|Publication number||US20060004431 A1|
|Application number||US 11/172,138|
|Publication date||Jan 5, 2006|
|Filing date||Jun 30, 2005|
|Priority date||Jul 1, 2004|
|Also published as||CA2613121A1, CA2613121C, EP1895936A2, EP1895936A4, US8135466, US8620431, US9008770, US20100100188, US20100198357, US20120316655, US20140094750, US20150182645, WO2007005842A2, WO2007005842A3|
|Publication number||11172138, 172138, US 2006/0004431 A1, US 2006/004431 A1, US 20060004431 A1, US 20060004431A1, US 2006004431 A1, US 2006004431A1, US-A1-20060004431, US-A1-2006004431, US2006/0004431A1, US2006/004431A1, US20060004431 A1, US20060004431A1, US2006004431 A1, US2006004431A1|
|Inventors||Thomas Fuller, Richard Wysk, Wayne Sebastianelli|
|Original Assignee||Fuller Thomas A, Wysk Richard A, Sebastianelli Wayne J|
|Export Citation||BiBTeX, EndNote, RefMan|
|Patent Citations (28), Referenced by (38), Classifications (97), Legal Events (1)|
|External Links: USPTO, USPTO Assignment, Espacenet|
This application claims priority from U.S. Provisional Patent Application Ser. No. 60/585,159, filed Jul. 1, 2004, the entire content of which is incorporated herein by reference.
The invention relates to systems and methods for inhibition of microbial infection related to surgical implant devices. In particular, the invention relates to systems and methods for inhibition of microbial infection related to orthopedic implants.
Joint degeneration is the leading chronic condition in the elderly; it affects one in every eight Americans and almost half the population over the age of 65. (Brooks, P. M, Med. J. Aust., 173:307-308, 2000) The most common form of joint degeneration is osteoarthritis. Osteoarthritis weakens and breaks down cartilage and bone, causing pain as bones rub together. Eventually the constant rubbing of the bony surfaces destroys the surfaces that are rubbing against one another leading to rough, painful movement. Total joint replacement, or arthroplasty, represents a significant advance in the treatment of painful and disabling joint pathologies. Arthroplasty can be performed on almost any joint of the body including the hip, knee, ankle, foot, shoulder, elbow, wrist, and fingers. Total joint replacement: whether hip, knee, ankle, foot, shoulder, elbow, wrist, and fingers or other, is typically done as a final stage treatment for a patient who suffers from some form of joint degeneration.
In its early stages, many people manage arthritis pain conservatively by using anti-inflammatory medicines, weight reduction, lifestyle modification, physiotherapy, or occupational therapy. However, as the disease progresses the pain intensifies. When the pain gets to the point where everyday, normal activities such as putting on shoes and socks or walking up stairs become too painful, total joint replacement surgery is an attractive option to restore movement and independence, and to dramatically reduce pain.
Although joint replacement is a relatively large field within orthopedics, the number of fracture fixation devices utilized around the world far outranks the number of artificial joints. Fracture fixation is growing daily as the number of fractures associated with trauma accidents is increasing. Fixation devices can be internal or external in nature and include devices such as a plate, wire, screw, pin, rod, nail or staple, which aid in maintaining fracture fragments in proper position during healing. Such devices are usually inserted after open reduction of the fracture and will remain for the entirety of the healing process, often becoming a permanent structure within the body.
Joint replacement surgery began in the early 1950's, and its frequency has grown as surgical techniques and medical care associated with surgery improves. In the late 1980's between 500,000 and 1 million total hip replacements were performed per year, while in 2004 it is estimated that approximately 600,000 joint prosthesis and 2,000,000 fracture-fixation devices will be inserted into patients in the United States.
Unfortunately, as the number of implant surgeries increases, the number of associated infections also increases. Any person who has an implant is at risk for developing an infection associated with the device. It is estimated that 2% of joint prostheses and 5% of fixation devices will become infected. Taking 3% as an average estimate of infected implants, as many as 30 million incidents of infection may occur.
