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ULTRAMULSION CONTAINING
INTERDENTAL DELIVERY DEVICES
BACKGROUND OF THE INVENTION
The present invention relates to unique interdental delivery devices, other than dental floss, which are suitable for cleaning, massaging and/or treating surfaces of teeth and gums including interproximal and subgingival areas, containing a dispersion of certain silicones in certain surfactants. When added to water these dispersions are stable and are distinct from solutions, emulsions and microemulsions. These dispersions are referred to hereinafter as ULTRAMULSIONTM dispersions. This trademark is the property of Whitehill Oral Technologies, Inc. For further information regarding ULTRAMULSIONTM dispersions, see copending application Ser. No. 08/144,778, now U.S. Pat. No. 5,538, 667, the disclosure of which is hereby incorporated herein by reference. See also copending patent application Ser. Nos. 08/462,613; 08/462,203; 08/462,600; 08/463,010; 08/461,698; 08/464,403; and 08/462,930; all filed on Jun. 5, 1996, the disclosures of which are hereby incorporated by reference.
The interdental devices of the present invention include interdental stimulators, massagers, and the like, including elastomeric massagers and wooden sticks, typically from about 5-10 cm long, tapered at one or both ends with cross sectional dimensions from between about 0.5 mm and about 5 nun. Elastomeric, rubber type massagers such as those attached to special handles or the end of toothbrushes are of particular use for the purposes of the present invention.
The interdental devices of the present invention contain ULTRAMULSIONTM dispersions at from between about 1% and about 50% by weight of the device. Preferably these devices are wooden (balsa or bass wood are preferred) or composed of an elastomeric substance with some flexibility. All the devices provide various passageways, voids etc. suitable for loading ULTRAMULSIONTM dispersions that can be released during cleaning, massaging or treating of surfaces in the oral cavity.
The interdental stimulators and massagers of the invention do not require the dexterity required by dental floss. Wolffe, G. N., J. of Clinical Periodontal, 3:145-156 (1976) reported 51.4% of subjects tested preferred interdental stimulators vs. 11.5% preferring dental floss. If periodontal disease is to be controlled, then the accumulation of plaque around the gingival margins of the teeth and also on proximal surfaces must be prevented. Ibid.
The ULTRAMULSIONTM dispersions released from the interdental delivery devices of the present invention exhibit unique and unexpected substantivity to oral surfaces including teeth and gums while providing a reservoir for various lipid soluble and/or lipid dispersible active ingredients resulting in antiplaque, antibacterial, antigingivitis cleaning and treating benefits that last for extended periods. This combination of enhanced substantivity and the reservoir effect described in detail below are further combined with excellent particle size to provide optimum treatment coatings to the interproximal and subgingival areas of the mouth when released from the interdental delivery devices of the present invention.
Other oral care products containing the ULTRAMULSIONTM dispersions of the present invention include: rinses, spray, gels, creams, toothpastes, tooth powders, denture cleaning tablets, dental floss, mints, and chewing gums as described and claimed in copending patent applications referenced above.
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The interdental delivery devices of the present invention may be used by dentists and hygjenists in various professional oral hygiene treatments and/or may be used by consumers for various at-home and away-from-home treat
5 ments ranging from massaging and cleaning to antiplaque, anti-gingivitis and anti-tartar hypersensitivity treatment, remineralizing, whitening, stain removal, and the like. As to Antiplaque Benefits: The present invention further relates to the interference
10 with the formation of plaque. Plaque is a microbial coating on tooth surfaces, bound together by natural polymers (e.g., mucopolysaccharides) formed by microbial action on the cell debris, food remnants, sugars and starches in the mouth. Embedded in this polymer matrix are the bacteria normal to
15 the oral cavity but, when trapped against tooth surfaces and protected by the matrix from easy removal, are in excellent position for "mischief." Most dental texts implicate plaque in the formation of caries, or tooth decay. In addition, these embedded bacteria release toxins that cause gingivitis,
20 bleeding and swelling of the gums. Gingivitis can lead to periodontitis in which gums recede, pockets of infection form and teeth loosen.
