AU2626700A - Chewing gum with dental health benefits employing calcium lactate - Google Patents

Description

WO 00/42861 PCT/US00/01733 SPECIFICATION TITLE "CHEWING GUM WITH DENTAL HEALTH BENEFITS EMPLOYING CALCIUM LACTATE" 5 BACKGROUND OF THE INVENTION The present invention relates generally to chewing gums. More specifically, the present invention relates to chewing gums that can provide dental benefits. 10 Except for the common cold, dental caries (tooth decay) is the most prevalent human disorder. See, The Merck Manual, Sixteenth Edition, p. 2480. Even though, many steps have been taken to reduce dental caries and tooth decay, such as fluoridation and improved dental care, tooth decay continues to be a significant problem. This is especially true in the adult population; 80% of the tooth decay occurs in 20% of the 15 population. See Featherstone, An Updated Understanding of the Mechanism ofDental Decay and its Prevention, Nutrition Quarterly, Vol. 14, No. 1, 1990, pp. 5-11. To protect a normal tooth, a thin layer of dental enamel forms a protective coating over the tooth. This coating consists mainly of calcium, phosphate, and other ions in a hydroxyapatite-like structure. The enamel contains 2 to 5 percent carbonate; this 20 carbonate content makes the enamel susceptible to acid dissolution. See, Featherstone, id. at6. The interaction of three factors is believed to result in dental caries: a susceptible tooth surface; the proper microflora; and a suitable substrate for the microflora. Although several acidogenic micro-organisms that are present in the mouth can initiate carious 25 lesions, Streptococcus mutans is believed to be the primary pathogen. See, The Merck Manual, supra. It is known that foods containing fermentable carbohydrates can promote dental caries. Tooth decay begins when the Streptococcus mutans, that reside principally in the plaque that adheres to a tooth surface, metabolize the fermentable carbohydrates 30 consumed by the host. During the metabolism of the fermentable carbohydrates by the bacteria, lactic acid and other organic acids are secreted as a by-product. These acids reduce the pH of the surrounding plaque/tooth environment. -1- WO 00/42861 PCT/US00/01733 When the pH of the plaque/tooth environment drops below a critical level of 5.5 to 5.7, hydroxyapatite (calcium phosphate hydroxide, CaI 0 (PO4) 6

(OH)

