CA2907012C - Concurrent treatment of oral and systemic maladies using direct current electricity - Google Patents

Abstract

A method and apparatus for the concurrent treatment of multiple oral diseases and defects while promoting general oral hygiene utilizing direct current electricity. Electrodes are used to deliver a direct current to the gingival tissues of a mouth in order to achieve a number of therapeutic, prophylactic, and regenerative benefits. These benefits include killing oral microbes, increasing oral vasodilation, reducing oral biofilm, improving oral blood circulation, reversing oral bone resorption, promoting oral osteogenesis, treating gum recession, and fostering gingival regeneration. Other benefits include the treatment of gingivitis, periodontitis, and oral malodor, and other systemic diseases correlated with oral pathogens.

Description

CONCURRENT TREATMENT OF ORAL AND SYSTEMIC MALADIES
USING DIRECT CURRENT ELECTRICITY
Technical Field The technical field relates to systems and methods for conducting an electric current within a mouth of patient.
More particularly, the technical field relates to a mouthpiece that includes electrodes for conducting an electric current across gingival tissue.
Background 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 Date Recue/Date Received 2020-07-13

- 2 -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_ 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:
1. Direct effect of oral infections: Oral microbes and their byproducts can gain systemic access via die circulatory system through traveling through compromised tissue and inflamed periodoncium in the oral cavity. In gaining systemic access, oral microbes have the potential to directly influence subolinical mediators of various systemic diseases.
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.

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 croteins expressed on cells of the damaged tissues.
Cardiovascular Disease 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 healLh and Lhe 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.
While it has not been definitively shown it these bacteria initiate ae,herosclerosis 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. Fureher, 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

- 4 -the development of atherosclerotic plague. 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 ini,'-iating 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 Fusobaceterium nucleatum, one of ihe most prevalent species of bacteria found in amniotic fluid and placental infections thai 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 quanitie3 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 amnioeic fluid infection or an oral source resulted in fetal death.
Recen7_1y, a human seillbirth case was analyzed and it was found that the F. nucleatum did indeed originate from the mother's oral cavity, a fact that had not yet been proven. It is likely that the F.
nucleatum translocated from Lhe mother's mouth via Lhe blood stream where it was then able to cross the

- 5 -endothelium to proliferate and colonize within the fetal membranes, amniotic fluid and fefus whereupon its presence lead to feral demise. In a mouse model, hematogenous injection of F. nucleatum into pregnant mice resulted in specific bacterial colonizat,ion in the placenta causing localized inflammation_ F_ nucleatum was completely cleared from the maternal circulation after 24 hours of injection. However, once colonized in Lhe 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 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

- 6 -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 F. nucleatum has recently been Implicated in pyogenic liver abscess (PLA). Normally caused by biliary tract pathology, diverLicular 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 extracoion. 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 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

7 believed that due to the patient's poor oral hygiene, F. nucleatum bacteremia may have developed and lead to a hematogenous osteomyeli-tis of the lower leg.
Arthritis 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 Lhe 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 paeients 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 Lhe synovial fluid, as F. nucleatum was also found in the patient's plague sample.

- 8 -Oral Biofilm 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. rails, are the early colonizers that begin forming the initial biofilm colony, primarily through cellular division of the adherent bacteria.
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 One aspec,_ of die present invention is to provide a method including the steps of oroviding 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.

- 9 -The method also includes positioning the mouthpiece such that the first electrode is in electrical contact with at least a portion of the patient's lingual gingival tissue and the second electrode is in electrical contact with at least a portion of the patient's buccal gingival tissue Tfe method also includes delivering current from the power source to said gingival tissue according to a predetermined treatment protocol.
According to another aspect of the present invention the delivering step may further include regulating the current delivered to Lhe gingival tissue.
According to another aspect of the present invention the delivering step may further include administering the predeeermined treatment protocol to a patient in a dental office.
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.
According to another aspect of the invention the dental procedure may be cleaning or prophylaxis.
According to another aspect of the invention the dental procedure may be scaling.
According to another aspect of The invention the dental procedure may be root planing.
According to anoeher aspect of the invention the current delivered to the gingival tissue is from 50 pA up to and including 500 pA.
According to another aspect of the present invention the delivering step may further include delivering current to the gingival tissue for a

