CATHETER COMPRISING METAL ALLOY FOR DELIVERY OF THERAPEUTIC IONS - Patent application

Abstract

The present invention relates to a device and method for efficiently and safely killing pathogens in blood systems by generating metal ions in situ. Such metal ions include silver, copper, and gold ions, although additional metals including platinum, iridium, and zinc can be used for in situ ion generation. The action of the device and method of the present invention is extremely broad and can kill pathogenic bacteria, viruses, and fungi. The action of the device and method of the present invention is not dependent on a specific interaction between the device and the surface of the pathogen to be killed. In addition, the action of the device and method does not result in the development of resistance by the pathogen, as can occur following the administration of conventional antibacterial, antifungal, or antiviral agents.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Patent Application No. 63 / 173,844, filed April 12, 2021 by T. Koehler et al., entitled “Catheters Including Metallic Alloys for Introduction of Therapeutic Ions,” the contents of which are incorporated herein by reference.

[0002] The present invention relates to devices and methods for killing pathogens in the blood and treating diseases caused by pathogens, as well as devices and methods for stimulating the immune system, as well as devices and methods for intravenous delivery of drugs or fluids, and devices and methods for draining bodily fluids. [Background technology]

[0003] Although great advances have been made in the treatment of bacterial, viral, and fungal infections through the use of antibacterial, antiviral, and antifungal therapeutic agents, blood-borne pathogenic infections and air-borne infections remain a major concern in medical practice. Even infectious agents that primarily attack other tissues or organs, such as severe acute respiratory syndrome coronavirus 2, which causes COVID-19 and primarily attacks the lungs, can infect the blood, thereby making the treatment and control of COVID-19 extremely complicated. More generally, pathogenic infections of the blood can have serious consequences for patients, with the pathogen infecting the host. In many cases, such infections result in the death of the host. Among the most serious blood-borne infectious diseases are pathogens such as human immunodeficiency virus (HIV), i.e., the virus that causes AIDS, hepatitis A virus, hepatitis B virus, hepatitis C virus, Ebola virus, severe acute respiratory syndrome coronavirus 2, antibiotic-resistant bacteria such as MRSA (methicillin-resistant Staphylococcus aureus), and vector-borne viruses such as dengue virus, West Nile virus, and Zika virus. HIV can mutate rapidly and therefore treatments for it can be difficult to generate, and furthermore, HIV is a retrovirus with an RNA genome that is reverse transcribed into DNA, which can then be integrated into the genome of cells that it infects. This can make eradication of the virus extremely complicated, and after more than 20 years of research, a vaccine for the prevention of infection by HIV is still not available. With hepatitis C virus, there are many different strains and therefore available drug therapies, such as antivirals, may be ineffective and / or have debilitating side effects. Patients for whom available antiviral drugs are ineffective are classified as non-responders, and their chances of survival are quite grim. One particular strain of Hepatitis C has been linked to a new, previously unseen form of liver cancer. Similarly, there has been a worldwide increase in the incidence of Hepatitis C, due to several factors including the growing popularity of tattooing and the associated lack of proper hygiene, as well as the risky intravenous injection of street-sold illegal drugs such as heroin.

[0004] In particular, the treatment of viral infections is complicated by the fact that viruses are structurally and biologically very diverse and have many different life cycles. Thus, most antiviral drugs have only a relatively limited spectrum of action compared to the relatively broad spectrum of action for many antibacterial antibiotics such as penicillin or azithromycin. For example, oseltamivir, an antiviral drug used to treat influenza, has essentially no activity against other viruses, including severe acute respiratory syndrome coronavirus 2. Furthermore, even when used to treat seasonal influenza, oseltamivir must be administered early in the disease process to achieve maximum efficacy.

[0005] Other important blood-borne bacterial pathogens include Staphylococcus epidermidis, Bacillus cereus, Enterococcus faecalis, Clostridium faecium, Listeria monocytogenes, Streptococcus pneumoniae, Streptococcus pyogenes (group A hemolytic streptococci), group B hemolytic streptococci, Escherichia coli, Klebsiella pneumoniae, Haemophilus influenzae, Pseudomonas aeruginosa, Acinetobacter baumannii, Neisseria meningitidis, Bacteroides fragilis, Bacillus anthracis, Yersinia pestis, Francisella tularensis, and Borrelia abortus (MR Ringle et al., Multiplexed Identification of Blood-Borne Bacterial Pathogens by Use of a Novel 16S rRNA Gene PCR-Ligase Detection Reaction-Capillary Electrophoresis). Assay), J. Clin. Microbiol. 45, 1927-1235 (2007).

[0006] Particularly significant bacterial infections are those caused by the aforementioned methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, and vancomycin-resistant Enterococcus.

[0007] Blood-borne fungal infections include candidiasis, including infections caused by Candida auris, aspergillosis, blastomycosis, coccidioidomycosis, Cryptococcus neoformans infections, and Cryptococcus gattii infections.

[0008] Blood-borne protozoal infections include malaria.

[0009] These shortcomings have led to attempts to destroy blood-borne pathogens through the use of metal ions.

[0010] One process that has been used to introduce metal ions for the treatment of blood-borne infectious diseases is iontophoresis. Iontophoresis is a physical process in which ions diffuse through a medium driven by an electric field. Prior art uses silver iontophoresis by inserting a catheter into the subclavian or superior vena cava vein and then placing a silver probe through the catheter directly into the bloodstream. A small prescribed amount of electrical current is then applied to the wire, releasing the correct amount of silver nanoparticles with a slight positive charge that bind to the virus, which has a slight negative charge. This process destroys the virus by disrupting the function of the virus' membrane and thus its survival function. This procedure has various challenges associated with it due to its proximity to the heart, the time required to be successful, and the possibility of generating a secondary infection at the entry site.

[0011] The prior art also provides devices and methods for removing blood from a patient's body, rerouting the blood through a device that uses nanoparticles to kill viruses, and then reinjecting the blood back into the patient's body.

[0012] These devices and methods include the BioSpleen device developed at the Wyss Institute, which uses nanoparticles with proteins that attach to the surface of magnetic nanoparticles that are injected into the patient's bloodstream and that adhere to bacteria, viruses, and fungi. The BioSpleen device then uses a magnet to pull out the nanoparticles and the pathogens attached to them. Additionally, these devices and methods include the Seraph 100 device, which uses heparin-coated microbeads to bind to viruses, allowing the device to remove the viruses from the bloodstream. However, these methods rely on large machines and the ability of the patient to remain "held" by the machine for a long enough period of time to provide an improvement in the pathogen counts, e.g., viral, bacterial, or fungal counts, within the patient.

[0013] The prior art also discloses a method and apparatus for destroying blood-borne pathogens that utilizes low-intensity direct current to generate positive particles from various metals that destroy viral pathogens (U.S. Patent No. 6,539,252 to Fields et al.). A first electrode, constructed of a metal such as silver, is inserted into the venous system of a patient. A second electrode is then placed outside the patient's body near the first electrode. A low-intensity direct current is applied to the first metal electrode, which releases silver cations that bind to the virus, resulting in denaturation of the virus. The first electrode is placed through a catheter into the venous system of an infected patient. However, this prior art method relies on the use of two separate electrodes, one inserted into the patient's body and the other on the patient's skin, and some patients may further require an electrode to be inserted into the patient's jugular vein. This prior art placement is complicated and may result in complications such as infections due to the multiple insertions required.

[0014] U.S. Patent No. 9,849,282 to Fuller et al. discloses a medical implant device for inhibiting infection associated with prosthetic joint implants using electrical currents, but because the medical implant device is entirely implanted within the body, options for controlling and programming the device are very limited.

[0015] Another alternative for using electric current to treat pathogens is described in U.S. Patent Application Publication No. 2020 / 0009375 by Koehler. [Prior art documents] [Patent documents]

[0016] [Patent Document 1] U.S. Patent No. 6,539,252 [Patent Document 2] U.S. Pat. No. 9,849,282 [Patent Document 3] U.S. Patent Application No. 2020 / 0009375 [Patent Document 4] U.S. Patent No. 8,660,645 [Non-patent literature]

[0017] [Non-Patent Document 1] MR Ringle et al., "Multiplexed Identification of Blood-Borne Bacterial Pathogens by Use of a Novel 16S rRNA Gene PCR-Ligase Detection Reaction-Capillary Electrophoresis Assay," J. Clin. Microbiol. 45, 2007, pp. 1927-1235. Summary of the Invention [Problem to be solved by the invention]

[0018] The treatment of blood-borne infections using the antimicrobial activity of metal ions requires new approaches due to the suboptimal performance of prior art devices and methods.

[0019] Current alternatives for antimicrobial catheters use coatings that rely on chemical reactions for the release of antimicrobial agents. Typically, the antimicrobial agents released are ions, most commonly silver ions. This chemical release is uncontrolled, inconsistent in its action, and diminishes over time. Again, new approaches are needed to treat blood-borne infections using the antimicrobial action of metal ions due to the suboptimal performance of prior art devices and methods.

[0020] That is, there is a long felt need for devices and methods that efficiently and safely kill pathogens in blood that do not require the removal of blood from a patient to achieve the desired result and that use minimally invasive techniques to minimize the risk of complications such as infection. Preferably, such devices and methods are capable of killing a broad range of pathogens, including viruses, bacteria, fungi, and protozoa, and do not depend on a specific interaction between the device and the surface of the pathogen for their action. Preferably, such devices are not subject to the development of resistance to the device by the pathogen being treated, as can occur with conventional antibacterial, antiviral, antifungal, and antiprotozoal pharmaceutical agents.

[0021] Further, a need exists for improved antimicrobial catheters that have consistent effectiveness that does not decrease over time. [Means for solving the problem]

[0022] The present invention relates to a device and method for efficiently and safely killing pathogens in blood systems by generating metal ions in situ. Such metal ions include silver, copper, and gold ions, although additional metals including platinum, iridium, and zinc can be used for in situ ion generation. The operation of the device and method of the present invention can kill a very wide range of pathogenic bacteria, viruses, fungi, and protozoa. The operation of the device and method of the present invention is not dependent on a specific interaction between the device and the surface of the pathogen to be killed. In addition, the operation of the device and method of the present invention does not result in the development of resistance by pathogens, as may occur following administration of conventional antibacterial, antifungal, antiviral, or antiprotozoal agents.

[0023] One aspect of the present invention is (a) a wire comprising a metal or metal alloy that releases ions when a low intensity direct current is applied to the wire; (b) an insulating covering for insulating the wire, said insulating covering being inserted through a catheter into the bloodstream of a patient to be treated; (c) male connector, (d) a female connector in operative contact with the male connector, such that the male and female connectors protect the components of the device and allow connection to a catheter; (e) a pin of conductive material within the male connector for transmitting low intensity direct current from a power source connected to the device; and (f) optionally, a side port for the introduction of drugs; A device for the treatment or prevention of bacterial, viral, fungal, or protozoal infections or for stimulation of the immune system comprising:

[0024] In another version of this alternative of the device, the catheter may include a cable that provides a direct connector to the wires such that the cable is actually part of the catheter.

[0025] In yet another version of this alternative of the device, the pins of conductive material, typically copper, can be replaced with a heat shrink connector incorporating a circular solder ring. With the use of a heat shrink connector, the two wires to be connected are placed at either end of the connector adjacent within the circular solder ring, heat is applied to the connector exterior, which activates the solder ring to connect the wires, and an exterior plastic material subsequently shrinks to encapsulate the connected wires. This alternative can be used with other embodiments of the invention described as having copper conductive pins or conductive pins of another conductive metal.

[0026] The device may further comprise a power source in electrical contact with the device, hi one alternative, the power source in electrical contact with the device is capable of adjusting the current based on the therapeutic application of the device.

[0027] In this and similar devices described below, the wires comprising metals or metal alloys are typically (1) Gold and silver alloys containing 70% or more gold and 30% or less silver; (2) Gold-silver alloys containing 70% or more silver and 30% or less gold; (3) Gold, silver and copper alloys containing 70% or more gold and a total of 30% or less silver and copper; (4) Silver, copper and gold alloys containing 70% or more silver and a total of 30% or less copper and gold; (5) Silver-copper-gold alloys containing 70% or more copper and a total of 30% or less silver and gold; (6) Alloys of silver, copper and gold containing between 1% and 99% of each of gold, silver and copper; (7) Alloys of gold containing 70% or more of gold and not more than 30% in total of silver, copper, platinum, iridium, or zinc with one or more of the following: silver, copper, platinum, iridium, and zinc; (8) Alloys of silver containing 70% or more of silver and not more than 30% in total of gold, copper, platinum, iridium, or zinc, and one or more of the following: (9) Alloys of copper containing 70% or more copper and not more than 30% in total of gold, silver, platinum, iridium, or zinc, and one or more of the following: (10) Alloys of platinum containing 70% or more platinum and not more than 30% in total of gold, silver, copper, iridium, or zinc, and one or more of the following: (11) Alloys of iridium containing 70% or more iridium and not more than 30% in total of gold, silver, copper, platinum, or zinc, and any one or more of the following: gold, silver, copper, platinum, and zinc; and (12) Alloys of zinc containing 70% or more of zinc and one or more of gold, silver, copper, platinum, or iridium in the aggregate not exceeding 30% of gold, silver, copper, platinum, or iridium; However, other alternatives to these wires are within the scope of the present invention.

[0028] Typically, the device operates at about 2×10 9 From about 7 × 10 12 ions. Typically, the device uses a voltage of about 1.2V or less. Preferably, the device uses a voltage of about 0.5V to about 0.92V, and in some alternatives, a voltage of 0.87V or 0.89V is used. Typically, the device uses a current of less than about 10 μA. Preferably, the device uses a current of less than about 6 μA. More specifically, the device uses a current of about 4.9 μA.

[0029] In one alternative, the device provides a constant current with a voltage cap. In another alternative, the device provides a constant voltage with a current cap.

[0030] Another aspect of the present invention is a method for producing a (1) A wire comprising a metal or metal alloy that releases ions when a low intensity direct current is applied to the wire; (2) an insulating covering for insulating the wire, said insulating covering being inserted through a catheter into the bloodstream of a patient to be treated; (3) male connector, (4) a female connector in operative contact with a male connector, such that the male and female connectors protect the components of the device and allow connection to a catheter; (5) a pin of conductive material within the male connector for transmitting low intensity direct current from a power source connected to the device; (6) a stylet for insertion into a vein of the subject to be treated; (7) an insulator for insulating the stylet; and (8) optionally, a side port for the introduction of chemicals; A device for the treatment or prevention of bacterial, viral, fungal, or protozoal infections or for stimulation of the immune system comprising:

[0031] In another version of this alternative of the device, the stylet may include a cable that provides a direct connector to the wire such that the cable is actually part of the stylet.

[0032] In this alternative, the wire comprising a metal or metal alloy is as described above, and the ion emission rate, voltage, and current are as described above.

[0033] This alternative device may further comprise a power source as described above.

[0034] Yet another aspect of the present invention is a method for producing a medicament for use in a method for the treatment of osteoporosis, comprising: (a) a wire comprising a metal or metal alloy that releases ions when a low intensity direct current is applied to the wire; (b) an insulating covering insulating a portion of the wire; (c) Connectors, and (d) an insulating covering and an electrode that rests on the patient's skin when the wire is inserted into the patient's vein; A device for the treatment or prevention of bacterial, viral, fungal, or protozoal infections or for stimulation of the immune system comprising:

[0035] In this alternative, the wire comprising a metal or metal alloy is as described above. The ion emission rate, voltage, and current are as described above. In this alternative, the electrode that rests on the patient's skin is typically a conductive patch, such as an EKG patch, that is connected to a cable that connects to a power source to complete the electrical circuit. This electrode acts as the cathode.

[0036] This alternative device may further comprise a power source as described above.

[0037] Yet another aspect of the present invention is a method for producing a medicament for use in a method for the treatment of osteoporosis, comprising: (1) A wire comprising a metal or metal alloy that releases ions when a low intensity direct current is applied to the wire; (2) An insulating covering that insulates a portion of the wire; (3) a dome-shaped cap covering one end of the wire; (4) one or more notches exposing a portion of the wire for delivery of ions when a low intensity direct current is applied to the wire; (5) male connector, (6) a female connector in operative contact with the male connector, the male and female connectors protecting the components of the device and allowing connection to a catheter or stylet for insertion of the device; and (7) optionally, a side port for the introduction of chemicals; A device for the treatment or prevention of bacterial, viral, fungal, or protozoal infections or for stimulation of the immune system comprising:

[0038] In another alternative to this embodiment of the device, the catheter or stylet may include a cable that provides a direct connection to the wire such that the cable is actually part of the catheter. Alternatively, it is contemplated that either the female or male connector may include a pin of conductive material as described above.

[0039] In this aspect of the invention, the length of the insulated wire extending from the proximal or origin of the male connector is: (a) from about 1.5 inches (3.81 cm) to about 6 inches (15.24 cm) for use with peripheral venous electrodes; (b) from about 4 inches (10.16 cm) to about 9 inches (22.86 cm) for a central venous electrode; or (c) from about 6 inches (15.24 cm) to about 32 inches (81.28 cm) for electrodes placed in a peripheral insulated central catheter (PICC); The range may be:

[0040] In this alternative, the wire comprising a metal or metal alloy is as described above, and the ion emission rate, voltage, and current are as described above.

[0041] This alternative device may further comprise a power source as described above.

[0042] Yet another aspect of the present invention is a method for producing a medicament for use in a method for the treatment of a pulmonary artery (1) A wire comprising a metal or metal alloy that releases ions when a low intensity direct current is applied to the wire, wrapped or braided around a catheter for insertion of the device into a patient's bloodstream; (2) two cap connectors in electrical contact with the wires and connected to the device, each connected to a power source that delivers low intensity direct current to the device; and (3) A power supply connected to the two cap connectors; A device for the treatment or prevention of bacterial, viral, fungal, or protozoal infections or for stimulation of the immune system comprising:

[0043] In this alternative, the wire is (1) spiral on the outside of the catheter; (2) Spiral inside the catheter, (3) hexagonal shape on the outside of the catheter; (4) Hexagonal shape inside the catheter; (5) Braided on the outside of the catheter; (6) The inside of the catheter is braided. The catheter may be disposed with an alternative selected from the group consisting of:

[0044] In this alternative, the wire comprising a metal or metal alloy is as described above, and the ion emission rate, voltage, and current are as described above.

[0045] This alternative device may further comprise a power source as described above.

[0046] Yet another aspect of the present invention is a method for producing a medicament for use in a method for the treatment of a pulmonary artery (1) A wire comprising a metal or metal alloy that releases ions when a low intensity direct current is applied to the wire; (2) An insulating covering that covers the entire wire except for one or more notches; (3) a dome-shaped cap sealing the open end of the insulating covering; and (4) a power source connected to the device and delivering low intensity direct current to the device; A device for the treatment or prevention of bacterial, viral, fungal, or protozoal infections or for stimulation of the immune system.

[0047] In this alternative, the dome-shaped cap covers the distal end of the stylet or catheter used to insert the wire into the vein so that the bare wire is not exposed and potentially causing irritation or damage to the inner wall of the vein. In another alternative to this embodiment of the device, the device can include a cable that provides a direct connector to the wire such that the cable is actually part of the stylet. In yet another alternative to the device, the device can include a pin of conductive material as described above.

[0048] In this alternative, the wire comprising a metal or metal alloy is as described above, and the ion emission rate, voltage, and current are as described above.

[0049] Yet another aspect of the present invention is a method for producing a medicament for use in a method for the treatment of a pulmonary artery (1) A wire that is inserted into a patient's vein through a catheter, the wire containing a metal or metal alloy that releases ions when a low intensity direct current is applied to the wire; (2) an insulating covering to protect the wires; (3) Cap connector, (4) a male connector attached near one end of the wire; (5) A female connector attached closer to the end of the wire than the male connector is attached to it; (6) a pin of conductive material within the male connector for transmitting low intensity direct current from a power source connected to the device; and (7) optionally, a side port for the introduction of chemicals; A device for the treatment or prevention of bacterial, viral, fungal, or protozoal infections or for stimulation of the immune system comprising:

[0050] In this alternative, the wire comprising a metal or metal alloy is as described above, and the ion emission rate, voltage, and current are as described above.

[0051] In yet another version of this alternative device, the pins of conductive material, typically copper, can be replaced with a heat shrink connector incorporating a circular solder ring as described above.

[0052] This alternative device may further comprise a power source as described above.

[0053] Yet another aspect of the present invention is a method for producing a medicament for use in a method for the treatment of a pulmonary artery (1) A wire that includes a metal or metal alloy that releases ions when a low intensity direct current is applied to the wire within the stylet, the wire being inserted into a patient's vein by insertion of the stylet; (2) an insulating covering surrounding the wire; (3) a domed cap in which the insulating covering extends entirely to the domed cap; (4) one or more notches providing access for wires to the patient's bloodstream; (5) male connector, (6) female connector, (7) a pin of conductive material within the male connector and protected by the male and female connectors for transmitting low intensity direct current from a power source connected to the device; and (8) optionally, a side port for the introduction of chemicals; A device for the treatment or prevention of bacterial, viral, fungal or protozoal infections or for stimulation of the immune system, the device being adapted for use in conjunction with a PICC catheter (peripheral insulated central catheter).

[0054] In this alternative, the wire comprising a metal or metal alloy is as described above, and the ion emission rate, voltage, and current are as described above.

[0055] In yet another version of this alternative device, the pins of conductive material, typically copper, can be replaced with a heat shrink connector incorporating a circular solder ring as described above.

[0056] This alternative device may further comprise a power source as described above.

[0057] Yet another aspect of the present invention is a method for producing a medicament for use in a method for the treatment of a pulmonary artery (1) an open lumen catheter; (2) a hemostatic seal that is attached to the catheter to close the space around the catheter; (3) a side port to allow for the administration of intravenous antibiotics or other medications; and (4) A wire comprising a metal or metal alloy that releases ions when a low intensity direct current is applied to the wire, the wire being inserted into a patient's vein through a catheter, the inner diameter of the catheter being larger than the outer diameter of the wire to allow both insertion of the wire and as an auxiliary intravenous drug delivery port through a side port and in combination with a proximal hemostatic seal; A device for the treatment or prevention of bacterial, viral, fungal, or protozoal infections or for stimulation of the immune system.