2 ), the key component of tooth enamel, begins to dissolve. This critical pH can change depending on the concentration of the key ions. Typically, the dissolution begins below the tooth's 5 porous surface. With repeated acid attacks, caused by the further metabolism of fermentable carbohydrates by the bacteria, subsurface lesions expand. The body's natural remineralization mechanism, however, at this point, can still reverse the decay process. But, if the lesions expand to the point that the enamel surface breaks, a cavity is formed 10 and the process is no longer reversible. The natural remineralization process involves, in part, the flow of saliva over the plaque. The saliva can raise the pH of the environment. Additionally, calcium and phosphate ions in the saliva precipitate out to replace the hydroxyapatite that was dissolved by the organic acids created during the metabolism of the fermentable 15 carbohydrates. However, typically, this remineralization process only occurs at significant levels when the pH is above the critical level. Therefore, if the saliva does not sufficiently raise the pH, significant remineralization will not occur. But, the remineralization process may be enhanced by fluoride in the oral cavity that speeds up new crystal growth and makes 20 a flurorapatite-like material that is precipitated on the surface of the crystals inside the caries lesion. See, Featherstone, id. at 7. A number of salts have been reported in certain experiments to counteract demineralization. One of the difficulties is providing a viable vehicle for delivering the salts. Still further, a number of safety issues are raised by some of the salts. 25 Furthermore, sensory problems with respect to some of the salts prevent these salts from being taken on a regular basis by a patient to provide prophylactic benefits. U.S. Patent No. 5,378,171 discloses a sugar chewing gum with dental health benefits that includes calcium glycerophosphate. 30 -2- WO 00/42861 PCT/US00/01733 SUMMARY OF THE INVENTION The present invention provides a composition and method for the remineralization of enamel. Pursuant to the present invention, sugar free chewing gum is provided that includes a therapeutically effective amount of calcium lactate. 5 It has been found that calcium lactate counteracts the decaying process. Calcium lactate is believed to function by promoting remineralization of the tooth enamel caused by dental caries. Calcium lactate has been found to be an effective enamel remineralization agent that is acceptable from sensory and safety standpoints. Pursuant to the present invention, calcium lactate can be used in chewing gum. 10 Chewing gum is an especially good vehicle for delivering calcium lactate because it can deliver the ingredient over prolonged periods of time. Additionally, chewing gum can be conveniently used almost anywhere, at anytime, as opposed to a rinse or dentifrices. To this end, a method for remineralizing enamel is provided comprising the step of providing a chewing gum that includes a therapeutically effective amount of calcium 15 lactate. In an embodiment, two pieces of chewing gum are chewed at a time. In an embodiment of the method, the gum is chewed at least twice a day. In an embodiment of the method, the chewing gum produces a calcium ion concentration in the saliva of the mouth of the chewer of at least 200 ppm. 20 In an embodiment of the method, the gum is chewed for at least two minutes. The present invention also provides a chewing gum for reducing the generation of dental caries comprising a water insoluble base, water soluble portion and flavor, and calcium lactate. In an embodiment, the chewing gum is sugarless. 25 In an embodiment, the chewing gum is wax-free. In an embodiment, the chewing gum is a low calorie chewing gum. In an embodiment, the chewing gum contains other therapeutic agents. In an embodiment, the chewing gum includes at least 40 mg of calcium lactate. In an embodiment, the chewing gum is in the form of a stick. 30 In an embodiment, the chewing gum is in the form of a pellet. In an embodiment, the chewing gum includes an additional therapeutic agent. -3- WO 00/42861 PCT/US00/01733 An advantage of the present invention is to provide a method for preventing, or reducing the risk of, dental caries of the remineralization of enamel. Another advantage of the present invention is to treat dental caries. Additionally, an advantage of the present invention is to provide a chewing gum 5 that can be used to improve dental health. Further, an advantage of the present invention is to provide a chewing gum that does not have the sensory drawbacks of other sources of calcium. Moreover, an advantage of the present invention is to provide an easy and enjoyable way to improve dental health. 