| PATENT NUMBER | This data is not available for free |
| PATENT GRANT DATE | July 19, 1994 |
| PATENT TITLE |
Dental varnish composition, and method of use |
| PATENT ABSTRACT | The invention relates to an oral composition for plaque prevention or tooth hypersensitivity comprising either an antibacterial agent or a hypersensitivity agent embedded in a sustained release carrier such as an acrylic polymer, and a method for the use of said compositions in preventing dental caries, periodontal disease, and tooth hypersensitivity |
| PATENT INVENTORS | This data is not available for free |
| PATENT ASSIGNEE | This data is not available for free |
| PATENT FILE DATE | June 21, 1989 |
| PATENT REFERENCES CITED |
Translated Abstract of Japanese patent document JP 60228410 from Dialog f 351. English abstract of the patent family of European patent document No. EP 0 298 271 from Dialog file 351. Translated Abstract of Japanese document JP 63044518 from Dialog file 351. Wood, D. A., Int. J. Pharmaceut. 7:1-18 (1980). Goodson, J. M. in Medical Applications of Controlled Release, vol. II, Langer, R. S. et al. Eds., CRC Press Inc. (1984) 115-138. Chang, R.-K. et al., Drug Dev. and Ind. Pharm. 15:361-372 (1989). Thoennes, C. J. et al., Drug Dev. and Ind Pharm. 15:165-185 (1989). Goto, S. et al., J. Microencap. 5:343-360 (1988). |
| PATENT PARENT CASE TEXT | This data is not available for free |
| PATENT CLAIMS |
What is claimed is: 1. A sustained release liquid varnish composition which consists essentially of: (a) a sustained release acrylic polymer; and (b) either (i) a bacteriocidal quaternary ammonium salt or (ii) a hypersensitivity agent; in a pharmaceutically acceptable vehicle, wherein said sustained release acrylic polymer is selected from the group consisting of (1) an anionic copolymer based on methacrylic acid and methylmethacrylate wherein the ratio of free carboxyl groups to the ester groups is approximately 1:1, (2) an anionic copolymer based on methacrylic acid and methylmethacrylate wherein the ratio of free carboxyl groups to the ester groups is approximately 1:2, (3) a copolymer based on acrylic and methacrylic acid esters with a low content of quaternary ammonium groups wherein the molar ratio of the ammonium groups to the remaining neutral methacrylic acid esters is 1:20, and (4) a copolymer based on acrylic and methacrylic acid esters with a low content of quaternary ammonium groups wherein the molar ratio of the ammonium groups to the remaining neutral methacrylic acid esters is 1:40, and wherein the concentration of the copolymers in the liquid varnish is 9.9% or greater. 2. The varnish composition of claim 1, wherein said sustained release acrylic polymer is an anionic copolymer based on methacrylic acid and methylmethacrylate wherein the ratio of free carboxyl groups to ester groups is approximately 1:1. 3. The varnish composition of claim 1, wherein said composition contains a bacteriocidal quaternary ammonium salt. 4. The varnish composition of claim 3 wherein said bacteriocidal quaternary ammonium salt is selected from the group consisting of cetylpyridinium chloride and benzalkonium chloride. 5. The varnish composition of claim 4, wherein said bacteriocidal quaternary ammonium salt is cetylpyridinium chloride. 6. The varnish composition of claim 4, wherein said bacteriocidal quaternary ammonium salt is benzalkonium chloride. 7. The varnish composition of claim 1, wherein said composition contains a hypersensitivity agent. 8. The varnish composition of claim 7 wherein said hypersensitivity agent is selected from the group consisting of a strontium salt, and a potassium salt. 9. The varnish composition of claim 8, wherein said strontium salt is selected from the group consisting of strontium chloride and strontium citrate. 10. The varnish composition of claim 8, wherein said potassium salt is selected from the group consisting of potassium chloride and potassium hydrogen tartrate. 11. The varnish composition of claim 1, wherein said pharmaceutically acceptable vehicle comprises an agent selected from the group consisting of water; ethyl alcohol; and ethyl alcohol and water. 