- 10 -duration of at least 10 minutes up to and including 30 minutes.
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.
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's mandibular lingual gingival tissue, the second electrode is in electrical contact with at least a portion of the patient's mandibular buccal gingival tissue, the third electrode is in electrical contact with at least a portion of the patient's maxillary lingual gingival tissue, and the fourth electrode is in electrical contact with at least a portion of Lhe patient's maxillary buccal gingival tissue.
According to another aspect of the invention the method may include reducing the amount of oral biofilm in said patient.
According to another aspect of the invention the method may include reducing oral bacterial to prevent, treat and/or mitigate systemic disease.
According to another aspect of 7_,hc invention the method may include reducing F. nucleatum to prevent, treat and/or miLigate cardiovascular disease.

- 11 -According to another aspect of the invention the method may include reducing F. nucleatum to prevent still birth.
According to another aspect of the invention the method may include reducing S. oralis to prevent, treat and/or mitigate diabetes.
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.
According to another aspect of the invention the method may include reducing F. nucleatum to prevent, treat and/or mitigate arthritis.
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.
In accordance with another aspect, there is provided a method for delivering an electric current in a mouth of a person, the method comprising:
positioning a first electrode in electrical contact with at least a portion of lingual gingival tissue of the mouth of the person, and a second electrode in electrical contact with at least a portion of buccal gingival tissue of the mouth of the person;
Date Recue/Date Received 2021-06-09 - ha -placing an electrically conductive medium between the first electrode and the second electrode, the electrically conductive medium including a teeth whitening agent; and conducting a pulsed electrical current through the electrically conductive medium and between the first electrode and the second electrode and across gingival tissue defined between the lingual gingival tissue and the buccal gingival tissue according to a predetermined protocol.
In accordance with another aspect, there is provided a method for increasing cellular permeability of bacteria in a mouth of a person, the method comprising:
positioning a first electrode in electrical contact with at least a portion of lingual gingival tissue of the mouth of the person and a second electrode in electrical contact with at least a portion of buccal gingival tissue of the mouth of the person, the first electrode and the second electrode being coupled to a power source; and conducting an electrical current from the power source between the first electrode and the second electrode and across gingival tissue defined between the lingual gingival tissue and the buccal gingival tissue according to a predetermined protocol.
In accordance with another aspect, there is provided a system for delivering an electric current in a mouth of a person, the system comprising:
a first electrode having a first polarity, the first electrode being configured to be in electrical contact with at least a portion of lingual gingival tissue of the mouth of the person;
a second electrode having a second polarity opposite the first polarity, the second electrode being configured to be in electrical contact with at least a portion of buccal gingival tissue of the mouth of the person; and Date Recue/Date Received 2022-03-30 - llb -a programmable power supply electrically coupled, through conductors at least partially composed of an electrically conductive polymer, to the first electrode and the second electrode and configured for conducting a pulsed electrical current between the first electrode while at the first polarity and the second electrode while at the second polarity and across gingival tissue defined between the lingual gingival tissue and the buccal gingival tissue.
In accordance with another aspect, there is provided a use of the system as described herein, for at least one of killing oral microbes, increasing oral vasodilation, improving oral blood circulation, teeth whitening, reversing oral bone resorption, increasing oral osteogenesis, reducing gum tissue recession, increasing gingival regeneration, and reducing oral malodor.
In accordance with another aspect, there is provided a use of the system as described herein, for reducing a concentration of bacteria in the mouth of the person.
In accordance with another aspect, there is provided a use of the system as described herein, for increasing cellular permeability of bacteria in the mouth of the person.
In accordance with another aspect, there is provided a use of the system as described herein, for treating a systemic disease.
In accordance with another aspect, there is provided a use of a pair of electrodes and a power supply for conducting electrical current between the pair of electrodes across gingival tissue defined between lingual gingival tissue and buccal gingival tissue.
Brief Description of the Drawings Figure 1 demonstrates the overall structure of the first embodiment of our invention, including a microcontrolled power source, user input, user feedback and oral electrodes.
Figure 2 shows a top-down view of another Date Recue/Date Received 2022-03-30