10 Still further, an advantage of the present invention is to provide a composition and method for delivering a therapeutic agent over a prolonged period of time to the oral region. Additional features and advantages of the present invention are described in, and will be apparent from, the detailed description of the presently preferred embodiments. 15 DETAILED DESCRIPTION OF THE PRESENTLY PREFERRED EMBODIMENTS The present invention provides a method and composition for remineralizing tooth enamel and thereby preventing and/or treating dental caries. Pursuant to the present 20 invention, a chewing gum is provided that includes a therapeutically effective amount of calcium lactate. The chewing gum of the present invention, by including a therapeutically effective amount of calcium lactate, can improve dental health when chewed. Calcium lactate is believed to function by the remineralization of tooth enamel. 25 Calcium lactate when provided in a chewing gum can produce a calcium ion concentration in the saliva during chewing which is effective to remineralized carious lesions in teeth. For example, it has been found that 80 mg of calcium lactate in chewing gum will produce saliva calcium levels greater than 500 parts per million, this level has been shown to remineralize teeth. 30 It is believed that the calcium ion concentration in the saliva should be above 200 ppm in order to initiate the remineralization process. Preferably the calcium ion concentration should be above 350 ppm and most preferably above 500 ppm. These -4- WO 00/42861 PCT/US00/01733 levels should be provided for at least one minute, preferably more than two minutes, and most preferably more than four minutes upon chewing the gum. It has been found that these levels can be accomplished by the inclusion of at least 40 mg, preferably at least 60 mg and most preferably at least 80 mg of calcium lactate 5 in a piece of chewing gum. In some cases, it may be desirable to divide the prescribed dosage among two or more smaller pieces of gum which are intended to be chewed together. In another embodiment of the invention, a method for the remineralization of carious lesions in teeth is provided that comprises providing a sugarless chewing gum 10 comprising calcium lactate. The gum is chewed for at least two minutes (preferably at least 5 minutes and most preferably at least 20 minutes) whereby the calcium is released by the gum in a quantity sufficient to produce a calcium concentration which is effective to remineralized the carious lesions. This treatment is repeated at least twice, preferably at least three times, and most preferably at least five times daily until the lesion has been 15 remineralized. The chewing gum composition may be any chewing gum formula and most preferably a sugarless formulation. Such formulas typically contain a major amount of a sugar alcohol bulking agent, a substantial portion of gum base, minor amounts of syrups, softeners, flavors, color and high intensity sweeteners. Low calorie gums which 20 contain reduced levels of sugar alcohols and increased levels of base and/or low calorie or calorie-free bulking agents are also anticipated. The product may be formed into tabs, sticks, chunks or coated pellets. A piece size of 1 to 4 grams is preferred. As previously mentioned, with smaller pieces sizes, it may be desirable to split the calcium lactate dosage between two or more pieces to reduce the concentration for improved sensory 25 acceptability. Chewing gum generally consists of a water insoluble gum base, a water soluble portion, and flavors. The water soluble portion dissipates with a portion of the flavor over a period of time during chewing. The gum base portion is retained in the mouth throughout the chew. 30 The insoluble gum base generally comprises elastomers, resins, fats and oils, softeners, and inorganic fillers. The gum base may or may not include wax. The -5- WO 00/42861 PCT/US00/01733 insoluble gum base can constitute approximately 5 to about 95 percent, by weight, of the chewing gum, more commonly, the gum base comprises 10 to about 50 percent of the gum, and in some preferred embodiments, 20 to about 35 percent, by weight, of the chewing gum. 5 In an embodiment, the chewing gum base of the present invention contains about 20 to about 60 weight percent synthetic elastomer, 0 to about 30 weight percent natural elastomer, about 5 to about 55 weight percent elastomer plasticizer, about 4 to about 35 weight percent filler, about 5 to about 35 weight percent softener, and optional minor amounts (about one percent or less) of miscellaneous ingredients such as colorants, 10 antioxidants, etc. Synthetic elastomers may include, but are not limited to, polyisobutylene with GPC weight average molecular weight of about 10,000 to about 95,000, isobutylene isoprene copolymer (butyl elastomer), styrene-butadiene copolymers having styrene butadiene ratios of about 1:3 to about 3:1, polyvinyl acetate having GPC weight average 15 molecular weight of about 