Patent Document

CROSS-REFERENCE TO RELATED APPLICATIONS 
       [0001]    This application is a continuation-in-part of co-pending U.S. Ser. No. 12/205,062 filed Sep. 5, 2008, which is incorporated herein by reference and which is a continuation-in-part of now abandoned U.S. Ser. No. 11/850,661 filed on Sep. 5, 2007. 
     
    
     BACKGROUND 
       [0002]    This invention relates to a method of concurrently promoting general oral hygiene, treating periodontal diseases such as gingivitis and periodontitis, killing oral microbes including cavity-causing bacteria, reducing oral biofilms, increasing blood flow in oral tissues, increasing salivation, promoting gingival tissue regeneration, fostering osteogenesis in the boney structures of the teeth, mouth and related areas, treating systemic diseases associated with oral bacteria, and treating other periodontal and oral maladies through the non-invasive application of weak direct current electricity to the surfaces in the oral cavity, and it also relates to an apparatus suitable for providing direct current electricity for these therapeutic, prophylactic, and regenerative effects. 
         [0003]    Periodontal disease has been identified as a risk factor for various systemic diseases by both dentists and physicians. Included in these diseases are cardiovascular disease, adverse pregnancy outcomes, and diabetes with newfound evidence supporting its association with pancreatic diseases and arthritis. While many of the studies establish correlation between the presence of periodontal disease and these systemic conditions, causation, with most of these conditions, is still a subject of ongoing research. A few of the biological mechanisms which have been proposed as to how oral bacteria stemming from periodontal disease can cause systemic disease are as followed: 
         [0004]    1. Direct effect of oral infections: Oral microbes and their byproducts can gain systemic access via the circulatory system through traveling through compromised tissue and inflamed periodontium in the oral cavity. In gaining systemic access, oral microbes have the potential to directly influence subclinical mediators of various systemic diseases. 
         [0005]    2. Inflammation: People with periodontal disease have elevated levels of systemic inflammatory markers due to the burden of increased levels of oral bacteria. Treatment for periodontal disease has been reported to decrease systemic inflammation levels. 
         [0006]    3. Cross-reactivity: The progression of systemic diseases can be accelerated by the immune response to bacterial heat-shock proteins creating antibodies that cross-react with innate heat shock proteins expressed on cells of the damaged tissues. 
       Cardiovascular Disease 
       [0007]    Studies investigating the potential association between periodontal disease and cardiovascular diseases, including atherosclerosis, coronary heart disease, and stroke have found a significant positive correlation between poor oral health and the prevalence of cardiovascular disease. While both diseases share several common risk factors, recent studies suggest that periodontitis may precede and therefore contribute to atherosclerotic complications. In fact, meta-analyses show that subjects suffering from periodontitis experience an increased risk for developing cardiovascular diseases. 
         [0008]    While it has not been definitively shown if these bacteria initiate atherosclerosis or rather invade an already compromised artery, antibodies to periodontal bacteria, including  Fuseobacterium nucleatum  and  Streptococcus oralis , have been found in blood serum and are associated with an increased risk of coronary heart disease. A mouse study found that intravenous inoculation with  Porphyromonas gingivalis  accelerated atherosclerotic development. Further, following oral inoculation,  P. gingivalis  DNA was found in the aortic tissue of those infected mice that showed observable signs of accelerated early atherosclerosis. Another study has named  F. nucleatum  as a synergistic agent with  P. gingivalis. F. nucleatum  enhances the ability of  P. gingivalis  to invade host cells due to a coaggregating effect between the two organisms. This is significant as bacteria within the atheroma may lead to the development of atherosclerotic plaque. The evidence thus far supports the idea that periodontitis leads to systemic exposure to oral bacteria which serves as a potential source of systemic inflammatory mediators, cytokines produced in the infected periodontal tissues, capable of initiating or worsening atherosclerosis and coronary heart disease when they enter into the blood stream. Clinical studies on periodontal disease have also revealed a positive association with coronary disease and emphasis is now being placed on understanding the exact relation between periodontal disease and atherosclerosis. 
       Pre-Term Birth 
       [0009]      Fusobaceterium nucleatum , one of the most prevalent species of bacteria found in amniotic fluid and placental infections that cause preterm birth, is also often named the sole infectious agent in preterm labor with intact fetal membranes.  F. nucleatum  is also highly associated with various types of periodontal disease. During periodontal infection, when the oral mucosa is injured and flamed and the quantities of periodontal pathogens increase dramatically, transient levels of bacteria can appear in the blood leading to selective colonization of undesired sites. One study demonstrated that pregnant mice injected hematogenously with  F. nucleatum  isolated from either amniotidluid infection or an oral source resulted in fetal death. 
         [0010]    Recently, a human stillbirth case was analyzed and it was found that the  F. nucleatum  did indeed originate from the mother&#39;s oral cavity, a fact that had not yet been proven. It is likely that the  F. nucleatum  translocated from the mother&#39;s mouth via the blood stream where it was then able to cross the endothelium to proliferate and colonize within the fetal membranes, amniotic fluid and fetus whereupon its presence lead to fetal demise. In a mouse model, hematogenous injection of  F. nucleatum  into pregnant mice resulted in specific bacterial colonization in the placenta causing localized inflammation.  F. nucleatum  was completely cleared from the maternal circulation after 24 hours of injection. However, once colonized in the immune privileged placenta, the bacteria proliferated quickly and caused fetal death within 3 days. Chronic periodontal disease could mediate infection through the translocation of periodontal bacteria/inflammatory markers to the fetoplacental unit. 
       Diabetes 
       [0011]    Diabetes mellitus is an endocrine disease that stems from genetic, environmental and behavioral risk factors. For the past several decades, diabetes has been considered a modifying factor for periodontal disease with recent years suggesting a bidirectional relationship between the two. Further, presence of periodontal disease has been implicated as a risk for diabetic complications, namely poor glycemic control. Recent longitudinal and systemic studies have seen periodontal disease correlated to higher risks of death from ischemic heart disease, diabetic nephropathy, end-stage renal disease and increased insulin resistance compared to patients with mild or no periodontal disease. In type II diabetes, insulin resistance is linked to the actions of pro-inflammatory cytokines. It is believed that periodontal disease leads to a significantly higher amount of these serum markers of inflammation, thus conferring insulin resistance. A human study examining the bacterial content of adults with and without type II diabetes found diabetic patients had significantly more severe periodontitis and higher levels of many oral bacteria, including  Streptococcus oralis.    
       Pyogenic Liver Abscess 
       [0012]      F. nucleatum  has recently been implicated in pyogenic liver abscess (PLA). Normally caused by biliary tract pathology, diverticular disease and bowel malignancy, atrophic gastritis and cryptogenic liver disease, PLA caused by  F. nucleatum  is very rare with  Escherichia coli, Klebsiella  and  Enterobacter  being the most commonly isolated microorganisms in the drained abscesses.  F. nucleatum  was found in the liver abscess with no other infectious source being found, except for a dental extraction. It is hypothesized that due to the coaggregation properties of  F. nucleatum , it is able to transport and breach the mucosa of the colon and lead to bacteremia which results in hepatic abscess. 
       Osteomyelitis 
       [0013]    Osteomyelitis is a bone infection caused by bacteria, fungi or other germs. Commonly, bacteria spreads to the bone from infected skin, muscles or tendons and often time occur under a skin sore. The infection can also start in another part of the body and spread hematogenously. Occasionally  Fusobacterium  species have been isolated from bone/joint infections in the head and neck area and were associated with chronic periodontitis. A recent study has reported a case of osteomyelitis caused by  F. nucleatum  in conjunction with muscle abscess. The patient had no known predisposing factors and had no other infection sources except a history of periodontal disease. It is believed that due to the patient&#39;s poor oral hygiene,  F. nucleatum  bacteremia may have developed and lead to a hematogenous osteomyelitis of the lower leg. 
       Arthritis 