12. A sustained release liquid varnish composition which consists essentially of: (a) a sustained release acrylic polymer; (b) either (i) a bacteriocidal quaternary ammonium salt or (ii) a hypersensitivity agent; and (c) an agent selected form the group consisting of a flavoring agent, and a coloring agent; in a pharmaceutically acceptable vehicle, wherein said sustained release acrylic polymer is selected from the group consisting of (1) an anionic copolymer based on methacrylic acid and methylmethacrylate wherein the ratio of free carboxyl groups to the ester groups is approximately 1:1, (2) an anionic copolymer based on methacrylic acid and methylmethacrylate wherein the ratio of free carboxyl groups to the ester groups is approximately 1:2, (3) a copolymer based on acrylic and methacrylic acid esters with a low content of quaternary ammonium groups wherein the molar ratio of the ammonium groups to the remaining neutral methacrylic acid esters is 1:20, and (4) a copolymer based on acrylic and methacrylic acid esters with a low content of quaternary ammonium groups wherein the molar ratio of the ammonium groups to the remaining neutral methacrylic acid esters is 1:40, and wherein the concentration of the copolymers in the liquid varnish is 9.9% or greater. 13. A sustained release liquid varnish composition which consists essentially of: (a) a sustained release acrylic polymer; (b) either (i) a bacteriocidal quaternary ammonium salt or (ii) a hypersensitivity agent; and (c) a plasticizer; in a pharmaceutically acceptable vehicle, wherein said sustained release acrylic polymer is selected from the group consisting of (1) an anionic copolymer based on methacrylic acid and methylmethacrylate wherein the ratio of free carboxyl groups to the ester groups is approximately 1:1, (2) an anionic copolymer based on methacrylic acid and methylmethacrylate wherein the ratio of free carboxyl groups to the ester groups is approximately 1:2, (3) a copolymer based on acrylic and methacrylic acid esters with a low content of quaternary ammonium groups wherein the molar ratio of the ammonium groups to the remaining neutral methacrylic acid esters is 1:20, and (4) a copolymer based on acrylic and methacrylic acid esters with a low content of quaternary ammonium groups wherein the molar ratio of the ammonium groups to the remaining neutral methacrylic acid esters is 1:40, and wherein the concentration of the copolymers in the liquid varnish is 9.9% or greater. 14. A sustained release liquid varnish composition which consists essentially of: (a) a sustained release acrylic polymer; (b) either (i) a bacteriocidal quaternary ammonium salt or (ii) a hypersensitivity agent; and (c) an agent selected from the group consisting of: polyethylene glycol and dibutyl phthalate; in a pharmaceutically acceptable vehicle, wherein said sustained release acrylic polymer is selected from the group consisting of (1) an anionic copolymer based on methacrylic acid and methylmethacrylate wherein the ratio of free carboxyl groups to the ester groups is approximately 1:1, (2) an anionic copolymer based on methacrylic acid and methylmethacrylate wherein the ratio of free carboxyl groups to the ester groups is approximately 1:2, (3) a copolymer based on acrylic and methacrylic acid esters with a low content of quaternary ammonium groups wherein the molar ratio of the ammonium groups to the remaining neutral methacrylic acid esters is 1:20, and (4) a copolymer based on acrylic and methacrylic acid esters with a low content of quaternary ammonium groups wherein the molar ratio of the ammonium groups to the remaining neutral methacrylic acid esters is 1:40, and wherein the concentration of the copolymers in the liquid varnish is 9.9% or greater. 15. A method of treating tooth hypersensitivity comprising application of the varnish composition of claim 7 to the teeth or gingival tissues of an animal. 16. A method of oral plaque prevention comprising application of the varnish composition of claim 3 to the teeth or gingival tissues of an animal. 17. The method of claim 16, wherein said application is by brush. 18. The method of claim 16, wherein said application is by spray. 19. The method of claim 16, wherein said animal is a human. 20. The method of claim 16, wherein said animal is a domesticated animal. 21. The method of claim 15, wherein said animal is a domesticated animal. 22. The method of claim 15, wherein said application is by brush. 23. The method of claim 15, wherein said application is by spray. 24. The method of claim 15, wherein said animal is a human. -------------------------------------------------------------------------------- |
