Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
  • A61K8/04—Dispersions; Emulsions
  • A61K8/046—Aerosols; Foams
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
  • A61K8/0216—Solid or semisolid forms
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
  • A61K8/20—Halogens; Compounds thereof
  • A61K8/21—Fluorides; Derivatives thereof
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses

Definitions

• This invention relates to dental hygiene and more particularly to chewable tablets for improving dental hygiene.
• U.S. Patent No. 1,262,888 discloses a tablet comprised of tartaric and citric acid, sodium bicarbonate and desiccated fruit pulp which dissolves with effervescence in the mouth into a thin slurry. The tablet may also "sparingly” incorporate “precipitated chalk to reinforce the desiccated pulp”.
• U.S. Patent No. 3,962,417 discloses an effervescent dentifrice in chewable tablet form, again employing a high percentage of a carbon dioxide producing couple, namely 68% by weight, magnesium carbonate 11%, and stannous fluoride.
• the prior art can be categorized as disclosing self-effervescent, that is, CO 2 producing tablets, containing a major portion of CO 2 couple and a minor proportion of polishing agents; these tablets being designed to rapidly dissolve in the mouth to form a liquid or at best a thin slurry.
• the other prior art tablets are not effervescent, merely tabletted toothpaste, which contains sodium lauryl sulfate, a foam stabilizing agent, which will stabilize any foam formed upon brushing, or a detergent to aid in foaming or sudsing, during brushing or by sucking air into the mouth as proposed by Gyarmathy et al.
• Recently issued Gioffre et al U.S. Patent No. 4,627,972 proposed the use of zeolites having adsorbed carbon dioxide to produce the carbon dioxide upon wetting in the mouth for dentifrices and suggests that they may be used in chewable dental tablets.
• the tooth cleaning tablet of the invention is designed to form a self-foaming paste when chewed in the mouth.
• the paste is then swished around the mouth and through the teeth for about 1 to 2 minutes (preferably at least 2 minutes) and then swallowed.
• This cleans and polishes the tooth surfaces by mechanical action and brings the fluoride and tin ions into contact with the tooth surfaces and the bacterium in the mouth.
• the fluoride ion in the mouth penetrates the enamel and the tin ion becomes incorporated into the plaque and caries bacteria and has a bacteriostatic action.
• the swallowed fluoride ion becomes incorporated into newly formed tooth enamel.
• a composition producing carbon dioxide in order to provide a paste rather than a thin slurry, which would not be as effective mechanically cleaning or delivering the fluoride and tin ions to the tooth surfaces, we employ less than about 50% by weight of a composition producing carbon dioxide and greater than about 35% by weight of a substantially insoluble filling and polishing composition which forms a paste on chewing in the mouth.
• a filling and polishing composition which comprises greater than about 50% by weight of the tablet and a carbon dioxide producing composition comprising less than about 25% by weight of the tablet to prevent excess, foaming which would excessively thin the paste.
• the filling and polishing composition is preferably substantially insoluble in the mouth when the tablet is used and may contain about 34% polishing agent and about 31% filling agent.
• the tablet may contain 13% sodium carbonate and 5% acid.
• the tablets are substantially water free to prevent degradation of the stannous fluoride and the stannous fluoride is employed in an effective amount, preferably less than about 3% of the tablet.
• the object of the invention is to provide a tooth cleaning, caries and plaque reducing tablet for use in the mouth and a method of using the tablet.
• Another object of the invention is to provide such a tablet which provides improved anti-caries and anti-plaque activity than heretofore achieved.
• the invention accordingly comprises an article of manufacture possessing the features, properties and the relation of elements, a composition of matter possessing the characteristics, properties and the relation of components and a method of using the article and composition, all of which will be exemplified in the articles, compositions, and methods hereinafter described.
• the scope of the invention will be indicated in the claims.
• the tablet of the invention preferably comprises;
• a tooth protecting agent preferably stannous fluoride.
• the polishing agent should be substantially insoluable in the mouth and may be an appropriate phosphate, a carbonate or silica, such as pyrogenic silica.
• the phosphate may be a metal phosphate.
• Typical metal phosphates are sodium metaphosphate, potassium metaphos- phate, calcium pyrophosphate, magnesium orthophosphate, trimagnesium phosphate, tricalcium phosphate and dicalcium phosphate.
• the swelling agent may be sodiumcarboxymethylcellulose, irish moss, tragacanth gum, accacia gum, gelatin, an alginic compound, methylcellulose polyvinylpyrrolidone, xanthan gum or the like.
• the alginic compound may be an alginic acid, an alginic salt, or an alginic ester.
• the tooth cleaning tablet may contain more than one foaming agent if desired.
