

Antimicrobial agents may also be encapsulated or entrapped to give a delayed release from chewing gum. Antimicrobial agents may be encapsulated with sweeteners, specifically high-intensity sweeteners such as thaumatin, dihydrochalcones, acesulfame K, aspartame, sucralose, alitame, saccharin and cyclamates to give improved taste when the antimicrobial agent is released.

The encapsulation techniques described herein are standard coating techniques and generally give varying degrees of coating from partial to full coating, depending on the coating composition used in the process. Generally, compositions that have high organic solubility, good film-forming properties and low water solubility give better delayed release, while compositions that have high water solubility give better fast release. Such low water-solubility compositions include acrylic polymers and copolymers, carboxyvinyl polymer, polyamides, polystyrene, polyvinyl acetate, polyvinyl acetate phthalate, polyvinylpyrrolidone and waxes. Although all of these materials are possible for encapsulation of antimicrobial agents, only food-grade materials should be considered. Two standard food-grade coating materials that are good film formers but not water soluble are shellac and Zein. Others which are more water soluble, but good film formers, are materials like agar, alginates, a wide range of cellulose derivatives like ethyl cellulose, methyl cellulose, sodium hydroxymethyl cellulose, and hydroxypropylmethyl cellulose, dextrin, gelatin, and modified starches. These ingredients, which are generally approved for food use, may give a fast release when used as an encapsulant for antimicrobial agents. Other encapsulants like acacia or maltodextrin can also encapsulate antimicrobial agents and give a fast release rate from gum.

The amount of coating or encapsulating material on the antimicrobial agents may also control the length of time for its release from chewing gum. Generally, the higher the level of coating and the lower the amount of active antimicrobial agents, the slower the release during mastication with low water soluble compositions. The release rate is generally not instantaneous, but gradual over an extended period of time. To obtain the delayed release to blend with a gum's flavor release, the encapsulant should be a minimum of about 20% of the coated antimicrobial agents. Preferably, the encapsulant should be a minimum of about 30% of the coated antimicrobial agents, and most preferably should be a minimum of about 40% of the coated antimicrobial agents. Depending on the coating material, a higher or lower amount of coating material may be needed to give the desired release.

Another method of giving a modified release of antimicrobial agents is agglomeration with an agglomerating agent which partially coats the antimicrobial agents. This method includes the step of mixing antimicrobial agents and an agglomerating agent with a small amount of water or other solvent. The mixture is prepared in such a way as to have individual wet particles in contact with each other so that a partial coating can be applied. After the water or solvent is removed, the mixture is ground and used as a powdered, coated antimicrobial agent.

Materials that can be used as the agglomerating agent are the same as those used in encapsulation mentioned previously. However, since the coating is only a partial encapsulation, some agglomerating agents are more effective in increasing the antimicrobial agents' release than others. Some of the better agglomerating agents for delayed release are the organic polymers like acrylic polymers and copolymers, polyvinyl acetate, polyvinylpyrrolidone, waxes, shellac and Zein. Other agglomerating agents are not as effective in giving a delayed release as are the polymers, waxes, shellac and Zein, but can be used to give some delayed release. Other agglomerating agents that give a fast release include, but are not limited to, agar, alginates, a wide range of water soluble cellulose derivatives like ethyl cellulose, methyl cellulose, sodium hydroxymethyl cellulose, hydroxypropylmethyl cellulose, dextrin, gelatin, modified starches, and vegetable gums like guar gum, locust bean gum and carrageenan. Even though the agglomerated antimicrobial agent is only partially coated, when the quantity of coating is increased compared to the quantity of antimicrobial agent, the release of antimicrobial agent can also be modified for mastication. The level of coating used in the agglomerated product is a minimum of about 5%. Preferably, the coating level is a minimum of about 15% and more preferably about 20%. Depending on the agglomerating material, a higher or lower amount of material may be needed to give the desired release of antimicrobial agent.

Antimicrobial agents may be coated in a two-step process or a multiple step process. Antimicrobial agents may be encapsulated with any of the materials as described previously and then the encapsulated antimicrobial agents can be agglomerated as previously described to obtain an encapsulated/agglomerated/antimicrobial agent product that could be used in chewing gum to give a delayed release of the antimicrobial agent.