[0058] In this alternative, the wire comprising a metal or metal alloy is as described above, and the ion emission rate, voltage, and current are as described above.

[0059] This alternative device may further comprise a power source as described above.

[0060] Yet another aspect of the present invention is a method for producing a medicament for use in a method for the treatment of osteoporosis, comprising: (1) Catheter, (2) Wiring surrounding a catheter, the wiring configuration being: (a) An outer spirally wound wiring surrounding the catheter; (b) A straight longitudinal trace surrounding the catheter; (c) a wire in the shape of a ring at the distal end of the catheter, at the proximal end of the catheter, or at both the distal and proximal ends of the catheter; (d) hexagonal pattern wiring on the exterior of the catheter; and (e) wiring having periodic exposed sections of wire from the proximal end to the distal end of the catheter, or alternatively only at the distal end of the catheter; is selected from the group consisting of The wire comprises a metal or metal alloy that releases ions when a low intensity direct current is applied to the wire; and (3) a connector that connects the hexagonal design wiring to a power source to deliver low strength direct current to the device; A device for the treatment or prevention of bacterial, viral, fungal, or protozoal infections or for stimulation of the immune system comprising:

[0061] In this alternative, the wire comprising a metal or metal alloy is as described above, and the ion emission rate, voltage, and current are as described above.

[0062] This alternative device may further comprise a power source as described above.

[0063] Yet another aspect of the present invention is a method for producing a medicament for use in a method for the treatment of osteoporosis, comprising: (1) Catheters having either a single lumen or multiple lumens; (2) a wire embedded in a catheter having a milled window embedded therein, the wire comprising a metal or metal alloy wire that releases ions when a low intensity direct current is applied to the wire; and (3) a connector that connects the wiring to a power source to deliver low intensity direct current to the device; A device for the treatment or prevention of bacterial, viral, fungal, or protozoal infections or for stimulation of the immune system comprising:

[0064] In this alternative, the wire comprising a metal or metal alloy is as described above, and the ion emission rate, voltage, and current are as described above.

[0065] This alternative device may further comprise a power source as described above.

[0066] Yet another aspect of the present invention is a method for producing a medicament for use in a method for the treatment of a pulmonary artery (1) a substantially planar patch or bandage having a top side and a bottom side; (2) a coating on the bottom side of a patch or bandage comprising a first wire thereon comprising a metal or metal alloy that releases ions when a low intensity direct current is applied to the first wire; (3) A snap connector on the top of the patch or bandage; (4) a second wire in electrical contact with the snap connector; and (5) a power source in electrical contact with the first and second wires for delivering low intensity direct current to the device; A wound care bandage or patch comprising: a device for the treatment or prevention of bacterial, viral, fungal, or protozoal infections or for stimulation of the immune system.

[0067] In this alternative, the wire comprising a metal or metal alloy is as described above, and the ion emission rate, voltage, and current are as described above.

[0068] Yet another aspect of the invention is a device for the treatment or prevention of bacterial, viral, fungal or protozoal infections or for stimulation of the immune system for incorporation into an intravenous line or other device intended to deliver fluids, the device comprising: (1) a hub cap which acts as a covering for the device; (2) a cell battery acting as a power source; (3) a printed circuit board in electrical contact with the cell battery for controlling the current output; (4) a cathode wire comprising a metal or metal alloy; (5) an anode wire comprising a metal or metal alloy; (6) a fluid-absorbing material in electrical contact with the cathode and anode wires to provide an electrical circuit as fluid flows through the device; (7) a first connector; (8) a second connector, wherein the first connector and the second connector allow for placement of the device into an intravenous line for delivering fluid to a patient; (9) an anode metal pin that joins the first connector and the second connector; and (10) A cathodic metal pin joining a first connector and a second connector, the cathodic metal pin being adapted for insertion into an intravenous line or other device intended to deliver a fluid; Equipped with.

[0069] In this alternative, the cathode and anode wires, comprising a metal or metal alloy, are as described above, and the ion emission rate, voltage, and current are as described above.

[0070] Yet another aspect of the present invention is a method for producing a medicament for use in a method for the treatment of osteoporosis, comprising: (1) a hub cap which acts as a covering for the device; (2) a cell battery acting as a power source; (3) a printed circuit board in electrical contact with the cell battery for controlling the current output; (4) a cathode wire comprising a metal or metal alloy; (5) an anode wire comprising a metal or metal alloy; (6) a fluid-absorbing material in electrical contact with the cathode and anode wires to provide an electrical circuit as fluid flows through the device; (7) solid cap, (8) Connector, (9) a fluid source in operative contact with the connector; (10) an anode metal pin in operative contact with the connector; and (11) a cathode metal pin in operative contact with the connector; A device for the treatment or prevention of bacterial, viral, fungal, or protozoal infections or for stimulation of the immune system, comprising:

[0071] In this alternative, the cathode and anode wires, comprising a metal or metal alloy, are as described above, and the ion emission rate, voltage, and current are as described above.

[0072] Yet another aspect of the present invention is a method for producing a medicament for use in a method for the treatment of a pulmonary artery (1) a generator attached to the patient's skin; (2) A means for regulating the output of the generator; and (3) an implantable stylet comprising a wire, the generator being in electrical contact with the wire for transmitting low intensity direct current through the wire and into the patient's skin; A device for the treatment or prevention of bacterial, viral, fungal, or protozoal infections or for stimulation of the immune system comprising:

[0073] In this alternative, the cathode and anode wires, comprising a metal or metal alloy, are as described above, and the ion emission rate, voltage, and current are as described above.

[0074] Yet another aspect of the invention is a device comprising a chewable gum wafer or layer having incorporated therein particles of a metal or metal alloy, which are released upon chewing by the hydrolytic action of saliva allowing the release of the particles, thereby allowing the particles to be absorbed into the bloodstream. The metal or metal alloy is as described above. Such a device according to the invention may be an adjunct to infusion therapy as described herein.

[0075] Yet another aspect of the present invention is a method for producing a medicament for use in a method for the treatment of a pulmonary artery (1) Catheter, (2) a wire extending within the catheter; (3) 1 to 5 outer conductive rings surrounding the catheter; (4) Insulated wire containing a metal or metal alloy; (5) a connector in operative contact with the catheter; (6) a wire disposed inside the connector for connection to a power source for transmitting low strength direct current to the device, the power source being in electrical contact with the wire; and (7) optionally, a side port for the introduction of chemicals; A device for the treatment or prevention of bacterial, viral, fungal, or protozoal infections or for stimulation of the immune system comprising:

[0076] In this alternative, the wire comprising a metal or metal alloy is as described above, and the ion emission rate, voltage, and current are as described above.

[0077] This alternative device may further comprise a power source as described above.

[0078] Yet another aspect of the present invention is a method for producing a medicament for use in a method for the treatment of a pulmonary artery (1) an introduction needle; (2) Dual-lumen or multi-lumen catheters, (3) a primary lumen for fluid flow within a dual or multi-lumen catheter; (4) A secondary lumen in a dual or multi-lumen catheter; (5) an insulating stylet for insertion into a secondary lumen of a dual or multi-lumen catheter; (6) a wire constructed of a metal or metal alloy in electrical contact with an insulating stylet; (7) removable spacer, (8) a connector for attaching an insulating stylet to a dual or multi-lumen catheter adjacent to a removable spacer; (9) Internal copper pins for attachment to power supply; (10) an injection side port for adding fluid; and (11) a hemostatic seal to prevent backflow of blood from the secondary lumen in which the stylet is placed; A device for the treatment or prevention of bacterial, viral, fungal, or protozoal infections or for stimulation of the immune system comprising:

[0079] In this alternative, the wire comprising a metal or metal alloy is as described above, and the ion emission rate, voltage, and current are as described above.

[0080] In yet another version of this alternative device, the copper pins of conductive material can be replaced with heat shrink connectors incorporating circular solder rings.

[0081] This alternative device may further comprise a power source as described above.

[0082] In this alternative, the device may be used in conjunction with a catheter selected from the group consisting of a central catheter, a midline catheter, a PICC catheter, and a central venous catheter.

[0083] Yet another aspect of the present invention is a method for producing a medicament for use in a method for the treatment of osteoporosis, comprising: (1) a proximal end for connection to a fluid-containing device; and (2) a distal end for insertion into a vein; A needleless injector stylet comprising:

[0084] Yet another aspect of the present invention is a method for producing a medicament for use in a method for the treatment of osteoporosis, comprising: (1) a catheter for insertion into a vein, having a proximal end and a distal end; (2) a battery-powered power source; (3) a circuit board in operative contact with a battery-powered power source for controlling the voltage and current supplied by the device; (4) cathode, (5) an anticoagulant coating over the cathode; (6) an ion-generating anode wire comprising 1 to 5 wires comprising a metal or metal alloy; and (7) A pump to promote blood flow, and for treating or preventing bacterial, viral, fungal, or protozoal infections with an external catheter, for stimulating the immune system, or for providing a zone of inhibition around the catheter placement location to prevent the development of microbial biofilms or infection from a puncture site.

[0085] In this alternative, the wire comprising a metal or metal alloy is as described above, and the ion emission rate, voltage, and current are as described above.

[0086] Yet another aspect of the present invention is a method for producing a medicament for use in a method for the treatment of a pulmonary artery (1) placing a device for treating or preventing a bacterial, viral, fungal, or protozoal infection, for stimulating the immune system, or for providing a zone of inhibition around a catheter placement site, as described above, in operative contact with a subject in need of treatment for a blood borne pathogen infection, such that the device is capable of providing metal ions to the bloodstream of the subject; and (2) causing the device to release metal ions into the subject's bloodstream to treat infection, stimulate the immune system, or provide a zone of inhibition around the catheter placement site; The present invention relates to a method for treating blood-borne pathogen infections such as bacterial, viral, fungal, or protozoal infections, including , ...

[0087] Typically, the device is in operative contact with the subject by placing the wire in a vein of the subject such that the wire releases metal ions into the patient's bloodstream. The device can be placed in-line in the intravenous line or in-line in the fluid source.

[0088] When the method is used to treat a bacterial infection, typically the bacterial infection is an infection caused by a bacterium selected from the group consisting of Staphylococcus aureus, Staphylococcus epidermidis, Bacillus cereus, Clostridium faecalis, Clostridium faecium, Listeria monocytogenes, Streptococcus pneumoniae, Group A Streptococcus, Group B Streptococcus, Escherichia coli, Klebsiella pneumoniae, Haemophilus influenzae, Pseudomonas aeruginosa, Acetinobacter baumannii, Neisseria meningitidis, Bacteroides fragilis, Bacillus anthracis, Yersinia pestis, Francisella tularensis, and Bordetella abortus. In particular, the method can be used to treat an infection caused by Staphylococcus aureus that is methicillin-resistant Staphylococcus aureus (MRSA).

[0089] The devices and methods according to the present invention can also be used as a sole treatment against blood borne pathogens including bacteria, viruses, fungi, and protozoa, as a means to modulate the immune system, and as a means to provide a zone of inhibition around the catheter placement location to account for infection from microbial biofilms or catheter puncture sites.

[0090] When the method is used to treat a viral infection, typically the viral infection is an infection caused by a virus selected from the group consisting of human immunodeficiency virus (HIV), hepatitis A virus, hepatitis B virus, hepatitis C virus, Ebola virus, Zika virus, dengue virus, West Nile virus, dengue virus, and severe acute respiratory syndrome coronavirus 2.

[0091] When the method is used to treat a fungal infection, typically the fungal infection is an infection selected from the group consisting of candidiasis, aspergillosis, blastomycosis, coccidioidomycosis, infection with Cryptococcus neoformans, and infection with Cryptococcus gattii.

[0092] When the method is used to treat a protozoal infection, typically the protozoal infection is malaria, although other protozoal infections may also be treated.

[0093] The method may further comprise administration of a therapeutically effective amount of an antimicrobial agent, which may be selected from the group consisting of antibacterial agents, antiviral agents, antifungal agents, and antiprotozoal agents.

[0094] The method comprises: (3) determining the outcome of the treatment by detecting or determining the amount or concentration of bloodborne pathogens remaining in the subject's blood following initiation of administration of the treatment; and (4) adjusting the treatment, as needed, by modifying the amount of ions administered, the current, voltage, or waveform used, or, if an additional antibacterial, antiviral, or antifungal agent is administered, modifying a factor selected from the group consisting of the identity of the additional agent being administered, the dosage of the additional agent, the frequency of administration of the additional agent, the duration of administration of the additional agent, the route of administration of the additional agent, or another factor associated with administration of the additional agent; It may further include.

[0095] Yet another aspect of the present invention is a method for producing a medicament for use in a method for the treatment of a pulmonary artery (a) placing a device for the treatment or prevention of bacterial, viral, fungal, or protozoal infection or for stimulation of the immune system as described above in operative contact with a subject in need of stimulating the production of natural killer cells, such that the device is capable of providing metal ions to the bloodstream of the subject; and (b) causing the device to release metal ions into the subject's bloodstream to stimulate the body's production of natural killer cells and other innate immune responses to treat neoplastic cells, including breast cancer; The present invention relates to a method for stimulating the production of natural killer (NK) cells, including

[0096] In methods according to the invention, the means for stimulating the immune system may involve an electric field generated by a generator and delivered through a catheter or stylet, which activates calcium influx and efflux channels on lymphocytes, which in turn activates signaling within the immune system.

[0097] The method according to the invention may also be used for immune system stimulation.

[0098] These and other features, aspects, and advantages of the present invention will become better understood with reference to the following description, appended claims, and accompanying drawings. [Brief description of the drawings]

[0099] [Figure 1] 1 is a front view of a device for killing pathogens in a patient's blood in accordance with selected embodiments of the present invention. FIG. [Diagram 2] FIG. 2 is another front view of a device for killing pathogens in a patient's blood in accordance with selected embodiments of the present invention. [Diagram 3] 1A-1D are front and side views of a device for killing pathogens in a patient's blood in accordance with selected embodiments of the present invention. [Figure 4] 1 is a series of front views of a device for killing pathogens in a patient's blood in accordance with selected embodiments of the present invention; [Diagram 5] 1 is another series of front views of a device for killing pathogens in a patient's blood in accordance with selected embodiments of the present invention; [Figure 6] 1 is a series of front perspective views of a device for killing pathogens in a patient's blood in accordance with selected embodiments of the present invention. [Figure 7] 1A-1C are a series of front views of a device fitted with a catheter that is inserted into a patient's vein or artery. [Figure 8] 1 is a series of front views of a PICC device. [Figure 9] 1 is a series of frontal views of an open lumen catheter for dual drug therapy, in which a hemostatic seal is installed to close around the catheter, in this case a specially designed catheter. [Figure 10A]FIG. 1 is a diagram of one of several catheter designs with an "inhibition zone" that delivers positively charged ions to stimulate the immune system and kill pathogens in the blood, with either internal or external spiral wound wiring. [Figure 10B] FIG. 1 is a diagram of one of several catheter designs with an "inhibition zone" that delivers positively charged ions to stimulate the immune system and kill pathogens in the blood; the diagram has straight longitudinal wiring with three to five wires that are either exposed internally, exposed externally, or exposed both internally and externally. [Figure 10C] FIG. 1 is a diagram of one of several catheter designs with an "inhibition zone" that delivers positively charged ions to stimulate the immune system to kill pathogens in the blood; the catheter can have rings at the distal end, the proximal end, or both, and all rings can be anodes, or alternate anodes and cathodes, or the catheter can be used with an external catheter cathode as used in EKG pathways. [Figure 10D] FIG. 1 is a diagram of one of several catheter designs with an "inhibition zone" that delivers positively charged ions to stimulate the immune system to kill pathogens in the blood, with a hexagonal design on the proximal outer surface and distal inner or outer surface, or on the proximal inner and distal inner or outer surfaces, distal, proximal, or both, with a cathode added externally, such as used in EKG pathways. [Figure 10E] FIG. 1 is a diagram of one of several catheter designs with an "inhibition zone" that delivers positively charged ions to stimulate the immune system to kill pathogens in the blood, with periodic exposed sections from the proximal to distal end or just at the distal end, with a length of 1 mm to 10 mm and a window of 35° to 180° exposure. [Figure 10F] FIG. 1 shows end views of several catheter designs with an "inhibition zone" that delivers positively charged ions to stimulate the immune system and kill pathogens in the blood: (i) an arrangement with three 30° windows and (ii) an arrangement with one 180° window. [Figure 10G]FIG. 1 is a diagram of one of several catheter designs that incorporate an "inhibition zone" that delivers positively charged ions to stimulate the immune system to kill pathogens in the blood. [Figure 10H] FIG. 1 is a diagram of one of several catheter designs that incorporate an "inhibition zone" that delivers positively charged ions to stimulate the immune system to kill pathogens in the blood. [Figure 11A] 1A-1C show alternative designs for catheters according to the present invention using either single lumen or multiple lumen designs that could be intended for either peripheral, central, midline and central, or peripherally inserted intravenous catheter (PICC) insertion: (i) (A) side view of a dual lumen with a metal alloy embedded in the catheter with a milled window at the distal end for ion release to stimulate the immune system to create an inhibition (antimicrobial activity) zone and (B) to release positively charged ions (cations) utilizing an external cathode as used in EKG pathways; and (ii) end view of a single lumen and electrode. [Figure 11B] 11B is an end view of the catheter of FIG. 11A, showing alternative designs for a catheter according to the present invention using either a single lumen design or a multi-lumen design that could be intended for either peripheral insertion, central insertion, midline and central insertion, or peripherally inserted intravenous catheter (PICC) insertion. [Figure 11C] FIG. 1 illustrates an end view of a similar multi-lumen catheter, showing alternative designs for a catheter according to the present invention using either a single lumen design or a multi-lumen design that could be intended for either peripheral insertion, central insertion, midline and central insertion, or peripherally inserted intravenous catheter (PICC) insertion. [Figure 12A] 1 is a schematic diagram of a wound care bandage or burn protection bandage according to the present invention, showing a patch incorporating an ion-emitting metal alloy, as described in more detail below, on the skin side (the side that comes into contact with the skin) of a patch of variable size for application to a site on the skin, the ion-emitting metal alloy receiving electrical current when connected to a low intensity direct current generator, as described in more detail below. [Figure 12B] FIG. 2 is a schematic diagram of a wound care bandage or burn care bandage according to the present invention, showing the underside of the wound care bandage or burn care bandage with an incorporated ion-releasing metal alloy representing the cathode and anode. [Figure 13] 13 is a diagram of a device according to the present invention that can be connected to other devices such as a catheter, an IV line, or another device through a luer lock, an IV hose clamp, an IV hose fitting, or other conventional fittings for connecting medical fluid flow components. In FIG. 13, X and Y indicate a pair of connectors for connection of the fluid-through device to other devices such as an IV line. The device has anode and cathode metal pins extending on both sides of it and a hub cap on the top surface of the device. The device contains a sintered porous plastic sheet (Porex®), and the cathode is surrounded by a sintered porous plastic sheet to absorb fluid and allow completion of the circuit from the anode to the cathode. The device also contains a small printed circuit board for controlling the current output. When the fluid passes through the connector and the sintered porous plastic sheet, a complete circuit is formed and ions are released. The anode and cathode are fabricated with an ion-releasing metal alloy as described above. In one alternative, one of the connections is connected to a fluid source such as a water bottle or a container for intravenous fluids. [Figure 14] FIG. 1 is an alternative diagram of a device according to the invention for insertion into a vein, typically in a limb such as an arm. In this alternative embodiment, a generator generating a low intensity direct current is attached to the ion-emitting alloy as described above. A temporarily implanted stylet or catheter is inserted into the vein. This alternative embodiment of a device according to the invention is also inserted into an intravenous line to release ions into the line. In this application, the device is attached to a small container of distilled water or other fluid for administration through an intravenous line capable of releasing ions into it, and when the container is inverted, the fluid activates the release of ions over a desired period of time to create an ion-filled solution. [Figure 15]FIG. 13 is a diagram of another alternative embodiment of a device according to the invention, intended to deliver metal ions as described above into a patient's veins through a temporarily implanted stylet or catheter. [Figure 16] 1 is a diagram of another alternative embodiment of a device according to the present invention which is a chewable gum that continuously releases metal ions into the bloodstream. Absorption can alternatively be oral. [Figure 17] FIG. 13 is a diagram of yet another alternative embodiment of a device according to the present invention which is a cathode catheter. [Figure 18] 1 is a diagram of a needleless injector stylet according to the present invention. [Figure 19] FIG. 13 is a diagram of yet another alternative device of the present invention incorporating a dual lumen catheter for fluid delivery, an injection side port, and a hemostatic valve or seal to prevent backflow of blood from the secondary lumen of the catheter. [Figure 20] 1 is a diagram of an extracorporeal catheter according to the present invention, comprising a battery as a power source, a circuit board for regulating voltage and amperage, cathode and anode wiring, the cathode of which is covered with an anticoagulant coating, and a pump for promoting blood flow. The extracorporeal catheter is designed to be inserted into larger veins for purposes of immune modulation and treatment of blood borne pathogens. [Figure 21A] 21 is a table showing the results of treatment of various diseases with the device according to the invention. Diseases treatable with the device according to the invention shown in Fig. 21 include HIV, Dengue, HSV-1 infection, and HSV-2 infection. The results in Fig. 21 include detailed blood test results. [Figure 21B] 21B is a table showing the results of treatment of various diseases with the device according to the present invention, which is a continuation of FIG. 21A. [Figure 21C] 21B is a table showing the results of treatment of various diseases with the device according to the present invention. FIG. 21B is a continuation of FIG. [Figure 21D] 21C is a table showing the results of treatment of various diseases with the device according to the present invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0100] The present invention employs the use of ions generated by an ion-generating metal by the passage of a low intensity direct current through the ion-generating metal. As used herein, the term "ion-generating metal" refers to (i) a metallic or metalloid element selected from the group consisting of silver, copper, gold, platinum, iridium, zinc, palladium, and osmium, and (ii) an alloy of two or more metallic or metalloid elements, each selected from the group consisting of silver, copper, gold, platinum, iridium, zinc, palladium, and osmium. As described below, the ion-generating metal is formed into an electrode for insertion into a patient, typically, the electrode is inserted into the venous system, such as through a catheter, as described below. As used herein, the term "catheter" refers to a conventional catheter, typically of Teflon, polyurethane, silicone, or any other form of plastic or other biocompatible material, whose length and diameter are compatible with the devices described herein. Catheters of length and diameter consistent with the devices described herein and constructed of the materials described herein can be used to drain bodily fluids to protect patients from hospital-acquired infections, including urinary catheters.

