WO2015088858A1

WO2015088858A1 - Concurrent treatment of oral and systemic maladies in animals using electrical current

Info

Publication number: WO2015088858A1
Application number: PCT/US2014/068361
Authority: WO
Inventors: Issam Nemeh; William J. LEIMKUEHLER; James G. AZLEIN
Original assignee: Bioelectrics Llc
Priority date: 2013-12-10
Filing date: 2014-12-03
Publication date: 2015-06-18
Also published as: AU2014364214A1; AU2014364214B2; CA2932413A1; CA2932413C; WO2015088858A8

Abstract

A method and apparatus for the concurrent treatment of multiple oral diseases and defects while promoting general oral hygiene utilizing electricity are provided for non-human animals. Electrodes are used to deliver an electrical 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 IN ANIMALS USING ELECTRICAL CURRENT

Related Applications

This application is a continuation-in-part of co-pending U.S. Patent Application Serial No. 13/839,513, filed March 15, 2013, and entitled "Concurrent Treatment Of Oral And Systemic Maladies Using Direct Current Electricity," which is a continuation-in-part of U.S. Patent Application Serial No. 12/205,062 filed September 5, 2008, now pending, and entitled "Concurrent Treatment of Oral Maladies Using Direct Current Electricity, " which is a continuation-in-part of U.S. Serial No. 11/850,661 filed on September 5, 2007, now abandoned, and entitled "Hygiene Mouthpiece," all of which are incorporated by reference herein in their entireties.

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 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 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.

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 proteins 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 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.

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

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 inflamed 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 amnioticfluid infection or an oral source resulted in fetal death.

Recently, a human stillbirth 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 the mother' 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

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 proinflammatory 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

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

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/ oint 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's poor oral hygiene, F. nucleatum bacteremia may have developed and lead to a hematogenous osteomyelitis 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 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's plaque sample.

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. oralis, 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

The present invention relates to a method and apparatus for aiding overall oral health of a non-human animal, and more particularly to 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.

One aspect of the present invention is to provide a method comprising the steps of providing a treatment apparatus and making the treatment apparatus accessible to a non-human animal. The treatment apparatus includes an electrical power source and a plurality of electrically conductive surfaces (which may include an electrically conductive polymer and/or fabric) on an external surface of the apparatus. The treatment device is provided to the animal to be drawn at least partially into its mouth and in contact with an oral secretion or tissue, such as at least one of saliva, lingual tissue, dental tissue, gingival tissue, periodontal tissue, and oral mucosa tissue. The oral secretion and/or tissue provides an electrically conductive path between at least two of the conductive surfaces and electrical current is delivered to the electrically conductive path by at least one of the conductive surfaces.

According to another aspect of a method according to the present invention, the treatment apparatus may regulate the current that is delivered, such as from about 50 microamps to about 500 microamps.

According to still another aspect of a method according to the present invention, the electrical current delivered to the oral secretion or tissue reduces the amount of oral biofilm and/or viable oral bacteria in the mouth of the animal. Such reduction may prevent, treat, and/or mitigate systemic disease in the animal. Types of oral bacteria, amounts of which may be reduced by systems and methods according to the present invention, include one or more of P. gingivalis, C. rectus, A. actinomycetemcomitans, P. intermedia, T. forsythensis, F. nucleatum, E. corrodens, P. denticanis, P. gulae, P. salivosa, S. oralis, and T. denticola.

According to yet another aspect of a method according to the present invention, the method may further include the step of activating the treatment apparatus, such as by operating an on/off switch, which may be a motion-activated switch (such as a reed switch in combination with a magnet) or a moisture-activated switch.

According to a further aspect of a method according to the present invention, the treatment apparatus may include a timer, which may cease delivery of electrical current or potential to the conductive surfaces, such as by disconnecting the power source from the conductive surfaces, after a predetermined time.

According to a still further aspect of a method according to the present invention, the method may comprise a step of diagnosing the animal with a disease, such as one or more of diabetes mellitus, kidney disease, cardiovascular disease, and periodontal disease. Where the disease is periodontal disease, the animal may also have been diagnosed with one or more of chronic bronchitis, pulmonary fibrosis, endocarditis, interstitial nephritis, glomerulonephritis, and hepatitis .