• the carbon dioxide foaming agent preferably comprises a carbon dioxide source selected from the group consisting of sodium bicarbonate, calcium bicarbonate and potassium bicarbonate and an acid selected from the group consisting of citric acid, tartaric acid, algeric acid and malic acid.
• gas (preferably carbon dioxide) adsorbing agents such as zeolites may be employed.
• the filling agent may be a waxy polyethylene glycol such as, for example, that known as carbowax 6000 or carbo- wax 4000.
• the filling agent may alternatively be a hexitol component such as, for example, mannitol or sorbitol or other sugars such as sucrose, xylitol, and fructose.
• a hexitol component such as, for example, mannitol or sorbitol or other sugars such as sucrose, xylitol, and fructose.
• the filling agent may be lactat, starch, a silicon oxide, floe or microcrystalline cellulose.
• polishing agents also act as fillers.
• the tooth cleaning tablet may contain more than one taste-giving agent if desired. Any taste-giving agent may be employed.
• the taste-giving agent comprises an aroma giving agent such as menthol, peppermint and spearmint, and a sweetner, either a sugar such as sucrose, mannitol, sorbitol, xylitol or fructose or a synthetic agent such as saccharin, cyclamate or aspertame.
• an aroma giving agent such as menthol, peppermint and spearmint
• a sweetner either a sugar such as sucrose, mannitol, sorbitol, xylitol or fructose or a synthetic agent such as saccharin, cyclamate or aspertame.
• the sugars may also act as polishing agents.
• the wetting agent may be an oxyethylenoxypropylene polymer, a polyoxyethylensorbitan derivative from a fatty acid, or sodium laurylsulphate.
• the derivative from the fatty acid may be polyoxyethylensorbitanstearate.
• a presently preferred wetting agent is sodium laurylsulphate.
• the lubricative agent may be magnesium stearate, calcium stearate, stearic acor, or hydrogenated vegetable oil such as Sterotex R , Lubritab R , and Comptritol R .
• the tooth cleaning tablet may also contain a plaque indicating agent.
• the tooth cleaning tablet preferably contains a tooth protective agent which acts to reduce tooth decay.
• the tooth protective agent will improve the resistance of the teeth to attach by acids.
• the tooth protective agent may also kill plaque producing germs.
• the tooth protective agent may be sodium fluoride, sodium tetrapyrophosphate, sodium monofluorophosphate, stannous fluoride, a chlorhexidine salt or hexachlorophene.
• the sodium fluoride may be used in amounts up to 0.3% by volume of the tablet.
• the sodium monofluorophosphate may be used in amounts up to 1% by volume of the tablet.
• Stannous fluoride is preferred.
• the milled tribasic calcium phosphate was mixed with an equal portion of unmilled TCP .
• the lubricant system was changed from 2% magnesium stearate to a mixture of 1% magnesium stearate + 2% stearic acid.
• Prototype tablets were prepared at 3 hardnesses for evaluation (see below). Tablets were made with stannous fluoride in place of sodium fluoride (.452%). This slight change in quantity was adjusted by slightly lowering the amount of tribasic calcium phosphate. This formula is labeled F-3 (Batch 87103). The concentrations of sodium lau- ryl sulphate and Nutrasweet were returned to their original values, 1.61% and .4% respectively.
• a blend of powders were prepared for feeding studies with three different flavors. Approximately 22 grams of each formulation was blended. Formulas contained stannous fluoride and milled tribasic calcium phosphate. Other blends of powders without test animal unpalatable ingredients (sodium lauryl sulphate, etc.) were also prepared with various flavors. An attempt was made to modify the original formula to improve both tabletting and taste properties. These changes are shown in Table IV. The level of Nutrasweet R and flavor were reduced slightly, so that they fell somewhere between the original formula and the modified formula. Tablets containing peppermint (Batch 87101) (F-5) and a peppermint/citrus (Batch 87102) (F-6) were prepared for concept testing.
• the fluidity of the formulation of the above identified Aberg application was increased by replacing a portion (50%) of the milled tribasic calcium phosphate with unmilled tribasic calcium phosphate.
• modified F-5 (87101) and modified F-6 (87102) were probably the best for both taste and flavor as well as tabletting properties.
• the lubricant concentrations should not be changed radically. Lower amounts would not provide a sufficient degree of lubrication and higher quantities would reduce tablet hardness.
• the proportion of fillers and polishing agents should be greater than about 50% and the carbon dioxide couple less than about 35% by weight to insure that a paste rather than a slurry is formed; preferably greater than about 50% and less than 25% respectively. If a zeolite is used the amount of carbon dioxide produced should be the same as in the couple percentages given.
• Silicon dioxide and pyrogenic silica can be used as flow conditioning agents (in small quantities) as well as polishing agents.