[0101] In particular, silver ions can be attached to the membranes of immune cells to depolarize these membranes from about -70 mV to about -50 mV, allowing a flow of positively charged sodium and calcium ions back into the cells through holes in the membranes called ion channels, although the applicant does not intend to be bound by this theory. This backflow of ions contains the signal that results in transcriptional changes in genes that cause the cells to become activated. Thus, the electrical current generates metal ions, such as but not limited to silver ions, in the bloodstream, which in turn cause the immune cells to become activated.

[0102] In addition, the device and method according to the invention uses a substantially weaker current than that in devices such as pacemakers, neurostimulators, or TENS units. One aspect of the function of the device and method according to the invention is to promote antigen presentation along with current-induced calcium ion influx in lymphocytes, thereby activating lymphocytes and further activating proliferation. Furthermore, virus-infected cells are more vulnerable to current than healthy eukaryotic cells. Excessive calcium ion influx and depolarization are known to be hallmarks of many virus infections. For this reason, it is believed that the current from the device and method according to the invention has a greater effect on virus-infected cells compared to non-infected eukaryotic cells, although the applicant does not intend to be bound by this theory.

[0103] In another aspect of the invention, the penetration of ions generated by the device and method according to the invention into the outer membrane of bacteria is enhanced by porins in the outer membrane, which enhances the ability of the ions to inhibit bacterial replication. Furthermore, the penetration of ions into bacteria can induce bacterial denaturation, thereby facilitating antigen production and subsequent antigen presentation to lymphocytes.

[0104] The present invention provides a hypothesis that the device and method modulate the immune system by inducing calcium influx into lymphocytes and signaling the immune system accordingly, but the applicant does not intend to be bound by this theory. When an antigen binds to a lymphocyte, potassium channels open, allowing the release of K from the cell. + The outflow of Ca produces hyperpolarization, making the cell even more negatively charged. As a result, voltage-sensitive Ca 2+ The Ca channel opens and generates a signal inside the lymphocyte. 2+ This signal causes lymphocytes to (i) change cell shape or volume, (ii) activate certain enzymes in an activation cascade, and (iii) induce K + and Ca 2+ In addition, it activates the gene that expresses the Ca ion channel. 2+The influx of K has also been shown to activate both T cells and NK cells, which function importantly in fighting infections and cancer in the body. + and Ca 2+ The more Ca channels present in the cell membrane, the more effective they are at activating lymphocytes. 2+ is highly effective, which is associated with the activity of the adaptive immune system.

[0105] Furthermore, by modulating the bioelectrical state of T cells, these cells can be activated or inactivated. Activation occurs when ion channels are overexpressed and thereby open, allowing the inward current of calcium ions into the cell and the reverse current of potassium and chloride ions out of the cell. The net effect is depolarization, where the cell membrane potential of the T cell is lowered. This depolarization has the following effects: (1) ion channels (and therefore associated ion currents) in the cell membrane of T cells differentially cluster at the immune synapse (i.e., where the T cell binds antigen) similar to the clustering of ion channels at neuronal synapses; (2) there is a storage effect on T cell depolarization, with subsequent binding to antigen resulting in the induction of higher calcium ion currents; (3) a similar phenomenon is recognized in NK cells in the innate arm of the immune system, where cell membrane depolarization due to inwardly flowing calcium ion currents can activate NK cells; and (4) silver ions can reversibly depolarize the cell membrane by promoting a similar inward calcium ion current.

[0106] Therefore, Ca 2+ When is pumped into lymphocytes, the lymphocytes change shape and activate enzymes to produce K + and Ca 2+ It transmits a signal to activate genes that express ion channels, which further opens the cell membrane and allows K + Ions are pumped out of the cell, generating a negatively (-85 mV) charged lymphocyte.

[0107] Thus, the devices and methods of the present invention function through two interaction mechanisms: (1) generation of antigens from pathogens that can be presented by lymphocytes, and (2) stimulation of T cells through activation induced by ions generated by the devices and methods of the present invention, although the applicant does not intend to be bound by this theory.

[0108] For ion-producing metals that are alloys, the percentage of each metal in the alloy may depend on the desired results. Typically, however, the primary metal in the alloy should be present in a proportion equal to or greater than 70% to achieve optimal results in destroying pathogens when the alloy is used. The goal is to destroy blood-borne pathogens with ion-producing metals that are either inserted directly into the bloodstream of the patient to be treated or inserted in an arrangement such that the ion-producing metal is in contact with the bloodstream. The appropriate concentration and duration of administration of the metal ions can kill pathogens without affecting the patient's cells such as erythrocytes (red blood cells) and leukocytes (white blood cells including lymphocytes that function critically in the establishment and maintenance of cellular and humoral immune responses).

[0109] In one alternative according to the invention, the ion-producing metal is a gold-silver alloy comprising 70% or more gold and 30% or less silver. In another alternative according to the invention, the ion-producing metal is a gold-silver alloy comprising 70% or more silver and 30% or less gold. In yet another alternative according to the invention, the ion-producing metal is a gold-silver-copper alloy comprising 70% or more gold and 30% or less silver and copper in total. In yet another alternative according to the invention, the ion-producing metal is a silver-copper-gold alloy comprising 70% or more silver and 30% or less copper and gold in total. In yet another alternative according to the invention, the ion-producing metal is a silver-copper-gold alloy comprising 70% or more copper and 30% or less silver and gold in total.

[0110] Typically the electrodes comprise between 1% and 99% each of gold, silver, and copper.

[0111] In another alternative according to the invention, the ion-producing metal can include one or more of platinum, iridium, and zinc. Thus, further possible combinations of metals are: (1) an alloy of gold with one or more of silver, copper, platinum, iridium, and zinc, with 70% or more gold and a total of 30% or less silver, copper, platinum, iridium, or zinc, (2) an alloy of silver with one or more of gold, copper, platinum, iridium, and zinc, with 70% or more silver and a total of 30% or less gold, copper, platinum, iridium, or zinc, (3) an alloy of copper with one or more of gold, silver, platinum, iridium, and zinc, with 70% or more copper and a total of 30% or less gold, silver, platinum, iridium, or zinc, (5) alloys of platinum with one or more of gold, silver, copper, iridium, and zinc, containing 70% or more platinum and a total of 30% or less gold, silver, copper, iridium, or zinc, (5) alloys of iridium with one or more of gold, silver, copper, platinum, and zinc, containing 70% or more iridium and a total of 30% or less gold, silver, copper, platinum, or zinc, (6) alloys of zinc with one or more of gold, silver, copper, platinum, and iridium, containing 70% or more zinc and a total of 30% or less gold, silver, copper, platinum, or iridium, are within the invention. Other metal combinations can be used in the alloys according to the invention.

[0112] Use of the devices and methods according to the present invention will significantly reduce exposure to life threatening complications resulting from infection and will also result in a significant reduction in the turnaround time required for treatment. The methods and devices according to the present invention can be used in the doctor's office, at home, in a hospital or clinic, on the battlefield, or as vacation treatment.

[0113] The system is fairly basic and simple in both construction and use. A wire, either manufactured as part of a catheter or with an insulating covering, is inserted into the patient's bloodstream for treatment of blood borne pathogens. The details of the design depend on the patient's characteristics, the particular pathogen being treated, and the duration of the treatment. The duration and intensity of the ion release is controlled by a proprietary control system or other suitable control unit, which has a PCB (printed circuit board) with proprietary software therein that controls the current, waveforms, and output for various programs for treating blood borne pathogens using external software programs.

[0114] Typically, when activated, the device produces approximately 2×10 blood cells per second for the treatment of blood-borne pathogens or stimulation of the immune system. 9 From about 7 × 10 12 ions are released. In the method and device according to the invention, the voltage applied to generate the metal ions is typically about 1.2V or less. Preferably, the applied voltage is about 0.5V to about 0.92V, and in some alternatives, a voltage of 0.87V or 0.89V is used. The applied voltage depends on the tissue resistance. Typically, the current used is less than about 10 μA, more commonly about 6 μA or less, and preferably about 4.9 μA. In most applications, it is important to keep the voltage applied to generate the metal ions at about 1.2V or less, as voltages greater than this range tend to cause the generated ions to combine with chloride in the bloodstream, and further lead to the formation of particles that lack therapeutic effect.

[0115] In one alternative, the device provides a constant current with a voltage cap. In another alternative, the device provides a constant voltage with a current cap.

[0116] Typically, the length of exposed metal wire from the distal end of a fully exposed wire design is about 0.1 inch (0.254 cm) to about 1.0 inch (2.54 cm). Typically, the wire is surfaced to prevent breakage and for safety purposes, as discussed in more detail below. Typically, the range of exposed metal wire area for proper release of ions is about 0.0005 square inches (0.0032 cm). 2 ) to approximately 0.70 square inches (4.52 cm 2 Typically, the electrodes are placed into the venous system such that at least 0.5" (1.27 cm) of electrode length is present within the venous system.

[0117] When surface stripping electrodes are used, it is preferable to protect the extension tip with a domed end. This allows for a safer and more comfortable electrode insertion placement. The insulation extending beyond the last milled or open window exposing the metal is a minimum of 0.5" (1.27 cm) and has a domed end, which also covers the blunt end allowing the actual tip of the wire to be seen.

[0118] As used herein, the term "patient" refers not only to humans but also to mammals and typically animals. The devices and methods according to the present invention can be used to treat pathogenic infections in humans as well as animals of social or economic importance, including but not limited to dogs, cats, horses, sheep, cows, pigs, rabbits, and goats.

[0119] As used herein, the term "wire" refers to a thin, straight, rigid or flexible conductor having the characteristics described above and in detail below. Typically, the wire is circular or elliptical in cross section. The term "tip-protected" refers to being completely covered or insulated except for a small portion. Typically, the insulation of the insulated portion of the electrode is achieved by using an electrical insulator for low-strength direct current insulation, typically a silicone-based insulator for medical applications. Silicone-based insulators for medical applications are approved by the FDA or equivalent regulatory agencies in other countries.

[0120] FIG. 1 is a front view of a device and method for killing pathogens such as bacteria, viruses, fungi, or protozoa, modulating the immune system, or creating a zone of inhibition to prevent bacterial growth on a catheter or bacterial infection at a catheter puncture site in a patient's blood, according to an embodiment of the present invention. The device 10 includes a wire 12 protected by an insulating covering 14. The wire 12 and insulating covering 14 are inserted into the patient's bloodstream through a catheter 16. As detailed above, the actual composition of the wire 12 may vary depending on the desired treatment. Upon coming into contact with the patient's bloodstream, the wire 12 releases ions that kill pathogens present in the bloodstream flowing around it. The insulating covering 14 prevents the wire 12 from being damaged. Additionally, the insulating covering 14 prevents trauma to the patient from a broken wire 12 in the patient's bloodstream, and further ensures that the correct amount of therapeutic ions are delivered to destroy one or more pathogens, including the treatment target. The proximal portion of the device has a male connector 18 that connects to a female connector 20. The connectors 18 and 20 provide threads or other mating mechanisms that protect sensitive components and allow these connectors to be connected to the catheter 16. Within the male connector 18 is a copper pin 22 or a pin of another conductive material for the transmission of low density direct current that connects the device 10 to a power source (not shown). The purpose of the pin 22 is to provide the device 10 with a low intensity direct current that accelerates the release of ions. The wire 12 in the blood will release ions on its own, but not at the rate or volume required to substantially destroy pathogens. The device may optionally include a side port 24 for the introduction of drugs.

[0121] In an alternative to this device, the pins of conductive material, typically copper, can be replaced with a heat shrink connector incorporating a circular solder ring. In using a heat shrink connector, the two wires to be connected are placed at either end of the connector adjacent within the circular solder ring, and heat is applied to the exterior of the connector, which activates the solder ring to connect the wires, after which the exterior plastic material shrinks to encapsulate the connected wires.

[0122] 1 also shows a different embodiment of the same basic concept. Instead of having an insulating covering 14 that covers all of the wire 12 except the tip, this embodiment has an insulating covering 14 that covers all of the wire, and a dome-shaped cap 26 completes the protection of the wire 12. This embodiment has one or more cutouts 28 that expose the wire 12 to the bloodstream and allow the wire 12 to emit the desired ions. This second embodiment is safer than the first embodiment due to the absence of bare wire 12 in the bloodstream.

[0123] The device of FIG. 1 operates generally according to the following method: The electrode wires, critical to this therapy, are annealed and insulated up to the exposed tip or notch (if present) so that ions are not released from any part of the wire other than the intended release point well into the vein and bloodstream. This ensures that there is no exposed wire prior to the release point where ion release is intended to occur, preventing ion release that would result in a sub-ideal volume of ions being released to reach and treat the target pathogen. Due to the rapid release of up to trillions of ions per second, the proximity of free or bare metal or wire must be a minimum of 0.5″ (1.27 cm) or greater beyond the tip of the introducer needle or catheter or from the entry point of the vein. This distance is selected to prevent insertion of an excessive length of exposed metal surface into the vein for ion release.

[0124] It has been found that the volume of ions released by the wire depends on the length and / or area of ​​exposed metal, and thus having the correct exposed wire length, either in terms of length or area, is directly related to the potential or effectiveness for killing the target pathogen. Thus, since the length and area of ​​exposed wire is important to the actual ion release mediated by low intensity direct current (LIDC), various exposed wire lengths and alternatives on how to expose such proper lengths have been considered. It has been shown that various pathogens require different ion loads, ion release volumes, or ion volumes as well as different doses of pharmaceuticals that may be required to kill a particular pathogen; typically, for pharmaceutical drugs, these doses are expressed in mg, but the dosage will vary according to the particular drug, the infection being treated, pharmacokinetic factors such as renal and liver function, and other factors known in the art.

[0125] The present invention contemplates the use of three different applied electrodes, each more or less effective depending on the target pathogen. These electrodes include the central venous electrode (CVE), the peripheral venous electrode (PVE), and the PICC electrode (PICCE), which is an electrode placed in a peripherally inserted central catheter (PICC). The length of the annealed or insulated wire extending from the proximal or origin of the male and female connectors is important for proper placement and delivery of metal ions for the treatment of blood borne pathogens. Thus, the length of the tip guard wire for the various electrode designs varies, but is typically from about 1.5" (3.81 cm) to about 32" (81.28 cm) (about 1.5" (3.81 cm) to about 6" (15.24 cm) for PVE, about 4" (10.16 cm) to about 9" (22.86 cm) for CVE, and about 6" (15.24 cm) to about 32" (81.28 cm) for PICC).

[0126] Devices according to the invention, including but not limited to the device shown in Figure 1, further rely on waveforms to facilitate and improve safety during treatment using same and methods according to the invention. A background current waveform from devices according to the invention is delivered by the generator to facilitate blood flow to the area where the electrodes are placed and also to facilitate the dispersion of metal ions into the venous system to improve the efficacy of treatment.

[0127] Typically, a device according to the present invention will generate approximately 2.0×10 9 from about 7.0×10 per second 12 ions per second. Over time, the current will be increased to approximately 7.0 x 10 ions per second. 12 10, then increases to about 2.0 x 10 per second. 9 , then gradually decreases to about 7.0×10 per second. 12 By gradually returning to about 2.0 × 10 9 from about 7.0×10 per second 12 The variable as to how long it takes for the volume of emitted ions to rise and fall is a variable that can be set from the device controller. This cycle can be, for example, to generate approximately 2.0×10 ions per second at preset intervals. 9 from about 7.0×10 per second 12 ions per second, then the number of ions generated is reduced to about 2.0 × 10 9 ions per second, or alternatively, the number of ions generated may be increased to about 2.0×10 per second such that the duration of the increase in the number of ions generated and the subsequent decrease in the number of ions generated are varied. 9 from about 7.0×10 per second 12 ions per second, then the number of ions generated is reduced to about 2.0 × 10 9 The variable cycle may be a cycle that returns to a fixed value. There are some alternatives for the variable cycle, for example the duration of the cycle may vary linearly, either linearly increasing or linearly decreasing from a fixed initial value. Alternatively, the duration may first increase and then decrease. Other alternatives for the variable cycle are possible.

[0128] Of great importance to the operation of the device is the use of a graded output current. A timed or graded release of the output current allows for a more rapid metal ion release over a pre-determined treatment period and a slower metal ion release over the remaining period of the treatment duration. One such example is lowering the metal ion release rate due to the improvement of factors such as bacteremia (a certain concentration of a particular pathogenic bacteria, e.g., Staphylococcus aureus, in the blood) or viremia (a certain concentration of a particular pathogenic virus, e.g., Severe Acute Respiratory Syndrome Coronavirus 2, in the blood) during the course of treatment. Another example is lowering the metal ion release rate during bedtime to make the treatment more effective and at the same time more comfortable for the patient.

[0129] The ion release rate and the particular usage release cycle can be modified as needed depending on factors such as the age, sex, and weight of the patient, the particular pathogen (bacterial, viral, or fungal) infecting the patient, the severity of the infection, particularly the concentration of the pathogen present in the blood, other drugs being administered to the patient, and the patient's hepatic and renal function that may affect pharmacokinetics.

[0130] In some alternatives, a patient to be treated by the devices and methods according to the present application may be infected with more than one pathogen. For example, it is common for patients infected with influenza or other respiratory viruses to also suffer from secondary bacterial infections. This is more likely to occur in patients with immunosuppression, which may be induced, for example, by administration of antitumor drugs that suppress bone marrow function. In such cases, the ion release rate and the particular release cycle used may be modified depending on the particular pathogen infecting the patient and the concentration of the pathogen in the patient's blood, among other factors mentioned above.

[0131] The present invention also contemplates a combination catheter that allows for both the release of metal ions as described above and the administration of intravenous antibiotics, antivirals, antifungals, or other drugs through different or separate lumens in the same catheter simultaneously for the treatment of bloodborne pathogens, including but not limited to antibiotic resistant bacteria. As described above, the treatment can result in activation of the immune system and prevention of bacterial growth on the catheter or bacterial infection at the catheter puncture site. The combination catheters range from 12-26 gauge or sheath introducers up to 12 FR (French) for proper introduction of electrodes. This catheter size range allows for electrodes of various diameters to be inserted into the patient's bloodstream. This catheter size range allows for various electrode diameters to treat various patients, including both adolescents and adults. The connection would be a threaded connector or a universal connector allowing for the acceptance of multiple available intravenous connection systems. The exterior or interior surface of the catheter has the helically wound metal wire as described above designed for the specific ion release required for the applicable treatment or the like. Alternatively, the metal wire can be arranged in a mesh, braid, or hexagonal pattern. The factors influencing optimal ion release are set forth above. Typically, in this alternative, the exposed spiral wire has a range of about 0.5" (1.27 cm) to about 2" (5.08 cm) of the distal end of this form of catheter, either with a wide or tight spiral. The spiral can be either internal or external. In another alternative, the wire can be braided into the inner or outer surface of the catheter. Typically, the braid distance from the end of the catheter is 0.5" (1.27 cm) to about 2" (5.08 cm) from the distal end of the catheter. In this alternative, the range of spiral or braided wire incorporated into the catheter is that required to achieve the proper ion release volume as determined by the factors set forth above regarding the patient profile, any infections affecting the patient, and other medications being administered to the patient.The basic design of this embodiment of the invention allows the catheter to be inserted with a helical or mesh-wound metal wire as part of its structure, allowing the catheter to have the flexibility required to allow it to be inserted into the venous system. Additionally, the catheter has sufficient metal exposed to achieve the desired volume and rate of metal ion release for the treatment of blood-borne infections. Additionally, the catheter has a connection point at its proximal end for connecting a source of low intensity direct current, such as a generator, to the catheter so that when a current is applied, metal ions are released for dispersion into the venous system. Additionally, such catheters, single or multi-lumen, have a connection to an external intravenous antibiotic or treatment bag so that a desired solution can be administered through its internal lumen and flushed directly into the venous system. Such a combination catheter according to the invention allows for simultaneous metal ion release and administration of intravenous antibiotics, antivirals, or antifungals for the treatment of the above-mentioned blood-borne pathogen infections. Typically, the diameter of the helically wound or braided wire ranges in size from about 0.001" (0.00254 cm) to about 0.020" (0.0508 cm).

[0132] Power supplies used to provide low intensity DC typically include a clamp to regulate the input voltage, a regulator to regulate the actual current flowing to the control board (printed circuit board (PCB)) and prevent excessive voltage or current from flowing to the control board for the purpose of protecting the control board, and output current and output voltage regulators to protect the electrodes and to prevent excessive ion release by the electrodes in order to provide optimal therapeutic effect and protect the patient from excessive current.

[0133] The goal of the present invention is to combine multiple techniques to allow the use of the device and method according to the present invention to treat infections caused by more types of pathogens. The above-mentioned alternatives allow the user of the present invention to customize the iontophoretic release of metal ions to one or more target pathogens, taking into account other factors such as the age, weight, and sex of the patient, the severity of one or more infections, or pharmacokinetic requirements that affect other drugs administered simultaneously with the use of the device and method according to the present invention. This combination also reduces the manufacturing costs of the electrodes, thereby making the treatment more accessible. Similarly, this combination provides a wider therapeutic window for the treatment. Furthermore, this combination makes the placement of the electrodes safer and more comfortable for the patient. Furthermore, this combination makes the use of the device less invasive for the patient.

[0134] Figure 2 is a front view of another embodiment of a device according to the invention for killing bacteria, viruses, or fungi in blood, modulating the immune system, or creating a zone of inhibition to prevent bacterial growth on a catheter or bacterial infection at a catheter puncture site. The device 40 includes a wire 42 similar to that of Figure 1, an insulating covering 44 similar to that of Figure 1, a copper pin 46 or a pin of another conductive material, male luer lock or other connector 48, similar to that of Figure 1, a female luer lock or other connector 50, and optionally a side port 52 for administration of intravenous antibiotics or other desired medications. The copper pin or pin of another conductive material can be replaced by a heat shrink connector incorporating a circular solder ring as described above.