       [0014]    Numerous clinical studies have suggested a potential association between rheumatoid arthritis (RA) and periodontal disease as several oral bacteria species, such as  P. gingivalis  and  Prevotella intermedia , have been isolated from the synovial fluid of patients. Periodontal disease is thought to allow bacteria to penetrate through the permeable pocket epithelial in the oral cavity to reach the underlying gingival connection tissue. From there, it may be transported out into the bloodstream with the ability to colonize elsewhere within the body. The oral bacteria found in the synovial fluid of patients suffering from RA has been attributed to synovial inflammation favorably trapping oral bacteria DNA, which suggests periodontal disease may have a perpetuating effect on joint diseases. Therefore, periodontitis may in fact be a factor leading to the autoimmune inflammatory responses characteristic of RA. Patients suffering from RA may also be at a higher risk of developing periodontal disease thus suggesting a bidirectional relationship between the two conditions. One particular study examined the presence of bacterial DNA in the synovial fluids of native and failed prosthetic joints of patients suffering from arthritis. Out of the 5 patients where bacterial DNA was found,  F. nucleatum  was detected in 4 of these 5 patients. This suggests that this bacterium can translocate from the oral cavity to the synovial fluid, as  F. nucleatum  was also found in the patient&#39;s plaque sample. 
       Oral Biofilm 
       [0015]    Periodontitis, gingivitis, and caries are infectious diseases of the oral cavity in which oral biofilm plays a causative role. Biofilm formation is also involved in the pathogenesis of dental implant failures such as peri-implantitis, denture stomatitis, and oral yeast infections such as candidiasis. Oral biofilms begin with dental pellicle formation on the teeth. This pellicle is composed of salivary proteins that coat the exposed surfaces of the teeth, primarily the supra-gingival ones, to which the planktonic bacteria begin to adhere. The aerobic bacteria, including gram-positive cocci, such as  S. oralis , are the early colonizers that begin forming the initial biofilm colony, primarily through cellular division of the adherent bacteria. 
         [0016]    Once the initial colony has been established, other co-aggregating bacteria species, such as  F. nucleatum, P. gingivalis , and other gram-negative, anaerobic bacteria attach to the previously formed colonies. As these colonies mature, they grow to cover the sub-gingival surfaces of the teeth and begin to induce inflammation in the periodontium. 
       SUMMARY OF THE INVENTION 
       [0017]    One aspect of the present invention is to provide a method including the steps of providing a mouthpiece having a first electrode and a second electrode where the first and second electrodes having opposite polarities and are coupled to a power source. The method also includes positioning the mouthpiece such that the first electrode is in electrical contact with at least a portion of the patient&#39;s lingual gingival tissue and the second electrode is in electrical contact with at least a portion of the patient&#39;s buccal gingival tissue. The method also includes delivering current from the power source to said gingival tissue according to a predetermined treatment protocol. 
         [0018]    According to another aspect of the present invention the delivering step may further include regulating the current delivered to the gingival tissue. 
         [0019]    According to another aspect of the present invention the delivering step may further include administering the predetermined treatment protocol to a patient in a dental office. 
         [0020]    According to another aspect of the present invention the delivering step may further include administering a predetermined treatment protocol to a patient in a dental office prior to a dental procedure. 
         [0021]    According to another aspect of the invention the dental procedure may be cleaning or prophylaxis. 
         [0022]    According to another aspect of the invention the dental procedure may be scaling. 
         [0023]    According to another aspect of the invention the dental procedure may be root planing. 
         [0024]    According to another aspect of the invention the current delivered to the gingival tissue is from 50 μA up to and including 500 μA. 
         [0025]    According to another aspect of the present invention the delivering step may further include delivering current to the gingival tissue for a duration of at least 10 minutes up to and including 30 minutes. 
         [0026]    According to another aspect of the present invention the delivering step may further include administering the predetermined treatment protocol to a patient in a dental office before or after a dental procedure. 
         [0027]    According to another aspect of the invention, the mouthpiece may further include a third electrode and a fourth electrode, the third and fourth electrodes having opposite polarities and being coupled to a power source. The positioning step may further include positioning the mouthpiece such that the first electrode is in electrical contact with at least a portion of the patient&#39;s mandibular lingual gingival tissue, the second electrode is in electrical contact with at least a portion of the patient&#39;s mandibular buccal gingival tissue, the third electrode is in electrical contact with at least a portion of the patient&#39;s maxillary lingual gingival tissue, and the fourth electrode is in electrical contact with at least a portion of the patient&#39;s maxillary buccal gingival tissue. 
         [0028]    According to another aspect of the invention the method may include reducing the amount of oral biofilm in said patient. 
         [0029]    According to another aspect of the invention the method may include reducing oral bacterial to prevent, treat and/or mitigate systemic disease. 
         [0030]    According to another aspect of the invention the method may include reducing  F. nucleatum  to prevent, treat and/or mitigate cardiovascular disease. 
         [0031]    According to another aspect of the invention the method may include reducing  F. nucleatum  to prevent still birth. 
         [0032]    According to another aspect of the invention the method may include reducing  S. oralis  to prevent, treat and/or mitigate diabetes. 
         [0033]    According to another aspect of the invention the method may include reducing  F. nucleatum  to prevent, treat and/or mitigate pyogenic liver abscess. According to another aspect of the invention the method may include reducing  F. nucleatum  to prevent, treat and/or mitigate osteomyelitis. 
         [0034]    According to another aspect of the invention the method may include reducing  F. nucleatum  to prevent, treat and/or mitigate arthritis. 
         [0035]    Another aspect of the present invention is a method including the step of providing a first mold, threading one or more wires through the first mold, injecting a nonconductive material into the first mold, curing the nonconductive material, removing the partially molded mouthpiece from the first mold, trimming the excess wire from the partially molded mouthpiece, providing a second mold, placing the partially molded mouthpiece within the second mold, injecting a conductive material into the second mold, curing the conductive material, and removing a finished mouthpiece from the second mold. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0036]      FIG. 1  demonstrates the overall structure of the first embodiment of our invention, including a microcontrolled power source, user input, user feedback and oral electrodes. 
           [0037]      FIG. 2  shows a top-down view of another embodiment that includes a mouthpiece with two continuous electrodes and associated conductors. 
           [0038]      FIG. 3  shows a perspective view of the same embodiment of  FIG. 2 , with two electrodes embedded in a mouthpiece. 
           [0039]      FIG. 4  offers a top-down view of another embodiment similar to  FIG. 2  that includes a mouthpiece, but with a plurality of discrete electrodes. 
           [0040]      FIG. 5  provides a perspective view of an additional embodiment similar to  FIG. 4  with a plurality of electrodes that are electrically connected by embedded conductors. 
           [0041]      FIG. 6  shows an additional embodiment of with an analog power supply using a dual unit, three-port switch. 
           [0042]      FIG. 7  is an exploded view of a first mold for molding a mouthpiece according to the present invention. 
           [0043]      FIG. 8  is a cross sectional view of a first mold for molding a mouthpiece according to the present invention. 
           [0044]      FIG. 9  is an exploded view of a first mold for molding a mouthpiece according to the present invention with a partially molded mouthpiece. 
           [0045]      FIG. 10  is an exploded view of a second mold for molding a mouthpiece according to the present invention with a partially molded mouthpiece. 
           [0046]      FIG. 11  is perspective view of a second mold for molding a mouthpiece according to the present invention with a partially molded mouthpiece. 
           [0047]      FIG. 12A  is a cross section of the mold of  FIG. 11  with a partially molded mouthpiece in its unfilled state. 
           [0048]      FIG. 12B  is a cross section of the mold of  FIG. 11  with a partially molded mouthpiece in its filled state. 
           [0049]      FIG. 13  is a perspective view of a mouthpiece molded according to an embodiment of the present invention. 
       