Plaque formation is an ongoing process. Various gel and paste dentifrice preparations, mouth rinse and mouth pre
25 rinse preparations make plaque and/or tartar control claims. One disadvantage of these preparations is that only a relatively short time during which the teeth are being cleaned or the mouth is being rinsed is available for these preparations to take effect. These preparations generally have little
30 residual effect on plaque formation. Additionally, some of these preparations such as mouth rinses and pre-rinses contain various antimicrobial substances which may alter the critically balanced microflora of the mouth. Another disadvantage of these preparations is the general infre
35 quency of use. That is, most are used once or perhaps twice daily and seldom when they are most needed, e.g., after meals, snacks, smoking, drinking, coffee breaks, etc.
The ULTRAMULSIONTM dispersion containing interdental devices of the present invention are particularly
40 effective at removing plaque mechanical cleaning while simultaneously helping to fight plaque buildup and/or treat gingivitis by releasing some of the ULTRAMULSIONTM dispersion onto the area being treated. The role of controlling supragingival plaque in the prevention and treatment of
45 periodontal disease is reviewed by Korman K. S. Journal of Periodontal Research Supplement. 5-22 (1986).
According to Bass C. C. in Dent. Items of Interest, 70:921-34, (1948) there is " . . . considerable area on proximal surfaces of teeth, which cannot be reached by the
50 bristles of the toothbrush." The efficacy of wooden interdental stimulators (I & J STIM-U-DENTS®) vs. PeridexTM Rinse is detailed by Mankodi et al., /. of Dental Res. Special Issue, 246 (1988). "The greatest incidence and severity of inflammatory periodontal disease has been reported in the
55 interproximal area." Ibid.
Wooden interdental stimulators which are round or rectangular in cross section remove plaque from the bowel part of the proximal surfaces, whereas triangular interdental stimulators are effective on both buccal and lingual parts of
60 proximal surfaces according to Bergenholtz et al., /. of Clinical Perio. Res., 1:160-165 (1974).
Effective oral hygiene requires that three control elements be maintained by the individual:
1. Physical removal of stains, plaque and tartar. This is
65 accomplished in the strongest sense by scraping and abrasion in the dentist's office. Self administered procedures are required frequently between visits and
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range from tooth brushing with an appropriate abrasive toothpaste through flossing and water jet action down to certain abrasive foods and even the action of the tongue against tooth surfaces.
2. Surfactant Cleansing. This is required to remove: food 5 debris and staining substances before they adhere to the tooth surfaces; normal dead cellular (epithelial) material which is continually sloughed off from the surfaces of the oral cavity and microbial degradation products derived from all of the above. Besides the obvious 10 hygienic and health benefits related to simple cleanliness provided by surfactants, there is an important cosmetic and sense-of-well-being benefit provided by surfactant cleansing. Research has shown that the primary source of bad breath is the retention and subsequent degradation of dead cellular material sloughed 15 off continuously by the normal, healthy mouth.
3. Frequency of Cleansing. This is perhaps the most difficult to provide in today's fast-paced work and social environment. Most people recognize that their teeth should be brushed at least 3 times a day plus after 20 each snacking occasion.
The simple fact is that most of the population brush once a day, some brush morning and evening, but precious few carry toothbrush and dentifrice to use the other three or four times a day for optimal oral hygiene. 25 Consumer research suggests that the population brushes an average of 1.2 times a day. Thus, the 24 hour period between brushings for a majority of the population provides optimum plaque forming conditions with no interruptions. 30 Since plaque is regarded by most of the dental profession as a causative agent leading to various dental pathologies as noted above, there is considerable desire by most consumers to disrupt or prevent the formation of plaque on a daily basis. There are three oral care strategies which address the prob- 35 lem of plaque: abrasion, anti-microbial agents and removal of precursors to plaque.
1. Abrasive removal of the plaque film, once it has firmly adhered to the tooth surface, is the only totally effective cleansing mechanism Again, professional dental hygiene is 40 the most effective, but recently a number of special abrasive toothpastes have been accepted by dental organizations as partially removing adhered plaque and the tartar which subsequently forms from the plaque.