[0135] FIG. 3 is a front view (top panel) and a side view (bottom panel) of another embodiment of a device according to the invention showing insertion of the device into a patient's arm. In the top panel, the device 100 includes a wire 102 similar to that of FIGS. 1 and 2, illustrating how the length of the wire 102 that is not covered by the insulating covering 104 can vary. In a preferred embodiment, the length of the wire 102 that is not covered by the insulating covering 104 can vary from about 0.1″ (0.254 cm) to about 1.0″ (2.54 cm). In FIG. 3, a luer lock or other connector 106 is connected to an electrode 108. The electrode 108 rests on the patient's skin, while the insulating covering 104 and wire 102 are inserted into the patient's vein, such that the voltage and current delivered to the wire 102 can be electrically controlled to release metal ions as described above to kill blood-borne pathogens. The width of the wire 102 and insulating covering 104 can vary. A typical range is from about 0.005" (0.127 cm) to about 0.025" (0.635 cm), although preferred embodiments require an insulation of about 0.010" (0.254 cm). The device of FIG. 3 further includes a male luer lock or other connector 110, a female luer lock or other connector 112, and optionally a side port 114 for administration of intravenous antibiotics or other desired medications.

[0136] As can be seen from Figure 3, introduction of metal ions by insertion of a wire into a patient's venous system is superior to the prior art because the prior art methods of intravenous infusion and iontophoretic release through pads attached to the skin do not generate enough ions, nor do they place the ions in a large enough volume into the venous system, to be effective in denaturing, destroying or otherwise inactivating the targeted bloodborne pathogens. Thus, the introduction of metal ions by insertion of a wire into a patient's venous system is superior to the prior art methods because the prior art methods of intravenous infusion and iontophoretic release through pads attached to the skin do not generate enough ions, nor place the ions in a large enough volume into the venous system ... 9 It is necessary to generate ions directly within the venous system that will penetrate the bloodstream.

[0137] Research by the inventors has shown that, especially for certain pathogens, the time required for treatment may be longer than 1-2 days, and that having ion release within the chest area can be superior and faster for treatments requiring longer periods of time. To facilitate this method of treatment, the device and method according to the invention may rely on a peripherally inserted central catheter (PICC). The use of a PICC requires the device user to measure the proper length required for the patient and cut the PICC to the proper length during placement, and therefore the electrodes must also be modified.

[0138] The inventors have also found that theory aside, the actual ion release volume per unit is important to the success of the treatment obtained. Metal ions, such as but not limited to gold, silver, or copper, have a short lifespan within the body and venous system. After a short period of time, these metal ion changes are neutralized and then filtered out of the body. It is therefore important to reach a certain level of metal ion concentration to have the highest efficiency in treating the target pathogen, and therefore, approximately 2×10 9 From 7×10 / sec 12 A constant iontophoretic release rate of metal ions in the range of particles / second is preferred.

[0139] Using a range of wire diameters, various lengths of bare wire, annealed wire, and the required ion volume to provide adequate iontophoretic release of metal cations according to the variables noted, an output current from the device within about 1.25 μA to about 6.0 μA is optimal for release of metal cations for the treatment of blood borne pathogens. Preferably, the current is about 4.9 μA.

[0140] FIG. 4 is a series of front views of a device 140 for treating blood-borne pathogens in blood, activating the immune system, or creating a zone of inhibition to prevent bacterial growth on a catheter or bacterial infection at a catheter puncture site. The device 140 comprises a wire 142 and an insulating covering 144. FIG. 4 illustrates how the length of the wire 142 and insulating covering 144 can be varied. FIG. 4 also illustrates that when the wire 142 is completely covered by the insulating covering 144 and dome-shaped cap 148 except for one or more notches 146, the length of the exposed wire can be equal to the exposed wire when the wire is allowed to trail from the end of the insulating covering 144. This figure also illustrates some alternative lengths of the insulating covering 144 and wire 142 for various end uses. The device of FIG. 4 further comprises a male luer lock or other connector 150 and a female luer lock or other connector 152. The device of FIG. 4 may optionally further include a side port 154 for administration of intravenous antibiotics or other desired medications.

[0141] 5 is a series of front views of a device for killing antibiotic resistant bacteria or other blood borne pathogens, activating the immune system, or creating a zone of inhibition to prevent bacterial growth on a catheter or bacterial infection at a catheter puncture site in accordance with the present invention. In FIG. 5, device 200 includes a wire 202 wrapped or braided around a catheter 204, with the entire unit being inserted into the patient's bloodstream. Each end of wire 202 is connected to a cap connector 206, which in turn is connected to a power source as described above that controls the energization of wire 202, such as for the release of metal ions to perform therapy.

[0142] 6 is a series of front views of a device for killing antibiotic resistant bacteria or other blood borne pathogens, activating the immune system, or creating a zone of inhibition to prevent bacterial growth on a catheter or bacterial infection at a catheter puncture site according to the present invention. FIG. 6 provides a detailed view of some of the device 240 according to the present invention in which an insulating covering 244 covers the entire wire 242 except for one or more notches 246. Further, the wire 242 is retained within the insulating covering 244 by a dome-shaped cap 248 that seals the open end of the insulating covering 244.

[0143] 7 is a series of front views of a device according to the present invention mounted on a catheter that is inserted into a patient's vein. The device 300 includes a wire 302 that is inserted into the patient's vein and protected by an insulating covering 304. A cap connector 306, a male luer lock or other connector 308, and a female luer lock or other connector 310 protect a copper pin 312 or a pin of another conductive material for connection to a power source as described above. The insulating covering 304 may include one or more cutouts 314 and may be secured by a dome-shaped cap 316. The device 300 is mounted within a catheter 318. The device 300 may further include a side port 320 for administration of intravenous antibiotics or other desired medications.

[0144] 8 is a series of front views of a PICC device according to the present invention. In this embodiment of the invention, the device 340 has wires 342 surrounded by an insulating covering 344. The insulating covering 344 extends all the way to a dome-shaped cap 346. One or more cutouts 348 provide access for the wires 342 to the patient's bloodstream. The device 340 further has a male luer lock or other connector 350 and a female luer lock or other connector 352 that protect a copper pin 354 or a pin of another conductive material. Optionally, the device can have a side port 356 for administration of intravenous antibiotics or other desired medications. Typically, the device is in the form of a single lumen catheter such that intravenous antibiotics or other desired medications can be administered through the side port 356. The insulating covering 344, which can be incorporated into the catheter, is larger in diameter than the wires 342 and is typically tapered for the distal end that is inserted into the patient's vein. The side port 356 can be valved or covered.

[0145] 9 is a series of frontal views of an auxiliary lumen catheter for dual drug therapy according to the present invention. The auxiliary lumen catheter 400 has a hemostatic seal or side port hemostatic valve 402 attached to close the space around it. There is a side port 404 to allow for administration of intravenous antibiotics or other desired medications. The inner diameter of the catheter 400 is larger than the outer diameter of the inserted electrode (not shown) so that anything added through the side port 404 will easily flow into the patient's bloodstream. This alternative of the claimed device according to the present invention can be used for treatment of blood borne pathogens in the blood, to activate the immune system, or to create a zone of inhibition that prevents bacterial growth on the catheter or bacterial infection at the catheter puncture site.

[0146] A particularly preferred embodiment of the present invention is described below. This particularly preferred embodiment comprises: (1) a catheter that is inserted into a patient's vein and extends at least about 0.5" (1.27 cm) beyond the tip of the introducer needle and introducer catheter, has a length between about 0.2" (0.508 cm) and about 1.0" (2.54 cm), and has a diameter of about 0.005 square inches (0.0322 cm); 2 ) and approximately 0.70 square inches (4.52 cm 2 iontophoresis wire including one or more electrodes comprising a vein portion having an area between the vein portion and the vein portion, and an outer surface portion positioned outside the patient's vein; (2) an outer insulator that insulates the exterior surface of the electrode so that ions are not released anywhere other than at the intended release point located inside the patient's vein, the outer insulator being an FDA approved material selected from the group consisting of synthetic and plastic materials, the outer insulator having a durometer hardness low enough so that the outer insulator is flexible enough to be safely placed within the patient's venous system without causing significant irritation; (3) a transformer intended to provide low intensity direct current, the transformer including one or more resistors and converters, the transformer being in electrical contact with the iontophoretic wire; and (4) A power source in electrical connection with a transformer; a device for treating blood borne pathogens in a patient's bloodstream comprising: 9 ions are generated.

[0147] The metal comprising electrode(s) may be as described above.

[0148] In another alternative, the electrode is a two-part electrode having a first electrode part and a second electrode part. The first electrode part is a proximal end unit containing a conductive pin, the conductive pin comprising copper or another conductive material. The conductive pin is held in a luer lock or other connector. The conductive pin allows for the transfer of low intensity direct current from a power source to the iontophoretic wire. The conductive pin can be clamped onto the second electrode part by use of a clamping device. The second electrode part has a length of exposed wire at the distal end of the exposed wire.

[0149] Alternatively, the pins of conductive material, typically copper, can be replaced with heat shrink connectors incorporating circular solder rings as described above.

[0150] In alternative embodiments, the fastening device may be a set screw or a sufficient amount of biocompatible conductive adhesive, such as that described in U.S. Patent No. 8,660,645 to Stevenson et al.

[0151] In other alternative embodiments, the segment of exposed wire at the distal end is a bare wire, such as, but not limited to, a silver wire or a window milled to expose the wire.

[0152] In yet another alternative embodiment, the wire may be tempered and / or annealed to achieve the proper ion release and safety of the wire for use within the venous system.

[0153] In yet another alternative embodiment, the device according to the invention may include a combination catheter for dual drug therapy, which allows for the simultaneous release of metal ions in an amount sufficient to treat blood-borne pathogens and the administration of an amount of another intravenous drug, such as an antibiotic, another antibacterial drug that may be administered intravenously, an antiviral drug that may be administered intravenously, or an antifungal drug that may be administered intravenously. The metal ions and additional intravenous drug are administered to treat blood-borne pathogens, such as, but not limited to, antibiotic-resistant bacteria. In these alternative embodiments, the gauge of the device typically ranges from 12 gauge to 26 gauge for proper introduction of electrodes. This catheter size range allows for electrodes of various diameters to be inserted into the patient's bloodstream. This catheter size range provides for various electrode diameters to treat a variety of patients, including both adolescents and adults. The device includes an intravenous connection that allows a universal connector similar to those conventionally used in the art to accept multiple available intravenous connection systems. In this alternative, the exterior surface of the catheter comprises a helically wound metal wire, such as, but not limited to, a silver wire, where the exposed helical wire has a length ranging from about 0.5" (1.27 cm) to about 2.0" (2.54 cm) and a helical diameter ranging from about 0.001" (0.00254 cm) to about 0.1" (0.254 cm). The inner diameter of the catheter is larger than the outer diameter of the inserted electrode, allowing additional intravenous medications, such as antibiotics, as discussed above, to easily flow along and around the electrode and thus into the patient's bloodstream.

[0154] Figure 10 is an illustration of several catheter designs with an "inhibition zone" that delivers positively charged ions to stimulate the immune system to kill pathogens in the blood. Figure 10A has an external spiral wound wiring. Figure 10B has an internal spiral wound wiring. Figure 10C has a straight longitudinal wiring with 3 to 5 wires that are either internally exposed, externally exposed, or both internally and externally exposed. Figure 10D is an end view of the catheter of Figure 10C illustrating two alternatives (exposed externally on the top row, exposed internally on the bottom row). FIG. 10E has rings at the distal end, proximal end, or both, where all rings can be anodes, or anodes and cathodes can alternate every other ring, or the catheter can be used with an external catheter cathode as used for EKG pathways; FIG. 10F has a hexagonal design on the proximal outer surface and distal inner or outer surface or on the proximal inner and distal inner or outer surfaces at the distal, proximal, or both, where a cathode is added externally as used for EKG pathways; FIG. 10G has periodic exposed sections from the proximal to distal end or only at the distal end, with lengths of 1 mm to 10 mm and windows with 35° to 180° exposure; and FIG. 10H illustrates end views of (i) an arrangement with three 30° windows and (ii) an arrangement with one 180° window.

[0155] In the catheter design shown in FIG. 10A, a catheter 500 has a wider proximal section 502 and a narrower distal section 504, wrapped with a helically wound wiring 506.

[0156] In the catheter design shown in FIG. 10B, a catheter 510 has a wider proximal section 512 and a narrower distal section 514 and includes an internal spirally wound wiring 516.

[0157] In the catheter design shown in FIG. 10C, the catheter 520 has a wider proximal section 522 and a narrower distal section 524, and includes wiring 526 that is either internally exposed, externally exposed, or both internally and externally exposed.

[0158] In the catheter design shown in FIG. 10D, which is an end view of the catheter design shown in FIG. 10C, the top panel shows externally exposed wires 526, whereas the bottom panel illustrates internally exposed wires 526.

[0159] 10E, a catheter 530 has a wider proximal section 532 and a narrower distal section 534 and includes rings 536. The rings 536 can be located in the proximal section 532, the distal section 534, or both the proximal section 532 and the distal section 534. The rings 536 can be anodes for all rings or can alternate between anode and cathode, or can alternatively include an external catheter cathode such as an EKG patch.

[0160] In the catheter design shown in Figure 10F, a catheter 540 has a wider proximal section 542 and a narrower distal section 544 and includes wires 546 arranged in a hexagonal pattern. The wires 546 can be located on the exterior surface of the proximal section 542 and either the exterior or interior surface of the distal section 544, or alternatively, the interior surface of the proximal section 542 and either the exterior or interior surface of the distal section 544. As with the catheter design shown in Figure 10E, an external catheter cathode, such as an EKG patch, can alternatively be included.

[0161] In the catheter design shown in FIG. 10G, the catheter 550 has a wider proximal section 552 and a narrower distal section 554, and includes wiring 556 with periodic exposed wire sections either from the proximal end to the distal end or only at the distal end, providing a window of 1 mm to 10 mm in length and 30° to 180° exposure.

[0162] In the catheter design shown in FIG. 10H, which is an end view of the catheter design shown in FIG. 10E, the left panel shows a wiring 556 with three 30° windows, while the right panel illustrates a wiring 556 with one 180° window.

[0163] Figure 11 illustrates alternatives for the design of catheters according to the invention using either single or multiple lumen designs that could be intended for either peripheral, central, midline, or PICC insertion: Figure 11A shows (i) a side view of a dual lumen with a metal alloy embedded in the catheter with a window milled at the distal end for (A) creating an inhibitory (antimicrobial activity) zone, and (B) ion release utilizing an external cathode as used in EKG pathways to release positively charged ions (cations) to stimulate the immune system, and (ii) an end view of the single lumen and electrodes, and Figure 11B illustrates an end view of a similar multiple lumen catheter.

[0164] Figure 11A illustrates a side view of a catheter 580 having a wider proximal section 582 and a narrower distal section 584, with a window 586 machined at the distal end, and with a dual lumen 588 having a hollow section 590 and a metal alloy 592. Figure 11B is an end view of the catheter of Figure 11A.

[0165] 11C is an end view of a similar multi-lumen catheter having two open lumens and one lumen for the insertion of a metal alloy. Catheter 600 has a first open lumen 602, a second open lumen 604, and a third lumen 606 for the insertion of a metal alloy 608.

[0166] Figure 12 is a schematic diagram of a wound care bandage or burn protectant bandage, also referred to as a patch, according to the present invention. Figure 12A illustrates a patch incorporating an ion-emitting metal alloy, as described in more detail below, on the skin side (the side that comes into contact with the skin) of a patch of variable size for application to an area of ​​skin. The ion-emitting metal alloy accepts electrical current when connected to a low intensity direct current generator, as described in more detail below. Figure 12B illustrates the bottom side of the wound care bandage or burn protectant bandage with the incorporated ion-emitting metal alloy representing the cathode and anode.

[0167] 12A, patch 620 has a top side 622 and a bottom side 624. Attached to top side 622 is a snap connector 626 that is connected to a wire 628 that is connected to a power source 630 to provide low intensity direct current to patch 620.

[0168] In FIG. 12B, the bottom side 624 of the patch has a medical coating incorporating a metal alloy 632 that releases metal ions as described above when a low intensity direct current is applied to the metal alloy. The metal alloy has a cathode 634 and an anode 636. The material to be used on the skin side of the patch is typically a hydrogel. A hydrogel is a network of hydrophilic cross-linked polymer chains that are sometimes seen as colloidal gels in which water is the dispersion medium. The hydrophilic polymer chains are held together by cross-links resulting in a three-dimensional solid. The cross-links that connect the polymers of a hydrogel belong to two basic categories: physical and chemical. Physical cross-links consist of hydrogen bonds, hydrophobic interactions, and chain entanglements (among others). Due to the intrinsic cross-links, the structural integrity of the hydrogel network does not disappear as a result of high water concentrations. Hydrogels are highly absorbent (can contain more than 90% water) natural or synthetic polymer networks. Other alternatives for the materials used on the skin side of the patch can be used and are known in the art.

[0169] FIG. 13 illustrates an alternative embodiment of the present invention for incorporation into an intravenous line or other device intended to supply fluids, such as, but not limited to, plasma, medicines, nutritional supplements, or electrolytes, to a patient.

[0170] In FIG. 13, device 650 has a hub cap 652 for covering the device. Located within device 650 are a cell battery 654 and a printed circuit board 656 for controlling current output. Additionally, device 650 includes a cathode wire 658 and an anode wire 660. Cathode wire 658 is in electrical contact with fluid absorbing material 662, which is also in electrical contact with anode wire 660, providing an electrical circuit when fluid flows through device 650. Additionally, device 650 includes a first connector 664 and a second connector 666, illustrated in FIG. 13 as "X" and "Y", that allow device 650 to be placed into an intravenous line or other device to deliver fluid to a patient as described above. First connector 664 and second connector 666 can be female or male luer locks, intravenous hose clamps, intravenous hose connectors, or other connectors conventionally used in the art. The first connector 664 and the second connector 666 are joined by an anode metal pin 668 and a cathode metal pin 670 .

[0171] Another version of the device described above is shown in FIG. 14. This version of the device has the device attached to a fluid source that allows for the generation of metal ions without the insertion of the device into an IV line. In the version of the device shown in FIG. 14, the device 700 has a hub cap 702 for covering the device. Located within the device 700 are a cell battery 704 and a printed circuit board 706 for controlling the current output. The device 700 further comprises a cathode wire 708 and an anode wire 710. The cathode wire 708 is in electrical contact with a fluid absorbing material 712, which is also in electrical contact with the anode wire 710, providing an electrical circuit when fluid flows through the device 700. The device 700 further comprises a solid cap 714 and a connector 716. The connector 716 is connected to a fluid source 718. The fluid source 718 provides distilled water, saline, or another biocompatible aqueous solution to allow the device 700 to generate metal ions. The solid cap 714 and the connector 716 are joined by an anode metal pin 720 and a cathode metal pin 722 .

[0172] Yet another embodiment of a device according to the invention is shown in Figure 15. The device of Figure 15 is intended for delivery of metal ions into a patient's veins as described above through a temporarily implanted stylet or catheter.

[0173] In the version of the device shown in FIG. 15 , the device 740 includes a generator 742 that is attached to the patient's skin. The generator 742 transmits an electrical current through an implantable stylet 744, and wires 746 generate the metal ions as described above. Typically, the implantable stylet 744 is implanted in a patient's vein, such as in the patient's arm. Instead of a cable providing an electrical current from the generator 742 to the stylet 744, typically the generator 742 is attached to the patient's skin and transmits a signal through the skin to the implantable stylet 744, which will activate the release of the metal ions.

[0174] Yet another embodiment of a device according to the present invention is shown in Figure 16. The device of Figure 16 is a chewable gum that continuously releases silver or metal ions that can be rapidly absorbed orally into the bloodstream for health reasons or to provide a nutritional supplement.

[0175] In the device of Figure 16, the device 760 comprises a chewable gum wafer or layer 762 incorporating particles of the metal or metal alloy described above, which are released upon chewing by the hydrolytic action of saliva allowing the particles to be released so that they are absorbed into the bloodstream and ions are released for therapeutic or immune stimulating activity.

[0176] Yet another embodiment of the device according to the invention is shown in FIG. 17. In the device of FIG. 17, the catheter can be a single lumen or multi-lumen catheter that can be used in conjunction with the generator described above or can be used as a device to provide intravenous fluids with the release of metal ions when stimulated by the generator described above. The premise behind this embodiment is that a cathode with 1 to 5 rings is fabricated into the catheter so that no external add-on patch is needed to complete the circuit with the generator. This provides a more consistent resistance and ensures a more consistent voltage delivery from the generator. In this alternative, the anode is constituted by a stylet that is inserted into the venous system through the catheter. In this alternative, there is a metal ring fabricated into the catheter and attached to a surface point at the proximal end of the catheter. There is a metal surface area in the connector hub of the anode stylet that makes electrical contact with the catheter cathode to complete the circuit when the stylet is locked through this connector.

[0177] In the device of Figure 17, device 800 includes a catheter 802 having an internally extending wire 804 and one to five external conductive rings 806. Additionally, device 800 includes an insulated wire 808 constructed from a metal or metal alloy as described above. The device further includes a connector 810 in operative contact with the catheter, optionally having a side port 812 for administration of intravenous antibiotics or other desired medication. Inside connector 810 is a wire 814 for connection to a generator. Although device 800 is shown in the context of a single lumen catheter, dual lumen or multiple lumen catheters could alternatively be used.