According to yet a further aspect of a system or method according to the present invention, the electrical current delivered by the treatment apparatus may be direct current, which may be pulsed direct current. Additionally or alternatively, the treatment apparatus may be capable of delivering alternating current, which may be pulsed, and delivered at a constant or variable frequency.

Brief Description of the Drawings

Figure 1 demonstrates the overall structure of the first embodiment of a device according to the present invention, including a microcontrolled power source, user input, user feedback and oral electrodes.

Figure 2 shows a top-down view of another 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 that includes a mouthpiece, but 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 that are electrically connected by embedded conductors .

Figure 6 shows an additional embodiment of a device according to the present invention 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 the mold of Figure 11 with a partially molded mouthpiece in its unfilled state.

Figure 12B is a cross section of the 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.

Figure 14 is a perspective view of another embodiment of a device according to the present invention with an enclosed power supply.

Figure 15 is a side view of the embodiment shown in Figure 14.

Figure 16 is a top view of the embodiment shown in Figure 14.

Figure 17A is a partially-exploded perspective view of the embodiment shown in Figure 14.

Figure 17B is a partial schematic cross- section taken along line 17B-17B of Figure 15. Figure 18 is a schematic illustrating an electrode arrangement according to the present invention. Detailed Description

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 .

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. Patent 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.

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.

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' 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 .

In addition, 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 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 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 an 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 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.

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 50 μΑ or 500 μΑ for 5, 10, 20 and 30 minute durations for bacterial cultures ranging from 10⁴ to 10⁷ colony forming units (CFU) of Streptococcus oralis in a saline solution.

TABLE 1

Table 2 below shows the efficacy of treatment to the present invention at current levels of 50 μΑ or 500 μΑ for 5, 10, 20 and 30 minute durations for bacterial cultures ranging from 10⁴ to 10⁷ CFU of Streptococcus oralis in a saliva solution. TABLE 2

Table 3 below shows the efficacy of treatment to the present invention at current levels of 50 μΑ or 500 μΑ for 5, 10, 20 and 30 minute durations for bacterial cultures ranging for 10⁴ and 10^s CFU of Fusobacterium nucleatum in a saline solution.

TABLE 3

Table 4 below shows the efficacy of treatment according to the present invention at current levels of 50 μΑ or 500 μΑ for 5, 10, 20 and 30 minute durations for bacterial cultures ranging from 10⁴ to 10⁶ CFU of Fusobacterium nucleatum in saliva. TABLE 4

Table 5 below shows the efficacy of treatment to the present invention at current levels of 50 μΑ or 500 μΑ for 5, 10, 20 and 30 minute durations for bacterial cultures ranging for 10⁵ CFU of Porphyromonas gingivalis in a saline solution.

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, 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. 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.

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 .

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 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 .

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 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 .

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 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.

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 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. An optional user feedback device 130 is shown in Figure 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.

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, 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.

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, 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.

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.

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 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 Figure 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.

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 a 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 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 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 Figure 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 the positive and negative poles of a direct current power source, similar to that of 110 or Figure 6.

Figure 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, ΙΟΟμΑ 612, or 200μΑ 616. Switch option 614 simply does not complete a circuit, preventing current from flowing. Switch 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 665kQ resistor 624 in series with a 2 volt LED 626. These two components are in parallel with a 97.6kQ 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 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.

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'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 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.

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 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'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's blood stream. Such a pre-procedural treatment would be used for approximately 10 to 20 minute with a current level ranging from 50μΑ to 500μΑ 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 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 50μΑ to 500μΑ. 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

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

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.

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 500μΑ. 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

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 500μΑ 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 10⁷ colony-forming units (CFU) .

