Fluoride free dental remineralization

Drug – bio-affecting and body treating compositions – Dentifrices

Reexamination Certificate

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C424S054000

Reexamination Certificate

active

06207138

ABSTRACT:

BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to oral compositions in the form of dentifrices and mouthwashes providing improved remineralization effects.
2. The Prior Art
In the mouth, there is a natural equilibrium between hydroxyapatite being dissolved from the enamel of teeth, on the one hand, and hydroxyapatite being formed on or in the teeth from substances occurring naturally in the saliva, on the other. The equilibrium is such that hydroxyapatite is dissolved, a cariogenic condition arises which is referred to as demineralization. If the equilibrium is such that hydroxyapatite is being formed in demineralized enamel, this is referred to as remineralization. By remineralization, pre-existing tooth decay and caries can be reduced or eliminated by natural means.
It has long been known that fluoride-providing compounds, even in low concentrations, are a safe and effective route for the promotion of the remineralization process. Although effective, excess amounts of fluoride releasing compounds have produced cosmetically objectionable fluorosis (mottling) in developing teeth in geographic areas in which the water supply contains relatively high levels of fluoride compounds.
Xylitol in combination with fluoride releasing compounds is known for the treatment of dental structures to provide prophylactic prevention of carious conditions, and/or remineralization of pre-existing carious conditions for example U.S. Pat. No. 5,089,255. EP Publication No. 0138705, discloses anticaries compositions containing xylitol and mixtures of at least two fluoride salts providing 2,000-20,000 ppm fluoride ion. EP Publication No. 0251146 discloses an oral composition having a dental plaque preventing activity containing a mixture of xylitol, a fluoride releasing compound, and one zinc ion releasing compound Xylitol alone, even at concentration levels of 10% by weight in the absence of fluoride releasing compounds, does not provide a remineralization effect comparable to that provided by fluoride releasing compounds. when incorporated in oral compositions.
Therefore there is a need in the art for a xylitol based oral composition, which is substantially free of fluoride ion releasing compounds which provides a remineralization effect comparable to that observed when used in combination with fluoride ion releasing compounds.
SUMMARY OF THE INVENTION
In accordance with the present invention there is provided a substantially fluoride-free composition and method of remineralizing demineralized portions of tooth structures which comprises applying to such portions an oral composition in the form of a dentifrice or mouthwash containing about 1.0 to about 20% by weight xylitol and about 10 to about 20% by weight of a casein glycomacropeptide.
In the practice of the present invention, the defined combination of xylitol and casein glycomacropeptide employed in amounts within the indicated ranges to achieve optimum remineralization effects, have unexpectedly been found to coact synergistically to yield remineralization results equal to or greater than those obtainable when xylitol and fluoride ion-releasing compounds are used in combination.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
In the practice of the present invention, xylitol is present in the oral composition at a concentration of about 1 to about 20% by weight, preferably about 5 to about 15% by weight and most preferably about 7 to about 12% by weight.
Casein glycomacropeptide compounds useful in the practice of the present invention are known to the art to be effective antibacterial agents against microorganisms responsible for dental plaque and caries. For example, U.S. Pat. Nos. 4,992,420 and 4,994,441 disclose that casein phosphopeptides derived from kappa-casein are effective for inhibiting the growth of streptococcus mutans, a bacteria species associated with dental caries and plaque formation.
The term “kappa-caseino glycopeptides” includes within its meaning a caseino glycopeptide, which is the water soluble component emanating from the hydrolysis of kappa-casein by rennet, and a caseino-glycopeptide obtained by proteolysis of caseino-macroglycopeptide. Desialylated derivatives are obtained from caseino glycopeptides by more or less complete elimination of the sialic acids, i.e., N-acetylneuraminic and N-glycollylneuraminic acids, from the oligosaccharide chains of the caseino glycopeptide. The preparation of kappa-caseino-glycopeptides is disclosed in U.S. Pat. No. 4,992,420. Other casein glycomacropeptide compounds useful in the practice of the present invention are the kappa-caseino glycomacropeptides disclosed in U.S. Pat. No. 5,075,424.
The casein glycomacropeptide is incorporated in the oral composition of the present invention at a concentration of at least about 10% by weight, and preferably at about 10 to about 20% by weight.
In the preparation of oral compositions utilizing casein glycomacropeptides it has been previously determined that these compounds are not compatible with anionic surfactants such as sodium lauryl sulfate conventionally used to prepare dentifrice compositions such as toothpastes and gels, the casein glycomacropeptide being biologically inactivated by the surfactant.
To avoid the biological inactivation of the casein glycomacropeptide, a hydrolyzed protein compound is incorporated in the oral composition of the present invention, as disclosed in copending patent application Ser. No. 08/639,871 filed Apr. 26, 1996.
Hydrolyzed protein compounds useful to preserve the biological activity of the casein glycomacropeptides include hydrolyzed collagen proteins, specifically positively charged hydrolyzates containing high concentrations of basic amino acids obtained by extraction from a partially hydrolyzed collagen faction and isolation by ion exchange treatment with an anion exchange resin or a partially charged hydrolyzed collagen protein. Such hydrolyzed collagen proteins are known to the art and are more fully described in U.S. Pat. No. 4,391,798. Commercially available hydrolyzed collagen proteins include Crotein Q®, a quaternary derivative of hydrolyzed collagen protein available commercially from Croda Inc., New York, N.Y. Crotein Q has a minimum pH of 9.5-10.5, is an off-white, free flowing powder and its adopted name is steartrimonium hydrolyzed animal protein. Another example of a commercially available hydrolyzed collagen protein is gelatin (food grade) available from American Gelatin Company, a hydrolyzed collagen protein prepared by boiling animal parts such as skin, tendons, ligaments and bones with water.
The presence of about 0.1 to about 2.5% by weight of the hydrolyzed protein compound in the oral composition of the present invention is sufficient to inhibit any biological inactivation of the casein glycomacropeptide caused by the concurrent presence of an anionic surfactant in the composition.
To prepare a dentifrice composition such as a toothpaste or gel, abrasives including conventional dentifrice abrasives, such as finely divided silica, hydrated alumina, calcined alumina, calcium carbonate, sodium bicarbonate and dicalcium phosphate (anhydrous and/or dihydrate) are incorporated in a vehicle at a concentration of about 10 to about 30% by weight based on the composition and preferably at a concentration of about 15 to about 25% by weight. At these abrasive levels, the vehicle is comprised of about 25 to about 40% by weight water as well as a humectant such as glycerol, sorbitol, propylene glycol or mixtures thereof at a concentration of about 25 to about 45% by weight and preferably about 25 to about 35% by weight of the composition.
Thickeners or gelling agents are used in the preparation of the dentifrices of the present invention and include silica thickeners, carboxymethyl cellulose, sodium carboxymethyl cellulose, carob bean gum, iota carrageenan, gum tragacanth, hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, and alginates and are incorporated in the oral compositions at concentrations from about 0.2 to about 3.0% by weight.
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