In another embodiment of this invention, antimicrobial agents may be absorbed onto another component which is porous and become entrapped in the matrix of the porous component. Common materials used for absorbing antimicrobial agents include, but are not limited to, silicas, silicates, pharmasorb clay, spongelike beads or microbeads, amorphous carbonates and hydroxides, including aluminum and calcium lakes, all of which result in a delayed release of antimicrobial agents. Other water soluble materials including amorphous sugars such as spray-dried dextrose, sucrose, alditols and vegetable gums and other spray-dried materials result in a faster release of antimicrobial agents.

Depending on the type of absorbent materials and how it is prepared, the amount of antimicrobial agents that can be loaded onto the absorbent will vary. Generally materials like polymers or spongelike beads or microbeads, amorphous sugars and alditols and amorphous carbonates and hydroxides absorb about 10% to about 40% of the weight of the absorbent. Other materials like silicas and pharmasorb clays may be able to absorb about 20% to about 80% of the weight of the absorbent.

The general procedure for absorbing an antimicrobial agent onto the absorbent is as follows. An absorbent like fumed silica powder can be mixed in a powder blender and an aqueous solution of an antimicrobial agent can be sprayed onto the powder as mixing continues. The aqueous solution can be about 10% to 30% solids, and higher solid levels may be used if temperatures up to 90° C. are used. Generally water is the solvent, but other solvents like alcohol could also be used if approved for use in food. As the powder mixes, the liquid is sprayed onto the powder. Spraying is stopped before the mix becomes damp. The still free-flowing powder is removed from the mixer and dried to remove the water or other solvent, and is then ground to a specific particle size.

After the antimicrobial agent is absorbed or fixed onto an absorbent, the fixative/inhibitor can be coated by encapsulation. Either full or partial encapsulation may be used, depending on the coating composition used in the process. Full encapsulation may be obtained by coating with a polymer as in spray drying, spray chilling, fluid-bed coating, coacervation, or any other standard technique. A partial encapsulation or coating can be obtained by agglomeration of the fixative antimicrobial mixture using any of the materials discussed above.

Another form of encapsulation is by entrapment of an ingredient by fiber extrusion or fiber spinning into a polymer. Polymers that can be used for extrusion are PVAC, hydroxypropyl cellulose, polyethylene and other types of plastic polymers. A process of encapsulation by fiber extrusion is disclosed in U.S. Pat. No. 4,978,537, which is hereby incorporated by reference. The water insoluble polymer may be preblended with the antimicrobial agent prior to fiber extrusion, or may be added after the polymer is melted. As the extrudate is extruded, it results in small fibers that are cooled and ground. This type of encapsulation/entrapment generally gives a very long, delayed release of an active ingredient.

The four primary methods to obtain a modified release of the antimicrobial agent are: (1) encapsulation by spray drying, fluid-bed coating, spray chilling and coacervation to give full or partial encapsulation, (2) agglomeration to give partial encapsulation, (3) fixation or absorption which also gives partial encapsulation, and (4) entrapment into an extruded compound. These four methods, combined in any usable manner which physically modifies the release or dissolvability of the antimicrobial agent, are included in this invention.

A method of modifying the release rate of the antimicrobial agents from the chewing gum is to add the antimicrobial agents to the dusting compound of a chewing gum. A rolling or dusting compound may be applied to the surface of chewing gum as it is formed. This rolling or dusting compound serves to reduce sticking of the chewing gum product to machinery as it is formed and as it is wrapped, and sticking of the product to its wrapper after it is wrapped and is being stored. The rolling compound comprises an antimicrobial agent powder in combination with mannitol, sorbitol, sucrose, starch, calcium carbonate, talc, other orally acceptable substances or a combination thereof. The rolling compound constitutes from about 0.25% to about 10%, but preferably about 1% to about 3% by weight of the chewing gum composition. The amount of an antimicrobial agent powder added to the rolling compound is about 0.05% to about 10% of the rolling compound or about 5 ppm to about 1000 ppm of the chewing gum composition. This method of using an antimicrobial agent powder in the chewing gum allows for a lower usage level of the antimicrobial agent, gives an antimicrobial agent a fast release rate, eliminates absorption by the gum base, and reduces or eliminates any possible reaction with gum base, flavor components, or other components, yielding improved shelf stability.