3. Diabetes

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 500μΑ 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 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 500μΑ 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

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 500μΑ 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

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 500μΑ 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 Biofilm and Preventing Biofilm Formation

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. glnglvalls, 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 500μΑ 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 50μΑ to effectively reduce oral levels of P. glnglvalls bacteria to prevent further biofilm formation caused by P. glnglvalls and to reduce the viability of existing biofilm colonies of P. glnglvalls.

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 500μΑ 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.

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. Treatment of Non-human Animals

Systems and methods according to the present invention may be used to reduce oral bacteria and/or biofilm, as well as to treat systemic diseases that may be associated with oral bacteria, in non-human animals, such as dogs, cats, sheep, horses, cows, pigs, etc.

For instance, periodontal disease is one of the most common health problems affecting dogs (> 75%) . The prevalence of periodontal disease has been found to increase age but decrease with body weight. Various systemic diseases have been suggested as a strong co- factor for periodontal disease in animals, just as in humans . It has been suggested that periodontal disease could have a causal relationship with systemic diseases in both humans and animals. For dogs, and animals in general, periodontitis is a recurrent and persistent disease and exposes the host to negative systemic effects over an extended period of time, e.g. several years.

It has been observed that, over the course of several years, frequent exposure of bacteremia as a result of minor trauma at sites of periodontal inflammation may cause infection or induce inflammation at distant sites with the body. The pathogenesis of periodontal disease in dogs has been linked with gram- negative anaerobic bacteria upon accumulation within the gingival sulcus causing inflammation and the formation of periodontal pockets . The inflammatory response to periodontal pathogens promotes the formation and release of endotoxins and inflammatory cytokines that can decrease functions of vital organs over time. It has been suggested that systemic diseases may be associated with periodontal disease in dogs, including chronic bronchitis, pulmonary fibrosis, endocarditis, interstitial nephritis, glomerulonephritis, and hepatitis. Periodontal organisms present in dogs with periodontitis have been isolated and identified previously. For instance, the following periodontal pathogens have been found to be associated with periodontal disease in dogs: P. gingivalis (64% of periodontitis-positive dogs) , C. rectus, A. actinomycetemcomitans, P. intermedia, T. forsythensis, F. nucleatum (4% of periodontitis-positive dogs), E. corrodens, P. denticanis, P. gulae, P. salivosa. Recommended treatments using systems and/or methods according to the present invention to treat and/or prevent periodontal disease by reducing or controlling such types of bacteria, may include a predetermined time, such as 20 minutes, of oral secretions and/or tissue (i.e., saliva, lingual tissue, dental tissue, gingival tissue, periodontal tissue, and/or oral mucosa tissue) exposure to an electrical current (alternating or direct current, constant or pulsed) level of between about 50 microamps (μΑ) and about 500 microamps (μΑ) . Devices according to the present invention have been shown to be effective at reducing the count of bacterial species in this current range.

As with dogs, periodontal disease in cats is associated with local inflammation and is purported to influence and induce systemic responses and organ function in distal sites. One of the common oral pathogens found in the oral cavity of cats is P. gingivalis . Studies have demonstrated that indeed measureable systemic changes arise during the progression of periodontal disease, such as increased levels of serum IgG. Further, these levels could be altered with periodontal treatment. Recommended treatments using systems and/or methods according to the present invention to treat and/or prevent periodontal disease in cats by reducing or controlling such types of bacteria, may include a predetermined time, such as 20 minutes, of oral tissue exposure to an electrical current (alternating or direct current, constant or pulsed) level of between about 50 microamps (μΑ) and about 500 microamps (μΑ) . Devices according to the present invention have been shown to be effective at reducing the count of such bacterial species in this current range.

Periodontitis may also be found in sheep, also referred to as "broken mouth", and is associated with severe degradation of periodontal collagen, loss of alveolar bone, appearance of periodontal pockets and premature tooth loss. Although morphological and histological differences exist between the periodontium of sheep and humans, the histopathological appearance is similar in periodontal disease, including the role that P. gingivalis plays in the progression of the disease. Recommended treatments using systems and/or methods according to the present invention to treat and/or prevent periodontal disease in sheep by reducing or controlling such types of bacteria, may include a predetermined time, such as 20 minutes, of oral tissue exposure to an electrical current (alternating or direct current, constant or pulsed) level of between about 50 microamps (μΑ) and about 500 microamps (μΑ) . Devices according to the present invention have been shown to be effective at reducing the count of such bacterial species in this current range.