The effects of implant infection are expensive as well as a danger to the health and well-being of the affected individual. For example, infection results in direct medical and surgical costs and additionally may cause patient pain, suffering, lost wages, lost work and decreased productivity. On average an infected hip prosthesis patient spends six times the number of days in the hospital when compared to the non-infected prosthetic hip patient. In 1991, the total cost of an infected patient, both in hospital and as an outpatient, was $45,000 as compared to the total cost of $8,600 associated with a non-infected patient. (Bengston, S., Ann. Med., 25:523-529, 1993)
Joint replacement implants and fixation devices include a variety of materials foreign to the human body, such as metals, plastics, and polymeric substances, all of which have the potential to serve as substrates for attachment and growth of microorganisms.
In particular, certain microorganisms may exude a glycocalyx layer that protects certain bacteria from phagocytic engulfment by white blood cells in the body. The glycocalyx also enables some bacteria to adhere to environmental surfaces (metals, plastics, root hairs, teeth, etc.), colonize, and resist flushing.
Once microorganisms colonize an implant, it is often very difficult to eradicate or even inhibit the infection. For example, systemic administration of antibiotics is often ineffective due to limited blood supply to the areas of the implant. Additionally, many bacterial species today are resistant to antibiotics.
Where infection cannot be inhibited it may spread and become even more serious, as in patients who have an infection within the bone, osteomyelitis. Such patients often must undergo a difficult and costly treatment involving extended hospitalization, joint debridement, aggressive antimicrobial therapy, total joint removal followed by total joint replacement and possible amputation if the infection can not be eliminated.
Since implantation of an orthopedic implant device, such as a joint replacement prosthesis or fixation device, is quite common and associated infection frequent, there is a continuing need for new approaches to inhibition of infection. In particular, it would be very desirable for both the physician as well as the patient to be able to treat a prosthetic osteomyelitic infection without the removal of an implant. Further, economical and safe apparatus and methods of inhibiting implant associated infections are needed.
A medical implant system is provided which includes an orthopedic implant body made of a biocompatible material. In one option, the implant body is a joint replacement prosthesis implant. In a further option, the implant body is an orthopedic fixation device. Optionally, more than one implant body is provided as part of an inventive system. The implant body has an external surface and a metal component is disposed on the external surface of the implant body. An inventive system further includes a conduit for electrical current wherein the conduit is in contact with the metal component. A power source is also included which is in electrical communication with the conduit for electrical current. More than one power source may be provided, for example, where more than one implant body is included.
Optionally, an implant body is a joint replacement prosthetic implant. In a further option an implant body is a part of a joint replacement prosthetic implant
In one embodiment, an internal cavity having a wall and an opening is included in the implant body and a cap is provided to close the opening of the internal cavity. A power source is positioned in the internal cavity. The conduit for electrical current provided in such an embodiment is optionally the implant body itself. Thus, a current from the power source may be connected to the metal component through the biocompatible material of the implant body.
In a further option, the implant body is adapted to be disposed totally within a human body when in use as an implant.
Also optionally, a metal component disposed on a portion of the internal cavity wall, preferably such that the portion of the metal component in the cavity is continuous with the portion of the metal component disposed on the external surface of the implant body. Also preferably, the metal component in the cavity has the same composition as the metal component on the external surface. Optionally, the form of the metal component in the cavity is the same or different compared to the form of the metal component on the external surface. For example, a wire or metal ribbon may be attached to the metal component on the external surface and to the cavity wall. In one embodiment, the metal component in the cavity is in contact with a terminal of a power source disposed therein.
In a preferred option, the metal component includes a transition metal, selected from gold, zinc, copper, cadmium, cobalt, nickel, platinum, palladium, manganese, and chromium. In a further preferred option, the metal component includes silver.
In a further preferred option, the metal component is more electrically conductive than the biocompatible material of the implant body.
One form of a metal component is a coating disposed on the external surface of the implant body. Such a metal coating ranges in thickness between 1×10−9-5×10−3 meters, inclusive.
Optionally, a metal coating disposed on a portion of the external surface of the implant body covers a portion of the external surface ranging from 1-100% of the total external surface of the implant body. Further optionally, the metal coating disposed on a portion of the external surface of the implant body covers a portion of the external surface ranging from 50-99% of the external surface of the implant body. Preferred is a configuration in which the metal coating is disposed as a single region of continuous coating on the external surface.