Another method of modifying the release rate of an antimicrobial agent is to use it in the coating/panning of a pellet chewing gum. Pellet or ball gum is prepared as conventional chewing gum, but formed into pellets that are pillow shaped or into balls. The pellets/balls can then be sugar coated or panned by conventional panning techniques to make a unique sugar coated pellet gum. Some antimicrobial agents may generally be very stable and water soluble and can be easily dispersed in a sugar solution prepared for sugar panning. Other non-soluble antimicrobial agents can be added to flavors used in the coating or added as a powder blended with other powders often used in some types of conventional panning procedures. Using an antimicrobial agent in a coating isolates it from other gum ingredients and modifies its release rate in chewing gum, Levels of an antimicrobial agent may be about 100 ppm (0.01%) to about 25,000 ppm (2.5%) in the coating and about 50 ppm (0.005%) to about 10,000 ppm (1%) of the weight of the chewing gum product. The weight of the coating may be about 20% to about 50% of the weight of the finished gum product.

Conventional panning procedures generally coat with sucrose, but recent advances in panning have allowed the use of other carbohydrate materials to be used in the place of sucrose. Some of these components include, but are not limited to, dextrose, maltose, palatinose, xylitol, lactitol, hydrogenated isomaltulose and other new alditols or a combination thereof. These materials may be blended with panning modifiers including, but not limited to, gum arabic, maltodextrins, corn syrup, gelatin, cellulose type materials like carboxymethyl cellulose or hydroxymethyl cellulose, starch and modified starches, vegetable gums like alginates, locust bean gum, guar gum, and gum tragacanth, insoluble carbonates like calcium carbonate or magnesium carbonate and talc. Antitack agents may also be added as panning modifiers which allow for the use of a variety of carbohydrates and sugar alcohols in the development of new panned or coated gum products. Flavors may also be added with the sugar coating and with antimicrobial agents to yield unique product characteristics.

Another type of pan coating would also modify the release rate of antimicrobial agents from the chewing gum. This technique is referred to as film coating and is more common in pharmaceuticals than in chewing gum, but procedures are similar. A film like shellac, Zein, or cellulose-type material is applied onto a pellet-type product forming a thin film on the surface of the product. The film is applied by mixing the polymer, a plasticizer and a solvent (pigments are optional) and spraying the mixture onto the pellet surface. This is done in conventional type panning equipment, or in more advanced side-vented coating pans. When a solvent like alcohol is used, extra precautions are needed to prevent fires and explosions, and specialized equipment must be used.

Some film polymers can use water as the solvent in film coating. Recent advances in polymer research and in film coating technology eliminates the problem associated with the use of flammable solvents in coating. These advances make it possible to apply aqueous films to a pellet or chewing gum product. Since some antimicrobial agents are water soluble, they may be added to this aqueous film solution and applied with the film to the pellet or chewing gum product. The aqueous film, or even the alcohol solvent film, in which antimicrobial agents are dispersed may also contain a flavor along with the polymer and plasticizer.

The previously described encapsulated, agglomerated or absorbed antimicrobial agents may readily be incorporated into a chewing gum composition. The remainder of the chewing gum ingredients are noncritical to the present invention. That is, the coated particles of antimicrobial agents can be incorporated into conventional chewing gum formulations in a conventional manner. Coated antimicrobial agents may be used in a sugar chewing gum or a sugarless chewing gum. The coated antimicrobial agents may be used in either regular chewing gum or bubble gum.

In general, a chewing gum composition typically comprises a water-soluble bulk portion, a water-insoluble chewable gum base portion and typically water-insoluble flavoring agents. The water-soluble portion dissipates with a portion of the flavoring agent over a period of time during chewing. The gum base portion is retained in the mouth throughout the chew.