2. Antimicrobial action could affect plaque formation in 45 two ways, (a) reducing the number of bacteria in the mouth which form the mucopolysaccharides and (b) killing those bacteria trapped in the film to prevent further growth and metabolism. However, the medical and dental community is divided about the advisability of frequent use of antimicro- 50 bial agents in the mouth in rinses or pre-rinses, especially the most effective ones, except under strict supervision of licensed practitioners. There are a number of reasons given, but one concern is that such materials would upset the ecological balance of the mouth. A balanced, "friendly" 55 microbial population is necessary to prevent pathogenic organisms from taking over.
3. Removal of plaque precursors requires the reduction of food sources and building blocks required for the bacteria to synthesize the mucopolysaccharides which polymerize into 60 the plaque film. Going far back into the chain of events leading to plaque formation and interrupting the chain has much to commend it as a sound oral hygiene strategy. However, for this strategy to be effective, the plaque building blocks must be interrupted periodically. As noted above, 65 heretofore, the oral hygiene preparations described above fall short on "frequency-of-use" basis.
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For reference see: L. Menaker, The Biologic Basis of Dental Caries, Chapters 5, 11, 12, 14, 16 and 18, Harper & Row (1980). See also U.S. Pat. Nos. 4,465,661; 3,507,955; 4,902,497; 4,661,341; 4,666,708; 4,537,778; 4,657,758; 3,624,120; 4,525,342; 4,476,107; 5,078,988; 2,806,814; 4,774,077; 4,612,191; 4353,890; 4,894,220; British Pat. No. 689,679, Garter et al., Journal of Pharmaceutical Sciences, 74:1228-1232 (1985); and Bass, Dent. Items of Interest, 70:21-34 (1948). As to Antitartar Benefits:
Dental calculus, or tartar as it is sometimes called, is a deposit which forms on the surfaces of the teeth at the gingival margin. Supragingival calculus appears principally in the areas near the orifices of the salivary ducts; e.g., on the lingual surfaces of the lower anterior teeth and on the buccal surfaces of the upper first and second molars, and on the distal surfaces of the posterior molars.
Mature calculus consists of an inorganic portion which is largely calcium phosphate arranged in a hydroxyapatite crystal lattice structure similar to bone, enamel and dentine. An organic portion is also present and consists of desquamated epithelial cells, leukocytes, salivary sediment, food debris and various types of microorganisms.
As the mature calculus develops, it becomes visibly white or yellowish in color unless stained or discolored by some extraneous agent. In addition to being unsightly and undesirable from an aesthetic standpoint, the mature calculus deposits are regarded by many as a constant source of mechanical irritation of the gingiva.
A wide variety of chemical and biological agents have been suggested in the art to retard calculus formation or to remove calculus after it is formed.
Mechanical removal of this material periodically by the dentist is, of course, routine dental office procedure.
The chemical approach to calculus inhibition generally involves chelation of calcium ion and/or crystal growth inhibition which prevents the calculus from forming and/or breaks down mature calculus by removing calcium.
The prior art discloses a number of chelating agents for this purpose. British Pat. No. 490384, Feb. 15, 1937, discloses oral compositions containing emylenediaminetetraacetic acid, nitrilotriacetic acid and related compounds as anticalculus agents. U.S. Pat. No. 3,678,154, Jul. 18,1972 to Widder et al. discloses oral compositions containing certain polyphosphonates and fluoride.