- 12 -embodiment that includes a mouthpiece with two continuous electrodes and associated conductors.
Figure 3 shows a perspective view of the same embodiment of Figure 2, with two electrodes embedded in a mouthpiece.
Figure 4 offers a top-down view of another embodiment similar to Figure 2 chat includes a mouthpiece, out with a plurality of discrete electrodes.
Figure 5 provides a perspective view of an additional embodiment similar to Figure 4 with a plurality of electrodes thaL are electrically connected by embedded conductors.
Figure 6 shows an additional embodiment of with an analog power supply using a dual unit, three-port switch.
Figure 7 is an exploded view of a first mold for molding a mouthpiece according to the present invention.
Figure 8 is a cross sectional view of a first mold for molding a mouthpiece according to the present invention.
Figure 9 is an exploded view of a first mold for molding a mouthpiece according to the present invention with a partially molded mouthpiece.
Figure 10 is an exploded view of a second mold for molding a mouthpiece according to the present invention with a partially molded mouthpiece.
Figure 11 is perspective view of a second mold for molding a mouthpiece according to the present invention with a partially molded mouthpiece.
Figure 12A is a cross section of ,he mold of Figure 11 with a partially molded mouehpiece in its

- 13 -unfilled state.
Figure 12B is a cross section of i_he mold of Figure 11 with a partially molded mouThpiece in its filled state.
Figure 13 is a perspective view of a mouthpiece molded according to an embodiment of the Present invention.
Detailed Description Although Lhe disclosure hereof is detailed and exact to enable chose 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 wii,hout departing from the invention, which is defined by the claims.
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 gingivi-J,is has been demonstrated in Nachman, U.S.
Pat. No. 4,244,373 of Jan. 13, 1981 and in Detsch, U.S.
Patent 4,509,519 of Apr. 9, 1985. Killing oral bacteria has i,he 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 inducing aerobic and anaerobic bacteria on a species-by-species level and instead teaches a generic, untargeted treatment.
While researching the effect of direct current electricity on the mouth, the applicants

- 14 -discovered -chat by increasing the current level to the approximate range of 50 to 250 microamperes, a direct current elecirical treatment was able to deliver new and unexpected therapeutic, prophylactic, and regenerative benefits previously unknown in the art.
Specifically, by utill7ing 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 Lhe podiatric field have shown -chat higher current levels than chose used in exiscing oral electrical treatments are necessary LAD effectively treat fungal infections ("Low-Voltage Direct Current as a Fungicidal Agent for Trcating Onychomycosis", Kalinowski, et al., Journal of the American Podiairic Medical Associacion 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' studies have shown that these mierobicidal properties begin to take effect within approximately 5 and 15 minutes of treatment, reducing both supra- and sub-gingival microbes.
In addiiion, the applicants 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

- 15 -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.
In further research, the applicants conducted preciliniral 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 solu_ions. 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.
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.
In addiLion, scanning electron microscopy (SEM) was conducted on F. nucleatum colonies before and

- 16 -after at 30 minute treatment, according to the method of this invention, to better understand the mechanism by which the meehod according to this invention is able to reduce bacterial levels. The SEM imagery suggested that che method according to this invention interferes with bacter al cellular division and can weaken the outer envelope (cell membrane) resuleing in fragile cellular structures that can easily break. It is contemplated LhaL Lhis is phenomenon is an example of electroporation, where the permeabilley of cellular membranes may be affected by electrical stimulation either temporarily or permanently. IL, 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.
Specifically, the method according to the present invention has been shown to reduce viable colony forming units (CFU) in various oral bacteria.
Table 1 below shows the efficacy of treatment according to the present invention at current levels of 5C pA or 500 pA for 5, 10, 20 and 30 minute durations for bacterial culeures ranging from 104 to 107 colony forming units (CFU) of Streptococcus rails in a saline solution.