The insoluble gum base generally comprises elastomers, resins, fats and oils, waxes, softeners and inorganic fillers. Elastomers may include polyisobutylene, isobutylene-isoprene copolymer and styrene butadiene rubber, as well as natural latexes such as chicle. Resins include polyvinylacetate and terpene resins. Fats and oils may also be included in the gum base, including tallow, hydrogenated and partially hydrogenated vegetable oils, and cocoa butter. Commonly employed waxes include paraffin, microcrystalline and natural waxes such as beeswax and carnauba. According to the preferred embodiment of the present invention, the insoluble gum base constitutes between about 5% and about 95% by weight of the gum. More preferably the insoluble gum base comprises between about 10% and about 50% by weight of the gum, and most preferably between about 20% and about 35% by weight of the gum.

The gum base typically also includes a filler component. The filler component may be calcium carbonate, magnesium carbonate, talc, dicalcium phosphate or the like. The filler may constitute between about 5% and about 60% by weight of the gum base. Preferably, the filler comprises about 5% to about 50% by weight of the gum base.

Gum bases typically also contain softeners, including glycerol monostearate and glycerol triacetate. Further, gum bases may also contain optional ingredients such as antioxidants, colors, and emulsifiers. The present invention contemplates employing any commercially acceptable gum base.

The water-soluble portion of the chewing gum may further comprise softeners, sweeteners, flavoring agents and combinations thereof. Softeners are added to the chewing gum in order to optimize the chewability and mouth feel of the gum. Softeners, also known in the art as plasticizers or plasticizing agents, generally constitute between about 0.5% and about 15% by weight of the chewing gum. Softeners contemplated by the present invention include glycerin, lecithin and combinations thereof. Further, aqueous sweetener solutions such as those containing sorbitol, hydrogenated starch hydrolyzates, corn syrup and combinations thereof may be used as softeners and binding agents in gum.

As mentioned above, the coated antimicrobial agent of the present invention may be used in sugar or sugarless gum formulations. Sugar sweeteners generally include saccharide-containing components commonly known in the chewing gum art which comprise, but are not limited to, sucrose, dextrose, maltose, dextrin, dried invert sugar, fructose, levulose, galactose, corn syrup solids and the like, alone or in any combination. Sugarless sweeteners include components with sweetening characteristics but which are devoid of the commonly known sugars and comprise, but are not limited to, sugar alcohols such as sorbitol, mannitol, xylitol, hydrogenated starch hydrolyzates, maltitol and the like, alone or in any combination.

Depending on the particular antimicrobial agent release profile and shelf-stability needed, the coated antimicrobial agent of the present invention can also be used in combination with uncoated high-potency sweeteners or with high-potency sweeteners coated with other materials and by other techniques.

A flavoring agent may also be present in the chewing gum in an amount within the range of from about 0.1% to about 15%, preferably from about 0.5% to about 3%, by weight of the gum. The flavoring agents may comprise essential oils, synthetic flavors, or mixtures thereof including, but not limited to oils derived from plants and fruits such as citrus oils, fruit essences, peppermint oil, spearmint oil, clove oil, oil of wintergreen, anise, and the like. Artificial flavoring components are also contemplated for use in gums of the present invention. Those skilled in the art will recognize that natural and artificial flavoring agents may be combined in any sensorally acceptable blend. All such flavors and flavor blends are contemplated by the present invention.

Optional ingredients such as colors, emulsifiers and pharmaceutical agents may be added to the chewing gum.

In general, chewing gum is manufactured by sequentially adding the various chewing gum ingredients to a commercially available mixer known in the art. After the ingredients have been thoroughly mixed, the gum mass is discharged from the mixer and shaped into the desired form such as by rolling into sheets and cutting into sticks, extruding into chunks or casting into pellets.

Generally, the ingredients are mixed by first melting the gum base and adding it to the running mixer. The base may also be melted in the mixer itself. Color or emulsifiers may also be added at this time. A softener such as glycerin may also be added at this time, along with syrup and a portion of the bulking agent. Further portions of the bulking agent may then be added to the mixer. A flavoring agent is typically added with the final portion of the bulking agent. The coated antimicrobial agent of the present invention is preferably added after the final portion of bulking agent and flavor have been added.
 

Claim 1 of 20 Claims

1. A method of producing a chewing gum product containing an antimicrobial agent wherein a rolling compound is applied on the chewing gum product and the antimicrobial agent is a part of the rolling compound applied on the chewing gum product.

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