In one embodiment of an inventive medical implant system the implant body includes an articular surface which does not include a metal component such as a metal coating.
In another option, metal component is provided in the form of a wire, ribbon, or foil disposed on the external surface.
An inventive system may be configured such that the power source is continuously powering a current conducted to the metal component for release of metal ions. Alternatively, a system includes a switch for powering the current on or off. In a further embodiment, the current is modulated by circuitry adapted to control the current so as to increase or decrease the amount of current flowing and the amount of metal ions released. Thus, a resistor in electrical communication with the power source is optionally included. In a preferred embodiment, the resistor and power source are positioned in an internal cavity of the implant body. Optionally, a switch in electrical communication with the power source is included to control the power source. Further optionally, a controller in signal communication with the switch is provided. Such a controller is operated to send a signal to a system component adapted to receive the signal and to control the switch. Preferably, a controller is external to an individual having the implant, such that activation of the switch may be performed by a doctor, technician or by the patient.
Also described is a method for inhibiting microbial infection associated with an orthopedic implant, which includes providing an inventive system and delivering a current to a metal component disposed on an external surface of an implant body, the implant body located in a human body at a site of potential infection. Delivery of current to the metal component is associated with antimicrobial action such as release of metal ions toxic to an infectious microbe at the site of potential infection, such that microbial infection is inhibited.
The present invention provides methods and apparatus for prevention and inhibition of implant-associated infection.
A medical implant system is provided which allows for release of microbe-inhibiting metal ions in the vicinity of a temporary or permanent surgically implanted device. In particular, metal ions are released from a metal component of an implant by application of an electrical current to the metal component. A power source for producing the electrical current is provided which may be external to the implant, or preferably, contained within the implant.
A medical implant system is provided which includes an implant body made of a biocompatible material. A metal component is disposed on the external surface of the implant body and a power source is included to power delivery of an electrical current to the metal component. The electrical current is delivered to the metal component via an electrical conduit. In a preferred embodiment, the metal component is different than the biocompatible material. Thus, where the biocompatible material is a metal, the metal component differs in composition from the biocompatible material. For instance, preferably, the metal component has a higher conductivity than the biocompatible material.
The term “implant body” as used herein refers to an orthopedic implant for replacement or repair of a component of the musculoskeletal system. For example, an orthopedic implant includes a joint replacement prosthetic implant for joint replacement or repair. Prosthetic implants include those for replacement or repair of any joint illustratively including a knee, a hip, an ankle, a shoulder, a wrist, and a finger or toe joint among others. Further, an orthopedic implant is an orthopedic fixation device used in replacement or repair of a component of the musculoskeletal system, such as a plate, wire, screw, pin, rod, nail or staple. In a preferred embodiment, an implant body is preferably an implant body which is wholly contained within a patient's body when in use for the purpose of the implant.
The term “biocompatible material” as used herein refers to a material which is relatively inert in use following surgical placement into an individual such that adverse reactions such as inflammation and rejection are rare. The biocompatible material is sufficiently strong and durable to allow the implant to perform its intended function, such as joint replacement or fixation. Exemplary biocompatible materials include metal materials such as surgical stainless steel, titanium, and titanium alloys; ceramics; plastics; and combinations of these.
The metal component includes a metal which inhibits infection by microbes, such as bacteria, protozoa, viruses, and fungi. Such antimicrobial metals are typically transition metals illustratively including silver, gold, zinc, copper, cadmium, cobalt, nickel, platinum, palladium, manganese, and chromium. A metal component preferably contains at least 50% by weight of an antimicrobial metal, further preferably contains at least 75% by weight of an antimicrobial metal and still further preferably contains at least 95% by weight of an antimicrobial metal. In another preferred embodiment, the metal component is substantially all antimicrobial metal. The antimicrobial properties of silver are particularly well characterized and a metal component preferably contains at least 50% by weight silver, further preferably contains at least 75% by weight silver and still further preferably contains at least 95% by weight silver. In another preferred embodiment, the metal component is substantially all silver. In particular, the metal component is capable of releasing a metal ion when an electrical current is applied to the metal component.