U.S. Pat. No. 3,737,533, Jun. 5,1973 to Francis discloses oral compositions containing certain carbonyl diphosphonates. In addition to the above references, the prior art discloses dentifrices and mouthwashes containing soluble pyrophosphate salts which have been included for a variety of purposes. Included among such references are U.S. Pat. No. 2,941,926, Jun. 21, 1960 to Salzmann et al. which discloses dental powders containing chlorophyll and pyrophosphate salts. U.S. Pat. No. 3,137,632, Jun. 16, 1964 to Schiraldi discloses toothpastes containing pyrophosphate salts. U.S. Pat. Nos. 3,927,201 and 202, Dec. 16, 1975 to Baines et al. and Harvey et al., respectively, disclose toothpastes which utilize soluble pyrophosphates as abrasives. U.S. Pat. Nos. 4,244,931, Jan. 13,1981 and 4,247,526, Jan. 27, 1981 to Jarvis et al. disclose pyrophosphate salts in dicalcium phosphate systems. Jap. Patent Application Disclosure No. 4945-1974 discloses soluble pyrophosphates in a variety of dentifrice systems. U.S. Pat No. 4333,551, Apr. 6, 1982 to Parran discloses tetralkali metal salts in mouthwash compositions.
In addition to the use of the above mentioned materials the use of certain acrylic acid polymers and other agents have
also been disclosed for use as anticalculus agents. Included among such agents are polyelectrolytes such as copolymers of maleic anhydride and ethylene disclosed in U.S. Pat. No. 3,429,963, Feb. 25, 1969 to Shedlovsky. Shedlovsky also discloses polyacrylic acid having an average molecular 5 weight of 1500 and greater. Other references disclosing polyacrylic acids in oral compositions are South African Pat No. 720898, Sept. 12, 1972 which discloses such acids having a molecular weight of from 1000 to 2,000,000; and U.S. Pat. No. 4304,766, Dec. 8, 1971 to Chang discloses 10 polyacrylic acid having a molecular weight in the range of 2,000 to 4,000,000 for use as a membrane to prevent the elution from teeth of previously applied agents. Finally U.S. Pat. No. 3,956,480, May 11, 1976 discloses complexes of anionic polymers (e.g., acrylic acid) and a cationic thera- 15 peutic agent (e.g., chlorhexidine) as anticalculus agents. As to Anti-Gingivitis Benefits:
It is generally accepted that antimicrobial substances are most effective in responding to gingivitis flare ups/infections of the gums. Suitable antimicrobials include stannous 20 fluoride, as described in: U.S. Pat. Nos. 5,057,308; 5,057, 309; 5,057,310 and in the FDA filing responsive to the Sep. 19, 1990 call-for-data (55 Fed. Reg. 38560) filed by WhiteHill Oral Technologies Jun. 17, 1991, Docket 81 N-0033, OTC 210246 to 210262 and 210339 and specifically the 25 "Annotated Bibliography set out in Vol. VI of said filing.
Other anti-gingivitis antimicrobials include chlorhexidine, halogenated diphenyl ethers such as triclosan, phenol and its homologs and the essential oils used in Listerine®. U.S. Pat. Nos. 4,022,880 and 4,894,220 30 disclose and claim various triclosan based oral care products. U.S. Pat. No. 4,894,220 includes an extensive teaching on phenol and its homologs suitable as antimicrobial agents. Metronidazole is discussed in detail in U.S. Pat. No. 4,568, 535. The Listerine® essential oils are described in detail by 35 Kornman in Journal of Periodontal Research, Supplement 1986:5-22 (1986).
Other anti-plaque active ingredients include:
a. Quaternary ammonium compounds including benzethonium chloride, cetylpyridinium chloride as described by 40 Volpe et al., Journal of Dental Research, 48:832-841 (1969) and Gjermo et al., Journal of Periodontal Research, 5:102-109 (1970).
b. Phenolic compounds including the mixture of thymol, eucalyptol, menthol along with methyl salicylate described 45 as "essentials oils" in Listerine®. See Fornell et al., Scandinavian Journal of Dental Research, 83:18-25 (1975), Lusk et al., Journal of the American Society of Preventive Dentistry, 4:31-37 (1974); Gomer et al., Journal of the American Society of Preventive Dentistry, 2:12-14 (1972). 50
The ULTRAMULSIONTM dispersion containing interdental delivery devices of the invention are particularly effective at delivering therapeutic agents, mterproximally, subgingivally and into certain periodontal pockets. Aportion of the ULTRAMULSIONTM dispersion containing the thera- 55 peutic agent is released during picking or massaging of the area being treated by the device. The released ULTRAMULSIONTM dispersion thereby provides continuous therapy for the site being treated.