[0178] In the device according to the invention, the metal alloys described above can be incorporated into a catheter in some alternative manner: The catheter can be a central venous catheter, a hemodialysis central venous catheter, a peripheral catheter, a PICC (peripherally inserted central catheter), a midline catheter, a urinary catheter, or a drainage catheter. Alternatives are: (1) wires that are exposed both internally and / or externally; (2) wires that are wrapped internally and / or externally through the catheter; (3) wires that run the length of the catheter internally and / or externally; (4) wires that are exposed internally and / or externally only at the distal tip of the catheter; (5) wires that are exposed internally and / or externally only at the surface of the skin; (6) wires that are exposed in multiple locations; (7) wires that are placed in a cuff that is placed on the catheter and slide but does not extend into the insertion site for the catheter to protect the puncture site; (8) wires that are arranged in rings or bands at periodic intervals along the length of the catheter; (9) wires that are helically wrapped internally and / or externally in a hexagonal design; or (10) wires that are arranged so that they are exposed periodically along the length of the catheter.

[0179] Other alternatives for devices according to the present invention include: (1) a catheter with an exterior wrapped in wire to control the release of metal ions; and (2) a coated catheter in which the conductive material has metal particles therein (such as, but not limited to, silver particles) arranged such that when an electrical current is passed through the coated catheter, the catheter releases metal ions (such as, but not limited to, silver ions).

[0180] In the device and method according to the present invention, the metal ion that can be released by the device and used in the method is typically an ion of copper, silver, gold, platinum, iridium, tin, osmium, palladium, or osmium. When the metal ion is a copper ion, the ion can have an oxidation state of +1 (cuprous ion) or +2 (cupric ion). When the metal ion is a silver ion, the ion can have an oxidation state of +1, +2, or +3, typically having an oxidation state of +1. When the metal ion is a gold ion, the ion can have an oxidation state of +1, +2, +3, or +5, typically having an oxidation state of +1 or +3. When the metal ion is a platinum ion, the ion can have an oxidation state of +1, +2, +3, or +4, typically having an oxidation state of +1 or +3. When the metal ion is an iridium ion, the ion can have an oxidation state of +1, +2, +3, +4, +5, +6, +7, +8, or +9, typically having an oxidation state of +3 or +4. When the metal ion is a tin ion, the ion can have an oxidation state of +2 or +4. When the metal ion is a palladium ion, the ion can have an oxidation state of +2, +3, or +4, typically having an oxidation state of +2. When the metal ion is an osmium ion, the ion can have an oxidation state of +1, +2, +3, +4, +5, +6, +7, or +8, typically having an oxidation state of +2, +3, +4, or +8.

[0181] In the methods and devices according to the invention, the voltage applied to generate metal ions is typically about 1.2 V or less. Preferably, the applied voltage is about 0.5 V to about 0.92 V. The applied voltage depends on the tissue resistance. Typically, the tissue resistance is about 5×10 4 ohms to about 3 x 10 5 Ohms, more commonly around 1×10 5 ohms to about 2 x 10 5 The output current is about 1.25 μA. For most applications, it is important to keep the voltage applied to generate metal ions below about 1.2 V, as voltages above this range tend to cause the generated ions to combine with chloride in the bloodstream, resulting in the formation of particles that lack therapeutic value.

[0182] In the device according to the invention described above, typically the generator or other power source has the ability to adjust the current based on the therapeutic application. As described in detail below, the current can be held constant, or alternatively the voltage can be held constant. The device can automatically hold the current constant. The firmware uses Ohm's law to maintain the current at, for example, 4.9 μA, but if the body resistance, typically less than about 200 kΩ, increases to a value that would require the output voltage to be higher than 0.87 V, 0.89 V, or 0.92 V to maintain the current value described above, the device will hold the output voltage at 0.87 V, 0.89 V, or 0.92 V, and will reduce the output current depending on this resistance, thereby allowing the treatment to remain constant at a lower output current and therefore a lower ion release rate.

[0183] In the device according to the invention described above, typically the device has wireless communication capability with a smartphone using an NFC connection. NFC is a set of communication protocols for communication between two electronic devices across distances of about 4 cm (1.5 inches) or less. NFC provides a low-speed connection with simple configuration. NFC is standardized in ECMA-340 and ISO / IEC 10892. Alternatively, the NFC connection can be replaced with a PCB modem that will be operated on a cellular service to allow both incoming and outgoing external communication. NFC allows a smartphone device to approach the device to upload or download data, change program parameters, and activate and start a therapy session. In another alternative, it is believed that communication can be through Bluetooth. Other alternatives for communication are known in the art.

[0184] In the device according to the invention described above, typically the device also has the capability of wireless communication using a cellular telephone system to download and upload data, firmware, or other information. The firmware can be programmed to control or adjust the pulse, frequency, current, voltage, vibration pattern, burst, or variable time for administration of therapeutic ions to the patient. Information that can be downloaded to the device for modification of the device's functionality can include, but is not limited to, the patient's age, the patient's race (especially if related to susceptibility to a particular disease or condition), the patient's weight, genetic information such as HLA haplotype that may affect the patient's sensitivity to a particular infectious agent, and the patient's relevant medical history such as onset of diabetes, onset of hypertension, tobacco smoking history, alcohol consumption history, or other relevant medical history that may affect sensitivity to a particular disease or condition, as well as the specific disease or condition to be treated or prevented by use of the device according to the invention, such as, but not limited to, stimulation of white blood cells to improve immune response, for example, severe acute respiratory syndrome coronavirus 2, infection, HIV infection, hepatitis A infection, hepatitis B infection, hepatitis C infection, dengue virus infection, Zika virus infection, bacterial infection, or fungal infection. This data transfer is fully HIPAA compliant such that no personal information is collected or stored that would allow anyone using or otherwise working with the device to identify a particular patient. The relevant information described above would be entered prior to starting the unit so that the unit stores the average voltage, current, and resistance, as well as the length of treatment, for a unit session. The relevant information is typically entered via an NFC connection, although other connection paths may alternatively be used as described herein. This input is used to initiate operation of the device.Following use of the unit, the unit will upload all stored data from the session to a central server, allowing an operator at the central server to collect a great deal of comprehensive data from the use of the device and determine device usage, including disease, pathology, or other symptoms being treated, outcomes, and other information that would allow validation and possible correction of the technology of the present invention. Again, this information transfer will be HIPAA compliant with respect to collection of data such as age, sex, race, pathogen being treated, parameters that should be correlated as far as necessary with actual treatment time, resistance over that period, voltage, and current to determine discernible trends regarding possible differences in pathogenicity and types of individuals being treated with the device. This information can be used to improve treatment efficiency and outcomes, and will be anonymized so that an individual cannot be determined as a result of transmission, analysis, or other use of the data. Typically, the device will include firmware that controls or fixes the output amperage while allowing the resistance to control the output voltage until or when the resistance reaches a point that is expected based on Ohm's law to increase the output current to greater than the maximum allowable output current, locks in the maximum output voltage at this point, and then pulls the output current down based on the resistance. At a particular point, under the control of the device operator, an alarm can be issued to notify the patient or clinician that the resistance is too high and the output current has reached a low setting, i.e., optimal ion release for therapeutic action is not occurring at this point.

[0185] In another alternative, a device according to the present invention may be portable.

[0186] In the device according to the invention described above, typically the device further has the capability of providing various waveforms or vibration signals or pulse signals. For the signal pulses, preferably the pulse rate is fast enough that the central nervous system (CNS) or peripheral nervous system (PNS) does not recognize the pulse. Preferably the pulse rate is also fast enough to reduce or eliminate the risk of thrombus formation. In another alternative, a burst waveform can be used. In yet another alternative, an oscillatory waveform can be used. In yet another alternative, the current used can be a rising current or a timed current. Typically, when pulses are used, the pulse rate is fast enough that the central nervous system (CNS) or peripheral nervous system (PNS) does not recognize the pulse, and is also fast enough to inhibit thrombus formation. Typically, the pulse width ranges from about 50 microseconds to about 1000 microseconds. When burst waveforms are used, a combination of multiple pulses is combined with multiple frequencies in rapid succession to stimulate the immune system. An example would be five 1 microsecond pulses with 1 microsecond pulse intervals at 500 Hz applied at a frequency of 40 Hz with passive regeneration of charge balance at the end of the pulse burst. The frequency used can range from about 40 Hz to a maximum of about 10 kHz. Typically, a frequency of about 10 kHz is preferred over background currents to facilitate blood flow and reduce the risk of phlebitis, and also to promote intravenous dispersion of ionic signals. When an oscillatory waveform is used, the temporal current application pattern is similar to that described above for the burst waveform, but can further include current intensity variations to modify the stimulation pattern. An example would be an oscillatory current of 3.0 μA to 4.9 μA for a specified period, then oscillating from 1.5 μA to 3.0 μA for the remaining time. This oscillatory current could be used for nighttime treatment, where a lower oscillatory current (maximum 3.0 μA) should be used, for example, in the evening or when the patient is considered to be in a sleep state. In one alternative, oscillating for a period of 16 hours followed by an 8-hour oscillation setting would be optimal. When a rising edge or timed waveform is used, the current is gradually increased linearly and then decreased linearly to control the delivered current.Typically, this occurs over a period of about 5 to about 10 seconds. For example, it is contemplated that 5 to 10 seconds could be used to ramp up to maximum power, and then 5 to 10 seconds could be used to ramp down. Typically, these alternatives would be programmable by a technician or other operator to optimize the therapeutic effect. Other alternatives to the use of leading edge or timed waveforms can be used.

[0187] In some alternatives according to the present invention, the system is programmable and various settings for current application can be programmed, such as, but not limited to, time of day, body position, application site, age, sex, and weight of the patient, the particular disease or condition being treated, its severity, other conditions affecting the patient, or other factors.

[0188] In one alternative, the system provides a constant current with a voltage upper limit. This means that the system will maintain a set constant current output unless the impedance of the system reaches a point where the voltage upper limit is reached. Once the voltage limit is reached, the system will reduce the output current or allow the output current to drop so as not to exceed the set upper limit voltage.

[0189] In another alternative, the system fixes the output voltage to a value between about 0.55V and about 0.95V. Preferably, in this alternative, the output voltage is fixed at about 0.92V, and in some alternatives, a fixed output voltage of 0.87V or 0.89V can be used. The initial output current is about 6μA or less, typically about 4.9μA. When the resistance increases to the point where the voltage requires more than about 0.95V, the voltage is limited and the output current is reduced to maintain the output voltage at a value below about 0.95V, preferably about 0.92V.

[0190] In yet another alternative, a second high frequency background signal is introduced that overlaps with the constant current with a voltage upper limit to facilitate blood flow and ion dispersion and reduce the risk of phlebitis. The frequency of the high frequency background signal is as described above.

[0191] Another embodiment of the invention is a miniature metal ion generator for generating solutions containing metal ions for various purposes including treating or preventing bacterial, viral or fungal infections, stimulating an immune response, or providing an inhibition zone around a catheter placement location to prevent the development of microbial biofilms or infection from a puncture site. The device incorporates a stationary miniature cell battery mounted on a miniature printed circuit board that controls both the output voltage and the output current to one or more permanently attached metal or metal alloy anodes and a single cathode. One to four anodes can be attached. The cathode is covered with a sponge-like material such as Porex manufactured by Porex Filtration Group (Fairburn, GA, USA). The generator has a twist connector around the open end of the exposed anode and coated cathode that allows for the placement of various accessories that will hold the fluid that will be treated with the generated metal ions. When a fluid-containing container is contacted with the metal ion generator, the fluid will complete the contact between the anode and cathode, allowing for the controlled release of metal ions into the fluid, generating an antibacterial solution that can be used for various purposes. These purposes include, but are not limited to, applying the solution to the skin for the treatment of conditions such as acne, the solution can be administered by nebulizer for nasal or pulmonary treatment, or the solution can be swallowed or used as a mouthwash. The antibacterial solution can be used for several other applications. Typically in this device, the battery is a 1.5V to 3.5V lithium cell battery. The dimensions of the battery typically range from about 0.5cm to about 3.0cm in diameter. The printed circuit board is 5cm 2 The printed circuit board functions similarly to that described above, typically producing a fixed drain current of 4.9 μA with an upper limit of 0.92 V, with some alternatives using voltages of 0.87 V or 0.89 V. Other alternatives for current and voltage are possible.

[0192] Another embodiment of the present invention is a battery-powered reusable or disposable device used to provide a constant current and upper voltage limit to a component such as the stylet of FIG. 14 described above to control the continuous release of metal ions. The metal ions triggered for release by the battery-powered device can be generated from alloys or pure metals as described above. The controlled current is preferably within the range of about 1.5 μA to about 10 μA, more preferably within the range of about 1.5 μA to about 6 μA, even more preferably within the range of about 1.5 μA to about 5 μA, and most preferably about 4.9 μA. This range will ensure that only ions and not larger particles are generated by the current. The upper voltage limit is preferably less than about 1.2 V, more preferably about 0.92 V, although other voltages can be used. This battery-powered device has a single female plug connector that provides current to the anode, typically the stylet described above acting as the anode, and a metal alloy and a female snap connector to a cathode EKG-type pad for return of the supplied current complete the circuit. Alternatively, the stylet may have a direct wire connection to the metal inside it. The battery powered device provides standard EKG electrodes. The battery powered device has the ability to adjust the constant current output based on input from the therapist as described above. The battery powered device also has the ability to wirelessly communicate with a smart phone using an NFC connection as described above. Additionally, the battery powered device has the ability to wirelessly communicate with a cellular phone system to download or upload data or firmware as described above. Additionally, the battery powered device has the ability to provide various current levels, voltage levels, waveforms, or vibration or pulse signals as described above.

[0193] In an alternative embodiment of the invention using a stylet such as, but not limited to, those described in Figure 14 or Figure 15, the device may further comprise a needleless injector stylet to allow for injection of fluids such as heparin by placement of a catheter and stylet for longer administration times and / or when the patient has high levels of vitamin D in the blood. A needleless injector stylet is shown in Figure 18.

[0194] 18, needle-free injector stylet 840 has a proximal end 842 for connection to a fluid containing device such as those typically used for fluid delivery and injection, and a distal end 844 for insertion into a vein 846. Vein 846 is not part of the needle-free injector stylet.

[0195] Yet another embodiment of a device according to the present invention is shown in FIG. 19, which is an illustration of yet another alternative of a device according to the present invention incorporating a dual or multi-lumen catheter for fluid delivery using a secondary lumen, an injection side port, and a hemostatic seal to prevent backflow of blood from the secondary lumen of the dual or multi-lumen catheter.

[0196] In the device of FIG. 19, the device uses a dual or multi-lumen catheter, where the primary lumen will provide intravenous fluids and the secondary lumen will house or incorporate a stylet connected to a wire made of the metal or metal alloy described above for sustained release of ions generated by a voltage provided by the power source described above. The stylet is fabricated into the catheter and held in a predetermined position by a red pull tab or removable spacer, which when removed, allows the user of the device to move the stylet forward to expose a wire made of a metal or metal alloy, which when connected to the power source described above, can provide a consistent and sustained release of ions for the treatment of bacterial, viral, fungal, or protozoal infections, can activate an immune response, or provide an inhibition zone around the catheter placement location to prevent the development of microbial biofilms or infection from the puncture site. This alternative allows for a more consistent, safe and effective design than existing catheters that have coatings containing antimicrobial metals for antimicrobial protection. The design key points for this alternative are (i) a molded stylet, (ii) a removable spacer that holds the stylet in a predetermined position and allows the introducer needle to position the catheter when retracted from the distal tip, and (iii) a stylet that is tightly designed for a particular catheter such that once the catheter is positioned in the predetermined position, the removable spacer is removed and the stylet is moved forward and locked in the predetermined position, exposing the distal tip to expose the wire comprised of metal or metal alloy for ion release. Typically, the exposed length is about 1 cm (0.39 inches) to about 4 cm (about 1.56 inches). This embodiment of the device according to the present invention can be used with central catheters, midline catheters, PICC catheters, central venous catheters, and other catheter types.

[0197] In the device of FIG. 19, the device 840 comprises an introducer needle 842 and a dual or multi-lumen catheter 844. The dual or multi-lumen catheter 844 can be of various sizes to meet the requirements of fluid flow and insertion into a vein. The dual or multi-lumen catheter 844 has a primary lumen 846 for fluid flow. Additionally, the dual or multi-lumen catheter 844 has a secondary lumen 848 for insertion of an insulating stylet 850. The insulating stylet 850 is in electrical contact with a wire 852 constructed from a metal or metal alloy as described above. The device 840 further comprises a removable spacer 854. The removable spacer 854 is adjacent a connector 856 for attaching the insulating stylet 850 to the catheter 844 for ion delivery. The device 840 further comprises an internal copper pin 858 for attachment to a power source. Similarly, the device 840 further comprises an injection side port 860 for adding fluids such as heparin to flush and rinse the lines and prevent fibrin buildup. The device further comprises a hemostatic seal 862 to prevent backflow of blood from the secondary lumen. In one alternative, the pins of conductive material, typically copper, can be replaced with a heat shrink connector incorporating a circular solder ring.

[0198] Yet another embodiment of a device according to the invention is an extracorporeal catheter as shown in Figure 20. Figure 20 is a diagram of an extracorporeal catheter according to the invention with a battery as a power source, a circuit board for regulating voltage and amperage, cathode and anode wiring covered with an anticoagulant coating, and a pump for promoting blood flow. The extracorporeal catheter is designed to be inserted into larger veins for purposes of immune modulation and treatment of blood borne pathogens.

[0199] In the device of FIG. 20, the device 900 comprises a battery powered power supply 902 and a circuit board 904 in operative contact with the battery powered power supply 902 for control of the voltage and current supplied by the device. The device 900 further comprises a cathode 906 covered by an anticoagulant coating 908 and an anode wire 910, which may comprise one to five wires. The device 900 further comprises a pump 912 for promoting blood flow. The device 900 further comprises a catheter 914 having a proximal end 916 and a distal end 918, the distal end 918 being narrower than the proximal end 916, such as for insertion into a vein of a subject to be treated by the device 900. The device 900 is intended to be inserted into a larger vein of the subject.

[0200] Other embodiments of the invention include devices incorporating dual or multiple lumen catheters with a primary function of delivering fluid. A gauge range can be used for the first lumen delivering fluid depending, for example, on the volume of fluid delivered, the viscosity of the fluid delivered, and the disease or condition being treated or prevented. The second lumen is typically 20 gauge and has a metal or metal alloy wire with a machined window at its distal end to allow for intravenous ion release. This embodiment includes a machined stylet integral to the catheter. In an alternative, the dual or multiple lumen catheter has a replaceable stylet rather than a machined stylet, and this alternative also has a window at the distal end of the catheter, allowing the distal bare wire of the stylet to be exposed for ion release through this machined window machined into the catheter.

[0201] In other alternative embodiments according to the present invention, a device such as the alternatives described above is incorporated into the connector to the IV line to provide metal ions for continuous or substantially continuous delivery.

[0202] Thus, one embodiment of the present invention is a device for treating or preventing bacterial, viral, fungal, or protozoal infections, for stimulating the immune system, or for providing a zone of inhibition around a catheter placement location to prevent the development of a microbial biofilm or infection from a puncture site. (1) A wire comprising a metal or metal alloy that releases ions when a low intensity direct current is applied to the wire; (2) an insulating covering for insulating a wire, the wire and insulating covering being inserted through a catheter into the bloodstream of a patient to be treated; (3) male connector, (4) a female connector in operative contact with a male connector, such that the male and female connectors protect the components of the device and allow connection to a catheter; (5) a conductive element intended to transmit low intensity direct current from a power source connected to the device, the conductive element being selected from the group consisting of: (i) a pin of conductive material located within a male connector; and (ii) a heat shrink connector incorporating a circular solder ring; and (6) optionally, a side port for the introduction of chemicals; Equipped with.

[0203] The device may further comprise a power source in electrical contact with the device.

[0204] This alternative is generally shown in FIG.

[0205] In this embodiment of the device according to the invention, the ion-producing metal wire can be, for example, (i) a metallic or semi-metallic element selected from the group consisting of silver, copper, gold, platinum, iridium, zinc, palladium, and osmium, and (ii) an alloy of two or more metallic or semi-metallic elements each selected from the group consisting of silver, copper, gold, platinum, iridium, zinc, palladium, and osmium, as described above.

[0206] Typically, when activated, the device produces approximately 2×10 blood cells per second for the treatment of blood-borne pathogens or stimulation of the immune system as described above. 9 From about 7 × 10 12 ions are released.

[0207] Typically, as described above, the voltage applied to generate metal ions is about 1.2 V or less. Preferably, the voltage applied is about 0.5 V to about 0.92 V. As described above, the voltage applied depends on the resistance of the tissue. Typically, the voltage applied to generate metal ions is less than about 10 μA, more typically less than about 6 μA, and preferably about 4.9 μA.

[0208] Typically, the power source is capable of adjusting the current based on the therapeutic application as described above. Typically, the device is also capable of wireless communication using a cellular telephone for downloading and uploading data, firmware, or other information as described above, although alternatively, other communication paths may be used as described above. The device may be portable as described above. The device may be capable of providing various waveforms or vibration or pulse signals.

[0209] In one alternative, the device provides a constant current with a voltage cap, as described above. In another alternative, the device provides a constant voltage with a current cap, as described above.

[0210] Another embodiment of the present invention is another alternative for a device for treating or preventing bacterial, viral, fungal, or protozoal infections, for stimulating the immune system, or for providing a zone of inhibition around the catheter placement location to prevent the development of microbial biofilms or infection from the puncture site. (1) A wire comprising a metal or metal alloy that releases ions when a low intensity direct current is applied to the wire; (2) an insulating covering for insulating a wire, the wire and insulating covering being inserted through a catheter into the bloodstream of a patient to be treated; (3) male connector, (4) a female connector in operative contact with a male connector, such that the male and female connectors protect the components of the device and allow connection to a catheter; (5) a conductive element intended to transmit low intensity direct current from a power source connected to the device and selected from the group consisting of: (i) a pin of conductive material located in a male connector, and (ii) a heat shrink connector incorporating a circular solder ring; (6) a stylet for insertion into a vein of the subject to be treated; (7) an insulator for insulating the stylet; and (8) optionally, a side port for the introduction of chemicals; Equipped with.

[0211] The device may further comprise a power source in electrical contact with the device.

[0212] This alternative is generally shown in FIG.

[0213] In this alternative, the ion-producing metal wire is as described above.

[0214] In this alternative, the ion release rates for the treatment of blood borne pathogens are as described above.