- 17 -In Vif,ro Efficacy of Device Against Streptococcus oralis in Saline CPU pA 0 Min 5 Min 10 Min 20 Min 30 Min 50pA 1120 1080 600 320 280 10e4 500pA 1120 1200 800 240 0 50pA 10000 9600 8400 9200 7600 10e5 500pA 11600 10400 11200 10800 8400 50pA 80000 63200 52800 32400 24800 10e6 500pA 80800 70000 15200 14000 15600 50pA 1280000 1080000 1040000 800000 440000 10e7 500pA 1080000 520000 160000 120000 320000 Table 1 Table 2 below shows the efficacy of treatment to the present invention at current levels of 50 pA or 500 pA for 5, 10, 20 and 30 minute durations for bacterial cultures ranging from 104 to 10 CPU of Streptococcus oralis in a saliva solution.
In Vitro Efficacy of Device Against Streptococcus oralis in Saliva CFU pA 0 Min 5 Min 10 Min 20 Min 30 Min 50pA 160 160 80 80 40 10e4 500pA 200 80 80 80 80 50pA 5600 5600 6800 5600 4000 10e5 500pA 8400 6800 7200 E400 2800 50pA 25600 25200 15200 17200 18400 10e6 500pA 23600 16800 15600 17600 15200 50pA 316000 284000 300000 27E000 220000 10e7 500pA 324000 328000 300000 292000 252000 Table 2 Table 3 below shows Lhe efficacy of treatment to the present invention at curren:, levels of 50 pA or 500 pA for 5, 10, 20 and 30 minute durations for bacterial cultures ranging for 104 and 10 CPU of

- 18 -Fusobacterium nucleatun in a saline solution.
In Vitro Efficacy of Device Against Fusobacterium nucleatum in Saline CFU pA 0 Min 5 Min 10 Min 20 Min 30 Min 50pA 480 280 280, 120, 40 10e4 500pA 560 440 400 200 120 50pA 94000 91600 85600 70400 84400 10e6 500pA 46400 45600 27200 Table 3 Table 4 below shows the efficacy of treatment according to the present inven-L.ion at current levels of 50 pA or 500 pA for 5, 10, 20 and 30 minute durations for bacterial cultures ranging from 104 to 106 CFU of Fusobacterium nucleatum in saliva.
In Vitro Efficacy of Device Against Fusobacterium nucleatum in Saliva CFU PA 0 Min 5 Min 10 Min 20 Min 30 Min 50pA 1480 1480 1560 680 880 10e4 500pA 2360 2360 1720 1240 1080 50pA 19600 19600 15200 14400 14000 10e5 500pA 18000 17200 14400 11200 10800 50pA 348000 112000 120000 72000 68000 10e6 504A 156000 128000 124000 32000 28000 Table 4 Table 5 below shows the efficacy of treatment to the present invention at current levels of 50 pA or 500 pA for 5, 10, 20 and 30 minute durations for bacterial cultures ranging for 105 CFU of Porphyromonas gingivalis in a saline soluLion.

- 19 -In ViLro Efficacy of Device AgainsL
Porphyromonas gingivalis in Saline CFU pA 0 Min 5 Min 10 Min 20 Min 30 Min 50pA 3440 2040 2720 1640 1640 10e4 500pA 2440 2120 2200 1880 Table 5 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, reduceion 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 condiLions correlated with oral pathogens, and generally improved oral hygiene.
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, seainless steel, copper, gold, platinum, palladium, aluminum, an alloy thereof, electrically-conductive nanoLubes, carbonized rubber, electrically-conductive silicone, Or electrically-conductive polymers. The electrodes may be composed of ehe same or

- 20 -of differing materials. These electrodes fit snuggly against the lingual and buccal sides of the gingiva and make direct contact widh each side of the gingiva to pass direct current electricity across the teeth and neighboring gingival tissues.
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 polariL.y. 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.
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.
Electrical conductors than 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 curren-z in the approximate range of 1 to