• sugar fillers sorbitol, mannitol, compressible sucrose, xylitol, fructose
• sugar fillers can be interchanged in various proportions but such changes can change tablet hardness.
• Sugars can also be used to replace portions of polishing agents depending upon abrasiveness desired.
• microcrystalline cellulose will increase tablet hardness - without affecting other properties.
• a small amount of disintegrating agent may be added.
• the chewed particles will disintegrate faster and foam will generate faster.
• 1-2% of crospovidone or croscarmellose may be used.
• the fluoride dentifrices accepted by the Council on Dental Therapeutics contain 0.1% fluoride ion. To achieve this level with sodium fluoride 0.22-0.24% is used; with sodium monofluorophosphate 0.76% is employed and with stannous fluoride, 0.4%. There are currently studies being conducted with 0.15% fluoride ion but these are not available at this time.
• the F-3 formula of the invention with 2.8 milligrams of stannous fluoride contains 0.7 milligrams of fluoride.
• the recommended level for children above the age of three is 1 milligram per day.
• School water supplies are fluoridated at 4.5 PPM which would deliver 4 milligrams per day if a liter of water was consumed.
• Water supplies containing up to 3.5 parts per million naturally do not have to de-fluoridate. It would therefore appear that with a precaution "not to use below the age of six" (to avoid any possible fluorosis in the front teeth), 203 tablets, per day, delivering 1.4 to 2.1 milligrams of fluoride ion, would be acceptable.
• Anti-plaque studies have employed from 0.1-0.4% stannous fluoride. Based upon these studies 0.4% stannous fluoride should exhibit an anti-plaque effect with continued use.
• This test measures the ability of the formulation to release fluoride into simulated saliva. Studies are done using water and also simulated salivas at pH 6.6 and 4.5 to simulate both resting saliva and the saliva composition after a meal.
• Fluoride release from tablets into water and pH 4.5 and pH 6.6 synthetic salivas was measured. In each case the stannous fluoride tablets released more fluoride than did the sodium fluoride tablets. Release into either water of pH 6.6 synthetic saliva was about 45% of the total fluoride from the stannous fluoride preparation and on the order of 20-25% from sodium fluoride into synthetic saliva and 25-30% from sodium fluoride into water. Release from both tablets into the pH 4.5 synthetic saliva was somewhat less, with about 25% of total fluoride released from the stannous fluoride tablet and 20% from the sodium fluoride. In all cases the release kinetics were rapid, essentially reaching equilibrium within 120 seconds.
• the procedure is as follows.
• the product sample is suspended or mixed with three times its weight of pH 4.5 synthetic saliva to form a slurry or solution.
• the mixture is agitated for 60 seconds and than a block of bovine enamel with a 0.25 cm 2 window is immersed in the slurry. After 5 minutes exposure to the mixture, the enamel is transferred to a vessel containing 10 ml of pH 6.6 synthetic saliva.
• Results were obtained for fluoride content in successive etches from teeth exposed to a slurry of either placebo or the stannous fluoride tablet for 60 seconds, followed by exposure to pH 6.6 synthetic saliva for 2 hours.
• fluoride content was increased by a factor of 4.15; the second layer by 2.75 and the third by 2.88.
• fluoride content for bovine teeth of about 200 ppm fluoride
• the in vitro testing procedure involves making an artificial lesion in a tooth, exposing this lesion to the product and then measuring the extent to which the lesion has been reversed. These effects are measured by using quantitative microradiography, a technique developed in our laboratory (see reprints) for application to dental studies. This technique can be used to measure the mineral content of the tooth as a function of position. Comparing the mineral content both before and after exposure to the product, we can quantitatively assess the extent to which the product has facilitated remineralization (reversal of "the carious lesion). The procedure is as follows.
• a 0.25 cm 2 enamel window is exposed to pH 4.5 synthetic saliva for 6 hours to produce an artificial lesion.
• the enamel is removed and half the window covered and the uncovered portion brushed for 2 minutes, with an aqueous slurry of the product. This slurry is prepared by grinding the tablet for 60 seconds. After this brushing the sample is placed in pH 6.6 synthetic saliva for 24 hours.
• the enamel specimen is then removed and the min- eral density profiles for the window exposed to product and the window subjected only to demineralization are determined. The difference in these two profiles is taken as the remineralization achieved during the 24 hour exposure. Triplicates of this test were done for brushing each of the products and the placebo product and also for a control exposed only to the synthetic salivas with no brushing.
• the tooth may have the same mineral content as does sound enamel.
• the resistance of this remineralized (repaired) lesion to subsequent acid attack is not necessarily the same as that of sound enamel.