    
    
     DETAILED DESCRIPTION 
       [0050]    Although the disclosure hereof is detailed and exact to enable those skilled in the art to practice the invention, the physical embodiments herein disclosed merely exemplify the invention which may be embodied in other specific structures. While the preferred embodiment has been described, the details may be changed without departing from the invention, which is defined by the claims. 
         [0051]    It is known in the art that oral bacteria cannot survive when exposed to low-microampere direct current electricity. This method of killing oral bacteria and treating bacteria-caused conditions such as gingivitis has been demonstrated in Nachman, U.S. Pat. No. 4,244,373 of Jan. 13, 1981 and in Detsch, U.S. Pat. No. 4,509,519 of Apr. 9, 1985. Killing oral bacteria has the added benefit of preventing tooth decay and dental caries, or cavities. Generally, tooth decay is attributed to aerobic acid-producing bacteria whose acid causes uncompensated demineralization of the teeth. However, Nachman does not instruct optimal approaches to reducing oral bacteria including aerobic and anaerobic bacteria on a species-by-species level and instead teaches a generic, untargeted treatment. 
         [0052]    While researching the effect of direct current electricity on the mouth, the applicants discovered that by increasing the current level to the approximate range of 50 to 250 microamperes, a direct current electrical treatment was able to deliver new and unexpected therapeutic, prophylactic, and regenerative benefits previously unknown in the art. 
         [0053]    Specifically, by utilizing a direct current in the aforementioned range, not only did such a treatment kill bacteria, but it was also found to kill or disable viruses and fungus as well. Studies from the podiatric field have shown that higher current levels than those used in existing oral electrical treatments are necessary to effectively treat fungal infections (“Low-Voltage Direct Current as a Fungicidal Agent for Treating Onychomycosis”, Kalinowski, et al., Journal of the American Podiatric Medical Association Vol. 94 No. 6: 565-572, 2004). By applying this knowledge of increased current levels from research outside the art, the applicants were able to add fungicidal and viricidal benefits to a method already known to be bactericidal. The applicants&#39; studies have shown that these microbicidal properties begin to take effect within approximately 5 and 15 minutes of treatment, reducing both supra- and sub-gingival microbes. 
         [0054]    In addition, the applicants&#39; clinical research unexpectedly demonstrated that a direct current in the approximate range of 50 to 250 microamperes was able to regenerate gingival tissues, providing a non-surgical treatment alternative for those with recessed gums. While the osteogenic properties of electricity have been known in the art, the connection between nonosseous tissue regeneration and electricity were not well known in the art prior to these experiments. The unique current range associated with the method and apparatus of this invention is one of a few effective methods in the dental field to accomplish effective gingival tissue regeneration in a non-surgical manner. 
         [0055]    In further research, the applicants conducted preclinical testing that examined the effects of direct current stimulation on three different oral bacteria ( F. nucleatum, S. oralis, P. gingivalis ) in both saline and saliva solutions. This testing varied the current levels, inoculum size of bacteria, solution medium, and treatment time to develop a optimal treatment to reduce these three bacteria species associated with both periodontal and systemic diseases. 
         [0056]    The results of this testing yielded unexpected results and showed that each different bacterium had a different dose response to DC stimulation. Through this testing, the applicants identified treatment parameters that were able to kill up to 100% of  S. oralis,  99.1% of  F. nucleatum , and 52.3% of  P. gingivalis  in a single treatment lasting thirty minutes or less. This research yielded specifications for DC-based treatments of targeted pathogens that was previously unknown in the art. The optimal treatment parameters discovered in this research and described in this method can provide an innovative way to reduce these three species of bacteria, in both supra- and sub-gingival environments, and thus prevent and/or treat their associated complications including periodontal disease, biofilm formation, as well as the systemic diseases correlated to these oral pathogens. 
         [0057]    In addition, scanning electron microscopy (SEM) was conducted on  F. nucleatum  colonies before and after at 30 minute treatment, according to the method of this invention, to better understand the mechanism by which the method according to this invention is able to reduce bacterial levels. The SEM imagery suggested that the method according to this invention interferes with bacterial cellular division and can weaken the outer envelope (cell membrane) resulting in fragile cellular structures that can easily break. It is contemplated that this is phenomenon is an example of electroporation, where the permeability of cellular membranes may be affected by electrical stimulation either temporarily or permanently. It is further contemplated that the electroporation caused by the method according to this invention could play a role in developing new therapies in molecular biology which would take advantage of this cellular permeability and introduce new material into the cells of oral pathogens or oral tissues through mechanisms including, but not limited to genetic material (transfection) such as DNA, RNA, sRNA, siRNA, plasmids, etc. These effects would prove a new tool in targeted gene therapies for oral applications. 
         [0058]    Specifically, the method according to the present invention has been shown to reduce viable colony forming units (CFU) in various oral bacteria. 
         [0059]    Table 1 below shows the efficacy of treatment according to the present invention at current levels of 50 μA or 500 μA for 5, 10, 20 and 30 minute durations for bacterial cultures ranging from 10 4  to 10 7  colony forming units (CFU) of  Streptococcus oralis  in a saline solution. 
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 1 
               
             
             
               
                   
               
               
                 In Vitro Efficacy of Device Against  Streptococcus oralis  in Saline 
               
             
          
           
               
                 CFU 
                 μA 
                 0 Min 
                 5 Min 
                 10 Min 
                 20 Min 
                 30 Min 
               
               
                   
               
             
          
           
               
                 10e4 
                  50 μA 
                 1120 
                 1080 
                 600 
                 320 
                 280 
               
               
                   
                 500 μA 
                 1120 
                 1200 
                 800 
                 240 
                 0 
               
               
                 10e5 
                  50 μA 
                 10000 
                 9600 
                 8400 
                 9200 
                 7600 
               
               
                   
                 500 μA 
                 11600 
                 10400 
                 11200 
                 10800 
                 8400 
               
               
                 10e6 
                  50 μA 
                 80000 
                 63200 
                 52800 
                 32400 
                 24800 
               
               
                   
                 500 μA 
                 80800 
                 70000 
                 15200 
                 14000 
                 15600 
               