[0215] In this alternative, the voltage for generating metal ions is as described above.

[0216] In this alternative, the functionality of the device with respect to power supply and communication is as described above. In this alternative, the device may be portable as described above. In this alternative, the device may provide various waveforms or may provide a vibration or pulse signal as described above.

[0217] In one alternative, the device provides a constant current with a voltage cap, as described above. In another alternative, the device provides a constant voltage with a current cap, as described above.

[0218] Another embodiment of the present invention is another alternative for a device for treating or preventing bacterial, viral, fungal, or protozoal infections, for stimulating the immune system, or for providing a zone of inhibition around the catheter placement location to prevent the development of microbial biofilms or infection from the puncture site. (1) A wire comprising a metal or metal alloy that releases ions when a low intensity direct current is applied to the wire; (2) An insulating covering that insulates a portion of the wire; (3) Connectors, and (4) an insulating covering and an electrode that rests on the patient's skin when the wire is inserted into the patient's vein; Equipped with.

[0219] The device may further comprise a power source in electrical contact with the device, the details and functionality of which are as described above.

[0220] This alternative is generally shown in FIG.

[0221] In this alternative, the ion-producing metal wire is as described above.

[0222] In this alternative, the ion release rates for the treatment of blood borne pathogens are as described above.

[0223] In this alternative, the voltage for generating metal ions is as described above.

[0224] In this alternative, the functionality of the device with respect to power supply and communication is as described above. In this alternative, the device may be portable as described above. In this alternative, the device may provide various waveforms or may provide a vibration or pulse signal as described above.

[0225] In one alternative, the device provides a constant current with a voltage cap, as described above. In another alternative, the device provides a constant voltage with a current cap, as described above.

[0226] Another embodiment of the present invention is another alternative for a device for treating or preventing bacterial, viral, fungal, or protozoal infections, for stimulating the immune system, or for providing a zone of inhibition around the catheter placement location to prevent the development of microbial biofilms or infection from the puncture site. (1) A wire comprising a metal or metal alloy that releases ions when a low intensity direct current is applied to the wire; (2) An insulating covering that insulates a portion of the wire; (3) a dome-shaped cap covering one end of the wire; (4) one or more exfoliated areas of the insulating covering exposing a portion of the wire for delivery of ions when a low intensity direct current is applied to the wire; (5) male connector, (6) a female connector in operative contact with a male connector, such that the male and female connectors protect the components of the device and allow connection to a catheter for insertion of the device; and (7) optionally, a side port for the introduction of chemicals; Equipped with.

[0227] This alternative is generally shown in Figure 4. Various options for this alternative are shown in Figure 4. In one alternative shown in Figure 4, the length of the insulated wire extending from the proximal or origin of the male connector can range from about 1.5 inches (3.81 cm) to about 6 inches (15.24 cm) for use with a peripheral venous electrode, about 4 inches (10.16 cm) to about 9 inches (22.86 cm) for a central venous electrode, and about 6 inches (15.24 cm) to about 32 inches (81.28 cm) for an electrode placed in a peripheral insulated central catheter (PICC).

[0228] In this alternative, the ion-producing metal wire is as described above.

[0229] In this alternative, the ion release rates for the treatment of blood borne pathogens are as described above.

[0230] In this alternative, the voltage for generating metal ions is as described above.

[0231] The device may further comprise a power source in electrical contact with the device, the details and functionality of which are as described above.

[0232] In this alternative, the functionality of the device with respect to power supply and communication is as described above. In this alternative, the device may be portable as described above. In this alternative, the device may provide various waveforms or may provide a vibration or pulse signal as described above.

[0233] In one alternative, the device provides a constant current with a voltage cap, as described above. In another alternative, the device provides a constant voltage with a current cap, as described above.

[0234] Yet another embodiment of the present invention is another alternative for a device for treating or preventing bacterial, viral, fungal, or protozoal infections, for stimulating the immune system, or for providing a zone of inhibition around the catheter placement location to prevent the development of microbial biofilms or infection from the puncture site. (1) A wire comprising a metal or metal alloy that releases ions when a low intensity direct current is applied to the wire, wrapped or braided around a catheter for insertion of the device into a patient's bloodstream; (2) two cap connectors in electrical contact with the wires, each connected to the device and to a power source that delivers low intensity direct current to the device; and (3) A power supply connected to the two cap connectors; Equipped with.

[0235] This alternative is generally shown in FIG. 5. Various options for this alternative are shown in FIG. 5. The arrangement of the wires with respect to the catheter can vary. The wires can be arranged in a helical arrangement on the exterior of the catheter. Alternatively, the wires can be arranged in a helical arrangement on the interior of the catheter. In yet another alternative, the wires can be arranged in a hexagonal arrangement on the exterior of the catheter. In yet another alternative, the wires can be arranged in a hexagonal arrangement on the interior of the catheter. In yet another alternative, the wires can be braided on the exterior of the catheter. In yet another alternative, the wires can be braided on the interior of the catheter.

[0236] In this alternative, the ion-producing metal wire is as described above.

[0237] In this alternative, the ion release rates for the treatment of blood borne pathogens are as described above.

[0238] In this alternative, the voltage for generating metal ions is as described above.

[0239] In this alternative, the functionality of the device with respect to power supply and communication is as described above. In this alternative, the device may be portable as described above. In this alternative, the device may provide various waveforms or may provide a vibration or pulse signal as described above.

[0240] In one alternative, the device provides a constant current with a voltage cap, as described above. In another alternative, the device provides a constant voltage with a current cap, as described above.

[0241] Yet another embodiment of the device is another alternative for a device for treating or preventing bacterial, viral, fungal, or protozoal infections, for stimulating the immune system, or for providing a zone of inhibition around the catheter placement location to prevent the development of microbial biofilms or infection from the puncture site. (1) A wire comprising a metal or metal alloy that releases ions when a low intensity direct current is applied to the wire; (2) An insulating covering that covers the entire wire except for one or more notches; (3) a dome-shaped cap sealing the open end of the insulating covering; and (4) a power source connected to the device and delivering low intensity direct current to the device; Equipped with.

[0242] The power supply for delivering low intensity direct current to the device is as described above, with the details and functionality of the power supply being as described above.

[0243] This alternative is generally shown in FIG.

[0244] In this alternative, the ion-producing metal wire is as described above.

[0245] In this alternative, the ion release rates for the treatment of blood borne pathogens are as described above.

[0246] In this alternative, the voltage for generating metal ions is as described above.

[0247] In this alternative, the functionality of the device with respect to power supply and communication is as described above. In this alternative, the device may be portable as described above. In this alternative, the device may provide various waveforms or may provide a vibration or pulse signal as described above.

[0248] In one alternative, the device provides a constant current with a voltage cap, as described above. In another alternative, the device provides a constant voltage with a current cap, as described above.

[0249] Yet another embodiment of the device is another alternative for a device for treating or preventing bacterial, viral, fungal, or protozoal infections, for stimulating the immune system, or for providing a zone of inhibition around the catheter placement location to prevent the development of microbial biofilms or infection from the puncture site. (1) A wire that is inserted into a patient's vein through a catheter, the wire containing a metal or metal alloy that releases ions when a low intensity direct current is applied to the wire; (2) an insulating covering to protect the wires; (3) Cap connector, (4) a male connector attached near one end of the wire; (5) a female connector attached to an end of a wire that is closer to the male connector than the male connector; (6) a pin of conductive material within the male connector for transmitting low intensity direct current from a power source connected to the device; and (7) optionally, a side port for the introduction of chemicals; Equipped with.

[0250] The power supply, as described above, is connected to the device as described above to deliver low intensity direct current to the device, the details and functionality of the power supply being as described above.

[0251] In this alternative, the device is inserted into a catheter that is inserted into the patient's vein. This alternative is generally shown in FIG.

[0252] In this alternative, the ion-producing metal wire is as described above.

[0253] In this alternative, the ion release rates for the treatment of blood borne pathogens are as described above.

[0254] In this alternative, the voltage for generating metal ions is as described above.

[0255] In this alternative, the functionality of the device with respect to power supply and communication is as described above. In this alternative, the device may be portable as described above. In this alternative, the device may provide various waveforms or may provide a vibration or pulse signal as described above.

[0256] In one alternative, the device provides a constant current with a voltage cap, as described above. In another alternative, the device provides a constant voltage with a current cap, as described above.

[0257] Yet another embodiment of the device is another alternative for a device for the treatment or prevention of bacterial, viral, fungal, or protozoal infections, for stimulating the immune system, or for providing a zone of inhibition around the catheter placement location to prevent the development of microbial biofilms or infection from the puncture site. The device is for use with a PICC catheter (peripheral insulated central catheter). The device comprises: (1) a wire that is inserted into a patient's vein and that contains a metal or metal alloy that releases ions when a low intensity direct current is applied to the wire; (2) an insulating covering surrounding the wire; (3) a dome-shaped cap with insulating covering extending all the way around; (4) one or more notches providing access for wires to the patient's bloodstream; (5) male connector, (6) female connector, (7) a pin of conductive material within the male connector and protected by the male and female connectors for transmitting low intensity direct current from a power source connected to the device; and (8) optionally, a side port for the introduction of chemicals; Equipped with.

[0258] Alternatively, the pins of conductive material, typically copper, can be replaced with heat shrink connectors incorporating circular solder rings as described above.

[0259] The power supply, as described above, is connected to the device as described above to deliver low intensity direct current to the device, the details and functionality of the power supply being as described above.

[0260] In this alternative, the device is inserted into a PICC catheter which is inserted into the patient's vein. This alternative is generally shown in FIG.

[0261] In this alternative, the ion-producing metal wire is as described above.

[0262] In this alternative, the ion release rates for the treatment of blood borne pathogens are as described above.

[0263] In this alternative, the voltage for generating metal ions is as described above.

[0264] In this alternative, the functionality of the device with respect to power supply and communication is as described above. In this alternative, the device may be portable as described above. In this alternative, the device may provide various waveforms or may provide a vibration or pulse signal as described above.

[0265] In one alternative, the device provides a constant current with a voltage cap, as described above. In another alternative, the device provides a constant voltage with a current cap, as described above.

[0266] Yet another embodiment of the device is another alternative of a device for the treatment or prevention of bacterial, viral, fungal, or protozoal infections, for stimulating the immune system, or for providing a zone of inhibition around the catheter placement location to prevent the development of microbial biofilms or infection from the puncture site. This alternative uses an auxiliary use side port catheter for dual drug therapy. The device comprises: (1) Auxiliary use side port catheter, (2) a hemostatic seal that is attached to the catheter to close the space around the catheter; (3) a side port to allow for the administration of intravenous antibiotics or other medications; and (4) a wire comprising a metal or metal alloy that releases ions when a low intensity direct current is applied to the wire, the wire being inserted into a patient's vein through a catheter, the catheter having an inner diameter larger than the outer diameter of the wire to allow both insertion of the wire and to serve as an auxiliary intravenous drug delivery port through a combination of a side port and a proximal hemostatic seal; Equipped with.

[0267] In this alternative, the low intensity direct current is provided by a power supply connected to the device, the details and functionality of which are as described above.

[0268] This alternative is generally shown in FIG.

[0269] In this alternative, the ion-producing metal wire is as described above.

[0270] In this alternative, the ion release rates for the treatment of blood borne pathogens are as described above.

[0271] In this alternative, the voltage for generating metal ions is as described above.

[0272] In this alternative, the functionality of the device with respect to power supply and communication is as described above. In this alternative, the device may be portable as described above. In this alternative, the device may provide various waveforms or may provide a vibration or pulse signal as described above.

[0273] In one alternative, the device provides a constant current with a voltage cap, as described above. In another alternative, the device provides a constant voltage with a current cap, as described above.

[0274] Yet another embodiment of the device is another alternative for a device for treating or preventing bacterial, viral, fungal, or protozoal infections, for stimulating the immune system, or for providing a zone of inhibition around the catheter placement location to prevent the development of microbial biofilms or infection from the puncture site. The device includes a catheter with wiring in various configurations as described below.

[0275] In a first configuration of this embodiment, the device comprises: (1) Catheter, (2) an outer helically wound wire surrounding the catheter, the wire comprising a metal or metal alloy that releases ions when a low intensity direct current is applied to the wire; and (3) a connector for connecting the external spiral wiring to the power source described above for delivering low intensity direct current to the device; Equipped with.

[0276] In a second configuration of this embodiment, the device comprises: (1) Catheter, (2) a straight longitudinal wire surrounding the catheter, the wire comprising three to five wires that are either internally exposed, externally exposed, or both internally and externally exposed, the wire comprising a metal or metal alloy that releases ions when a low intensity direct current is applied to the wire; and (3) a connector for connecting the straight longitudinal wire to the power source described above for transmitting low intensity direct current to the device; Equipped with.

[0277] In a third configuration of this embodiment, the device comprises: (1) Catheter, (2) A ring-shaped wire at the distal end of the catheter, at the proximal end of the catheter, or at both the distal and proximal ends of the catheter, where every ring can be an anode, or every other ring can be an anode and a cathode, or the catheter can be used with an external catheter cathode such as those used in EKG pathways, the wire comprising a metal or metal alloy that releases ions when a low intensity direct current is applied to the wire; and (3) a connector for connecting the ring-shaped wiring to the power source described above to deliver low intensity direct current to the device; Equipped with.

[0278] In a fourth configuration of this embodiment, the device comprises: (1) Catheter, (2) hexagonal pattern ("hexagonal design") wiring on the exterior of a catheter as used in EKG pathways, where the hexagonal design can be present distally, proximally, or both on the proximal exterior surface and the distal interior or exterior surface, or on the proximal interior and distal interior or exterior surfaces, with a cathode added externally as used in EKG pathways, comprising a metal or metal alloy that releases ions when a low intensity direct current is applied to the wire; and (3) a connector for connecting the hexagonal design wiring to a power source as described above to transmit low strength direct current to a device; Equipped with.

[0279] In a fifth configuration of this embodiment, the device comprises: (1) Catheter, (2) a wire having periodic exposed sections of wire from the proximal end to the distal end of the catheter or alternatively only at the distal end of the catheter, the wire having a window of length from about 1 mm to about 10 mm and of exposure from about 35° to about 180°, the wire comprising a metal or metal alloy that releases ions when a low intensity direct current is applied to the wire; and (3) a connector for connecting wiring having periodic exposed sections to the power source described above for transmitting low intensity direct current to the device; Equipped with.

[0280] These alternatives are generally illustrated in FIG. 10, which includes FIGS. 10A, 10B, 10C, 10D, 10E, 10F, 10G, and 10H.

[0281] The power supply, as described above, is connected to the device as described above to deliver low intensity direct current to the device, the details and functionality of the power supply being as described above.

[0282] In this alternative, the ion-producing metal wire is as described above.

[0283] In this alternative, the ion release rates for the treatment of blood borne pathogens are as described above.

[0284] In this alternative, the voltage for generating metal ions is as described above.

[0285] In this alternative, the functionality of the device with respect to power supply and communication is as described above. In this alternative, the device may be portable as described above. In this alternative, the device may provide various waveforms or may provide a vibration or pulse signal as described above.

[0286] In one alternative, the device provides a constant current with a voltage cap, as described above. In another alternative, the device provides a constant voltage with a current cap, as described above.

[0287] Yet another embodiment of the device is another alternative of a device for treating or preventing bacterial, viral, fungal, or protozoal infections, for stimulating the immune system, or for providing a zone of inhibition around the catheter placement location to prevent the development of microbial biofilms or infection from the puncture site. The device includes a catheter with wiring in various configurations as described below. The device can use a catheter with a single lumen. Alternatively, the device can use a catheter with multiple lumens. The catheter can be for peripheral insertion, central insertion, or PICC insertion.

[0288] The device is (1) Catheters having either a single lumen or multiple lumens; (2) a wire embedded in a catheter having a milled window embedded therein, the wire comprising a metal or metal alloy that releases ions when a low intensity direct current is applied to the wire; and (3) a connector for connecting wiring having periodic exposed sections to the power source described above for transmitting low intensity direct current to the device; Equipped with.

[0289] These alternatives are generally illustrated in FIG. 11, which includes FIGS. 11A and 11B.

[0290] The power supply, as described above, is connected to the device as described above to deliver low intensity direct current to the device, the details and functionality of the power supply being as described above.

[0291] In this alternative, the ion-producing metal wire is as described above.

[0292] In this alternative, the ion release rates for the treatment of blood borne pathogens are as described above.

[0293] In this alternative, the voltage for generating metal ions is as described above.

[0294] In this alternative, the functionality of the device with respect to power supply and communication is as described above. In this alternative, the device may be portable as described above. In this alternative, the device may provide various waveforms or may provide a vibration or pulse signal as described above.

[0295] In one alternative, the device provides a constant current with a voltage cap, as described above. In another alternative, the device provides a constant voltage with a current cap, as described above.

[0296] Yet another embodiment of the device is another alternative for a device for treating or preventing bacterial, viral, fungal, or protozoal infections, for stimulating the immune system, or for providing a zone of inhibition around the catheter placement location to prevent the development of microbial biofilms or infection from the puncture site, the device being a wound care bandage or patch for preventing or treating infections associated with wounds.

[0297] The device is (1) a substantially planar patch or bandage having a top side and a bottom side; (2) a coating on the bottom side of the patch or bandage that includes a first wire comprising a metal or metal alloy that releases ions when a low intensity direct current is applied to the first wire; (3) A snap connector on the top of the patch or bandage; (4) a second wire in electrical contact with the snap connector; and (5) a power source in electrical contact with the first and second wires for delivering low intensity direct current to the device; Equipped with.

[0298] The material of the patch is typically a hydrogel. A hydrogel is a network of hydrophilic cross-linked polymer chains that are sometimes seen as colloidal gels in which water is the dispersion medium. The hydrophilic polymer chains are held together by cross-links resulting in a three-dimensional solid. The cross-links that connect the polymers of a hydrogel belong to two basic categories: physical and chemical. Physical cross-links consist of hydrogen bonds, hydrophobic interactions, and chain entanglements (among others). Due to the intrinsic cross-links, the structural integrity of the hydrogel network does not disappear from high water concentrations. Hydrogels are highly absorbent (can contain more than 90% water) natural or synthetic polymer networks. Other alternatives are known in the art.

[0299] This alternative is generally shown in Figures 12A and 12B.

[0300] In this alternative, the ion-producing metal wire is as described above.

[0301] The details and functionality of the power supply are as described above.

[0302] In this alternative, the ion release rates for the treatment of blood borne pathogens are as described above.

[0303] In this alternative, the voltage for generating metal ions is as described above.

[0304] In this alternative, the functionality of the device with respect to power supply and communication is as described above. In this alternative, the device may be portable as described above. In this alternative, the device may provide various waveforms or may provide a vibration or pulse signal as described above.

[0305] In one alternative, the device provides a constant current with a voltage cap, as described above. In another alternative, the device provides a constant voltage with a current cap, as described above.

[0306] Yet another embodiment of the device is another alternative of the invention for incorporation into an intravenous line or other device intended to supply fluids to a patient, such as, but not limited to, plasma, medicines, nutritional supplements, or electrolytes.

[0307] The device is (1) a hub cap which acts as a covering for the device; (2) a cell battery acting as a power source; (3) a printed circuit board in electrical contact with the cell battery for controlling the current output; (4) cathode wire, (5) anode wire, (6) a fluid-absorbing material in electrical contact with the cathode and anode wires to provide an electrical circuit as fluid flows through the device; (7) a first connector; (8) a second connector, wherein the first connector and the second connector allow for placement of the device into an intravenous line for delivering fluid to a patient; (9) an anode metal pin that joins the first connector and the second connector; and (10) a cathode metal pin that joins the first connector and the second connector; Equipped with.

[0308] The first and second connectors may be female or male Luer locks, intravenous hose clamps, intravenous hose connectors, or other connectors conventionally used in the art.

[0309] This alternative is generally shown in FIG.

[0310] In this alternative, the ion-producing metal wire is as described above.

[0311] In this alternative, the ion release rates for treating blood borne pathogens, modulating the immune system, or providing a zone of inhibition around the catheter placement location to combat microbial biofilms and / or infection from the catheter puncture site are as described above.

[0312] In this alternative, the voltage for generating metal ions is as described above.

[0313] In this alternative, the functionality of the device with respect to power supply and communication is as described above. In this alternative, the device may be portable as described above. In this alternative, the device may provide various waveforms or may provide a vibration or pulse signal as described above.

[0314] In one alternative, the device provides a constant current with a voltage cap, as described above. In another alternative, the device provides a constant voltage with a current cap, as described above.

[0315] Yet another embodiment of the device is one that is attached to a fluid source and allows for the generation of metal ions without insertion of the device into an IV line.

[0316] The device is (1) a hub cap which acts as a covering for the device; (2) a cell battery acting as a power source; (3) a printed circuit board in electrical contact with the cell battery for controlling the current output; (4) cathode wire, (5) anode wire, (6) a fluid-absorbing material in electrical contact with the cathode and anode wires to provide an electrical circuit as fluid flows through the device; (7) solid cap, (8) Connector, (9) a fluid source in operative contact with the connector; (10) an anode metal pin in operative contact with the connector; and (11) a cathode metal pin in operative contact with the connector; Equipped with.

[0317] This alternative is generally shown in FIG.

[0318] In this alternative, the ion-producing metal wire is as described above.

[0319] In this alternative, the ion release rates for the treatment of blood borne pathogens are as described above.

[0320] In this alternative, the voltage for generating metal ions is as described above.

[0321] In this alternative, the functionality of the device with respect to power supply and communication is as described above. In this alternative, the device may be portable as described above. In this alternative, the device may provide various waveforms or may provide a vibration or pulse signal as described above.

[0322] In one alternative, the device provides a constant current with a voltage cap, as described above. In another alternative, the device provides a constant voltage with a current cap, as described above.

[0323] Yet another embodiment of the device is intended to deliver the aforementioned metal ions into the patient's veins through a temporarily implanted stylet or catheter.

[0324] The device is (1) a generator attached to the patient's skin; (2) A means for regulating the output of the generator; and (3) an implantable stylet comprising a wire, the generator being in electrical contact with the wire for transmitting low intensity direct current through the wire and into the patient's skin; Typically in this device, the generator is attached to the skin of the patient to be treated and transmits a signal through the skin to an implanted stylet that will activate the release of metal ions.