Cardiovascular-related conditions may also exist in non-human animals. For instance, there has in dogs been revealed an association between periodontal disease severity and risk of cardiovascular-related conditions, such as endocarditis and cardiomyopathy. Endocarditis is a result of infection and inflammation of the heart endothelium, or tissue lining the inner surface of the heart valves and can be caused by various microorganisms. Cardiomyopathy is characterized by an enlarged heart that does not function properly. Both diseases carry a poor prognosis based on the severity of the case. For dogs, it has been found that the risk of endocarditis was 6-fold higher in dogs with stage 3 periodontal disease than it was for healthy dogs and for cardiomyopathy it was about 4-fold. Cardiac disease progression may be affected by the presence and/or prevalence of certain oral bacteria, including S. oralis, F. nucleatum, and P. gingivalis. Recommended treatments using systems and/or methods according to the present invention to treat and/or prevent cardiac disease by reducing or controlling such types of bacteria, may include a predetermined time, such as 20 minutes, of oral tissue exposure to an electrical current (alternating or direct current, constant or pulsed) level of between about 50 microamps (μΑ) and about 500 microamps (μΑ) . Devices according to the present invention have been shown to be effective at reducing bacterial burden of all three species in this current range.

In addition to cardiac disease, a prior retrospective longitudinal study has established a relationship between periodontal disease and chronic kidney disease (CKD) . The hazard ratio of CKD in dogs, in conjunction with increased serum creatinine and blood urea nitrogen concentrations, has been shown to increase, with increasing severity of periodontal disease, from stage 1 to stage 4, thereby establishing a significant positive association between periodontal disease and CKD.

Both F. nucleatum and P. gingivalis are common oral pathogens presented in dogs, and may be linked to kidney disease. Accordingly, reduction of such pathogens may be used as a treatment or prevention thereof. Recommended treatments using systems and/or methods according to the present invention to treat and/or prevent kidney disease by reducing or controlling such types of bacteria, may include a predetermined time, such as 20 minutes, of oral tissue exposure to an electrical current (alternating or direct current, constant or pulsed) level of between about 50 microamps (μΑ) and about 500 microamps (μΑ) . Devices according to the present invention have been shown to be effective at reducing the count of such bacterial species in this current range.

Non-human animal diabetes may also be treated and/or prevented using systems and methods according to the present invention. In humans, as stated, there is an established link between diabetes mellitus and periodontal disease, and such a relationship has been suspected in veterinary medicine. One prior study has demonstrated that blood glucose concentrations are increased in relation to attachment loss and periodontal disease state in dogs. Additionally, these levels decreased following periodontal disease treatment.

The S. oralis bacterium has been associated with severe periodontitis and diabetes. Recommended treatments using systems and/or methods according to the present invention to treat and/or diabetes by reducing or controlling such types of bacteria, may include a predetermined time, such as 20 minutes, of oral tissue exposure to an electrical current (alternating or direct current, constant or pulsed) level of between about 50 microamps (μΑ) and about 500 microamps (μΑ) . Devices according to the present invention have been shown to be effective at reducing the count of such bacterial species in this current range. Such a reduction may help combat high levels of blood glucose.

Furthermore, systems and methods according to the present invention may be used to affect (preferably reduce and/or eliminate) the number of oral bacteria transferred between animals of different species, such as between a pet and its owner. It is well established that oral bacteria, including periodontal pathogens, can be transmitted between mothers and their children simply through everyday close contact. Therefore, it is not unfounded that transmission of such bacteria may occur between humans and their companion animals. One study investigated In fact, the prevalence of periodontal pathogen species in dogs and their owners to examine the possibility of pet-to-owner transmission has been studied. P. gulae was detected in 71.2% of dogs in the study and 16% in the owners. Interestingly, P. gulae is extremely uncommon in the human oral cavity, and each owner who harbored the bacteria had a dog that tested positive for the pathogen. Two additional species, E. corrodens and T. denticola, were found to correlate between owners and dogs indicating that oral bacteria species may be transmitted between dogs and their owners.

