Abstract:
A method for decreasing dental hypersensitivity, including sizing a plurality of non-functionalized microbeads to be between 0.01 μm to 3 μm in diameter, suspending the plurality of non-functionalized microbeads in a fluid matrix to define a dental delivery composition, introducing the dental delivery composition into an oral cavity, introducing respective non-functionalized microbeads into a dental tubule, adhering respective functionalized microbeads each other and to the dental tubule to define an aggregate, and occluding the dental tubule with the aggregate.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This patent application claims priority to co-pending U.S. patent application Ser. No. 13/438,318, filed on Apr. 3, 2012, which claimed priority to then co-pending U.S. Provisional Patent Application Ser. No. 61/471,649, filed on Apr. 4, 2011. 
    
    
     BACKGROUND 
     Dental hypersensitivity is a challenging problem since the oral environment is continuously cycled through periods of demineralization (i.e. loss of mineral through acid attack or physical attrition) and demineralization (i.e. seeding minerals such as fluoride, calcium and phosphate that combine with the existing tooth structure to grow new mineral that can strengthen the enamel and/or dentin). When too much mineral is lost and the demineralization processes cannot keep the pace of replacing the lost mineral, tooth sensitivities ultimately develop. This is further complicated due to natural aging of the tooth and tends to be more common when restorative or implant procedures have been performed. Such sensitivity is typically manifested in pain arising from sudden extreme temperatures (such as drinking ice cold or steamy hot beverages) or changes in pressure, including the act of chewing or biting on brittle surfaces or through probing with a dental explorer or pressurized air. The sensitivities develop due to the exposure of nerves positioned within the dentin component of the tooth structure. Over time, the penetration of acids into and/or the thinning of enamel increases the risk of demineralizing the thin mineral layers in dentin that surround and protect the sensitive nerve endings. These nerves are typically positioned in dentin tubules (about 1-3 μm in diameter and at least 5 μm in length). Without adequate acid-resistant support, these nerves become triggered during an extreme event, such as chewing food, eating ice cream or drinking a hot beverage. Based on various surveys and polls, at least 40% of the population exhibits some dental hypersensitivity. Thus, hypersensitivity remains a challenging problem and opportunity. 
     There are several treatments currently used to treat hypersensitivity. One treatment is the placement of resins or varnishes on the affected area. This is typically performed by the dental professional, which may require frequent dental visits. Other treatments may include treating with higher levels of fluoride, such as 5,000 ppm fluoride toothpaste available through the dentist, or using a multiple agent product, such as toothpastes containing combinations of calcium, silica, fluoride, phosphate, strontium, and the like. The most common over-the-counter approach typically involves toothpastes containing potassium nitrate: although a barrier is not formed, the nitrate responds to and neutralizes the exposed nerve ending. These approaches have all produces significant benefits, however, problems still occur. For instance, some have aversions to high fluoride products while others may not visit the dentist on a regular basis. Additionally, the resin and potassium nitrate approaches are temporary solutions, requiring continuous use in order to enjoy long-term relief from hypersensitivity. Separately, the mineral formations that develop in and on the dentin through use of a multiple agent combination product may, over time, not provide sufficient protection against acid challenges and/or physical attrition. Therefore, in this disclosure, we describe a novel combination of materials for improved relief from dental hypersensitivity that also avoids the weaknesses associated with these existing therapies. 
    
    
     
       DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is a perspective view of a functionalized microbead according to a first embodiment of the present novel technology. 
         FIG. 2A  is a schematic view of a tooth. 
         FIG. 2B  is an enlarged portion of the tooth of  FIG. 2A , illustrating the enamel outer surface. 
         FIG. 2C  is an enlarged portion of the enamel outer surface of  2 B, illustrating the tubules. 
         FIG. 3A  is an enlarged view of the tubules of  FIG. 2C  showing a tubule. 
         FIG. 3B  is a schematic view of the tubule of  FIG. 3A  occluded with an agglomeration of the microbeads of  FIG. 1 . 
         FIG. 4  illustrates a plan view of a microbead composition according to a second embodiment of the present novel technology. 
         FIG. 5A  is an enlarged view of dental tubules. 
         FIG. 5B  is a schematic view of the tubule of  FIG. 3A  occluded with the composition of  FIG. 4 . 
         FIG. 5C  is a schematic view of the tubule of  FIG. 3A  occluded with the composition of  FIG. 4  after hardening into an agglomeration. 
     