| PATENT DESCRIPTION |
FIELD OF THE INVENTION The invention is directed to a dental varnish composition which may be used to prevent bacterial dental plaque formation, to treat dental caries and periodontal disease, or to treat patients suffering from tooth hypersensitivity. BACKGROUND OF THE INVENTION I. Prevention of Plaque Formation, Caries, and Periodontal Disease The relationship between bacterial plaque and the development of periodontal disease and caries has been thoroughly established (Axelsson, P., et al., J. Clin. Perio. 5:133-151 (1978)). It has also been clearly shown that the bacterial flora of the gingival crevice is important in the etiology of periodontal disease (Slots, J., J. Clin. Perio. 6:351-382 (1979)). Therefore, treatment of periodontal and caries diseases is directed to controlling this flora. The most widely used approach to date has been mechanical cleaning methods such as tooth brushing. Although this method has proved to be fairly successful in treating individuals, there is still a high recurrence rate. There is also the problem of motivating people to good oral hygiene habits that they will maintain throughout their lives. Although systemic administration of antibiotics has been shown to be a useful method of controlling the subgingival flora, discontinuation of therapy will result in the return of the potential pathogens to the pockets (Genco, R. J., J. Perio. 52:545-558 (1981)). Long-term antibiotic therapy has been used, but the potential dangers associated with this form of treatment, which include the development of resistant strains and superimposed infections, do not warrant its serious consideration. Antibacterial agents such as chlorhexidine and quaternary ammonium salts in the form of mouth rinses, dentifrices, solutions and gels have not proven to be successful in preventing periodontal disease (see, for example, Ciancio, S. G., et al., Pharm. Therap. Dent. 3:1-6 (1978)), as these agents are unable to affect the subgingival flora when administered in these forms (Goodson, J. M., et al., J. Clin. Perio. 6:83-92 (1979)). In addition, reported side effects of chlorhexidine, including staining and altered taste sensation, have resulted in limited usage. Attempts to reduce the staining and bitter taste by using dilute solutions and flavoring agents, respectively, have been only partially successful. Sustained release has been reported to be achieved by embedding chlorhexidine in an ethyl cellulose polymer to form a varnish (Friedman, M., et al., J. Perio. Res. 17:323-328 (1982); Friedman, M., et al., IADR Prog. and Abstr. 59:No. 905 (1980)). This dosage form was used in the local treatment of periodontal disease (Soskolne, W. A., et al., J. Perio. Res. 18:330-336 (1983)) and in the treatment of plaque prevention in patients wearing orthodontic appliances (Friedman, M., et al., J. Dent. Res. 64:1319-1321 (1985)). A drawback to this plaque preventative system was that although plaque accumulation was decreased by the application of a varnish composed of chlorhexidine embedded in an ethyl cellulose polymer, the effectiveness of the system in decreasing plaque accumulation was present only for a period of four days subsequent to administration of the varnish. Friedman et al., (J. Dent. Res., supra), concluded that "clearly the conditions in the oral cavity and the formulation used do not, at present, facilitate such prolonged prevention of plaque accumulation." These authors also suggested that by altering the varnish components and method of preparation it might be possible in clinical use to sustain the necessary level of antibacterial agent release for longer periods. No suggestion was made in this publication as to how this could be accomplished. Other antibacterial preparations for plaque prevention have been disclosed. Gaffar (U.S. Pat. No. 4,339,430) discloses an antibacterial oral composition containing an agent such as bis-biguanidohexanes or quaternary ammonium salts, and an additive which reduces staining of dental surfaces such as copolymers of glutamic acid, tyrosine, and alanine. This preparation was reported to be applied as a