The P. gulae bacterium, a member of the Porphyromonas genus found in the oral cavity of dogs, has been shown to share 60% homology with P. glnglvalls . This suggests that P. gulae would respond similarly to treatment with the device as does P. gingivalis. Recommended treatments using systems and/or methods according to the present invention to remedy and/or prevent the transfer of oral bacteria between animals of different species by reducing or controlling such types of bacteria, may include a predetermined time, such as 20 minutes, of oral tissue exposure to an electrical current (alternating or direct current, constant or pulsed) level of between about 50 microamps (μΑ) and about 500 microamps (μΑ) . Either or both animals (e.g. a dog and/or its owner) may be so treated. Devices according to the present invention have been shown to be effective at reducing the count of such bacterial species in this current range. Such treatment should reduce levels of P. gulae and diminish the possibility of pathogen transmission to the animal's owner.

The treatment times may be a constant treatment time (e.g. 20 consecutive minutes) or treatments may be prescribed and/or delivered for a predetermined period of time (e.g. 1-60 minutes) within a treatment window (e.g. 24 hours, one week, one month, etc.) in shorter incremental treatments, such as two minutes, five times a day (to achieve 10 minutes of stimulation within a treatment window of 24 hours) .

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 embodiment the sealing means take the form of a cap 730A, 730B. 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 threaded through the top cap 730A and through the first mold 700 and a third and a fourth wire 780C,780D are 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, the third wire 780C extends through the 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 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 780A,780B, 780C,780D are now encapsulated by the non-conductive material. Preferably a wire 780A, 780B, 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, 780D is preferably inserted fully into its associated channel 800A, 800B, 800C, 800D.

A second mold 810 is preferably provided. The second mold preferably includes a top portion 810A and a bottom portion 810B. In the illustrated embodiment, each of the top and bottom portions of the second mold 810 preferably includes a mold base 820A, 820B, a center piece 830A, 830B, a first insert 840A,840B, and a second insert 850A, 850B. The pieces of the second mold 850 are preferably designed to allow the channels 800A, 800B, 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, 800C, 800D 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 810B of the second mold 810 is assembled first, with 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 thermosetting 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 the finished mouthpiece 760 is removed. Preferably, the top half 810A of the 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 the second mold may then be removed, again first removing the first 840B and second inserts 850B and then the center piece 830B.

Another embodiment 900 of a treatment apparatus is shown in Figures 14-17B. The treatment apparatus 900 comprises a first end 902, a second end 904 opposite the first end 902, and a body 910 extending between and including the first end 902 and the second end 904.

While the ends 902,904 may be formed integrally with the body 910, at least one of the first end 902 and the second end 904 may be separable from the body 910. The combination of the first end 902, the second end 904, and the body 910 defines a cavity 920. A control board 930 with power supply 932 is preferably configured to be positioned within the cavity 920 as shown in Figure 17A.

As further shown in Figures 17A and 17B, at least one and preferably a plurality of cathodic electrodes 940 and at least one and preferably a plurality of anodic electrodes 942 are spaced about the body 910. The electrodes 940, 942 may be spaced in an alternating fashion or in pairs. As shown here, the electrodes 940, 942 extend substantially longitudinally along the body 910 and alternate cathodic electrode 940/anodic electrode 942 about the body periphery. In the embodiment 900, the body 910 has an oval-type cross- section providing a first long side 912 and an opposing second long side 914, and a first short side 916 adjacent to the first long side 912 and the second long side 914, and a second short side 918 opposing the first short side 916. At least two electrodes, one cathode and one anode, are provided and electrically accessible through the material forming the outer surface of the device. On the first long side 912, a cathodic electrode 940 and an anodic electrode 942 may be placed adjacent to, but spaced from, one another. An alternating pattern of cathodic electrodes and anodic electrodes may provide a cathodic electrode 940 or an anodic electrode 942 on the first short side 916 depending on the placement of the electrodes 940 and 942 on the first long side 912. This pattern may be continued on the second long side 914 and the second short side 918. One alternating relationship is further shown in schematic form in Figure 18. It should be noted that alternative shapes and configurations that maintain a spaced cathodic electrode 940 and anodic electrode 942 configuration are within the scope of the present invention.