In a preferred embodiment, the metal component is in the form of a coating disposed on the external surface of the implant body. The coating can be applied by any of various methods illustratively including dunk coating, thin film deposition, vapor deposition, and electroplating. The metal component in the form of a coating ranges in thickness between 1×10−9-5×10−3 meters, inclusive, preferably 1×10−7-4×10−3 meters, inclusive, and more preferably between 0.5×10−6-5×10−4 meters in thickness.
In an example including a silver coating metal component, the total amount of silver used during the coating process ranges between 0.016 grams in weight and 8.95 grams in weight. Such a coating is at least 0.016 grams in weight in order for enough silver material to be present for the ionization to occur. The total weight of silver typically does not exceed 8.95 grams in order to maintain a nontoxic state for the patient.
In an embodiment including a metal coating disposed on the external surface of the implant body, a metal coating is preferably disposed on at least 50% of the external surface of the implant body, and more preferably a coating is disposed on at least 75% of the external surface of the implant body. In an embodiment including a metal coating disposed on the external surface of the implant body, the coating is optionally disposed on substantially all of the external surface of the implant body. In a further option, the implant body is coated with the metal coating on substantially all of the external surface excluding one or more articular wear surfaces. An “articular wear surface” is a portion of an implant body which is exposed to wear during normal use when implanted. For example, a hip joint implant includes articular wear surfaces at the interface of the “ball” and “socket” components of the joint prosthesis, that is, at the acetabular surfaces. Where the implant body is a fixation device, it is preferred that the coating is present on at least 50% of the external surface of the implant body, and more on at least 75% of the external surface of the implant body, and further preferably on substantially all of the external surface of the implant body, including threads where the device is a bone screw.
A metal coating is preferably disposed on the external surface as a single continuous expanse of the coating material.
Optionally, the metal component is in the form of a wire, ribbon, or foil disposed on the external surface of an implant body. Such a metal component may be attached to the implant body by welding, by an adhesive, or the like.
In order to deliver an electrical current to the metal component and release antimicrobial metal ions, a power source is included in an inventive system. A power source may be any of various power sources such as a battery, capacitor, or connection to external AC. Such power sources are known in the art.
In one embodiment of an inventive system, a power source is implanted in the body of an individual receiving a joint prosthesis. An implant power source in such an embodiment is self-contained, that is, requiring no connection to external power. Illustrative examples include an electrochemical cell such as a battery and a capacitor. In a preferred embodiment, the implant body has an internal cavity housing the power source and, optionally, other components of the system, including circuitry adapted to modulate a current from the power source.
An internal cavity in an implant body includes a wall defining the cavity and an opening for insertion of a power source and, optionally, other components of the system.
In general, a preferred power source housed in an implant body cavity is lightweight and sized to fit in the cavity. In addition, a power source housed in an implant body cavity is capable of producing electrical currents in the range of 0.1-200 microamps. A power source housed in an implant cavity may be selected according to the requirements of a patient. For example, a temporary implant may not require a power source having as long a life expectancy as a permanent implant.
In a further embodiment, circuitry adapted to modulate an electrical current is included in an inventive system. Metal ions can be mobilized in greater quantities by increasing the current that is applied to the implant. If the current is increased a greater concentration of metal ions, preferably silver ions, will be provided near the surface of the implant. The greater concentration of silver ions will create a greater diffusion constant and provide for a greater distance of penetration by the ions. Similarly, current may be modulated to decrease ion release as desired, such as where no infection is believed to be present.
For example, a resistor, a switch, a signal receiver, a relay, a signal transmitter, transformer, a sensor, or a combination of these or other such components and connectors may be included, optionally configured as a circuit board arrangement. In a preferred embodiment, all or part of the circuitry adapted to modulate an electrical current included in an inventive system is housed in a cavity in the implant body of an orthopedic implant.
Thus, optionally, the internal cavity also contains a resistor for modulation of the current. For example, a resistor in series with a battery allows use of a larger size battery with a greater lifetime. The resistor in series can be used to reduce current flow to a desired level.
Once a power source capable of producing the required current and of the appropriate size is determined, a resistance can be calculated by using the equation; V=I*R. Where V is the voltage of the battery that has been selected, I is the current, 1 microampere, and R is the resistance that will allow for the current to flow from the determined battery. This resistor then can be placed in series with the power source to yield the required current. It is noted that neither the current nor the voltage delivered from a power source will be altered by the size of the implant.