2,000 to about 90,000, polyisoprene, polyethylene, vinyl acetate-vinyl laurate copolymer having vinyl laurate content of about 5 to about 50 percent by weight of the copolymer, and combinations thereof. Preferred ranges are, for polyisobutylene, 50,000 to 80,000 GPC weight average molecular weight, for styrene-butadiene, 1:1 to 1:3 bound styrene-butadiene, for 20 polyvinyl acetate, 10,000 to 65,000 GPC weight average molecular weight with the higher molecular weight polyvinyl acetates typically used in bubble gum base, and for vinyl acetate-vinyl laurate, vinyl laurate content of 10-45 percent. Natural elastomers may include natural rubber such as smoked or liquid latex and guayule as well as natural gums such as jelutong, lechi caspi, perillo, sorva, 25 massaranduba balata, massaranduba chocolate, nispero, rosindinha, chicle, gutta hang kang, and combinations thereof The preferred synthetic elastomer and natural elastomer concentrations vary depending on whether the chewing gum in which the base is used is abhesive or conventional, bubble gum or regular gum, as discussed below. Preferred natural elastomers include jelutong, chicle, sorva and massaranduba balata. 30 Elastomer plasticizers may include, but are not limited to, natural rosin esters such as glycerol esters of partially hydrogenated rosin, glycerol esters polymerized rosin, -6- WO 00/42861 PCT/US00/01733 glycerol esters of partially dimerized rosin, glycerol esters of rosin, pentaerythritol esters of partially hydrogenated rosin, methyl and partially hydrogenated methyl esters of rosin, pentaerythritol esters of rosin; synthetics such as terpene resins derived from alpha pinene, beta-pinene, and/or d-limonene; and any suitable combinations of the foregoing. 5 the preferred elastomer plasticizers will also vary depending on the specific application, and on the type of elastomer which is used. Fillers/texturizers may include magnesium and calcium carbonate, ground limestone, silicate types such as magnesium and aluminum silicate, clay, alumina, talc, titanium oxide, mono-, di- and tri-calcium phosphate, cellulose polymers, such as wood, 10 and combinations thereof. Softeners/emulsifiers may include tallow, hydrogenated tallow, hydrogenated and partially hydrogenated vegetable oils, cocoa butter, glycerol monostearate, glycerol triacetate, lecithin, mono-, di- and triglycerides, acetylated monoglycerides, fatty acids (e.g. stearic, palmitic, oleic and linoleic acids), and combinations thereof. 15 Colorants and whiteners may include FD&C-type dyes and lakes, fruit and vegetable extracts, titanium dioxide, and combinations thereof. The base may or may not include wax. An example of a wax-free gum base is disclosed in U.S. Patent No. 5,286,500, the disclosure of which is incorporated herein by reference. 20 In addition to a water insoluble gum base portion, a typical chewing gum composition includes a water soluble bulk portion and one or more flavoring agents. The water soluble portion can include bulk sweeteners, high intensity sweeteners, flavoring agents, softeners, emulsifiers, colors, acidulants, fillers, antioxidants, and other components that provide desired attributes. 25 Softeners are added to the chewing gum in order to optimize the chewability and mouth feel of the gum. The softeners, which are also known as plasticizers and plasticizing agents, generally constitute between approximately 0.5 to about 15% by weight of the chewing gum. The softeners may include glycerin, lecithin, and combinations thereof. Aqueous sweetener solutions such as those containing sorbitol, 30 hydrogenated starch hydrolysates, corn syrup and combinations thereof, may also be used as softeners and binding agents in chewing gum. -7- WO 00/42861 PCT/US00/01733 Bulk sweeteners include both sugar and sugarless components. Bulk sweeteners typically constitute 5 to about 95% by weight of the chewing gum, more typically, 20 to 80% by weight, and more commonly, 30 to 60% by weight of the gum. Sugar sweeteners generally include saccharide-containing components commonly 5 known in the chewing gum art, including, but not limited to, sucrose, dextrose, maltose, dextrin, dried invert sugar, fructose, levulose, galactose, corn syrup solids, and the like, alone or in combination. Sugarless sweeteners include, but are not limited to, sugar alcohols such as sorbitol, mannitol, xylitol, hydrogenated starch hydrolysates, maltitol, and the like, alone 10 or in combination. High intensity artificial sweeteners can also be used, alone or in combination with the above. Preferred sweeteners include, but are not limited to sucralose, aspartame, salts of acesulfame, alitame, saccharin and its salts, cyclamic acid and its salts, glycyrrhizin, dihydrochalcones, thaumatin, monellin, and the like, alone or in combination. In order 15 to provide longer lasting sweetness and flavor perception, it may be desirable to encapsulate or otherwise control the release of at least a portion of the artificial sweetener. Such techniques as wet granulation, wax granulation, spray drying, spray chilling, fluid bed coating, coacervation, and fiber extension may be used to achieve the desired release characteristics. 