               
                 10e7 
                  50 μA 
                 1280000 
                 1080000 
                 1040000 
                 800000 
                 440000 
               
               
                   
                 500 μA 
                 1080000 
                 520000 
                 160000 
                 120000 
                 320000 
               
               
                   
               
             
          
         
       
     
         [0060]    Table 2 below shows the efficacy of treatment to the present invention at current levels of 50 μA or 500 μA for 5, 10, 20 and 30 minute durations for bacterial cultures ranging from 10 4  to 10 7  CFU of  Streptococcus oralis  in a saliva solution. 
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 2 
               
             
             
               
                   
               
               
                 In Vitro Efficacy of Device Against  Streptococcus oralis  in Saliva 
               
             
          
           
               
                 CFU 
                 μA 
                 0 Min 
                 5 Min 
                 10 Min 
                 20 Min 
                 30 Min 
               
               
                   
               
             
          
           
               
                 10e4 
                  50 μA 
                 160 
                 160 
                 80 
                 80 
                 40 
               
               
                   
                 500 μA 
                 200 
                 80 
                 80 
                 80 
                 80 
               
               
                 10e5 
                  50 μA 
                 5600 
                 5600 
                 6800 
                 5600 
                 4000 
               
               
                   
                 500 μA 
                 8400 
                 6800 
                 7200 
                 6400 
                 2800 
               
               
                 10e6 
                  50 μA 
                 25600 
                 25200 
                 15200 
                 17200 
                 18400 
               
               
                   
                 500 μA 
                 23600 
                 16800 
                 15600 
                 17600 
                 15200 
               
               
                 10e7 
                  50 μA 
                 316000 
                 284000 
                 300000 
                 276000 
                 220000 
               
               
                   
                 500 μA 
                 324000 
                 328000 
                 300000 
                 292000 
                 252000 
               
               
                   
               
             
          
         
       
     
         [0061]    Table 3 below shows the efficacy of treatment to the present invention at current levels of 50 μA or 500 μA for 5, 10, 20 and 30 minute durations for bacterial cultures ranging for 10 4  and 10 6  CFU of  Fusobacterium nucleatum  in a saline solution. 
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 3 
               
             
             
               
                   
               
               
                 In Vitro Efficacy of Device Against 
               
               
                   Fusobacterium nucleatum  in Saline 
               
             
          
           
               
                 CFU 
                 μA 
                 0 Min 
                 5 Min 
                 10 Min 
                 20 Min 
                 30 Min 
               
               
                   
               
             
          
           
               
                 10e4 
                  50 μA 
                 480 
                 280 
                 280 
                 120 
                 40 
               
               
                   
                 500 μA 
                 560 
                 440 
                 400 
                 200 
                 120 
               
               
                 10e6 
                  50 μA 
                 94000 
                 91600 
                 85600 
                 70400 
                 84400 
               
               
                   
                 500 μA 
                 46400 
                 45600 
                 27200 
                 2000 
                 400 
               
               
                   
               
             
          
         
       
     
         [0062]    Table 4 below shows the efficacy of treatment according to the present invention at current levels of 50 μA or 500 μA for 5, 10, 20 and 30 minute durations for bacterial cultures ranging from 10 4  to 10 6  CFU of  Fusobacterium nucleatum  in saliva. 
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 4 
               
             
             
               
                   
               
               
                 In Vitro Efficacy of Device Against 
               
               
                   Fusobacterium nucleatum  in Saliva 
               
             
          
           
               
                 CFU 
                 μA 
                 0 Min 
                 5 Min 
                 10 Min 
                 20 Min 
                 30 Min 
               
               
                   
               
             
          
           
               
                 10e4 
                  50 μA 
                 1480 
                 1480 
                 1560 
                 680 
                 880 
               
               
                   
                 500 μA 
                 2360 
                 2360 
                 1720 
                 1240 
                 1080 
               
               
                 10e5 
                  50 μA 
                 19600 
                 19600 
                 15200 
                 14400 
                 14000 
               
               
                   
                 500 μA 
                 18000 
                 17200 
                 14400 
                 11200 
                 10800 
               
               
                 10e6 
                  50 μA 
                 348000 
                 112000 
                 120000 
                 72000 
                 68000 
               
               
                   
                 500 μA 
                 156000 
                 128000 
                 124000 
                 32000 
                 28000 
               
               
                   
               
             
          
         
       
     
         [0063]    Table 5 below shows the efficacy of treatment to the present invention at current levels of 50 μA or 500 μA for 5, 10, 20 and 30 minute durations for bacterial cultures ranging for 10 5  CFU of  Porphyromonas gingivalis  in a saline solution. 
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 5 
               
             
             
               
                   
               
               
                 In Vitro Efficacy of Device Against 
               
               
                   Porphyromonas gingivalis  in Saline 
               
             
          
           
               
                 CFU 
                 μA 
                 0 Min 
                 5 Min 
                 10 Min 
                 20 Min 
                 30 Min 
               
               
                   
               
             
          
           
               
                 10e4 
                  50 μA 
                 3440 
                 2040 
                 2720 
                 1640 
                 1640 
               
               
                   
                 500 μA 
                 2440 
                 2120 
                 2200 
                 1880 
                 1840 
               
               
                   
               
             
          
         
       
     