In a specific example, a surface mounted chip resistor will satisfy the requirements of the resistor for use in this application. Surface mounted chip resistors come in a variety of resistances, ranging form 1 ohms up to 51 mega-ohms. Surface mounted chip resistors are manufactured in a variety of sizes which will meet the size constraints. For example, the Ohmite, thick film high voltage SMD chip, series MMCO8 will easily fit within the shaft of the redesigned hip implant. The MMCO8 has dimensions of over all length of 2.0 millimeters and over all width of 1.25 millimeters. This particular resistor is manufactured in resistance between 100 ohms and 51 mega-ohms.
An inventive implant system may be configured such that a desired amount of an antimicrobial metal ion is released over a specified period of time so as to optimize the inhibitory effects on undesirable microbes and minimize any unwanted side effects. In one embodiment, an inventive implant system is configured such that an included power source is in continuous operation and metal ions are released continuously.
In a preferred option, a switch is included in an inventive system to control current to flow from the power source to the metal component. A switch allows antimicrobial ions to be released during specified periods of time by controlling current flow. For example, the switch is turned on to activate current and release antimicrobial ions at regular intervals, such as once a week or once a month, for a time following implantation in order to prevent infection. Further, where an infection is detected or suspected, the switch is activated to allow current flow and release of metal ions to combat the infection. An included switch is capable of withstanding the current and the voltage transferred across it.
A switch is optionally and preferably controlled by a controller external to the body of the individual having an implanted prosthesis. An external controller may emit a signal operative to control a switch. In one example, a magnetically controlled switch, such as a reed switch is used. Magnetically based switches that are externally controlled by a controller are currently manufactured and are available from commercial sources. Such switches are controlled by a controller including a magnet which is placed in proximity to the switch in order to turn the switch on or off. For example, a magnet may be positioned in the vicinity of a patient's hip in order to activate a magnetically controlled switch in an internal cavity of a hip prosthesis implant. Thus, the switch is in signal communication of with the controller.
Optionally, a transmitter is included in an inventive system which is in signal communication with receiver circuitry adapted to operate a switch and modulate current flow. Preferably the transmitter is activated external to the body of an individual having an implanted prosthesis as described herein. For example, a radio frequency transmitter may be used to transmit a radio frequency signal to receiver circuitry in the internal cavity of the implant body adapted to operate a switch and modulate current flow.
In a further embodiment, microchip circuitry, programmed to modulate current flow is included in an inventive system. Preferably, the microchip circuitry is included in a cavity of an inventive implant body. In a further embodiment, such microchip circuitry may be implanted at a second location in the implant patient, such as just under the skin, to remotely control the current flow.
A sensor may be included to sense microbial growth, such as bacterial growth on an external surface of an implant body. Such a sensor communicates a signal indicating bacterial growth to circuitry adapted to activate a switch, stimulating release of metal ions and inhibiting the microbes.
Preferably, the implant body having a power source in an internal cavity is adapted to be disposed totally within a human body when in use. Thus, the implant body preferably has substantially the same dimensions and shape of a conventional implant body.
In a preferred option, a portion of the metal component is disposed in the internal cavity. For example, in a preferred option, a metal coating is present on a portion of the wall of the internal cavity. Such a metal coating is preferably continuous with a metal component, such as a coating, disposed on the external surface of the implant body. Optionally, and preferably, a metal component present in the internal cavity is in electrical contact with one terminal of a power source present in the cavity. A metal component present in the cavity may also be in the form of a wire, ribbon, or foil. Preferably the metal component in the cavity is in the same form as the metal component present on the external surface of the implant body and is continuous therewith.
In a preferred option, a metal component disposed on the external surface and/or internal cavity wall is more electrically conductive than the biocompatible material of which the implant body is made.
The internal cavity has an opening which can be closed using a cap which may be attached to the implant body, such as by a hinge, or completely detachable.
In a preferred option, the cap is made of an electrically insulating material.
In a further option, an electrically insulating material is disposed between the external surface of the implant body and the metal component.