Therapeutic delivery devices suitable for treating peri- 60 odontal pockets are described and claimed in U.S. Pat Nos. 4,764,377 and 4,892,736. Impregnated and treated dental stimulators are disclosed in U.S. Pat. No. 4,942,034.
Oral therapeutic delivery devices are also discussed in: Goodson et al., J. Periodontal, 54:575-579 (1983); U.S. 65 Pat. Nos. 3,674,901; 3,849,185; 4,042,871; and Goodson J. M. Medical Applications of Controlled Release, Vol. II,
Chapter 7, CRC Press, Boca Raton 115-138 (1984); Bergenholtz et al., J. Clin. Periodontal, 1:160-165 (1974); Addy et al., Journal of Clinical Periodontology, 11:467-474, (1984); and Golomb et al., Journal of Dental Res., 63:1149-1153 (1984). As to Periodontitis Benefits:
The main cause of tooth loss in adults is periodontal disease. Yet, surprisingly, less than one percent of the public expenditures for dental treatment is for periodontal disease (see J. Dent. Educ, 43:320 (1979). This is because conventional periodontal treatment is too expensive for most individuals, mainly due to the labor intensive, symptomatic treatment that is usually performed by highly skilled specialists.
Periodontal disease is an all-inclusive term for a variety of clinical entities that are forms of either gingivitis or periodontitis. Gingivitis is an inflammation of the gingiva or gums that can be associated with poor oral hygiene and/or hormonal states of the host. It is assumed, but not proven in the human, that gingivitis will progress to periodontitis, which is the form of the disease in which the infection has progressed to involve the oral tissues which retain the teeth in the jaw bone. Periodontitis is the more severe form of the disease, and if untreated, will eventuate in the loss of the tooth.
Dentists have long assumed that periodontal disease originates by the overgrowth of bacteria on the tooth surfaces in aggregates known as dental plaque. If this plaque persists for long periods of time on the tooth surfaces, it may in some instances calcify, forming the hard substance known as calculus. Numerous studies describe chemical agents which can in vitro and in vivo reduce plaque formation and calculus. However, none of these chemical agents has been reported to be successful in treating periodontitis.
A substantial number of different types of compounds and compositions have been developed for use as antibacterial and antiplaque agents, e.g., benzethonium chloride and cetyl pyridinium chloride, disclosed in U.S. Pat. No. 4,110,429, or as anticalculus agents, e.g., 2-phosphono-butane 1,2,4tricarboxylic acid, disclosed in U.S. Pat. No. 4,224,308. These compounds are designed to be used by the individual in dentifrices, dental powders, pastes, mouthwashes, nonabrasive gels, chewing gums, topical solutions and the like, e.g., see U.S. Pat. No. 4,205,061. They are designed to be used as prophylactic agents, usually without requiring a prescription or supervision during usage, e.g., see U.S. Pat. No. 4,251,507. Often they are compounded with detergents and other cleaning agents, and this cleaning action is often an important aspect of the invention, e.g., see U.S. Pat Nos. 4,251,507 and 4,205,061. None of these compounds or compositions are designed to be used as antimicrobial agents for the treatment of periodontitis, nor are they formulated to be slow release devices for these antimicrobial agents in vivo.
Recent research in periodontal disease (see, for example, Chemotherapy of Dental Plaque Infections, Oral Sci. Rev., 9:65-107 (1976) indicates that gingivitis and periodontitis are characterized by different types of bacteria. Gingivitis is associated with the accumulation of Gram positive cocci and actinomyces, whereas periodontitis is characterized by proportional increases in anaerobic bacteria, such as spirochetes and black pigmented bacteroides (see "Host-Parasite Interactions in Periodontal Disease," R. J. Genco and S. E. Mergenhagen, ads., Amer. Soc. for Microbiol. Washington, D.C. p. 27-45, 62-75, 1982). The different bacterial compositions of plaque associated with either gingivitis or periodontitis suggest that a mode of treatment that is effec
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