         [0064]    Thus, this method and corresponding apparatus are able to achieve multiple prophylactic, therapeutic, and regenerative effects whose combination was not previously known or available in the art. Namely, these effects are: promotion of oral osteogenesis, destruction or disabling of oral microbes, gingival tissue regeneration, reduction and prevention of the formation of oral biofilms, caries prevention, increased oral vasodilation and oral blood flow, treatment of common oral conditions such as gingivitis and periodontitis, treatment of systemic diseases and conditions correlated with oral pathogens, and generally improved oral hygiene. 
         [0065]    These effects are accomplished by the delivery of direct current to the gingiva through a plurality of electrodes in direct contact with the lingual and buccal gingival surfaces. The electrodes may be fashioned out of any electrically-conductive material, including but not limited to metals such as silver, stainless steel, copper, gold, platinum, palladium, aluminum, an alloy thereof, electrically-conductive nanotubes, carbonized rubber, electrically-conductive silicone, or electrically-conductive polymers. The electrodes may be composed of the same or of differing materials. These electrodes fit snuggly against the lingual and buccal sides of the gingiva and make direct contact with each side of the gingiva to pass direct current electricity across the teeth and neighboring gingival tissues. 
         [0066]    The electrodes on each side (lingual or buccal) of the gingiva are of the same polarity. Electrodes on opposite sides of the gingiva are of the opposite polarity. This allows the current to flow across the teeth and gums to the electrodes positioned on the transverse gingiva to complete the electrical circuit. Put another way, all electrodes on the lingual side of the gingiva will be completely anodic or completely cathodic. All electrodes on the buccal surfaces of the gingiva, transverse the lingual surfaces of the gingiva, would have the opposite polarity. The polarization of these electrodes may be reversed during treatment or in between treatments. 
         [0067]    The mandibular and maxillary gingiva each have a set of a plurality of polarized electrodes as previously described. This allows for treatment of both the maxillary and mandibular periodontium either simultaneously or in isolation. The maxillary and mandibular sets of electrodes may be powered by two different adjustable power supplies or by the same adjustable power supply. 
         [0068]    Electrical conductors then connect these electrodes to an adjustable power supply. All of the anodic electrodes will connect to the positive pole of the power supply and all of the cathodic electrodes will connect to the negative pole of the power supply. The adjustable power supply is capable of delivering a stable, direct current in the approximate range of 1 to 500 microamperes. The preferred current setting for most treatments is in the approximate range of 50 to 250 microamperes. 
         [0069]    In order to increase conductivity in the tissues adjacent to the electrodes, an ionic or colloidal liquid or gel may be used as a conductive medium to decrease electrical resistance in the mouth. 
         [0070]    This medium would be placed along any desired areas of desired electrical contact, such as the teeth, gums, or surrounding oral tissues. Examples of such a medium would include, but not be limited to, colloidal silver gel, liquid colloidal silver, colloidal copper gel, liquid colloidal copper, colloidal gold gel, liquid colloidal gold, saline gel, liquid saline or any combination thereof. 
         [0071]    Colloidal silver, in whole or in combination, has great promise not only in increasing electrical current flow, but also in offering additional bactericidal benefits. Colloidal silver, in concentrations as little as five parts per million, is known to be bactericidal by inhibiting a bacterium&#39;s production of adenosine triphosphate. 
         [0072]    This conductive medium may also contain dietary supplements including, but not limited to, oil of oregano. Oil of oregano is believed to have many health benefits and may also be microbicidal. Such microbicidal properties would be effective in treating common oral infections and diseases as well as aiding in preventative oral care. 
         [0073]    This conductive medium may also contain teeth whitening agents. This would allow for the addition of teeth whitening to the list of benefits offered by an embodiment of this invention. A whitening agent that is catalyzed by direct current electricity could be included and may even offer reduced teeth whitening treatment times when compared with nonelectrically-catalyzed whitening agents. 
         [0074]    Artificial or natural flavorings may also be added to this conductive medium to offer a more appealing taste to the user, similar to the method of flavoring dental fluoride treatments. This flavoring would mask any unpleasant tastes from the ingredients of the conductive medium or as well as any taste of the mouthpiece or electrodes themselves. 
         [0075]      FIG. 1  shows one embodiment of a treatment apparatus according to this invention. A user input device  120  is connected to a microcontrolled direct current power supply  110 . This input device  120  may include, but not be limited to potentiometer dials, push buttons, switches, toggles, etc. User input device  120  allows the patient to control various aspects of the treatment including but not limited to power on or off, output current levels, treatment program selection, treatment duration, treatment reminders, polarity, etc. Input device  120  may also be used to run pre-programmed treatment regimens as described by this method targeted at specific pathogens, including but not limited to,  S. oralis, P. gingivalis , and  F. nucleatum . Microcontrolled power supply  110  reads the state of input device  120  and adjusts the output current to compensate for the continually varying resistance across cathodic electrodes  140  and anodic electrodes  150 . 
         [0076]    An optional user feedback device  130  is show in  FIG. 1  connected to microcontrolled power supply  110 . Feedback device  130  may contain various methods and devices capable of relaying treatment information to the user. Feedback device  130  could include, but not be limited to an LCD display, LCD matrix display, color LCD displays, indicator LEDs, LED bar graphs, LED segment displays, OLED displays, audio speakers, vibrating devices, or any combination thereof. Feedback device  130  offers the user information including, but is not limited to, output current level, treatment time elapsed, treatment time remaining, date, time of day, battery power level, treatment reminder indicators or sound alarms, recharging indicators, etc. Feedback device  130  also provides information regarding any state change from input device  120 . This allows the user to receive information on how his/her input is affecting the treatment. Feedback device  130  is not required for the operation of this embodiment of the treatment apparatus and may be omitted. 
         [0077]    Microcontrolled power supply  110  contains a microcontroller  112  and a direct current power source  116 . Microcontroller  112  is electrically connected to input device  120  and is capable of reading the device&#39;s state(s). Microcontroller  112 , upon reading these state(s), is able to dynamically adjust the output of power source  116 . This allows the user to control the level of current generated by the power source  116 . Microcontroller  112  is also connected to an optional user feedback device  130 . Microcontroller  112  is able to output information related to the treatment duration, current timer status, current levels, and other information to feedback device  130 . Microcontroller  112  also has timing capabilities, represented by timer  114 , that allow for limiting treatment time based on some predetermined treatment duration. Timer  114  is also used to output the elapsed treatment time to feedback device  130 , if present. The user is able to input desired treatment parameters such as treatment duration, treatment current levels, etc. to microcontroller  112  by way of input device  120 . 
         [0078]    The programmable nature of microcontroller  112  allows for advanced functionality not present in other oral electrical treatment devices. For example, the software on microcontroller  112  could be programmed to run a predetermined treatment regimen. This treatment regimen could include but not be limited to such factors as: treatment duration, targeted pathogen, treatment current levels, treatment time-of-day, treatment reminders, etc. This treatment regimen could also be programmed by a dental professional by way of input device  120  so that a patient&#39;s treatment may be simplified and guaranteed to follow set parameters. 
         [0079]    Cathodic electrodes  140  are connected to the positive pole of power source  116  and anodic electrodes  150  are connected to the negative pole of power source  116 . These electrodes are placed in direct contact with the gingiva, mounted transversely from one another. This allows a current flow from cathodic electrodes  140  to the gingival tissues, surrounding teeth, boney structures, and connected mouth tissues to anodic electrodes  150  mounted on the transverse gingiva and then back to power supply  110 , forming a complete circuit. 