- 21 -500 microamperes. The preferred current setting for most treatments is in the approximate range of 50 to 250 microamperes.
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.
This medium would be placed along any desired areas of desired electrical contact, such as the Leeth, 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.
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's production of adenosine triphosphate.
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.
This conductive medium may also contain teeth whitening agents. This would allow for the addition of teeth whiLening to the list of benefits offered by an embodiment of this invention. A whitening

- 22 -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.
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.
Figure 1 shows one embodiment of a treatment apparatus according to this invention. A user input device 120 is connected to a microcontrolled dircct 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. oralas, P. gingivalis, and F.
nucleatum. Microcontrolled power supply 110 reads the state of input device 120 and adjusts thc outcut current to compensate for the continually varying resistance across cathodic electrodes 140 and anodic electrodes 150.
An optional user feedback device 130 is show in Figure 1 connected to microcontrolled power supply 110. Feedback device 130 may contain various methods

- 23 -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 informa-eion including, but is not limited to, output current level, treatment time elapsed, treatment Lime remaining, date, Lime 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.
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'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, curreneõ levels, and other information to feedback device 130.
Microcontroller 112 also has timing capabilities, represented by Limer 114, that allow for limiLing treatment time based on some predetermined treatment

- 24 -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.
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's treatment may be simplified and guaranteed to follow set parameters.
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, honey 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.
Power source 116 may be any known device capable of delivering an adjustable direct electrical current. This includes, but is not limited to disposable batL.eries, rechargeable batteries, Ac-DC
power converter, etc. Microcontroller 112 is able to

- 25 -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_ Microcontrollpr 112 is also able to reverse the polarity of the cathodic electrodes 140 and anodic electrodes 150 by controlling ihe 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.
Figure 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 7_he lingual gingival tissue of the mouth. A single buccal gingiva electrode 220 is attachcd to or embedded in mouthpiece 200 so that it is transverse from ehe lingual gingiva electrode 210 and fits snugly againsL 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 Figure 3.
Electrical conductors 230 arc insulated so thai 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, out 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

- 26 -conductors 230 may also be partially or wholly composed of an electrically conductive polymer.
Figure 3 shows a perspective view of the same type of embodiment shown in Figure 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 Figure 6.
Figure 4 presents another embodiment similar in nature to that, of Figures 2 and 3. In this embodiment, electrode sets are attached to or embedded in a mouehpiece 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

- 27 -embodiment allows for multiple, discrete points of electrical contact within the mouth. In Figure 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 Eigure 6.
Figure 5 offers a perspective view of an embodiment similar to Figure 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 t,he positive and negative poles of a direct current power source, similar to that of 110 or Figure 6.

- 28 -Figure 6 presents another embodiment of an adjustable direct current power source used to supply direct current to a plurali-sy 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 suilable 9-volt power source. A dual uniL, 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, 100pA 612, or 200pA 616.
Switch option 614 simply does not complete a circuit, preventing current from flowing. Swi-:ch option 612 comprises a 332kQ resistor 618 in series with a 2 volt LED 620. These two components are in parallel with a 48.7kQ resistor 622 to provide a 100 microamp current.
The Switch option 616 comprises a 665kg2 resistor 624 in series wich a 2 volt LED 626. These two components are in parallel with a 97.6kL2 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.
In another embodiment of this invention or

- 29 -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 resisance 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 thae, is catalyzed by the direct current would be most effective in this ionic or colloidal medium.
In yet another embodiment, microcontrolled power supply 110 would be miniaturized and be physically atached 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'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.
Thus the reader will see that at least one embodiment addresses a desired need in the oral hygiene

- 30 -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 Lissue regeneraLion, 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.
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 Figure 6 with standard diodes to achieve the same resultant circuit. Overall, the circuitry from Figures 1 and 6 could be altered in many ways to deliver the same electrical current to ,the oral electrodes.
In some cases dental procedures can break up oral bacterial colonies found in biofilms and introduce