A conduit for conduction of an electrical current from the power source is included in an inventive system. In one embodiment, the conduit is the biocompatible material of the implant body. In a further embodiment, a power source is external to the body of the individual having the implanted prosthesis and the conduit traverses the skin of the individual, connecting the metal component disposed on the implant body with the external power source.
A conduit from one terminal of the power source and a metal component is optionally provided in the form of a wire extending there-between. As noted above, a further connection between the metal component and a second terminal of the power source is optionally provided.
In a further preferred embodiment of the invention, a metal component is in removable contact with the implant. For example, a metal component is in removable contact with an implant may have the form of a metal wire in contact with an implant surface.
In another embodiment of an inventive system, a conduit is provided which extends outside of the body of an individual having an implant prosthesis according to the invention. For example, a conduit is provided in the form of a wire such that one end of the wire may be positioned in proximity to the metal component of an implanted prosthesis, preferably in contact with the metal component in order to deliver current and release metal ions from the metal component. The opposite end of the wire optionally may extend outside the body to contact a power source. The conduit is optionally removed when risk of infection is low and may be repositioned for stimulation of metal ion release as desired.
Another embodiment of an inventive apparatus is shown in
Joint replacement or repair implants include one or more implantable parts which may be included as an implant body in an inventive system. For example, a hip joint replacement implant typically includes a femoral part, replacing the natural femoral head, and a socket part, or acetabular cup or shell, replacing the natural acetabulum. While an inventive system is extensively discussed herein with regard to an implant body which is a femoral part of a hip joint replacement prosthetic implant, it is appreciated that the socket part, or cup portion of a hip implant prosthesis may also be included in an inventive system as an configured to include an internal cavity containing a power source and other components as described herein. A further example of joint replacement implant parts include a wrist implant having a carpal component, for instance present where a first row of carpal bones is removed, and a radial part, for instance inserted or attached to the radius bone. The radial part may provide an articular surface for interaction with a carpal part. Another example is a knee joint prosthetic implant, having a femoral part attached to the femur and a tibial part attached to the tibia, each having an articular surface for interaction with the other. It is appreciated that one or more parts of an implant prosthesis may be configured to include an internal cavity containing a power source and other components as described herein. Thus, an inventive system may include more than one implant body. In a further option, each of the multiple implant bodies may include a cavity and power source, and may further include other components, preferably a resistor and switch, as described. In a further option, multiple switches may be controlled separately, for instance where one implant body or region in the vicinity of the implant body is more vulnerable to infection than another, a switch in that implant body may be activated to turn on current in that implant body without turning on current in another implant body.
As noted, an implant may be a temporary implant, intended to remain implanted for a limited period of time, or a permanent implant, intended to remain implanted long-term, even as long as the remainder of the individual's life. One type of temporary implant is known as a “spacer” implant. A spacer implant typically has a similar size and shape compared to a permanent or short-term implant. A spacer implant is typically implanted in order to maintain the spatial integrity of an area where a permanent joint replacement implant will be positioned eventually. For example, where an individual has a badly infected implant which must be removed, a spacer implant may be implanted while the infection is being fought. An inventive system is particularly advantageous in such a situation since a synergistic effect of an inventive antimicrobial system with a course of systemic or local antibiotics is achieved. Further, an inventive spacer implant may lessen or eliminate the need for use of bone cement, currently used in this situation. The insertion of a spacer implant would allow the patient to be much more active than if the joint were filled with bone cement. Further, tissue encroachment at the site is decreased by placement of a spacer implant.
In one embodiment a power source, such as a battery, having a first terminal, a second terminal, and a potential difference between the first and second terminals, is provided. Further provided is a conduit for an electrical connection between the first terminal and the metal component. Also provided is a conduit for an electrical connection between the metal component and the second terminal.
A method for inhibiting microbial infection associated with an orthopedic implant is provided which includes providing an inventive system as described and delivering a current to a metal component disposed on an external surface of an implant body, the implant body located in a human body at a site of potential infection.
In one embodiment, an inventive method for inhibiting an infectious organism includes introducing an electrical current into a metal component of an implanted joint prosthesis to release metal ions from the component. The metal ions have a biostatic or biocidal effect on microorganisms such that growth and/or attachment of microorganisms on the implant and in the vicinity of the implant are inhibited.