         [0080]    Power source  116  may be any known device capable of delivering an adjustable direct electrical current. This includes, but is not limited to disposable batteries, rechargeable batteries, AC-DC power converter, etc. Microcontroller  112  is able to regulate the current output of power source  116  by a known method of electrical current control. Power supply  116  is capable of delivering a direct current of between 1 and 500 microamperes, with an approximate range of 50 to 250 microamperes used for most treatments. Microcontroller  112  is also able to reverse the polarity of the cathodic electrodes  140  and anodic electrodes  150  by controlling the output of power source  116 . This allows for dynamic changing of electrode polarity during treatment. Microcontroller  112  is also programmable to allow for pulsed application of direct current across the gingiva. 
         [0081]      FIG. 2  shows a top-down view of another embodiment of the treatment apparatus. In this embodiment, a mouthpiece unit  200 , known in the art, has two electrodes attached to or embedded in it, and is worn in the mouth. A single lingual gingiva electrode  210  fits snugly against the lingual gingival tissue of the mouth. A single buccal gingiva electrode  220  is attached to or embedded in mouthpiece  200  so that it is transverse from the lingual gingiva electrode  210  and fits snugly against the buccal gingival tissues of the mouth. Two electrical conductors  230  connect electrodes  210  and  220  to an adjustable current power supply, of whose embodiment may be similar to that of  110  or that of  FIG. 3 . Electrical conductors  230  are insulated so that a short circuit does not occur inside or outside of the mouth. Electrical conductors  230  are shown as attached to the anterior of mouthpiece  200 , but may be electrically connected to electrodes  210  and  220  at any point along mouthpiece  200 , so long as electrical conductors  230  are not attached to the same electrode. Electrical conductors  230  may also be partially or wholly composed of an electrically conductive polymer. 
         [0082]      FIG. 3  shows a perspective view of the same type of embodiment shown in  FIG. 2 . A mouthpiece  300  has a lingual gingiva electrode  310  and an buccal gingiva electrode  320  attached to or embedded it. Electrodes  310  and  320  span the lingual and buccal gingival surfaces of the mouth, respectively. A set of embedded electrical conductors  340  are connected to electrodes  310  and  320  on one end and on the other end to a set of conductors to the power supply  330 . Conductors  340  are embedded in the mouthpiece material and are electrically insulated. Conductors  330  then connect to the positive and negative poles of a direct current power source, similar to that of  110  or  FIG. 6 . 
         [0083]      FIG. 4  presents another embodiment similar in nature to that of  FIGS. 2 and 3 . In this embodiment, electrode sets are attached to or embedded in a mouthpiece unit  400 . A set of lingual gingiva electrodes  410  are affixed to or embedded in mouthpiece  400 . Electrode set  410  comprises a plurality of discrete lingual gingiva electrodes  4102 , which are electrically connected by embedded electrical conductors  4104 . Conductors  4104  are insulated and are embedded in or attached to mouthpiece  400 . Likewise, a set of buccal gingiva electrodes  420  are affixed to or embedded in mouthpiece  400  transverse of electrode set  410 . Electrode set  420  comprises a plurality of discrete lingual gingiva electrodes  4202 , which are electrically connected by embedded electrical conductors  4204 . Conductors  4204  are insulated and are embedded in or attached to mouthpiece  400 . This embodiment allows for multiple, discrete points of electrical contact within the mouth. In  FIG. 4 , conductors to the power supply  430  are shown as attached to the posterior electrodes in mouthpiece  400 . However, conductors  430  may be electrically connected to any point of electrode sets  410  and  420 , so long as conductors  430  are not connected to the same electrode set. Conductors  430  then connect to the positive and negative poles of a direct current power source, similar to that of  110  or  FIG. 6 . 
         [0084]      FIG. 5  offers a perspective view of an embodiment similar to  FIG. 4 . A lingual gingiva electrode set  510  and a buccal gingiva electrode set  520  are attached to or embedded in a mouthpiece  500 . Electrode set  510  comprises a plurality of lingual gingiva electrodes  5102  that are electrically connected by embedded electrical conductors  5104 . Conductors  5104  are electrically insulated and are embedded in or attached to mouthpiece  500 . Similarly, electrode set  520  comprises a plurality of buccal gingiva electrodes  5202  that are electrically connected by embedded electrical conductors  5204 . Conductors  5204  are electrically insulated and are embedded in or attached to mouthpiece  500 . Electrode set  520  is mounted transverse of electrode set  510  to allow direct current to flow across the tissue of the teeth and gums. Electrode sets  510  and  520  are connected to conductors to the power supply  530  by way of embedded electrical conductors  540 . Conductors  540  are electrically-insulated and are embedded in mouthpiece  500 . Conductors  530  then connect to the positive and negative poles of a direct current power source, similar to that of  110  or  FIG. 6 . 
         [0085]      FIG. 6  presents another embodiment of an adjustable direct current power source used to supply direct current to a plurality of oral electrodes. This particular circuit design is capable of delivering a steady current regardless of moderate fluctuations in the resistance between the electrodes. The circuit uses a 9-volt power supply  640 , which could be a disposable battery, a rechargeable battery, an AC-to-DC converter, or any other suitable 9-volt power source. A dual unit, three-port switch  610  is used to select the current level in the circuit. The three options of the switch circuit are power off  614 , 100 μA  612 , or 200 μA  616 . Switch option  614  simply does not complete a circuit, preventing current from flowing. Switch option  612  comprises a 332 kΩ resistor  618  in series with a 2 volt LED  620 . These two components are in parallel with a 48.7 kΩ resistor  622  to provide a 100 microamp current. The Switch option  616  comprises a 665 kΩ resistor  624  in series with a 2 volt LED  626 . These two components are in parallel with a 97.6 kΩ resistor  628  to provide a 200 microamp current. Cathodic upper mouth electrodes  630  and cathodic lower mouth electrodes  632  are in parallel with each other and are electrically connected to the output of switch  610 . Electrical current then travels from power supply  640  to these electrodes, through the gingival tissues of the mouth to anodic upper mouth electrodes  636  and anodic lower mouth electrodes  634  and finally back to power supply  640 . This circuit design will allow moderate and reasonable fluctuations in the resistance across the electrodes and prevent over driving the circuit should the resistance in the mouth vary. 
         [0086]    In another embodiment of this invention or in combination with those previously described, an ionic or colloidal medium in the form of a liquid or a gel may be used to decrease electrical resistance in the mouth and to facilitate a more even current distribution across oral electrodes. Any combination of one or more ionic or colloidal compounds may be used. Examples of such a medium would include, but not be limited to, colloidal silver gel, liquid colloidal silver, colloidal copper gel, liquid colloidal copper, colloidal gold gel, liquid colloidal gold, saline gel, liquid saline or any combination thereof. Artificial or natural flavorings may be added to this medium to offer a more appealing taste to the user. The medium may also contain dietary supplements including, but not limited to, oil of oregano. This medium may also contain teeth-whitening chemical agents. A whitening agent that is catalyzed by the direct current would be most effective in this ionic or colloidal medium. 
         [0087]    In yet another embodiment, microcontrolled power supply  110  would be miniaturized and be physically attached to or embedded in a mouthpiece similar to  200 ,  300 ,  400 , or  500 . This would allow for an all-in-one unit that would fit inside the user&#39;s mouth. In this embodiment, power source  116  would have to be of small physical size. One of many possible options is a watch-type battery or other small, portable power source. This circuitry would then be encased in a waterproof manner in the material of the mouthpiece itself. Input device  120  and feedback device  130  would be waterproofed and protected from any kind of electrical shorting, as well. 
         [0088]    Thus the reader will see that at least one embodiment addresses a desired need in the oral hygiene and dental fields to concurrently treat common oral diseases and conditions in a more effective, less invasive, and less expensive manner. These embodiments promote general oral hygiene, reduce oral biofilm, treat periodontal diseases such as gingivitis and periodontitis, kill oral microbes including bacteria and thus preventing cavities and tooth decay, increase vasodilation and blood flow in oral tissues, promote gingival tissue regeneration, foster osteogenesis in the boney structures of the teeth, mouth, and related areas, treat systemic diseases related to oral pathogens, and treat other periodontal and oral maladies through the non-invasive application of weak direct current electricity to the surfaces in the oral cavity. 