- 31 -bacteria into ehe bloodstream causing bacteremia and other infections. It is further contemplated thae it may be desirable to utilize a mouthpiece according to the present invention immediately prior to performing a dental procedure. The mouehpiece according to this invention may be used by the patient either at home or in the deneal office. In this manner, the living bacteria in the patient's mouth, both supra- and sub-gingival, can be reduced prior to the procedure and Lhe 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 nrophylaxis or a scaling and root planning procedure in a dental office to reduce the risks of ineroducing bacteria into the patient's blood stream. Such a pre-procedural ereaement would he used for approximately 10 to 20 minute with a current level ranging from 50pA to 500pA and would be timed to conclude immediately before the procedure.
A mouthpiece according to the present invention may also be utilized following a clinical procedure as prevenrion for infections, for scenarios including but not limited to post-extraction or post-implantation infection preveneion. Such a post-procedural treatment would last for approximately 10 to 20 minutes with a currene ranging from 50pA to 500pA.
This procedure may then be repeated at home by the eatient one or more times a week until the risk of infection has passed.
Prevention of Systemic Disease It is contemplated chat a mouthpiece according to Lhe present invention may be used to prevent or treat systemic diseases as will be outlined

- 32 -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 Tt 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. gingivalls, and 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.
It is contemplated chat 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 500pA. For acute

- 33 -cardiovascular conditions, this -_reatment 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 Tt 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 thc 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 Lhe 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 500pA for -the duration of the pregnancy. The treatmeno parameters outlined above have been demonstrated to be highly efficient at reducing levels of S. oralis and F. nucleatum at inoculation sizes of 10 colony-forming units (CFU).
3. Diabetes

- 34 -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. rails 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 bhat 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 500pA 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 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 pyogcnic 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

- 35 -treatment regimen, the patient will wear a mouthciece 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 presenL invention for 20 minutes once per day at a current level of 500pA
to effectively reduce oral levels of F. nucleatum which may prevent any bacteria from being transporLed from the oral cavity systemically. This treatment may be repeated multiple times per week until the abscess is reduced.
5. Osteomyelitis 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 500A to effectively reduce oral levels of F. nucleatum bacteria and prevent any bacteria from being

- 36 -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 condiLions.
6. Arthritis It is contemplated chat 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, tho 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 500p 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 condi Lion.
Reducing Blofilm and Preventing Bio film Formation

- 37 -It is contemplated chat 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 treatmenc regimen, the patient will wear a mouthpiece according to the present invention for a predetermined amounL of Lime at a Predetermined curreni 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 500pA 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.
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 50pA 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.
Furthermore, according to another embodiment of his invention, the L.reatment_ regimen would consist of a patient wearing a mouthpiece according to the

- 38 -present invention for 20 minutes once per day at a current level of 500pA to effectively reduce oral levels of S. oralis bacteria to prevene further biofilm formation caused by S. oralis and to reduce the viability of existing biofilm colonies of S. oralis.
These treatments for binfilm 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 blofilm issues.
Method of Manufacture 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 embodimen: the sealing means take the form of a cap 730A,7303. Each cap 730A,730B
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.
The pieces of the first mold 700 are preferably cleaned. A plurality of wires 780A,780B,780C,780D are then prepared and treaded through the first mold 700. In the preferred embodiment, the four wires 780A,780B,780C,780D are threaded through the first mold 700 as shown in Figure 8. Preferably a first and a second wire 780A,780B are Areaded Lhrough the top cap 730A and through ihe first mold 700 and a third and a fourth wire 780C,780D arE:

- 39 -threaded through the bottom cap 730 B and through the first mold 700. Preferably the first wire 780A extends through the first channel 740 in the top cap 730A and the second wire 780 B extends through the second channel 750 in the top cap 730A. Similarly, preferably, tho third wire 780C extends through tho first channel 740 in the bottom cap 730B and the fourth wire 780D
extends through the second channel 750 in the bottom cap 730B. 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.
When the non-conductive material is curcd, the first mold 700 is preferably opened and the partially formed mouthpiece 790 is removed from the first mold 700. The plurality of wires 780A,7805, 780C,780D are now encapsulated by the non-conductive material. Preferably a wire 780A,7808,780C,780D Is located in each of the four exposed channels 800 of the mouthpiece 790. Preferably the first wire 780A Is located in the inner upper channel 800A, the second wire 780B is located in the outer upper channel 800B, the third wire 780C is located in the inner lower channel 800C (not shown), and the fourth wire 780D is located in the outer lower channel 800D (not shown).
The excess wire is then preferably trimmed from the mouthpiece 790 and the remaining wire 780A,780B,780C,7801D is preferably inserted fully into its associated channel 800A,800B,800C,8000.