As discussed previously, the circuit will be completed by the animal's mouth. This is schematically represented in Figure 18 by impedences R₀, provided by the animal's mouth (e.g. saliva and/or oral tissues), extending between two or more electrodes. An alternating pattern of a plurality of cathodic electrodes 940 and a plurality of anodic electrodes 942 may provide a higher likelihood of circuit completion, as there is provided more opportunities therefore. As one of each type of electrode 940 and 942 come into contact with an animal's mouth or oral tissues or secretions, an electrical current flows from the contacted cathodic electrodes 940 to the saliva, gingival tissues, surrounding teeth, boney structures, and/or connected mouth tissues (R₀) to the contacted anodic electrodes 942 and then back to a power supply 932, forming a complete circuit. The power supply 932 may be a simple dry-cell battery, a rechargeable battery, a capacitor, a kinetic energy generator, a piezoelectric generator, a microcontrolled DC power supply (as previously discussed 110) or other power supply (such as a microcontrolled AC power supply) . Regardless of the power supply 932 used, it is most preferable to control the amount of electrical current delivered by the treatment device to provide a relatively constant current power source to provide up to about 500 microamps of direct or alternating current. Such control may be provided by a microcontroller or discrete monitoring circuitry (such as through current and/or impedance sensing) , or optimal dry-cell design if expected impedances are generally known. It is further contemplated by the present invention that the treatment apparatus 900 is preferably used by non-human animals, such as felines, bovines, ovines, canines, equines, porcines, etc.

Furthermore, a conductive material 950c, a is layered over the top of the electrodes 940, 942, respectively. Preferably, the conductive material 950 comprises a resilient material (preferably durometer Shore A range of about 25 to about 80, or even up to about 90-95) to encourage chewing of the treatment apparatus 900. As non-limiting examples, a conductive silicone, urethane, fluorosilicone, or other conductive polymer or a conductive fabric (e.g. silver-plated nylon, or non-woven conductive or conductive-through-adhesive fabric tape) may be used as, or as a part of, the covering material. Regardless of the covering material used, it is preferred that at least a portion of the material forming the outer surface of the apparatus conducts electricity from the power supply, or regulated amount thereof, to the animal's mouth. The conductive material portions 950 are preferably separated by non- conductive material 960, such as an insulative polymer (e.g. non-conductive silicone) or fabric, preferably having approximately the same durometer Shore A hardness as the conductive material, or a similar tooth feel thereto. Alternatively, in another preferred embodiment, the hardness of the non-conductive material 960 is less than that of the conductive material 950, such as about half.

The control board 930 and power supply 932 may be of any types known to provide an ability to transfer the power of the power supply 932 to the electrodes 940 and 942. Fully contemplated within the purview of the present invention are timers, audible and/or visible usage, activity and/or power indicators (e.g. beeper, buzzer, light-emitting diodes), motion activation, moisture activation, pressure activation, electrical current intensity adjustment (e.g., based on sensed impedance between a cathode 940 and an anode 942), and/or an on/off switch 934 to control the possible current delivery by the power supply 932. Optionally, a microcontroller could be used, as previously described, to control the various functions and could record various treatment parameters and/or treatment history in nonvolatile memory to be analyzed in real-time or post- treatment .