[0325] This alternative is generally shown in FIG.

[0326] In this alternative, the ion-producing metal wire is as described above.

[0327] In this alternative, the ion release rates for the treatment of blood borne pathogens are as described above.

[0328] In this alternative, the voltage for generating metal ions is as described above.

[0329] In this alternative, the generator functionality and device functionality with respect to communication are as described above. In this alternative, the device may be portable as described above. In this alternative, the device may provide various waveforms or may provide vibration or pulse signals as described above.

[0330] In one alternative, the device provides a constant current with a voltage cap, as described above. In another alternative, the device provides a constant voltage with a current cap, as described above.

[0331] Yet another embodiment of the present invention is a chewable gum that continuously releases silver or metal ions that can be rapidly absorbed orally into the bloodstream for health reasons or to provide a nutritional supplement.

[0332] This embodiment is generally shown in FIG.

[0333] This embodiment comprises a chewable gum wafer or layer incorporating particles of silver or another metal as described above that are released upon chewing, where the hydrolytic action of saliva enables the release of these particles, which are then absorbed into the bloodstream and release ions from the particles for therapeutic or immunostimulatory effects.

[0334] Yet another alternative to the device according to the present invention is one in which the cathode is fabricated directly into the catheter.

[0335] This alternative is generally shown in FIG.

[0336] The device is (1) a catheter, which may be either a single lumen catheter or a multi-lumen catheter; (2) a wire extending within the catheter; (3) 1 to 5 outer rings surrounding the catheter; (4) Insulated wiring containing a metal or metal alloy that releases ions when a low intensity direct current is applied to the insulated wiring; (5) Connector, (6) Optionally, a port for administration of intravenous antibiotics or other desired medications; and (7) a wire in electrical contact with the power source for connection to the power source described above for transmitting low intensity direct current to the device; Equipped with.

[0337] The device may further comprise a power source as described above, the details and functionality of which are as described above.

[0338] In this alternative, the ion-producing metal wire is as described above.

[0339] In this alternative, the ion release rates for the treatment of blood borne pathogens are as described above.

[0340] In this alternative, the voltage for generating metal ions is as described above.

[0341] In this alternative, the functionality of the device with respect to power supply and communication is as described above. In this alternative, the device may be portable as described above. In this alternative, the device may provide various waveforms or may provide a vibration or pulse signal as described above.

[0342] In one alternative, the device provides a constant current with a voltage cap, as described above. In another alternative, the device provides a constant voltage with a current cap, as described above.

[0343] Yet another alternative of the device according to the invention is a device for the treatment or prevention of bacterial, viral, fungal or protozoal infections or for stimulation of the immune system using an introducer needle and a dual lumen catheter, this alternative is generally shown in FIG.

[0344] The device is (1) an introduction needle; (2) Dual-lumen or multi-lumen catheters, (3) a primary lumen for fluid flow within a dual or multi-lumen catheter; (4) at least one secondary lumen in a dual or multi-lumen catheter; (5) an insulated stylet for insertion into the secondary lumen; (6) a wire constructed of a metal or metal alloy in electrical contact with an insulating stylet; (7) removable spacer, (8) a connector for attaching an insulating stylet to a dual or multi-lumen catheter adjacent to a removable spacer; (9) Internal copper pins for attachment to power supply; (10) an injection side port for adding fluid; and (11) a hemostatic seal to prevent backflow of blood from the secondary lumen; Equipped with.

[0345] The power supply, as described above, is connected to the device as described above to deliver low intensity direct current to the device, the details and functionality of the power supply being as described above.

[0346] In this alternative, the ion-producing metal wire is as described above.

[0347] In this alternative, the ion release rates for the treatment of blood borne pathogens are as described above.

[0348] In this alternative, the voltage for generating metal ions is as described above.

[0349] In this alternative, the functionality of the device with respect to power supply and communication is as described above. In this alternative, the device may be portable as described above. In this alternative, the device may provide various waveforms as described above, or may provide a vibration or pulse signal.

[0350] In one alternative, the device provides a constant current with a voltage cap, as described above. In another alternative, the device provides a constant voltage with a current cap, as described above.

[0351] This alternative of the device according to the invention can be used in conjunction with a catheter selected from the group consisting of a central catheter, a midline catheter, a PICC catheter, and a central venous catheter. As mentioned above, a dual lumen or multi-lumen catheter can be used, and when a multi-lumen catheter is used, more than one secondary lumen can be included in the catheter.

[0352] Another embodiment of the present invention is a needleless injector stylet that can be used with devices according to the present invention that use stylets. This device is generally shown in FIG. 18. The needleless injector stylet comprises: (1) a proximal end for connection to a fluid-containing device; and (2) a distal end for insertion into a vein; Equipped with.

[0353] Yet another alternative of the device according to the invention is a device for the treatment or prevention of bacterial, viral, fungal or protozoal infections or for the stimulation of the immune system using an external catheter. This alternative is generally shown in Figure 20. The external catheter comprises: (1) a catheter for insertion into a vein, having a proximal end and a distal end; (2) a battery-powered power source; (3) a circuit board in operative contact with a battery-powered power source for controlling the voltage and current supplied by the device; (4) cathode, (5) an anticoagulant coating over the cathode; (6) an ion-generating anode wire comprising 1 to 5 wires comprising a metal or metal alloy; and (7) A pump to promote blood flow, Equipped with.

[0354] In this alternative, the ion-producing metal wire is as described above.

[0355] In this alternative, the ion release rates for the treatment of blood borne pathogens are as described above.

[0356] In this alternative, the voltage for generating metal ions is as described above.

[0357] Yet another aspect of the invention is a method of treating a blood borne pathogen infection.

[0358] In general, this method (1) placing a device according to the present invention as described above in operative contact with a subject in need of treatment for a blood-borne pathogen infection such that the device is capable of providing metal ions to the bloodstream of the subject; and (2) causing the device to release metal ions into the subject's bloodstream to treat the infection; Includes.

[0359] Typically, the device is operatively contacted with the subject by placing a wire in a vein of the subject such that the wire releases metal ions into the patient's bloodstream. As used herein, the term "operatively contacted" means sufficient contact to provide sufficient current and voltage to the operative site of the device such that sufficient ions are released to perform the function of the device. However, as noted above, other arrangements are possible. For example, the device can be placed in-line in an IV line such that the device releases metal ions into a fluid being delivered to the subject by the IV line to reach the patient's bloodstream. Alternatively, the device can be placed in-line within another fluid source such that the device releases metal ions into the fluid source to reach the patient's bloodstream.

[0360] In this method, the voltage and current used to release the metal ions are as described above.

[0361] In this method, the ion release rate is as described above.

[0362] In this method, the mechanisms for adjusting the current and voltage, and the waveform, are as described above.

[0363] The methods according to the invention can be used to treat infections caused by bacteria, viruses, fungi, and protozoa.

[0364] When the method is used to treat an infection caused by bacteria, the bacterial infection may be, but is not limited to, an infection caused by Staphylococcus aureus, Staphylococcus epidermidis, Bacillus cereus, Bacillus faecalis, Bacillus faecium, Listeria monocytogenes, Streptococcus pneumoniae, Group A Streptococcus, Group B Streptococcus, Escherichia coli, Klebsiella pneumoniae, Haemophilus influenzae, Pseudomonas aeruginosa, Acetinobacter baumannii, Neisseria meningitidis, Bacteroides fragilis, Bacillus anthracis, Yersinia pestis, Francisella tularensis, Yersinia abortus, or Mycobacterium tuberculosis. A particularly important infection is methicillin-resistant Staphylococcus aureus (MRSA). Another particularly important infection is tuberculosis, typically caused by Mycobacterium tuberculosis or in some cases by Mycobacterium bovis.

[0365] When the method is used to treat an infection caused by a virus, the viral infection may be, but is not limited to, an infection caused by human immunodeficiency virus (HIV), hepatitis A virus, hepatitis B virus, hepatitis C virus, Ebola virus, Zika virus, dengue virus, West Nile virus, dengue virus, or severe acute respiratory syndrome coronavirus 2.

[0366] When the method is used to treat an infection caused by a fungus, the fungal infection may be, but is not limited to, candidiasis, aspergillosis, blastomycosis, coccidioidomycosis, or an infection with Cryptococcus neoformans, or an infection with Cryptococcus gattii. When the fungal infection is candidiasis, the candidiasis may be caused by Candida auris, but may alternatively be caused by other Candida strains.

[0367] When the method is used to treat an infection caused by a protozoan, the protozoan infection may be, but is not limited to, amebiasis, malaria, trypanosomiasis, Chagas' disease, leishmaniasis, toxoplasmosis, and cryptosporidiosis. A particularly important infection is malaria, which is typically caused by Plasmodium falciparum, and which may also be caused by Plasmodium vivax, Plasmodium ovale, or Plasmodium malariae.

[0368] In another alternative, the method further comprises administering a therapeutically effective amount of an antibacterial agent. The antibacterial agent may be selected from the group consisting of antibacterial agents, antiviral agents, antifungal agents, and antiprotozoal agents depending on the type of infection in the patient. More than one suitable antibacterial agent may be administered.

[0369] When the antibacterial agent is an antibacterial agent, the selection of a particular antibacterial agent depends on the particular bacteria infecting the patient and other factors such as the severity of the infection, the age, weight, and sex of the patient, pharmacokinetic factors such as the patient's liver and renal function, other drugs being administered to the patient, the patient's immune function, the toxicity of the administered antibacterial agent, any sensitivity or allergic reaction to the particular antibacterial agent or class being considered, and other factors known in the art and considered by those skilled in the art of prescribing and administering antibacterial agents. One of the factors considered in determining the appropriate antibacterial agent is whether the bacteria infecting the patient is gram-negative or gram-positive. Several classes of antibacterial agents are designed to target gram-negative bacteria, including aminopenicillins, ureidopenicillins, cephalosporins, beta-lactam-beta-lactamase inhibitor combinations, folate antagonists, quinolones, and carbapenems. Drugs that specifically target gram-negative organisms include aminoglycosides, monobactams, and ciprofloxacin. Drugs that specifically target gram-positive organisms include vancomycin, teicoplanin, quinupristin / dalfopristin, oxazolidinones, daptomycin, telavancin, and ceftaroline.

[0370] The antibiotics vancomycin, teicoplanin, linezolid, daptomycin, trimethoprim / sulfamethoxazole, doxycycline, ceftobiprole, ceftaroline, clindamycin, dalbavancin, fusidic acid, mupirocin, omadacycline, oritavancin, tedizolid, telavancin, and tigecycline are active against methicillin-resistant Staphylococcus aureus (MRSA).

[0371] Aminoglycosides, including kanamycin A, amikacin, tobramycin, dibekacin, gentamicin, sisomicin, netilmicin, neomycin B, neomycin C, paromomycin, streptomycin, and plazomicin; carbapenems, including thienamycin, imipenem, meropenem, ertapenem, doripenem, panipenem (typically administered with betamipron), biapenem, tebipenem, razupenem, lenapenem, and tomopenem; ceftazidime, cefepime, ceftobiprole, ceftolozane (typically administered with tazobactam), oxolinic acid, rosoxacin, and ciprole; The following antibiotics and classes are effective against P. aeruginosa: fluoroquinolones, including floxacin, fleroxacin, lomefloxacin, nadifloxacin, norfloxacin, ofloxacin, pefloxacin, rufloxacin, balofloxacin, grepafloxacin, levofloxacin, pazufloxacin, sparfloxacin, temafloxacin, clinafloxacin, gatifloxacin, moxifloxacin, sitafloxacin, prulifloxacin, besifloxacin, delafloxacin, ozenoxacin, piperacillin (typically administered with tazobactam), ticarcillin, and clavulanic acid.

[0372] The following antibiotics and classes of streptogramins, including linezolid, quinupristin, dalfopristin, pristinamycin, virginiamycin, tigecycline, and daptomycin, are active against vancomycin-resistant enterococci.

[0373] When the antibacterial agent is an antiviral agent, the selection of a particular antiviral agent depends on the particular virus infecting the patient and other factors such as the severity of the infection, the age, weight, and sex of the patient, pharmacokinetic factors such as the patient's liver and renal function, other drugs being administered to the patient, the patient's immune function, the toxicity of the administered antiviral agent, any sensitivity or allergic reaction to the particular antiviral agent or class being considered, whether the virus is a DNA or RNA virus, whether the genome of the predominant form of the virus is single-stranded or double-stranded, the life cycle of the virus, particularly with regard to whether the genome of the virus can become integrated into the DNA of the patient's cells, and other factors known in the art and taken into account by those skilled in the art of prescribing and administering antiviral agents. Furthermore, as mentioned above, it is known in the art that many antiviral agents have only a relatively narrow zone of spectrum of action due to the structural and biological diversity of viruses compared to the relatively broad spectrum of action for many antibacterial antibiotics such as penicillin or azithromycin. In addition to this, it should be taken into account that, as mentioned above, some RNA viruses, such as retroviruses, are able to become integrated in the form of DNA into the genome of the individual they infect, while other RNA viruses, such as severe acute respiratory syndrome coronavirus 2, lack this function.

[0374] Antiviral agents include abacavir, acyclovir, adefovir, amantadine, amprenavir, umifenovir, atazanavir, baloxavir marboxil, bictegravir, emtricitabine, tenofovir alafenamide, boceprevir, cidofovir, cobicistat, lamivudine, zidovudine, daclatasvir, sovosbuvir, ribavirin, darunavir, delavirdine, didanosine, docosanol, dolutegravir, doravirine, edoxudine, efavirenz, elvitegravir, enfuvirtide, entecavir, etravirine, famciclovir, fomivirsen, fosamprenavir, foscarnet, and ganciclovir. These include, but are not limited to, the following drugs: lovir, ibacitabine, ibalizumab, idoxuridine, indinavir, letermovir, lopinavir, loviride, maraviroc, methisazone, moroxydine, nelfinavir, nitazoxanide, ritonavir, oseltamivir, penciclovir, peramivir, pleconaril, raltegravir, remdesivir, rilpivirine, rimantadine, saquinavir, simeprevir, stavudine, telaprevir, telbivudine, tipranavir, trifluridine, tromantadine, valacyclovir, valganciclovir, vicriviroc, vidarabine, viramidine, zalcitabine, and zanamivir.

[0375] When the antibacterial agent is an antifungal agent, the selection of a particular antifungal agent will depend on the particular fungus infecting the patient and other factors such as the age, weight, and sex of the patient, pharmacokinetic factors such as the patient's liver and renal function, other drugs being administered to the patient, the patient's immune function, the toxicity of the antifungal agent being administered, any sensitivity or allergic reaction to the particular antifungal agent or class thereof being considered, and other factors known in the art and considered by those skilled in the art of prescribing and administering antifungal agents.

[0376] Antifungal agents include amphotericin B, candicidin, filipin, hamycin, natamycin, nystatin, bifonazole, butoconazole, clotrimazole, econazole, fenticonazole, isoconazole, ketoconazole, luliconazole, miconazole, omoconazole, oxiconazole, sertaconazole, sulconazole, tioconazole, albaconazole, efinaconazole, epoxiconazole, fluconazole, isavuconazole, and isofungal. Includes traconazole, posaconazole, propiconazole, ravuconazole, terconazole, voriconazole, abafungin, amorolfine, butenafine, naftifine, terbinafine, anidulafungin, caspofungin, micafungin, ciclopirox, 5-fluorocytosine, griseofulvin, tolnaftate, undecylenic acid, triacetin, orotomide, miltefosine, nikkomycin, piroctone olamine, and clioquinol.

[0377] Antiprotozoal agents include eflornithine, furazolidone, chloroquine, hydroxychloroquine, melarsoprol, metronidazole, nifurseisosone, nitazoxanide, ornidazole, paromomycin sulfate, pentamidine, pyrimethamine, quinapyramine, lonidazole, tinidazole, amodiaquine, proguanil, sulfonamides, mefloquine, atovaquone, primaquine, artemisinin, artemether, artesunate, dihydroartemisinin, arteether, halofantrine, lumefantrine, doxycycline, clindamycin, and these agents include agents that are effective against malaria.

[0378] Another aspect of the invention is a method for stimulating the production of natural killer (NK) cells using the device according to the invention as described above. NK cells are important cytotoxic lymphocytes for the innate immune system, providing a rapid response to virus-infected cells and acting around 3 days after infection to respond to the formation of tumors. NK cells are unique, but have the ability to recognize and kill stressed cells in the absence of antibodies and MHC, thus allowing a fairly fast immune response. These cells were named "natural killer" because they do not require activation to kill cells that lack the "self" marker of MHC class I. The role of natural killer cells is particularly important, since harmful cells that lack the marker of MHC class I cannot be detected and destroyed by other immune cells such as T lymphocyte cells. NK cells are characterized by their CD56 + CD3 - They can be recognized by their phenotype.

[0379] NK is known to function like a tumor immune monitor by directly inducing the death of tumor cells even in the absence of surface adhesion molecules and antigenic peptides (NK acts as a cytolytic effector lymphocyte). This role of NK cells is important for immune success, especially since T cells are unable to recognize pathogens in the absence of surface antigens. Detection of tumor cells leads to activation of NK cells and the resulting production and release of cytokines. Tumor cells would also be considered as self markers if they did not cause inflammation and would not elicit a T cell response. Several cytokines are produced by NK, including tumor necrosis factor alpha (TNFα), IFNγ, and interleukin 10 (IL-10). TNFα and IL-10 act as proinflammatory and immunosuppressive agents, respectively. NK cell activation and subsequent generation of cytolytic effector cells influence macrophages, dendritic cells, and neutrophils, thereby enabling subsequent antigen-specific T cell and B cell responses. Instead of acting through antigen-specific receptors, lysis of tumor cells by NK cells is mediated by alternative receptors including NKG2D, NKp44, NKp46, NKp30, and DNAM. NKG2D is a disulfide-linked homodimer that recognizes several ligands, including ULBPs and MICA, that are typically expressed on tumor cells.

[0380] Activation of NK cells by the methods of the present invention can be used to treat early stage malignant tumors, particularly breast cancer. In the treatment of breast cancer, activation of NK cells can be used in conjunction with other treatment methods, including other immunotherapies, surgery, radiation therapy, and chemotherapy. In the methods of the present invention, including the methods for activation of NK cells, the means for stimulating the immune system can involve an electric field generated by a generator and delivered through a catheter or stylet to activate calcium influx and efflux channels on lymphocytes, which in turn activates signaling in the immune system.

[0381] Generally, the method comprises: (1) placing a device according to the invention as described above in operative contact with a subject such that the device is capable of providing metal ions to the bloodstream of the subject in need of stimulating the production of natural killer cells; and (2) causing the device to release metal ions into the subject's bloodstream to stimulate the production of natural killer cells; Includes.

[0382] Yet another aspect of the present invention is a method for producing a medicament for use in a method for the treatment of osteoporosis, comprising: (1) placing a device according to the present invention as described above in operative contact with a subject such that the device is capable of providing metal ions to the bloodstream of the subject in need of stimulating the immune system; and (2) causing the device to release metal ions into the subject's bloodstream to stimulate the immune system; A method for stimulating the immune system comprising:

[0383] In the method according to the invention, the method comprises the steps of: (1) determining the outcome of the treatment by detecting or determining the amount or concentration of bloodborne pathogens remaining in the subject's blood following initiation of administration of the treatment; and (2) adjusting the treatment as needed by modifying the amount of ions administered, the current, voltage, or waveform used, or, if an additional antibacterial, antiviral, or antifungal agent is administered, modifying a factor selected from the group consisting of the identity of the additional agent being administered, the dosage of the additional agent, the frequency of administration of the additional agent, the duration of administration of the additional agent, the route of administration of the additional agent, or another factor associated with administration of the additional agent; It may further include.

[0384] Typically, the amount or concentration of a blood borne pathogen is detected or determined by conventional methods known in the art, such as, but not limited to, immunological assays for antigens for the blood borne pathogen, PCR assays or other nucleic acid based assays for the genome of the blood borne pathogen, culture methods for bacteria, histological methods based on bacterial staining, or other conventional methods.

[0385] Activation of NK cells by the methods according to the invention described can be used in particular to treat early stage malignancies, particularly breast cancer. In treating breast cancer, activation of NK cells can be used in conjunction with other therapeutic methods, including other immunotherapies, surgery, radiation therapy, and chemotherapy. Such additional methods of treatment are known in the art.

[0386] Another method according to the invention of using the above-mentioned devices is the use of these devices for extracorporeal or intravenous ion delivery to purify a patient's blood in a manner similar to an apheresis unit.

[0387] The invention is illustrated by the following examples, which are included for illustrative purposes only and are not intended to limit the invention.

[0388] Working Example [Example 1] Dengue treatment Dengue fever is a mosquito-borne viral disease caused by an RNA virus of the genus Flavivirus in the family Flaviviridae. The virus that causes dengue fever is related to the viruses that cause yellow fever, West Nile, Zika, St. Louis encephalitis, and other diseases. Dengue fever is endemic in many tropical regions, causing approximately 390 million infections annually, with approximately 500,000 of those infected requiring hospitalization, and approximately 40,000 deaths. Due to climate change and increased traffic, the incidence of dengue fever is increasing rapidly in warmer regions such as Europe and the southern United States.

[0389] The device according to the present invention was used to treat dengue fever. The device used a 20 gauge x 10 cm midline peripherally inserted catheter (PICC) with an insertion stylet as described above. The device used a silver / copper alloy as the metal or alloy. In this treatment, the ion release rate was approximately 2.5 x 10 per second. 12The voltage used was 0.92 V. The current used was 2.5 μA. The duration of treatment was 4 hours.

[0390] The results are shown in Table 1.

[0391] (Table 1) TIFF2024514179000002.tif60168

[0392] The results in Table 1 illustrate the effective treatment of dengue fever with the device described above. The patient's temperature decreased to normal, the platelet count returned to normal, the lymphocyte count returned to normal (high lymphocyte counts are evidence of ongoing infection and a drop in lymphocyte count indicates resolution of infection), and the hematocrit increased. These clinical improvements were maintained for 8 weeks or more.