20 Usage level of the artificial sweetener will vary greatly and will depend on such factors as potency of the sweetener, rate of release, desired sweetness of the product, level and type of flavor used and cost considerations. Thus, the active level of artificial sweetener may vary from 0.02 to about 8%. When carriers used for encapsulation are included, the usage level of the encapsulated sweetener will be proportionately higher. 25 Combinations of sugar and/or sugarless sweeteners may be used in chewing gum. Additionally, the softener may also provide additional sweetness such as with aqueous sugar or alditol solutions. If a low calorie gum is desired, a low caloric bulking agent can be used. Example of low caloric bulking agents include: polydextrose; Raftilose, Raftilin; 30 Fructooligosaccharides (NutraFlora); Palatinose oligosaccharide; Guar Gum Hydrolysate (Sun Fiber); or indigestible dextrin (Fibersol). However, other low calorie bulking agents -8- WO 00/42861 PCT/US00/01733 can be used. A variety of flavoring agents can be used. The flavor can be used in amounts of approximately 0.1 to about 15 weight percent of the gum, and preferably, 0.2 to 5%. Flavoring agents may include essential oils, synthetic flavors or mixtures thereof 5 including, but not limited to, oils derived from plants and fruits such as citrus oils, fruit essences, peppermint oil, spearmint oil, other mint oils, clove oil, oil of wintergreen, anise and the like. Artificial flavoring agents and components may also be used. Natural and artificial flavoring agents may be combined in any sensorially acceptable fashion. Additional oral health ingredients may be added including but not limited to, 10 antiplaque/anti-gingivitis agents (such as chlorhexidine, CPC, triclosan), pH control agents (including Urea and buffers,) other inorganic components for tarter or caries control (phosphates, fluoride) and biological agents (antibodies, enzymes). The only requirement is that the agents be safe and effective and that they do not react undesirably with each other such as may happen with phosphate salts. 15 Preferably the calcium lactate is mixed into the chewing gum mass but it may also be added to a coating syrup or used as a dry charge in a coating process in the case of a coated chewing gum. The following examples, which as of this time have not been made, illustrate some embodiments of the invention. Of course, many others are possible. 20 -9- WO 00/42861 PCT/US00/01733 EXAMPLES 1 2 3 4 Gum Base 30.0% 32.60% 30.0% 70.0% Sorbitol 40.0 - 25.4 10.4 5 Maltitol - 30.00 - Xylitol 0.5 15.00 30.0 Mannitol 7.0 5.00 2.0 2.0 Calcium Lactate 3.0 4.00 4.0 6.0 Aspartame 0.5 - 0.2 10 Acesulfame K - 0.15 0.1 Sucralose - 0.15 - 0.2 Alitame - - 0.1 Neotame -- 0.1 Sorbitol Solution 15.0 - 5.0 15 (70% solids) Hydrogenated Starch - 9.00 - 5.0 Hydrolysate Syrup (85% solids) Glycerin 3.0 3.00 2.0 5.0 20 Color - 0.10 0.2 0.3 Flavor 1.0 1.00 1.0 1.0 (Spearmint) (Cinnamon) (Peppermint) (Wintergreen) Total 100% 100% 100% 100% Form 3g stick 3g stick 2g tab Ig tab 25 -10- WO 00/42861 PCT/US00/01733 EXAMPLES 7 8 9 10 Gum Base 25.0% 35.00% 35.0% 30.0% 5 Sorbitol 31.9 - 35.0 39.50% Polydextrose - 40.88 - Xylitol 15.0 - 5.0 5.00 Mannitol 5.0 5.00 5.0 4.00 Calcium Lactate 3.0 2.00 4.0 4.00 10 Aspartame 0.5 0.50 0.3 0.50 Chlorhexidine - 0.17 - Triclosan - 0.25 - Urea 3.5 - - 0.50 S. Mutans Monclonal - - - 0.50 15 Antibodies Glycerin 5.0 5.00 5.0 15.00 Hydrogenated Starch 10.0 10.00 9.9 Hydrolysate Syrup (85% solids) 20 Color 0.1 0.20 0.1 0.15 Flavor 1.0 1.00 0.7 0.85 (Sweet Fruit) (Peppermint) (Menthol) (Spearmint) Total 100.0% 100.00% 100.0% 100.00% Form 3g stick 3g stick Ig pellet 3g stick center Notes on Examples: 25 Examples 4 and 8 are low caloric chewing gums. Example 9 may be coated with xylitol, sorbitol, palatinit or maltitol with added chlorhexidine, triclosan and/or cetylpyridinium chloride (CPC). Recommended dose is two pellets. 