As noted above, biocidal metals and ions include a transition metals and ions. Preferred metals and ions include silver, gold, zinc, copper and combinations thereof. Further, metals and ions such as cadmium, cobalt, nickel, platinum, palladium, manganese, chromium, and the like may be included.
Infectious organisms inhibited by such metals and metal ions illustratively include bacteria, viruses and fungi.
Generally, such metal ions inhibit infection at concentrations ranging between 1×10−3 M-1×10−7 M, inclusive, and is preferably delivered in amounts sufficient to achieve a concentration in this range. Optionally, and preferably, metal ions are delivered in amounts sufficient to achieve a concentration in the range between 5×10−5 M-0.25×10−6 M, inclusive. In particular, silver ions are delivered in amounts sufficient to achieve a concentration in the range between 5×10−5 M-0.25×10−6 M, inclusive.
A metal ion is released from a metal component by application of an electrical current to the metal component. Bone and soft tissue cells are affected by electrical current and thus the amount of current delivered and the length of time for which it is delivered must be considered in the context of the proximity of the implant to such cells. The amount of a metal ion released is dependant on the strength and duration of the electrical stimulus which is adjusted accordingly.
Generally, a current in the range of 0.1 microamps to 200 milliamps is delivered to a metal component. In general, a current is delivered to a metal component for periods of time ranging from about 1 minute to continuous delivery over the lifetime of the power source, that is, weeks, months or years. In general weaker currents are used for longer-term treatments. Thus, in a preferred embodiment, 0.3-1.5 micro-amperes of current is delivered in order to ionize a silver surface layer. Also preferred is an embodiment in which 0.8-1.2 microamps of current is delivered to a silver coating.
Small electrical currents in the ranges described are sufficient to ionize a solid silver coating, producing silver ions. Without wishing to be bound by theoretical considerations, according to Faraday's law, under ideal conditions 4 micrograms of silver will be liberated per hour per micro ampere of current applied to silver. Calculation 1 below details this.
Assuming the power source is capable of producing a 1 micro-ampere current and that the electrical current should not exceed 20 micro-amperes at any time, 10 micrograms/milliliter concentration of silver ions within a couple of hours. Additionally the maintenance of a 10 micrograms/milliliter concentration of silver ions is possible with very small electrical current requirements.
Additional theoretical considerations indicate that total lifetime exposure to silver ions advantageously do not exceed 8.95 grams for a person of average size, approximately 70 kilograms, and having an average life expectancy, about 70 years. This calculation is based on the assumption that about 0.35 milligrams of silver can be safely consumed each day, see Newman, J. R., Tuck Silver 100 Safety Report, Jan. 9, 1999. Thus, for a permanent implant, it is desirable that an inventive system not contain more than about this amount of silver. Similar calculations may be made for other metal ions as will be recognized by one of skill in the art.
In one embodiment, a method of inhibiting bacterial infection associated with an implant includes administration of a systemic or local antibiotic and administration of a metal antibiotic via an inventive implant. A synergistic effect of such treatment is achieved as a lower dosage of both the systemic or local antibiotic and the metal antibiotic is necessary to achieve a therapeutic effect.
While inventive methods and apparatus are generally described with reference to use in humans herein, the methods and apparatus are also used in other animals to inhibit infection. For example, an inventive apparatus and method is used in animals illustratively including cats, dogs, cattle, horses, sheep, goats, rats, and mice.
The apparatus and methods described herein are presently representative of preferred embodiments, exemplary, and not intended as limitations on the scope of the invention. Changes therein and other uses will occur to those skilled in the art. Such changes and other uses are encompassed within the spirit of the invention as defined by the scope of the claims.
An implant body is manufactured by obtaining a hip replacement prosthesis similar to a DePuy SUMMIT Tapered Hip System designed to include an internal cavity, about 10 millimeters in length and about 5 millimeters in width and a cap to close the opening of the cavity as described herein. Articular surfaces of the implant body are masked and the remaining external surfaces are coated with a silver metal film about 1 micron in thickness. A battery, resistor and switch are chosen to fit in the cavity. A portion of the cavity wall adjacent to the external surface of the implant body is also coated with silver metal to a depth adjacent the positive terminal of the battery.