mouthwash or as a toothpaste. Wahmi (U.S. Pat. No. 4,374,824) discloses dentifrices for cleaning and preserving teeth. Disclosed were compositions comprising ginger, magnesium silicate, sodium chloride, catechu, alum, seed and shell of sweet almond, pyrethrum, gum mastic, and tobacco. It was reported that gum mastic was added to the composition to assist in the prevention of tooth decay. The disclosed compositions were intended to be in the form of toothpaste or tooth powders. This patent does not disclose the possible long-term anti-plaque effect of the compositions; further, application of the disclosed compositions two to three times per day is required for anti-plaque activity. Mastic has been used previously for other dental purposes. U.S. Pat. No. 4,668,188 (Wolfenson, G. B.) discloses the use of a curable mastic in the production of an oral impression tray for making impressions of teeth and jaw structures. Mastics have been used in the production of dental molds (U.S. Pat. No. 4,500,288, Von Weissenfluh, H.) and as an adhesive to secure dental articulators (U.S. Pat. Nos. 4,548,581 and 4,382,787, Hoffman, R. E.). U.S. Pat. Nos. 4,532,126 and 4,428,927 (Ebert, W. R., et al.) disclose chewable, filled, one-piece soft elastic gelatin capsules, made chewable by a masticatory substance, such as a synthetic mastic. U.S. Pat. No. 4,459,271 (Kosti, C. M.) relates to novel anti-plaque compositions for use in evaluating oral hygiene practices. In brief, the patent discloses a water-insoluble, water-immiscible dye emulsified in fine droplets or rupturable capsules. The patent discloses the use of mastic resin as well as alginates, and other gums as an insoluble media for dye dispersion. In particular, sodium carboxymethylcellulose is disclosed. Also disclosed is the possibility of incorporating antibacterial agents such as stannous fluoride into the compositions. Significantly, the Kosti patent is concerned with diagnostic rather than therapeutic applications. The patent fails to suggest compositions exhibiting long-term plaque preventive activity. U.S. Pat. No. 3,956,480 (Dichter et al.) discloses the use of an anionic polymer to sorb a cationic germicidal polymer to a tooth surface. A topical, sustained-release form of an antibacterial agent could help prevent the above-discussed side effects. Such a dosage form would be able to release the drug at a lower therapeutic level over a long period of time and thus might prevent the bitter taste and tooth staining. II. Treatment of Tooth Hypersensitivity Dental hypersensitivity, especially that arising from dentin and cementum hypersensitivity, is a frequently encountered problem in dentistry and a very troublesome clinical complaint. Hypersensitivity may occur wherever the dentin or cementum of a tooth is exposed by attrition or abrasion, or when the tooth's fine root surface is exposed by periodontal disease. In about 12% of erupted teeth, there is a developmental lack of protective covering of cementum at the cementoenamel junction. As a result, when the exposed dentin is subjected to mechanical, thermal, chemical or osmotic stimuli, the sensory nerves of the teeth become excited and a very painful response results. For example, people with hypersensitive teeth find it very painful to orally ingest certain forms of nourishment, such as liquids or foods that are hot or cold, sweet, hypertonic or contain citric acid. Everyday stimuli such as brushing the teeth may also be painful. Many attempts have been made to control hypersensitivity of the teeth. For example, U.S. Pat. No. 3,863,006 (Hodosh, M.) describes the use of potassium, lithium or sodium nitrate; U.S. Pat. No. 4,751,072 and U.S. Pat. No. 4,631,185 (both to Kim, S.) describe the use of potassium bicarbonate and potassium chloride; U.S. Pat. No. 4,710,372 and U.S. Pat. No. 4,634,589 (both to Scheller, H. U.) describe the use of hydroxyapatite or fluorapatite; U.S. Pat. No. 4,057,621 Pashley, D. H., et al.) describes the use of an alkali metal or ammonium oxalate; U.S. Pat. No. 4,415,549 (Shah, N. B.) describes the use of strontium EDTA, fluoride and ammonium glycyrrhizzinate; and, GB patent No. 990957 (Rosenthal, M. W.) describes the use of strontium for the control of hypersensitivity. The use of strontium ions to treat hypersensitivity was also