- 40 -A second mold 810 is preferably provided.
The second mold preferably includes a top portion 810A
and a boteom portion 810B. In the illustrated embodiment, each of thc top and bottom portions of the' second mold 810 preferably includes a mold base 820A,8202, a center piece 830A,8302, a first insert 840A,8400, and a second insert 850A,850B. The pieces of the second mold 850 are preferably designed to silos Lhe channels 800A,80013,800C,800D 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 800A,800B,8000,8000 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.
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 Figures 10-12B. Preferably, the bottom portion 8100 of the second mold 810 is assembled first, wiLh the mouthpiece 790. The top portion 810A 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 thermoseeting elastomer, but may also be a thermoplastic, a thermoplastic elastomer, or other polymer.
After the conductive material is cured, the second mold 810 is opened and Lhe finished mouthpiece 760 is removed. Preferably, the top half 810A of the

- 41 -second mold 810 is removed first. The first 840A and second inserts 850A are preferably removed first. The center piece 830A can then be removed. The bottom half 810B of -,ihe second mold may then be removed, again first removing the first 840B and second inserts 850B
and then the center piece 830B.
The foregoing is considered as illustrative only of the principles of 7_,he inven7_ion. 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.

Claims (13)

WHAT IS CLAIMED IS:

1. A system for delivering an electric current in a mouth of a person, the system comprising:
a first electrode having a first polarity, the first electrode being configured to be in electrical contact with at least a portion of lingual gingival tissue of the mouth of the person;
a second electrode having a second polarity opposite the first polarity, the second electrode being configured to be in electrical contact with at least a portion of buccal gingival tissue of the mouth of the person; and a programmable power supply electrically coupled, through conductors at least partially composed of an electrically conductive polymer, to the first electrode and the second electrode and configured for conducting a pulsed electrical current between the first electrode while at the first polarity and the second electrode while at the second polarity and across gingival tissue defined between the lingual gingival tissue and the buccal gingival tissue.

2. The system of claim 1, further comprising a mouthpiece by which the first and second electrodes are carried.

3. The system of claim 1 or 2, wherein the power supply is programmable to provide the electrical current from 50 1.tA up to and including 500 1.1,A.

4. Use of the system as defined in any one of claims 1 to 3, for at least one of killing oral microbes, increasing oral vasodilation, improving oral blood circulation, teeth whitening, reversing oral bone resorption, increasing oral osteogenesis, reducing gum tissue recession, increasing gingival regeneration, and reducing oral malodor.

5. Use of the system as defined in any one of claims 1 to 3, for reducing a concentration of bacteria in the mouth of the person.

6. The use of claim 5, wherein the bacteria is at least one of F.
nucleatum, P.
gingivalis, and S. oralis.
Date Recue/Date Received 2022-03-30

7. Use of the system as defined in any one of claims 1 to 3, for increasing cellular permeability of bacteria in the mouth of the person.

8. The use of claim 7, wherein the bacteria is at least one of F.
nucleatum, P.
gingivalis, and S. oralis.

9. Use of the system as defined in any one of claims 1 to 3, for treating a systemic disease.

10. The use of claim 9, wherein the systemic disease is at least one of cardiovascular disease, diabetes, pyogenic liver disease, osteomyelitis, and arthritis.

11. The system of any one of claims 1 to 3, further comprising an electrically conductive medium disposed between the first electrode and the second electrode, the electrically conductive medium including a teeth whitening agent.

12. The system of claim 11, wherein the teeth whitening agent is catalyzable by the pulsed electrical current conducted between the first electrode and the second electrode.

13. The system of any one of claims 1 to 3, wherein the first polarity and the second polarity are selectable by the programmable power supply.
Date Recue/Date Received 2022-03-30