    
    
     DETAILED DESCRIPTION 
     For the purposes of promoting an understanding of the principles of the novel technology, reference will now be made to the embodiments illustrated in the drawings and specific language will be used to describe the same. It will nevertheless be understood that no limitation of the scope of the novel technology is thereby intended, such alterations and further modifications in the illustrated device, and such further applications of the principles of the novel technology as illustrated therein being contemplated as would normally occur to one skilled in the art to which the novel technology relates. 
     The present technology relates to the general reduction in dental hypersensitivity. One feature of this technology is the incorporation of microbeads  10  into exposed dentin tubules  15 . Another feature is the acid-resistant adhesion and retention of the microbeads  10  within the dentin tubules  15  as well as on the weakened dentin surfaces that has resulted from demineralization processes. The microbeads  10  typically include an inorganic microsphere  20  that is coated with a thin organic coating  30 . This two-phase system  10  provides a physically strong, acid-resistant layer  30  that adheres to the demineralized dentin surfaces and also occludes dentin tubules  15 . This two-phase system  10  can be implemented into dental vehicles including toothpastes, rinses, varnishes, gums, mints, gels, and the like. 
     Inorganic materials such as silica, titania, alumina, various glass compositions, and the like are commonly found in dental products and are used, for instance, as abrasives, fillers, pigments and/or for providing structural rigidity, and thus may also be used for the inorganic microsphere or core portion  20 . Alternately, polymeric microspheres  20  such as polyethylene may also be used for the core portion  20 . Microspherical shapes of these materials offer significant benefits relative to other geometries, including yielding large surface areas available for functionalization. Spherical or near-spherical geometry also provides a favorable shape for penetration into demineralized dentin tubules  15 , which are porous in nature with diameters between 1 and 4 μm. The spherical shape can also affect light reflection to create a ‘whitening-like’ effect, both from the reflectivity of the round unfunctionalized silica surfaces, the reflectivity of various coatings, and/or the white color of microspheres composed of titania, alumina or the like. 
     As shown through in microscopy analysis of demineralized dentin (see figure), the microspheres  10  can readily penetrate into the dentin tubule. Due to differences in the physical and chemical properties between organic (e.g. polymers and the like) and inorganic (e.g., silica and the like) materials, inorganic materials such as silica, titania, and the like can provide structural rigidity and resistance to acid attack, which are attractive and beneficial features when embedded into the relatively softer and acid-susceptible dentin tubules  15 . 
     The present novel technology relates to microbeads  10 , typically having dimensions between 0.01 μm to 10 μm, and more typically between 0.9 μm and 3 μm to encourage optimized packing within the dentin tubules. However, other convenient dimensions may be selected. More typically, microbeads  20  are provided with a particle size distribution (PED) defining a variety of diameters within this range for optimal packing and thus the provision of hypersensitivity benefits. Although the microspheres  20  are typically composed of inorganic materials, such as silica, titania, and the like, organic microspheres  20  made from such materials as polyethylene, polypropylene, cross-linked polymers and the like may also be used. 
     Although the microspheres  20  can penetrate readily into the dentin tubule  15 , they are less adept at attaching to the relatively flat dentin surfaces. Therefore, the microsphere surface  25  may include an adhesive coating  20  to encourage greater adhesion of the smooth spherical surface  25  to the smooth dentin surface. Once in the tubule  15 , a plurality of microbeads  10  adhere to the tubule walls and each other defining an agglomerate  40  that effectively occludes the tubule  15 . 