         [0089]    While our above descriptions contain many specificities, these should not be construed as limitations on the invention, but rather as an exemplification of several preferred embodiments thereof. Many other variations are possible. For example, electrodes may be attached directly to the gingiva without the use of a mouthpiece, perhaps using an electrically-conductive paste. Or electrodes may be placed in contact with tissues neighboring the gingiva, such as the teeth or tissues of the cheek, instead of directly on the gingiva to accomplish the same result. Another example would be replacing LEDs  626  and  620  from  FIG. 6  with standard diodes to achieve the same resultant circuit. Overall, the circuitry from  FIGS. 1 and 6  could be altered in many ways to deliver the same electrical current to the oral electrodes. 
         [0090]    In some cases dental procedures can break up oral bacterial colonies found in biofilms and introduce bacteria into the bloodstream causing bacteremia and other infections. It is further contemplated that it may be desirable to utilize a mouthpiece according to the present invention immediately prior to performing a dental procedure. The mouthpiece according to this invention may be used by the patient either at home or in the dental office. In this manner, the living bacteria in the patient&#39;s mouth, both supra- and sub-gingival, can be reduced prior to the procedure and the risk of bacteremia and other infections will be reduced. For example, and not by way of limitation, a mouthpiece according to the present invention may be utilized prior to a dental prophylaxis or a scaling and root planning procedure in a dental office to reduce the risks of introducing bacteria into the patient&#39;s blood stream. Such a pre-procedural treatment would be used for approximately 10 to 20 minute with a current level ranging from 50 μA to 500 μA and would be timed to conclude immediately before the procedure. 
         [0091]    A mouthpiece according to the present invention may also be utilized following a clinical procedure as prevention for infections, for scenarios including but not limited to post-extraction or post-implantation infection prevention. Such a post-procedural treatment would last for approximately 10 to 20 minutes with a current ranging from 50 μA to 500 μA. This procedure may then be repeated at home by the patient one or more times a week until the risk of infection has passed. 
       Prevention of Systemic Disease 
       [0092]    It is contemplated that a mouthpiece according to the present invention may be used to prevent or treat systemic diseases as will be outlined in more detail below. The method according to the present invention has been shown to be effective in reducing the amount of oral bacteria, specifically  F. nucleatum, P. gingivalis , and  S. oralis.    
       1. Cardiovascular Disease 
       [0093]    It is contemplated that use of a mouthpiece according to the present invention may be used to reduce microbial burdens caused by the translocation of oral bacteria, including but not limited to  S. oralis, P. gingivalis , and  F. nucleatum , from the gingival tissues to the rest of the body and also decrease the amount of inflammatory mediators produced by oral bacteria. Further, by reducing  F. nucleatum , it is contemplated that the ability of  P. gingivalis  to invade host cells will be lessened and thus diminishing the development of bacteremia that has been linked with the initiation/worsening of atherosclerosis and coronary heart disease. 
         [0094]    It is contemplated that a mouthpiece according to the present invention may be used according to a predetermined treatment regimen to prevent, treat and/or mitigate cardiovascular disease. In the predetermined treatment regimen, the patient will wear a mouthpiece according to the present invention for a predetermined amount of time at a predetermined current level and at predetermined time intervals. It is further contemplated that the specific treatment regimen may be determined based on the bacterial levels present in a patient. According to one embodiment of the invention, the treatment regimen would consist of a patient wearing a mouthpiece according to the present invention for 20 minutes once per day at a current level of 500 μA. For acute cardiovascular conditions, this treatment may continue on a daily basis until the conditions is resolved. For chronic cardiovascular disease, this treatment may be repeated a few times a week on a continuing basis. 
       2. Still Birth 
       [0095]    It is further contemplated that a treatment with a mouthpiece according to the present invention according to a predetermined treatment protocol would reduce the oral population of  F. nucleatum  associated with periodontal disease and thus prevent, treat and/or mitigate still birth. In turn, this reduction would lessen the likelihood of  F. nucleatum  translocating from the oral cavity into the bloodstream, where it could then migrate into the placenta and colonize. It is contemplated that a mouthpiece according to the present invention may be used according to a predetermined treatment regimen to prevent still birth. In the predetermined treatment regimen, the patient will wear a mouthpiece according to the present invention for a predetermined amount of time at a predetermined current level and at predetermined time intervals. It is further contemplated that the specific treatment regimen may be determined based on the bacterial levels present in a patient. According to one embodiment of the invention, the treatment regimen would consist of a patient wearing a mouthpiece according to the present invention for 20 minutes once per day at a current level of 500 μA for the duration of the pregnancy. The treatment parameters outlined above have been demonstrated to be highly efficient at reducing levels of  S. oralis  and  F. nucleatum  at inoculation sizes of 10 7  colony-forming units (CFU). 
       3. Diabetes 
       [0096]    It is contemplated that a mouthpiece according to the present invention according to a predetermined treatment protocol may be used to prevent, treat and/or mitigate diabetes by causing a reduction of  S. oralis  in the oral cavity and consequently reduce the amount of serum markers of inflammation produced by bacterial infections. In the predetermined treatment regimen, the patient will wear a mouthpiece according to the present invention for a predetermined amount of time at a predetermined current level and at predetermined time intervals. It is further contemplated that the specific treatment regimen may be determined based on the bacterial levels present in a patient. According to one embodiment of the invention, the treatment regimen would consist of a patient wearing a mouthpiece according to the present invention for 20 minutes once per day at a current level of 500 μA to effectively reduce oral levels of  S. oralis  that in turn will lower the amount of systemic inflammatory markers. This treatment may be repeated multiple times a week on an ongoing basis to help reduce inflammatory markers. 
       4. Pyogenic Liver Abscess 
       [0097]    It is contemplated that a mouthpiece according to the present invention according to a predetermined treatment protocol may be used to prevent, treat and/or mitigate pyogenic liver abscess by causing a reduction of  F. nucleatum . Specifically, it is contemplated that treatment with a mouthpiece according to the present invention would reduce bacterial levels and may stop  F. nucleatum  and other oral bacteria species from traveling to the liver and reduce overall bacteremia. In the predetermined treatment regimen, the patient will wear a mouthpiece according to the present invention for a predetermined amount of time at a predetermined current level and at predetermined time intervals. It is further contemplated that the specific treatment regimen may be determined based on the bacterial levels present in a patient. According to one embodiment of the invention, the treatment regimen would consist of a patient wearing a mouthpiece according to the present invention for 20 minutes once per day at a current level of 500 μA to effectively reduce oral levels of  F. nucleatum  which may prevent any bacteria from being transported from the oral cavity systemically. This treatment may be repeated multiple times per week until the abscess is reduced. 
       5. Osteomyelitis 
       [0098]    It is contemplated that a mouthpiece according to the present invention according to a predetermined treatment protocol may be used to prevent, treat and/or mitigate osteomyelitis by causing a reduction of  F. nucleatum . In the predetermined treatment regimen, the patient will wear a mouthpiece according to the present invention for a predetermined amount of time at a predetermined current level and at predetermined time intervals. It is further contemplated that the specific treatment regimen may be determined based on the bacterial levels present in a patient. According to one embodiment of the invention, the treatment regimen would consist of a patient wearing a mouthpiece according to the present invention for 20 minutes per treatment at a current level of 500 μA to effectively reduce oral levels of  F. nucleatum  bacteria and prevent any bacteria from being transported from the oral cavity systemically. This treatment may be used in conjunction with or separate from standard antibiotic-based treatments for osteomyelitis. When used in conjunction with antibiotics, treatment will normally continue for approximately 29 to 42 days. When used separately from antibiotics, this treatment may be used once a day for a few months for acute conditions, or a few times a week on a continuing basis for chronic conditions. 