disclosed in U.S. Pat. Nos. 3,122,483, 3,988,434 and 4,224,310. However, although clinically the most effective for reducing tooth hypersensitivity, the use of strontium salts for the treatment of hypersensitivity is disliked by patients due to the tendency of strontium salts to leave an unacceptably salty taste or metallic taste in the mouth, even when used in a toothpaste form. Another major disadvantage of strontium dentifrice is the long period of time of application which is required to achieve the clinical effect. A topical, sustained-release form of an agent capable of controlling dental hypersensitivity could help prevent undesirable taste side effects and still treat the hypersensitive condition. Such a dosage form would be able to release the agent controlling the hypersensitivity at a lower therapeutic level over a long period of time, for example, for weeks. Sustained localized release of the hypersensitivity agent, targeted directly to the hypersensitive site, would also solve the problem of the prolonged time and application currently required to obtain clinical effectiveness with strontium. III. Summary The background art thus fails to identify any compositions of matter comprising a sustained-release carrier which can be used in conjunction with a bacteriocidal agent, for use as a sustained plaque preventative by humans and other animals, under conditions in which the agents have no deleterious medical side effects, and do not cause staining of the teeth. Another highly desirable characteristic not found in the art of record is that the antibacterial agent should be released from the anti-plaque composition, not only in a sustained fashion, but over a sufficiently long period of time so as not to require excessive application of the composition. The background art also fails to identify any compositions of matter comprising an effective anti-hypersensitivity agent together with a long term sustained release carrier capable of providing efficacious levels of the anti-hypersensitivity agent, for use as a hypersensitivity preventative by humans and other animals, under conditions in which the anti-hypersensitivity agents have no undesirable side effects such as changes in taste sensations. SUMMARY OF THE INVENTION With the above-described needs in mind, the present inventors set out to find a composition which could be adapted to contain either (1) an antibacterial agent effective against those bacteria that are responsible for plaque, dental caries or periodontal disease, or (2) an agent effective against those dental conditions responsible for tooth hypersensitivity. The composition for treating plaque, dental caries or periodontal disease being such that the antibacterial agent can be released in a sustained, long-term fashion, and such that the antibacterial composition has the property of long-term adhesion to the gums and teeth, and such that the antibacterial composition remains plastic during the entire period of application. The composition for treating tooth hypersensitivity being such that the active anti-hypersensitivity agent is released in a sustained, long-term fashion, without a salty or metallic taste, and such that the hypersensitivity composition has the property of long-term adhesion to the teeth, and such that the hypersensitivity composition remains plastic during the entire period of application. With these goals in mind, the inventors have discovered a composition with these desirable characteristics, the composition comprising a degradable, but non-biodegradable, varnish. The varnish containing either an anti-plaque agent, or a metal salt or another agent to treat tooth hypersensitivity, embedded in a sustained release carrier composed of a biodegradable acrylic polymer, a hydrophilic polymer, or a combination of hydrophilic and hydrophobic polymers, in a pharmaceutically acceptable vehicle, optionally containing one or more agents such as a plasticizer (such as polyethylene glycol, dibutyl phthalate, etc.), an adhesive polymer (such as gum mastic, etc.), a cross-linking agent (such as citric acid, lysine, aspartic acid, glutaric acid, etc.), a flavorant, and/or a coloring agent. |
| PATENT EXAMPLES | Available on request |
| PATENT PHOTOCOPY | Available on request |
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