     One approach to providing an adhesive coating  30  is to coat or functionalize the inorganic sphere  20  with a hydrophilic or sticky material layer  30 . This material  30  can be organic, including a polymer such as polyacrylic acid (e.g. typical molecular weight range between 100,000 and 450,000 g/mol), or another, typically hydrophilic, material. The coating material  30  may be phosphate, such as derived from phosphoric acid. Alternately, the coating material  30  may be hydrophobic, such as derived from silanes or methanes. Typically, the material  30  used to coat the microbeads  20  has some character that encourages mineral seeding and growth so that new mineral can be formed over time within the dentin tubule as well as on the dentin surface. This coating material  30  can attract ions available from both the natural oral environment through saliva components, including calcium, phosphate and the like, and also from the use of dental products containing, for example, fluoride, calcium, phosphate, strontium, potassium, nitrate, tin and the like. 
     In constructing the functionalized microbeads  10 , the typical weight fraction of the organic material  30 , such as phosphoric acid, polyacrylic acid and the like, may typically range between 0.01% and 5%, more typically between 0.1% and 1%. The corresponding weight fraction of the organic material  30  should be combined with a suspension or dry powder of inorganic microspheres  20 , typically silica or titania. This combination can be achieved using typical chemical approaches including dehydration of a silica suspension followed by addition of the organic agent in the stated amounts coupled with a dehydration step to achieve a dry powder. Alternately, a suspension of the microspheres  20  can be combined with the stated amount of organic agent  30  and left as a suspension. 
     The two-phase combination  10 , comprising microspheres  20  coated with an adhesive layer  30 , are able to provide additional benefits relative to use of either agent alone. The adhesive property of the functionalized microsphere  10  can remain on the dentin surface despite challenge from an acid attack, providing structural stability and improved chemical resistance to demineralization from enamel and dentin. The coating  30  serves additional purposes: namely, a sacrificial layer  30  to subsequent acid attacks as well as to promote remineralization through contact with saliva and various dental products with or without fluoride. These factors bear directly on the relief from dentin demineralization and therefore dental hypersensitivity. While either the microbeads  10  alone or the organic coating material  30  alone could offer hypersensitivity relief, the two-phase composite bead  10  can extend hypersensitivity relief. Thus, these composite beads  10  may be implemented into mints, lozenges, gums, rinses, pastes, gels, and the like in form of dry powders or suspensions for delivery to tubules  15  and dentin upon introduction into the oral cavity. 
     One example of a treatment is the application of a 10% w/v suspension of 1 μm diameter silica microspheres  10  functionalized with 0.5% phosphoric acid coating  30  to demineralized dentin. Application of functionalized microbeads  10  to dentin/tubules may provide greater resistance to acid challenges compared to native (i.e. unfunctionalized) silica microspheres  20 . 
     DETAILED EXAMPLE 
     One method of functionalizing silica microspheres with phosphate (PO 4 ) was produced with phosphoric acid is as follows:
         1) Using a vortex mixer, shake silica suspensions (formulated as discussed above) thoroughly for several minutes.   2) Extract 1 ml of the silica microsphere solution (number of microspheres  10  is approximately 10 9 , 10 10 , and 10 11  microspheres  10  for 1.0, 2.5, and 4.0 μm diameter microspheres, respectively) and place in a glass container (i.e. 50 ml Pyrex beaker).   3) Place the beaker with the 1 ml solution into the vacuum oven (warmed to ˜100° C.) and slowly pull a vacuum—let it stand for about five minutes or later until the water is removed. Only the silica  20  should remain.   4) To clean the silica  20  and prepare it for functionalization, add several milliliters of ethanol to the resultant powder and then evaporate it—place it in the 100° C. oven for ˜10 minutes to remove ethanol.   5) If desired, repeat Step #4 one more time.   6) Separately, make ˜0.5% w/w H 3 PO 4 (aq) (i.e. 500-fold dilution of 85% w/w parent solution using distilled water).   7) Add 2 ml of the acidic solution  30  to the silica powder  10  and gently mix—place in oven (e.g. ˜100° C. for 15 minutes and slowly pull a vacuum to encourage evaporation.   8) Collect the resultant acid-functionalized silica powder  10 , weigh it, and set it aside in a sealed container for later use.
 