       6. Arthritis 
       [0099]    It is contemplated that a mouthpiece according to the present invention according to a predetermined treatment protocol may be used to prevent, treat and/or mitigate arthritis by causing a reduction of  F. nucleatum . In the predetermined treatment regimen, the patient will wear a mouthpiece according to the present invention for a predetermined amount of time at a predetermined current level and at predetermined time intervals. It is further contemplated that the specific treatment regimen may be determined based on the bacterial levels present in a patient. According to one embodiment of the invention, the treatment regimen would consist of a patient wearing a mouthpiece according to the present invention for 20 minutes once per day at a current level of 500 μA to effectively reduce oral levels of  F. nucleatum  bacteria and prevent any bacteria from being transported from the oral cavity and translocating to the synovial fluid and reducing the associated inflammation. This treatment may be repeated multiple times per week on a continual basis for this type of chronic condition. 
       Reducing Bio Film and Preventing Bio Film Formation 
       [0100]    It is contemplated that a mouthpiece according to the present invention according to a predetermined treatment protocol may be used to prevent, treat and/or mitigate oral biofilm by causing a reduction of  F. nucleatum, P. gingivalis , and/or  S. oralis , all of which are involved in oral biofilm formation. In the predetermined treatment regimen, the patient will wear a mouthpiece according to the present invention for a predetermined amount of time at a predetermined current level and at predetermined time intervals. It is further contemplated that the specific treatment regimen may be determined based on the bacterial levels of specific bacterial species present in a patient. According to one embodiment of the invention, the treatment regimen would consist of a patient wearing a mouthpiece according to the present invention for 20 minutes once per day at a current level of 500 μA to effectively reduce oral levels of  F. nucleatum  bacteria to prevent further biofilm formation caused by  F. nucleatum  and to reduce the viability of existing biofilm colonies of  F. nucleatum.    
         [0101]    According to another embodiment of this invention, the treatment regimen would consist of a patient wearing a mouthpiece according to the present invention for 20 minutes once per day at a current level of 50 μA to effectively reduce oral levels of  P. gingivalis  bacteria to prevent further biofilm formation caused by  P. gingivalis  and to reduce the viability of existing biofilm colonies of  P. gingivalis.    
         [0102]    Furthermore, according to another embodiment of this invention, the treatment regimen would consist of a patient wearing a mouthpiece according to the present invention for 20 minutes once per day at a current level of 500 μA to effectively reduce oral levels of  S. oralis  bacteria to prevent further biofilm formation caused by  S. oralis  and to reduce the viability of existing biofilm colonies of  S. oralis.    
         [0103]    These treatments for biofilm reduction and prevention may be repeated on a daily basis for a three to six weeks for acute biofilm-based issues or may be repeated once or more per week on a continuing basis for chronic biofilm issues. 
       Method of Manufacture 
       [0104]    A mouthpiece according to the present invention may be formed using any method and means known in the art. In one embodiment of such a method, a first mold  700  is provided. The first mold  700  preferably includes a top portion  710  and a bottom portion  720 . Each portion of the first mold  700  includes a sealing means for sealing the first mold  700 . In the illustrated embodiment the sealing means take the form of a cap  730 A,  730 B. Each cap  730 A,  730 B preferably has a first channel  740  and a second channel  750  therethrough. The first mold  700  preferably includes one or more fill ports  760  and one or more vents  770 . 
         [0105]    The pieces of the first mold  700  are preferably cleaned. A plurality of wires  780 A,  780 B,  780 C,  780 D are then prepared and treaded through the first mold  700 . In the preferred embodiment, the four wires  780 A,  780 B,  780 C,  780 D are threaded through the first mold  700  as shown in  FIG. 8 . Preferably a first and a second wire  780 A,  780 B are threaded through the top cap  730 A and through the first mold  700  and a third and a fourth wire  780 C,  780 D are threaded through the bottom cap  730  B and through the first mold  700 . Preferably the first wire  780 A extends through the first channel  740  in the top cap  730 A and the second wire  780  B extends through the second channel  750  in the top cap  730 A. Similarly, preferably, the third wire  780 C extends through the first channel  740  in the bottom cap  730 B and the fourth wire  780 D extends through the second channel  750  in the bottom cap  730 B. The first mold  700  is then closed. A non-conductive material is then injected through one or more fill ports  760  in the first mold  700 . The first mold  700  cavity is filled when material is coming out of all vents  770  in the first mold  700 . The non-conductive material may be a thermoplastic, a thermoplastic elastomer, a thermoset polymer, a room temperature vulcanizing elastomer, or other polymer. 
         [0106]    When the non-conductive material is cured, the first mold  700  is preferably opened and the partially formed mouthpiece  790  is removed from the first mold  700 . The plurality of wires  780 A,  780 B,  780 C,  780 D are now encapsulated by the non-conductive material. Preferably a wire  780 A,  780 B,  780 C,  780 D is located in each of the four exposed channels  800  of the mouthpiece  790 . Preferably the first wire  780 A is located in the inner upper channel  800 A, the second wire  780 B is located in the outer upper channel  800 B, the third wire  780 C is located in the inner lower channel  800 C (not shown), and the fourth wire  780 D is located in the outer lower channel  800 D (not shown). The excess wire is then preferably trimmed from the mouthpiece  790  and the remaining wire  780 A,  780 B,  780 C,  780 D is preferably inserted fully into its associated channel  800 A,  800 B,  800 C,  800 D. 
         [0107]    A second mold  810  is preferably provided. The second mold preferably includes a top portion  810 A and a bottom portion  810 B. In the illustrated embodiment, each of the top and bottom portions of the second mold  810  preferably includes a mold base  820 A,  820 B, a center piece  830 A,  830 B, a first insert  840 A,  840 B, and a second insert  850 A,  850 B. The pieces of the second mold  850  are preferably designed to allow the channels  800 A,  800 B,  800 C,  800 D of the mouthpiece  790  to be filled with an electrically-conductive material. The second mold  810  preferably includes one or more fill ports  760  for filling the mold cavities. As there are four channels  800 A,  800 B,  800 C,  800 D to be filled, the preferred embodiment includes four fill ports  760 . Further, the second mold  810  preferably includes one or more vents  770 . In the illustrated embodiment each cavity includes its own vent  770 . 
         [0108]    Preferably the pieces of the second mold  810  are cleaned and prepared. The second mold  810  is then assembled with the mouth piece  790  as shown in  FIGS. 10-12B . Preferably, the bottom portion  810 B of the second mold  810  is assembled first, with the mouthpiece  790 . The top portion  810 A of the second mold  810  is then assembled. A conductive material is then inserted into each of the fill ports  760 . The cavities are filled when material is coming out of all vents  770  in the second mold  810 . The conductive material is preferably a thermosetting elastomer, but may also be a thermoplastic, a thermoplastic elastomer, or other polymer. 
         [0109]    After the conductive material is cured, the second mold  810  is opened and the finished mouthpiece  760  is removed. Preferably, the top half  810 A of the second mold  810  is removed first. The first  840 A and second inserts  850 A are preferably removed first. The center piece  830 A can then be removed. The bottom half  810 B of the second mold may then be removed, again first removing the first  840 B and second inserts  850 B and then the center piece  830 B. 
         [0110]    The foregoing is considered as illustrative only of the principles of the invention. Furthermore, since numerous modifications and changes will readily occur to those skilled in the art, it is not desired to limit the invention to the exact construction and operation shown and described. While the preferred embodiment has been described, the details may be changed without departing from the invention, which is defined by the claims.

Technology Category: a