• the ability of a remineralized tooth to withstand a simulated acid attack is compared with that of sound enamel. Teeth that are remineralized with fluoride containing products often possess more acid resistance than does sound enamel. In other words, it can be more advantageous to have a lesion that has been repaired than to have sound enamel that has never had a lesion at all. Because of sensitivity problems with chemical assays, this test is most reliably accomplished by using the quantitative microradiography technique described above to assess mineral loss after the simulated attack.
• the procedure is as follows. A window of enamel is exposed to pH 6.6 synthetic saliva for either 7 or 14 days. Three times during each day the enamel is removed and placed in pH 4.5 synthetic saliva for 60 minutes. After each such exposure, the enamel is brushed for 2 minutes with a 1:3 aqueous slurry of the product and then placed back in the pH 6.6 medium. At the end of the treatment period, one half of the window is covered and the other exposed to the pH 4.5 synthetic saliva or to a 0.1 M pH 4.5 acetate buffer solution for 30, 60, 120, 240 or 480 minutes. During this exposure samples aliquots are taken at 4 predetermined spaced intervals and solution fluoride measured. The enamel is sectioned and mineral density profiles determined.
• the difference in total mineral content between the exposed and unexposed portions of the window is a measure of the demineralization that can occur after treatment with a given formulation.
• the stannous fluoride product, the placebo product and the absence of treatment were compared with respect to the relative amounts of enamel dissolved after treatment with each.
• Rationale for the use of programmed feeding machine Rodents (rats and hamsters) have been used extensively to estimate the cariostatic and plaque- reducing potential of a variety of agents. In many experiments care has not been taken to ensure that animals consumed the agent or that their frequency of eating has not been disturbed by the addition of the agent. To overcome these difficulties, which could have a significant effect on the incidence of dental caries or formation of dental plaque a Konig-Hofer programmed feeding machine has been employed in these studies. The programned feeding machine permits the feeding of measured amounts of food at predetermined intervals. Animals are housed in individual cages which have a disk containing 18 small trays mounted in front.
• a measured amount of food is placed in the trays and the disk, rotated by means of a motor, presents each tray at the appropriate intervals.
• the test agent is placed in one or more trays and the remainder of the diet is placed in the remaining feeding trays. Alternatively the test agent may be mixed with one or more of the meals.
• Each tray is observed to ensure that the rat consumes the food and/or agent, and the amount of food consummed by each rat is determined by weighing the disk before and after a feeding cycle. Purpose of the investigation
• the 5 groups were as follows:
• a F-3 tablet was crushed and suspended in 2 ml water to form a slurry.
• a volume of 0.2 ml (0.28 mg SnF 2 /0.059 mg F) was delivered into the mouth using a sterile 1 ml pipette 3 times daily.
• All animals were fed a cariogenic diet containing 282 sucrose. Deionized water was available ad libitum. All rats were weighed weekly. The duration of the experiment was 35 days.
• the mean caries and plague scores of the 5. groups of rats are shown in Tables 1 and 2.
• the purpose of the placebo groups was to determine whether components of F-3 other than the active agent (SnF 2 ) exhibit anti-plaque and/or anti-caries activity. It is clear that F-3 with SnF 2 exhibits significant cariostatic activity whether delivered as a rinse 3 times daily (66% reduction) or as an additive to the basal diet (77% reduction). Components of F-3 other than SnF 2 appear to contribute to Its cariostatic activity because F-4 without SnF 2 affected a reduction In dental caries of between 27 and 352.
• F-3 dentifrice tablets containing stannous fluoride (SnF 2 ) were tested fortheir ability to reduce dental caries and dental plaque formation using a rat model incorporating programmed feeding. Identical F-4 tablets lacking SnF 2 served as placebos. The rats were fed a highly cariogenic diet and infected with caries and plaque inducing bacteria. F-3 containing SnF 2 significantly reduced the incidence of dental caries and inhibited the formation of dental plaque whether provided as a rinse or added to food. The placebo tablets also resulted in some caries but not plaque reduction.
• SnF 2 stannous fluoride
• ingredients or compounds recited in the singular are intended to include compatible mixtures of such ingredients wherever the sense permits.

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• 1988
  • 1988-06-22 EP EP19880906439 patent/EP0394259A4/en not_active Withdrawn
  • 1988-06-22 BR BR888807582A patent/BR8807582A/pt unknown
  • 1988-06-22 JP JP50564988A patent/JPH02504030A/ja active Pending
  • 1988-06-22 WO PCT/US1988/002098 patent/WO1988010110A1/en not_active Application Discontinuation
  • 1988-06-22 AU AU19684/88A patent/AU1968488A/en not_active Abandoned
  • 1988-06-22 HU HU423888A patent/HUT53513A/hu unknown
• 1989
  • 1989-12-21 FI FI896183A patent/FI896183A0/fi not_active IP Right Cessation

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