30 -11- WO 00/42861 PCT/US00/01733 In-vitro testing was conducted to determine what level of calcium in saliva would remineralize softened tooth enamel. Enamel specimens were removed from extracted human teeth, polished and decalcified by exposure to 0.1M lactic acid solution. This treatment resulted in lesions with a surface hardness range of 25 to 45 Vicker's Hardness 5 Number (VHN) and an average lesion depth of 40-70 microns. Solutions of calcium and fluoride in artificial saliva (prepared from a formula in Caries Research, 16:201, 1982) were prepared to treat the enamel. The saliva formula includes 1.5mM (40 ppm) of calcium per liter. Two calcium levels were tested, 0 and 500 ppm and each level was prepared with 0, 0.05 and 0.10 ppm fluoride to simulate the 10 effect of tooth brushing. The "Zero" calcium level had no calcium added to the 40 ppm already present. The 500 ppm calcium level had 460 ppm additional calcium to bring the total concentration up to 500 ppm. The six solutions thus prepared are summarized in Table 1. Table 1 15 Solution Fluoride (ppm) Calcium (ppm) 1 0 0 2 0 500 3 0.05 0 20 4 0.05 500 5 0.10 0 6 0.10 500 Enamel samples were exposed to 20 minutes of acid challenge followed by 60 minutes of one calcium/fluoride solution (above) then 30 minutes of pure saliva. This 25 cycle was repeated three times daily, four days per week for 3 weeks. The samples were tested for hardness after each week. Each treatment was performed on 12 samples. The results are reported in Table 2. -12- WO 00/42861 PCT/US00/01733 Table 2 Change in Hardness Baseline VHN One Week Two Week Three Week Soln. F Ca n Mean SD. n Mean SD n Mean SD. n Mean SD (ppm) (ppm) 5 0 0 12 36.95 7.96 12 334 3.65 12 5.07 5.94 12 5.85 545 2 0 500 12 35.79 8.52 12 7.23 4.70 12 10.93 5.63 12 11.60 770 3 0.05 0 11 38.03 8.53 11 360 6.42 11 794 6.05 11 7.74 10.15 4 005 500 12 33.29 6.24 12 615 3.70 12 1379 12.09 12 15.92 538 5 01 0 12 3395 8.30 12 937 508 12 1082 6.08 12 12.65 640 10 6 01 500 12 37.52 6.25 12 1014 4.96 12 13 28 4.78 12 1699 912 Analysis of variance was used to determine the contribution of the two variables (fluoride and calcium) to the remineralization effect. The results are given as Tables 3 15 and 4. Table 3 Change in VHN Hardness Due to Fluoride (Comparison Groups*) 20 F (ppm) Week 1 Week 2 Week 3 0.00 5.27(A) 8.01(B) 8.72(C) 0.05 4.88(A) 10.88(B) 11.88 (C D) 0.10 9.76 12.04(B) 14.82(D) *Results of pairwise comparisons of treatments/effects. Groups marked with the same 25 letter did not differ significantly (p<0.05). Table 4 Change in VHN Hardness Due to Calcium (p values **) 30 Ca (ppm) Week 1 Week 2 Week 3 0 5.43 7.97 8.77 500 7.84 (0.0389) 12.65 (0.0079) 14.84 (0.0012) ** Probability that the difference between 0 and 500 ppm values is due totally to chance. 35 -13- WO 00/42861 PCT/US00/01733 From this analysis it was concluded that fluoride had little effect on remineralization but that 500 ppm calcium in saliva significantly increased remineralization of decalcified enamel over time. It is very likely that lower levels would also be effective given the magnitude of the effect and the strength of the statistical 5 significance. Four chewing gum compositions were prepared according to the formulas of Examples 11, 12, 13, and 14. Table 5 10 Example 11 Example 12 Example 13 Example 14 Gum Base 31.40% 32.40% 32.40 32.40 Sorbitol 38.78 38.75 41.75 41.75 Xylitol 15.60 15.60 15.60 15.60 Mannitol 4.00 4.00 4.00 4.00 15 Glycerin 3.00 3.00 3.00 3.00 Calcium Lactate 4.00 3.00 - Flavor 2.40 2.40 2.40 2.40*** Encapsulated 0.59 0.63 0.63 0.63 Acesulfame K 20 Encapsulated 0.12 0.12 0.12 0.12 Aspartame Acesulfame K 0.05 0.04 0.04 0.04 Red Color 0.06 0.06 0.06 0.06 Total 100.00 100.00 100.00 100.00 25 Form 2.0g Tab 2.7g Stick 2.0g Tab 2.7g Stick (Inventive) (Inventive) (Comparative) (Comparative) Calcium Lactate 80mg 81mg 0 0 per piece *** Example 14 used a different flavor from the other three Examples. 30 -14- WO 00/42861 PCT/US00/01733 Eight volunteers chewed the gums of Examples 11 and 12 for six minutes with saliva samples collected over two minute intervals. The saliva samples were analyzed for calcium by Direct Current Plasma. The two products delivered similar calcium levels reported in Table 6. 5 Table 6 Salivary Calcium Concentration (ppm) Time (min) Example 11 Example 12 10 Base line (no gum) 70 82 0-2 597 599 2-4 365 386 4-6 302 341 To demonstrate the sensory acceptability of the calcium lactate, consumer blind 15 taste tests were run using Examples 11, 12, 13 and 14. Eighty children (6-10 years old, 50:50 male:female) rated each sample on a five point scale ("5" being the best rating) for overall preference. The results were: Example 11 Example 12 Example 13 Example 14 Tab with 4% Stick with 3% Tab Control Stick Control Calcium Calcium For Ex. 11 For Ex. 12 Lactate Lactate 20 Overall 4.23 4.38 4.28 4.49 Preference ("5" = best) Based on these results it was concluded that calcium lactate had little or no effect on consumer preference. Note that the higher score for Ex. 14 may have been due to its 25 use of a different flavor from the other samples. -15- WO 00/42861 PCT/US00/01733 It should be understood that various changes and modifications to the presently preferred embodiments described herein will be apparent to those skilled in the art. Such changes and modifications can be made without departing from the spirit and scope of the present invention and without diminishing its intended advantages. It is therefore 5 intended that such changes and modifications be covered by the appended claims. -16-