Further contemplated is the use of a method according to the present invention for promoting oral hygiene in non-human animals, such as felines, bovines, ovines, canines, porcines, and/or equines. The method comprises the steps of providing a treatment apparatus comprising a power source and a plurality of electrodes electrically coupled to the power source. The power source may be an internal direct current power source, or other power source as described above. The plurality of electrodes includes at least one, but preferably a plurality of cathodic electrodes and at least one, but preferably a plurality of anodic electrodes. The electrodes may be positioned in a spaced arrangement about, and preferably conductive through, the exterior of the treatment apparatus by a conductive material. The electrodes may be arranged in an alternating cathodic/anodic fashion about the device. The method further comprises the step of providing such device to a non-human animal, thereby allowing delivery of electrical current from the power source, through the electrodes and to at least one of the animal's oral secretions (e.g., saliva) and oral tissue (e.g., lingual tissue, dental tissue, gingival tissue, periodontal tissue, and oral mucosa tissue) .

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 .

Claims

We Claim:

1. A method for promoting oral hygiene comprising the steps of:

providing a treatment apparatus comprising an electrical power source and a plurality of electrically conductive surfaces on an external surface of said apparatus; and

making the treatment apparatus accessible to a non-human animal to be drawn at least partially into the mouth of the non-human animal in contact with at least one of saliva, lingual tissue, dental tissue, gingival tissue, periodontal tissue, and oral mucosa tissue,

wherein said at least one of saliva, lingual tissue, dental tissue, gingival tissue, periodontal tissue, and oral mucosa tissue in the mouth provides an electrically conductive path between at least two of said plurality of electrically conductive surfaces and electrical current is delivered to said electrically conductive path by at least one of said electrically conductive surfaces.

2. The method of claim 1 wherein said apparatus regulates the current delivered to said at least one of the animal's saliva, lingual tissue, dental tissue, gingival tissue, periodontal tissue, and oral mucosa tissue.

3. The method of claim 2 wherein the electrical current delivered is from about 50 μΑ up to and including about 500 μΑ.

4. The method of claim 2 wherein the delivery of electrical current reduces the amount of oral biofilm in said animal.

5. The method according to claim 1 wherein the delivery of electrical current reduces an amount of viable oral bacteria to at least one of prevent, treat, and mitigate systemic disease in the animal.

6. The method of claim 1 further comprising the step of activating the treatment apparatus.

7. The method of claim 6 wherein the activating step comprises the step of operating an on/off switch .

8. The method of claim 7 wherein the on/off switch comprises a motion-activated switch.

9. The method of claim 8 wherein the motion activated switch comprises a reed switch.

10. The method of claim 7 wherein the on/off switch comprises a moisture-activated switch.

11. The method of claim 1 wherein the treatment apparatus further comprises a timer.

12. The method of claim 11 further comprising the step of disconnecting the power source from the electrodes after a predetermined time.

13. The method of claim 1 wherein the conductive surfaces comprise a conductive polymer.

14. The method of claim 1 wherein the conductive surfaces comprise a conductive fabric.

15. A method according to claim 1, further comprising the step of diagnosing the non-human animal with a disease.

16. A method according to claim 15, wherein the disease is one or more of diabetes mellitus, kidney disease, cardiovascular disease, and periodontal disease.

17. A method according to claim 16, wherein the disease is periodontal disease, and the non-human animal has been diagnosed with one or more of chronic bronchitis, pulmonary fibrosis, endocarditis, interstitial nephritis, glomerulonephritis, and hepatitis .

18. A method according to claim 15, further comprising the step of:

reducing an amount of oral bacteria in the non-human animal .

19. A method according to claim 18, wherein the oral bacteria is one or more of P. gingivalis, C. rectus, A. actinomycetemcomitans , P. intermedia, T. forsythensis, F. nucleatum, E. corrodens, P. denticanis, P. gulae, P. salivosa, S. oralis, and T. denticola.

20. A method according to claim 1 wherein said electrical current is direct current.

21. A method according to claim 20 wherein said direct current is pulsed direct current.

22. A method according to claim 1 wherein said electrical current is alternating current.

23. A method according to claim 22 wherein said alternating current is pulsed alternating current.

24. A method according to claim 22 wherein said alternating current is delivered at a constant frequency .

25. A method according to claim 23 wherein said alternating current is delivered at a first frequency for a first treatment time period and at a second frequency for a second treatment time period, wherein the first and second frequencies are different.