[0393] [Example 2] Treatment of various diseases with the device according to the present invention Treatment of various diseases with the device according to the present invention is illustrated in Figure 21. Diseases treatable with the device according to the present invention are illustrated in Figure 21, including HIV, Dengue, infection with HSV-1, and infection with HSV-2.

[0394] In FIG. 21, "BUN" is serum urea nitrogen, "AST / GOT" is aspartate aminotransferase, which is a measure of liver function (high values ​​can mean liver damage), "ALT / GLT" is alanine aminotransferase, which is another measure of liver function (high values ​​can mean liver damage), "WBC" is white blood cell (leukocyte) count (high values ​​may mean the presence of an ongoing infection), and "ESR" is erythrocyte sedimentation rate (high values ​​are a sign of inflammation, which may be due to infection or other causes such as autoimmune disease).

[0395] For the dengue and HIV results shown in Figure 21, the device used a 20 gauge x 10 cm midline peripherally inserted catheter (PICC) with the insertion stylet described above. The device used a silver / copper alloy as the metal or alloy. For this treatment, the ion release rate was approximately 2.5 x 10 per second. 12 The voltage used was 0.92 V. The current used was 2.5 μA. For dengue, the treatment duration was 4 hours, and for HIV, it was either 24 or 72 hours.

[0396] For the results shown in Figure 21 for HSV-1 and HSV-2 infections, the device used a 20 gauge x 10 cm midline peripherally inserted catheter (PICC) with the insertion stylet described above. The device used a silver / copper alloy as the metal or alloy. The ion release rate for this treatment was approximately 5.5 x 10 per second. 12 The voltage used was 0.89 V. The current used was 4.9 μA.

[0397] The results of Example 2 illustrate the effective treatment of HIV, dengue fever, infection with HSV-1, and infection with HSV-2.

[0398] Specific results from Example 2 for dengue patients are shown in Table 2.

[0399] (Table 2) TIFF2024514179000003.tif12797

[0400] In Table 2, "BIT" is total bilirubin, "BID" is direct bilirubin, and "ALK" is alkaline phosphatase. Abnormally high bilirubin levels can indicate various types of problems with the liver or bile ducts, and may be associated with the presence of hemolysis, as bilirubin is produced during the normal breakdown of red blood cells. Alkaline phosphate levels are another measure of liver damage, and high values ​​may indicate liver damage.

[0401] Table 3 illustrates a comparison of platelet counts in dengue patients following treatment with the NANDI system compared to an alternative system known as GENESYS. In the NANDI system, the device used a 20 gauge x 10 cm midline peripherally inserted catheter (PICC) with an insertion stylet as described above. The device used a silver / copper alloy as the metal or alloy. In this treatment, the ion release rate was approximately 2.5 x 10 per second. 12 The voltage used was 0.92 V. The current used was 2.5 μA. In the GENESYS system, the device used a 20 gauge x 10 cm midline peripherally inserted catheter (PICC) with an insertion stylet as described above. The device used a silver / copper alloy as the metal or alloy. In this treatment, the ion release rate was approximately 5.5 x 10 per second. 12 The voltage used was 0.89 V. The current used was 4.9 μA.

[0402] (Table 3) TIFF2024514179000004.tif117122

[0403] [Example 3] Improved liver and kidney function and white blood cell count The improvement in liver and kidney function with the device according to the invention is shown in Table 4.

[0404] (Table 4) TIFF2024514179000005.tif32169

[0405] The data in Table 4 demonstrate that treatment with a device according to the invention can improve renal and liver function in healthy patients as well as in HSV-1 infected patients.

[0406] In total, 12 patients experienced a mean decrease in BUN of 13.89% and a mean decrease in creatine of 6.4%, indicating improved renal function. These patients experienced a mean decrease in AST of 21.53% and a mean decrease in ALT of 11.75%, indicating improved liver function.

[0407] In addition to this, there was a 19.94% increase in white blood cell count over 12 healthy patients, indicating increased resistance to infection.

[0408] For the results shown in Table 4, the device was a 20 gauge x 10 cm midline peripherally inserted catheter (PICC) with the insertion stylet described above. The device used a silver / copper alloy as the metal or alloy. With this treatment, the ion release rate was approximately 5.5 x 10 per second. 12 The voltage used was 0.89 V. The current used was 4.9 μA. The treatment times are shown in Table 4.

[0409] [Example 4] Treatment of HIV The results for the treatment of HIV using a device according to the invention are shown in Table 5.

[0410] (Table 5) TIFF2024514179000006.tif124155

[0411] The device used for the results in Table 5 was a 20 gauge x 10 cm midline peripherally inserted catheter (PICC) with the insertion stylet described above. The device used a silver / copper alloy as the metal or alloy. The ion release rate for this treatment was approximately 2.5 x 10 per second. 12 The voltage used was 0.92 V. The current used was 2.5 μA. Treatment times were as described in Table 4.

[0412] These results were obtained in patients who were not taking antiviral drugs. The results showed that the device according to the present invention reduced viral load and CD4 + This indicates that it was effective in increasing the concentration of cells.

[0413] Advantages of the Invention The devices and methods according to the present invention provide improved methods for treating blood-borne pathogen infections, particularly bacterial, viral, and fungal infections, using new therapeutic mechanisms that do not rely on the specificity of conventional antibacterial, antiviral, or antifungal therapeutic agents. The devices and methods according to the present application are of broad therapeutic use, are well tolerated, and do not induce significant side effects. These devices and methods can be used in combination with conventional antibacterial, antiviral, or antifungal therapeutic agents, as well as other treatment methods, including, but not limited to, methods such as the use of mechanical ventilators to treat infections that affect the lungs, such as pneumonia or infections caused by severe acute respiratory syndrome coronavirus 2, and the use of steroids such as dexamethasone to prevent uncontrolled responses of the immune system (so-called "cytokine storm") that can complicate the treatment of viral diseases. The devices and methods according to the present invention can also act to stimulate the immune system along with inhibiting the growth of pathogens.

[0414] The device according to the present invention has industrial applicability as a beneficial medical device. The method according to the present invention has industrial applicability for the preparation of a medicament for treating the diseases and conditions described herein, further encompassing the use of the device according to the present invention for the treatment of the diseases and conditions described herein, including but not limited to bacterial infections, viral infections, and fungal infections.

[0415] In relation to ranges of values, the invention includes each intervening value between the upper and lower limit of the range to at least one-tenth of the unit of the lower limit, unless the context clearly dictates otherwise. Furthermore, the invention includes any other stated intervening value, including either or both of the upper and lower limits of the range, unless that value is specifically excluded from that range.

[0416] Unless otherwise defined, the meanings of all scientific and technical terms used herein are those typically understood by one of ordinary skill in the art to which this invention belongs. One of ordinary skill in the art will also further appreciate that any methods and materials similar or equivalent to those described herein can be used to practice or test the present invention.

[0417] The publications and patents disclosed herein are provided solely for the disclosure of those publications and patents prior to the filing date of the present application. Nothing herein should be construed as an admission that the present invention is not entitled to antedate such publications by virtue of prior invention. Further, the publication dates provided may be different from the actual publication dates, which may need to be independently confirmed.

[0418] The entire contents of all references mentioned, including all published patents, patent applications, and literature citations, and the literature incorporated within these publications, are incorporated herein by reference, but to the extent that any document incorporated herein by reference refers to information that becomes publicly available, applicants do not admit that any such information published after the filing date of this application is prior art.

[0419] As used in the present specification and claims, the singular includes the plural. For example, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. Furthermore, the term "at least" preceding a list of elements should be understood to refer to all elements in the list. The present invention illustratively described herein can be suitably practiced without any element or elements, limitation or limitations not specifically disclosed herein. That is, for example, the terms "comprises," "includes," "contains," or equivalent terms should be read in an open-ended and expansive sense. As used herein, the transitional phrase "comprises" encompasses the transitional phrases "consisting essentially of" and "comprises," unless these phrases having the narrower meaning are expressly excluded. In addition, the terms and expressions used herein are used as terms of description and not of limitation, and the use of such terms and expressions is not intended to exclude any equivalents or any portions thereof shown and described in the future, and it should be recognized that various modifications are possible within the claimed invention. Thus, although the present invention has been specifically disclosed by preferred embodiments and optional features, it should be understood that those skilled in the art may make modifications and alternatives to the invention disclosed herein, and such modifications and alternatives are considered to be within the invention disclosed herein. The present invention has been described herein generally and generically. Each of the narrower species and subgeneric groupings falling within the generic disclosure also form part of these inventions. This includes the generic description of each invention with a condition or negative limitation removing any subject matter from the genus, regardless of whether the deleting material is inherent. Furthermore, when features or aspects of the present invention are described in terms of a Markush group, those skilled in the art will recognize that the description also describes the invention in terms of any individual member or subgroup of the members of the Markush group. Similarly, it should be understood that the above description is intended to be illustrative and not limiting. Numerous embodiments will be apparent to those skilled in the art upon review of the above description.Accordingly, the scope of the invention should be determined not with reference to the above description, but instead with reference to the claims, along with the full scope of equivalents to which such claims are entitled. Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments described. Such equivalents are intended to be encompassed by the following claims.

Claims

1. 1. A device for treating or preventing bacterial, viral, fungal, or protozoal infections, for stimulating the immune system, or for providing a containment barrier around a catheter placement site to prevent the development of a microbial biofilm or infection from a puncture site, comprising: (a) a wire comprising a metal or metal alloy that releases ions when a low intensity direct current is applied to the wire; (b) an insulating covering insulating a portion of the wire; (c) a connector; and (d) an electrode that rests on the patient's skin when the insulating covering and wire are inserted into the patient's vein; 16. A device comprising:

2. The wire comprising a metal or metal alloy is (a) a gold and silver alloy containing at least 70% gold and not more than 30% silver; (b) a gold-silver alloy containing at least 70% silver and not more than 30% gold; (c) Gold-silver-copper alloys containing at least 70% gold and not more than 30% in total of silver and copper; (d) Silver-copper-gold alloys containing at least 70% silver and not more than 30% in total of copper and gold; (e) Silver-copper-gold alloys containing at least 70% copper and not more than 30% in total of silver and gold; (f) Silver-copper-gold alloys containing between 1% and 99% each of gold, silver, and copper; (g) Alloys of gold with one or more of silver, copper, platinum, iridium, and zinc, containing 70% or more gold and a total of 30% or less silver, copper, platinum, iridium, or zinc; (h) Alloys of silver with one or more of gold, copper, platinum, iridium, and zinc, containing 70% or more silver and a total of 30% or less gold, copper, platinum, iridium, or zinc; (i) Alloys of copper and one or more of gold, silver, platinum, iridium, and zinc, containing 70% or more copper and a total of 30% or less gold, silver, platinum, iridium, or zinc; (j) Alloys of platinum with one or more of gold, silver, copper, iridium, and zinc, containing 70% or more platinum and a total of 30% or less gold, silver, copper, iridium, or zinc; (k) Alloys of iridium with one or more of gold, silver, copper, platinum, and zinc, containing 70% or more iridium and a total of 30% or less of gold, silver, copper, platinum, or zinc; and (l) Alloys of zinc with one or more of gold, silver, copper, platinum, and iridium, containing 70% or more zinc and not more than 30% in total of gold, silver, copper, platinum, or iridium; selected from the group consisting of: The device of claim 1 .

3. Approximately 2 x 10 per second when activated 9 From about 7 x 10 12 13. The device of claim 1 which emits ions.

4. 10. The device of claim 1 , which utilizes a voltage of about 1.2V or less.

5. 10. The device of claim 1 using a current of less than about 10 μA.

6. The device of claim 1, further comprising a power source in electrical contact with the device.

7. The device described in claim 6, wherein the power source in electrical contact with the device has the function of adjusting the current based on the therapeutic use of the device.

8. The device of claim 1 , wherein a voltage cap is used to provide a constant current.

9. The device of claim 1 , wherein a current cap is used to provide a constant voltage.

10. 1. A device for treating or preventing bacterial, viral, fungal, or protozoal infections, for stimulating the immune system, or for providing a containment barrier around a catheter placement site to prevent the development of a microbial biofilm or infection from a puncture site, comprising: (a) a wire comprising a metal or metal alloy that releases ions when a low intensity direct current is applied to the wire, the wire being wrapped or braided around a catheter for insertion of the device into a patient's bloodstream; (b) two cap connectors in electrical contact with the wires, each cap connector being connected to a power source connected to the device for delivering low intensity direct current to the device; and (c) a power source connected to the two cap connectors; 16. A device comprising:

11. The wire is (a) spirally on the exterior of the catheter; (b) spirally within the catheter; (c) a hexagonal shape on the exterior of the catheter; (d) a hexagonal shape within the catheter; (e) braiding the exterior of the catheter; and (f) braiding the interior of the catheter; positioned relative to the catheter in an alternative selected from the group consisting of: The device of claim 10.

12. The wire comprising a metal or metal alloy is (a) a gold and silver alloy containing at least 70% gold and not more than 30% silver; (b) a gold-silver alloy containing at least 70% silver and not more than 30% gold; (c) Gold-silver-copper alloys containing at least 70% gold and not more than 30% in total of silver and copper; (d) Silver-copper-gold alloys containing at least 70% silver and not more than 30% in total of copper and gold; (e) Silver-copper-gold alloys containing at least 70% copper and not more than 30% in total of silver and gold; (f) Silver-copper-gold alloys containing between 1% and 99% each of gold, silver, and copper; (g) Alloys of gold with one or more of silver, copper, platinum, iridium, and zinc, containing 70% or more gold and a total of 30% or less silver, copper, platinum, iridium, or zinc; (h) Alloys of silver with one or more of gold, copper, platinum, iridium, and zinc, containing 70% or more silver and a total of 30% or less gold, copper, platinum, iridium, or zinc; (i) Alloys of copper and one or more of gold, silver, platinum, iridium, and zinc, containing 70% or more copper and a total of 30% or less gold, silver, platinum, iridium, or zinc; (j) Alloys of platinum with one or more of gold, silver, copper, iridium, and zinc, containing 70% or more platinum and a total of 30% or less gold, silver, copper, iridium, or zinc; (k) Alloys of iridium with one or more of gold, silver, copper, platinum, and zinc, containing 70% or more iridium and a total of 30% or less of gold, silver, copper, platinum, or zinc; and (l) Alloys of zinc with one or more of gold, silver, copper, platinum, and iridium, containing 70% or more zinc and not more than 30% in total of gold, silver, copper, platinum, or iridium; selected from the group consisting of: The device of claim 10.

13. 11. The device of claim 10, wherein when activated, the device emits from about 2 x 10 to about 7 x 10 ions per second.

14. 11. The device of claim 10, which utilizes a voltage of about 1.2V or less.

15. 11. The device of claim 10, utilizing a current of less than about 10 μA.

16. The device described in claim 10, wherein the power source in electrical contact with the device has the function of adjusting the current based on the therapeutic use of the device.

17. The device of claim 10 , wherein a voltage cap is used to provide a constant current.

18. 1. A device for treating or preventing bacterial, viral, fungal, or protozoal infections, for stimulating the immune system, or for providing a containment barrier around a catheter placement site to prevent the development of a microbial biofilm or infection from a puncture site, comprising: (a) an open lumen catheter; (b) a hemostatic seal attached to the catheter to close the space around the catheter; (c) a side port to allow for the administration of intravenous antibiotics or other medications; and (d) a wire comprising a metal or metal alloy that releases ions when a low intensity direct current is applied to the wire, said wire being inserted into a patient's vein through said catheter, the inner diameter of the lumen of said catheter being greater than the outer diameter of said wire to allow both the insertion of said wire and as an auxiliary intravenous medication port through said side port and in combination with a proximal hemostatic seal; 16. A device comprising:

19. The wire comprising a metal or metal alloy is (a) a gold and silver alloy containing at least 70% gold and not more than 30% silver; (b) a gold-silver alloy containing at least 70% silver and not more than 30% gold; (c) Gold-silver-copper alloys containing at least 70% gold and not more than 30% in total of silver and copper; (d) Silver-copper-gold alloys containing at least 70% silver and not more than 30% in total of copper and gold; (e) Silver-copper-gold alloys containing at least 70% copper and not more than 30% in total of silver and gold; (f) Silver-copper-gold alloys containing between 1% and 99% each of gold, silver, and copper; (g) Alloys of gold with one or more of silver, copper, platinum, iridium, and zinc, containing 70% or more gold and a total of 30% or less silver, copper, platinum, iridium, or zinc; (h) Alloys of silver with one or more of gold, copper, platinum, iridium, and zinc, containing 70% or more silver and a total of 30% or less gold, copper, platinum, iridium, or zinc; (i) Alloys of copper and one or more of gold, silver, platinum, iridium, and zinc, containing 70% or more copper and a total of 30% or less gold, silver, platinum, iridium, or zinc; (j) Alloys of platinum with one or more of gold, silver, copper, iridium, and zinc, containing 70% or more platinum and a total of 30% or less gold, silver, copper, iridium, or zinc; (k) Alloys of iridium with one or more of gold, silver, copper, platinum, and zinc, containing 70% or more iridium and a total of 30% or less of gold, silver, copper, platinum, or zinc; and (l) Alloys of zinc with one or more of gold, silver, copper, platinum, and iridium, containing 70% or more zinc and not more than 30% in total of gold, silver, copper, platinum, or iridium; selected from the group consisting of:

20. The device of claim 18.

20. Approximately 2 x 10 per second when activated 9 From about 7 x 10 12 20. The device of claim 18 which emits ions.

21. 20. The device of claim 18, which utilizes a voltage of about 1.2V or less.

22. 20. The device of claim 18, utilizing a current of less than about 10 μA.

23. The device of claim 18, further comprising a power source in electrical contact with the device.

24. The device described in claim 23, wherein the power source in electrical contact with the device has the function of adjusting the current based on the therapeutic use of the device.

25. 20. The device of claim 18, wherein a voltage cap is used to provide a constant current.

26. 20. The device of claim 18, wherein a current cap is used to provide a constant voltage.

27. 1. A device for treating or preventing bacterial, viral, fungal, or protozoal infections, for stimulating the immune system, or for providing a containment barrier around a catheter placement site to prevent the development of a microbial biofilm or infection from a puncture site, comprising: (a) a catheter; (b) wiring surrounding the catheter, the wiring having a configuration: (i) an outer helically wound wiring surrounding the catheter; (ii) a straight longitudinal wire surrounding the catheter; (iii) a wire in the shape of a ring at the distal end of the catheter, at the proximal end of the catheter, or at both the distal and proximal ends of the catheter; (iv) wiring in a hexagonal pattern on the exterior of the catheter; and (v) wiring having periodic exposed sections of the wiring from the proximal end to the distal end of the catheter, or alternatively only at the distal end of the catheter; is selected from the group consisting of the wiring comprises a metal or metal alloy that releases ions when a low intensity direct current is applied to the wiring; The wiring, and (c) a connector connecting the hexagonal design wire to a power source for transmitting low intensity direct current to a device; 16. A device comprising:

28. 28. The device of claim 27, wherein the wiring surrounding the catheter is in the configuration of an external spiral wound wiring surrounding the catheter.

29. 28. The device of claim 27, wherein the wiring surrounding the catheter is in the configuration of straight longitudinal wiring surrounding the catheter.

30. 28. The device of claim 27, wherein the wiring surrounding the catheter is in a configuration of wiring in the shape of a ring at the distal end of the catheter, at the proximal end of the catheter, or at both the distal and proximal ends of the catheter.

31. 28. The device of claim 27, wherein the wiring surrounding the catheter is in a hexagonal pattern of wiring configuration on the exterior of the catheter.

32. 28. The device of claim 27, wherein the wiring surrounding the catheter is in a wiring configuration having periodic exposed sections of the wiring from the proximal end to the distal end of the catheter or alternatively only at the distal end of the catheter.

33. The wiring including a metal or a metal alloy is (a) a gold and silver alloy containing at least 70% gold and not more than 30% silver; (b) a gold-silver alloy containing at least 70% silver and not more than 30% gold; (c) Gold-silver-copper alloys containing at least 70% gold and not more than 30% in total of silver and copper; (d) Silver-copper-gold alloys containing at least 70% silver and not more than 30% in total of copper and gold; (e) Silver-copper-gold alloys containing at least 70% copper and not more than 30% in total of silver and gold; (f) Silver-copper-gold alloys containing between 1% and 99% each of gold, silver, and copper; (g) Alloys of gold with one or more of silver, copper, platinum, iridium, and zinc, containing 70% or more gold and a total of 30% or less silver, copper, platinum, iridium, or zinc; (h) Alloys of silver with one or more of gold, copper, platinum, iridium, and zinc, containing 70% or more silver and a total of 30% or less gold, copper, platinum, iridium, or zinc; (i) Alloys of copper and one or more of gold, silver, platinum, iridium, and zinc, containing 70% or more copper and a total of 30% or less gold, silver, platinum, iridium, or zinc; (j) Alloys of platinum with one or more of gold, silver, copper, iridium, and zinc, containing 70% or more platinum and a total of 30% or less gold, silver, copper, iridium, or zinc; (k) Alloys of iridium with one or more of gold, silver, copper, platinum, and zinc, containing 70% or more iridium and a total of 30% or less of gold, silver, copper, platinum, or zinc; and (l) Alloys of zinc with one or more of gold, silver, copper, platinum, and iridium, containing 70% or more zinc and not more than 30% in total of gold, silver, copper, platinum, or iridium; selected from the group consisting of:

28. The device of claim 27.

34. Approximately 2 x 10 per second when activated 9 From about 7 x 10 12 28. The device of claim 27, which emits ions.

35. 28. The device of claim 27, which utilizes a voltage of about 1.2V or less.

36. 28. The device of claim 27, utilizing a current of less than about 10 μA.

37. The device of claim 27, further comprising a power source in electrical contact with the device.

38. The device described in claim 37, wherein the power source in electrical contact with the device has the function of adjusting the current based on the therapeutic use of the device.

39. 28. The device of claim 27, wherein a voltage cap is used to provide a constant current.

40. 28. The device of claim 27, wherein a current cap is used to provide a constant voltage.

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