Claims (25)

1. A sugar free chewing gum for promoting the remineralization of tooth enamel comprising: a water insoluble base portion; 5 a water soluble portion; a flavor; and calcium lactate.

2. The chewing gum of Claim 1 wherein the chewing gum contains at least 10 one other therapeutic agent.

3. The chewing gum of Claim 1 including at least 40 mg of calcium lactate.

4. The chewing gum of Claim 1 including at least 60 mg of calcium lactate. 15

5. The chewing gum of Claim 1 including at least 80 mg of calcium lactate.

6. The chewing gum of Claim 1 wherein the calcium lactate is divided among two or more pieces. 20

7. The chewing gum of Claim 1 wherein the gum is in the form of a stick.

8. The chewing gum of Claim 1 wherein the gum is in the form of a tab. 25

9. A method for promoting the remineralization of tooth enamel comprising the steps of chewing a chewing gum that includes a therapeutically effective amount of calcium lactate.

10. The method of Claim 9 wherein two pieces of chewing gum are chewed 30 at a time. -17- WO 00/42861 PCT/US00/01733

11. The method of Claim 9 wherein the gum is chewed at least twice a day.

12. The method of Claim 9 wherein the chewing gum produces a calcium ion concentration in the saliva of the mouth of the chewer of at least 200 ppm. 5

13. The method of Claim 9 wherein the chewing gum produces a calcium ion concentration in the saliva of the mouth of the chewer of at least 350 ppm.

14. The method of Claim 9 wherein the chewing gum produces a calcium ion 10 concentration in the saliva of the mouth of the chewer of at least 500 ppm.

15. The method of Claim 9 wherein a calcium ion concentration is maintained for at least 2 minutes. 15

16. A chewing gum for remineralizing tooth enamel comprising: a water insoluble portion; a water soluble portion; a flavor; and sufficient calcium lactate to produce a calcium ion concentration in the mouth of 20 the chewer of at least 200 ppm.

17. The chewing gum of Claim 16 wherein the chewing gum contains other therapeutic agents. 25

18. The chewing gum of Claim 16 including at least 40 mg of calcium lactate.

19. The chewing gum of Claim 16 including at least 60 mg of calcium lactate.

20. The chewing gum of Claim 16 including at least 80 mg of calcium lactate. 30

21. The chewing gum of Claim 16 wherein the gum is in the form of a stick. -18- WO 00/42861 PCT/US00/01733

22. The chewing gum of Claim 16 wherein the gum is in the form of a tab.

23. The chewing gum of Claim 16 wherein the gum is in the form of a stick wherein the calcium lactate is divided among two or more pieces. 5

24. The chewing gum of Claim 16 wherein the gum comprises sufficient calcium lactate to produce a calcium ion concentration in the mouth of the chewer of at least 350 ppm. 10

25. The chewing gum of Claim 16 wherein the gum comprises sufficient calcium lactate to produce a calcium ion concentration in the mouth of the chewer of at least 500 ppm. -19-