Using PO 4  functionalized microspheres  10 , bovine dentin was demineralized to expose the ˜2-5 μm diameter tubules (50% citric acid solution, ten minutes, room temperature), then treated with a small drop of a 10% suspension (30 mg into 0.3 ml distilled water). Observations were then obtained using scanning electron microscopy.
 
Amount of Recovered Sample After PO 4  Procedure:
       

                                             Silica Microsphere Diameter   Mass (mg)                           1.0 μm   110.1           2.5 μm   114.6           4.0 μm   110.6                        
Using PO 4  functionalized microspheres, bovine dentin was demineralized to expose the ˜2-5 μm diameter tubules (50% citric acid solution, 10 minutes, room temperature), then treated with a small drop of a 10% suspension (30 mg into 0.3 ml distilled water). Observations were then obtained using scanning electron microscopy.
 
     As illustrated in  FIGS. 4 and 5A-5C , another embodiment of the present novel technology relates to a system  100  including a plurality of unfunctionalized or ‘naked’ microbeads  20 , again typically having dimensions between 0.01 μm to 10 μm, and more typically between 0.9 μm and 3 μm, for packing within dentin tubules. More typically, microbeads  20  are provided with a particle size distribution (PED) defining a variety of diameters within this range for optimal packing and thus the provision of hypersensitivity benefits. Again, the microspheres  20  are typically composed of inorganic materials, such as silica, titania, glass (including bioresorbable glass such as 45S5 glass and like compositions), and/or organic materials such as polyethylene, polypropylene, cross-linked polymers and the like, or combinations thereof. 
     The microspheres  20  when introduced alone may penetrate readily into the dentin tubule  15 , where they can agglomerate to form occlusions. Typically, the microspheres  20  are introduced with a dental delivery mechanism  110 , such as a varnish, that both transports the microspheres  20  into the oral cavity to the dentition, and assists in adhering the microspheres  20  to the tubules  15 . Once in the tubule  15 , a plurality of microbeads  10  adhere to the tubule walls and to each other via the delivery fluid matrix  110  to define an agglomerate  40  that effectively occludes the tubule  15 . 
     As with the functionalized microbead embodiment discussed above, this system  100  defined by unfunctionalized microbeads  20  suspended in a delivery fluid  110  defines a two-phase combination  100 , comprising microspheres  20  suspended in a typically adhesive medium  110  for providing additional benefits relative to use of either agent alone. The unfunctionalized microsphere  20  may become adhered to a dentin surface via the delivery medium  110 , such as varnish, despite challenge from an acid attack, providing structural stability and improved chemical resistance to demineralization from enamel and dentin. The varnish  110  likewise serves additional purposes, such as providing a sacrificial layer to subsequent acid attacks as well as to promote occlusion and/or remineralization through contact with saliva and various dental products with or without fluoride. These factors bear directly on the relief from dentin demineralization and therefore dental hypersensitivity. While either the microbeads  10  alone or the (typically organic) coating material  110  alone could offer hypersensitivity relief, the composite agglomerate  40  extends hypersensitivity relief. 
     EXAMPLE 
     Non-Functionalized Silica Microspheres. 
     The second example is a variant of the first example, wherein increasing occlusion is achieved using non-functionalized silica microspheres  20 . The silica microspheres  20  are less than 3 μm in diameter and provide structural rigidity and resistance to acid attack of dentin. Much like the functionalized microspheres, the non-functionalized silica microspheres  20  are compatible with dentin and are able to attach to the walls of the tubules  15  as well as each other via the carrier medium  110 , to participate in occluding dentin and obstructing future acidic interactions or erosion. These naked microspheres  20  may be implemented into dental vehicles  110  including varnishes, dentifrices, mouthwash and the like and may include fluoride agents to assist in whitening and dentin remineralization. The non-functionalized silica microspheres  20  have been observed to form agglomerates  40  that occlude the dentin tubules  15  and resist acid attack. Dentin specimens were demineralized for 10 minutes using 50% citric acid (pH=1.59). The specimens were then treated with the non-functionalized silica microspheres  20  in a 10% w/v suspension, and then again exposed to a subsequent 1% citric acid (pH=3.8) for 5 minutes. The study showed the microspheres&#39;  20  ability to penetrate and remain in tubules  15  during the subsequent citric acid attack. 
     It will be appreciated that several of the above-disclosed and other features and functions, or alternatives thereof, may be desirably combined into many other different systems or applications. Also, that various presently unforeseen or unanticipated alternatives, modifications, variations or improvements therein may be subsequently made by those skilled in the art which are also intended to be encompassed by the following claims. 
     While the invention has been illustrated and described in detail in the drawings and foregoing description, the same is to be considered as illustrative and not restrictive in character. It is understood that the embodiments have been shown and described in the foregoing specification in satisfaction of the best mode and enablement requirements. It is understood that one of ordinary skill in the art could readily make a nigh-infinite number of insubstantial changes and modifications to the above-described embodiments and that it would be impractical to attempt to describe all such embodiment variations in the present specification. Accordingly, it is understood that all changes and modifications that come within the spirit of the invention are desired to be protected.