A battery with the desired profile is currently in production by many battery manufacturers. The Energizer battery number 337 satisfies all of the required size characteristics needed for implementation within a bactericidal hip implant. When examining the Energizer 337 battery one can see that the small size, 1.65 mm in height by 4.8 mm in diameter allow the battery to easily fit within the 5 mm compartment.
The 337 size battery provides a voltage of 1.55 volts, which is much greater than required for the application of ionizing a solid silver coating. Thus, a resistor is chosen to be placed in series with the battery. Using a voltage of 1.55 volts and a required current of 1 micro-ampere one can calculate the required resistor as shown in Equations 2.1 and 2.2 below.
The required resistor should have a resistance of approximately 15.5 mega-ohms. Additionally the resistor must conform to the size requirements as set by the diameter of the pocket within the shaft of the implant, 5 millimeters.
Utilizing a resistor with the required 15.5 mega-ohms rating in series with the 337 battery will provide for approximately 75573 hours of run time. The calculation of the run time for the battery under with this resistance is show in calculation # 3 below. During this running time the battery will be producing the required 1 micro-ampere current that is required to ionize the solid silver coating.
An included switch, like all other components, fits within the 5 millimeter diameter cavity that has been machined within the shaft of the original hip implant. Additionally the switch will have the ability to be turned ON and OFF once implanted within the human body. In this example, a magnetically based switch is selected. Coto Technology manufactures a switch, RI-80 Series Dry Reed Switch that is designed specifically for medical applications and which meets the design size constraints. The switch has a maximum dimension of the central tube of 5 millimeters in length and 1.8 millimeters in diameter. This switch will carry a maximum current of 0.5 amperes and a has a maximum operating voltage of 200 volts, both of which are satisfactory operating characteristics needed for a bactericidal hip implant according to the invention.
Any patents or publications mentioned in this specification are incorporated herein by reference to the same extent as if each individual publication is specifically and individually indicated to be incorporated by reference. In particular, U.S. Provisional Patent Application Ser. No. 60/585,159, filed Jul. 1, 2004, is hereby incorporated by reference in its entirety.
The compositions and methods described herein are presently representative of preferred embodiments, exemplary, and not intended as limitations on the scope of the invention. Changes therein and other uses will occur to those skilled in the art. Such changes and other uses can be made without departing from the scope of the invention as set forth in the claims.
|Cited Patent||Filing date||Publication date||Applicant||Title|
|US2655922 *||Oct 4, 1951||Oct 20, 1953||Vivadent Corp||Device for producing bactericide oh-ions through electrolysis for dental treatment|
|US3954407 *||Sep 12, 1974||May 4, 1976||Andary William A||Automatic toothbrush sterilizer|
|US4027393 *||Sep 19, 1975||Jun 7, 1977||Sybron Corporation||Method of in vivo sterilization of surgical implantables|
|US4291125 *||Jan 16, 1980||Sep 22, 1981||Greatbatch W||Method for electronic control of infections using silver ions|
|US4308859 *||Aug 1, 1979||Jan 5, 1982||Child Laboratories Inc.||Method of inhibiting mastitis in bovine animals|
|US4476590 *||Mar 26, 1981||Oct 16, 1984||National Research Development Corporation||Antimicrobial surgical implants|
|US4569673 *||Jan 12, 1984||Feb 11, 1986||Battelle Development Corporation||Bacterial barrier for indwelling catheters and other medical devices|
|US5100671 *||Jun 30, 1988||Mar 31, 1992||Karo Maeda||Coating material for medical care|
|US5322520 *||Nov 12, 1992||Jun 21, 1994||Implemed, Inc.||Iontophoretic structure for medical devices|
|US5358514 *||May 17, 1993||Oct 25, 1994||Alfred E. Mann Foundation For Scientific Research||Implantable microdevice with self-attaching electrodes|
|US5383935 *||Sep 28, 1993||Jan 24, 1995||Shirkhanzadeh; Morteza||Prosthetic implant with self-generated current for early fixation in skeletal bone|
|US5520664 *||Jan 11, 1994||May 28, 1996||Spire Corporation||Catheter having a long-lasting antimicrobial surface treatment|
|US5814091 *||Mar 24, 1997||Sep 29, 1998||Pacesetter Ab||Active medical implant having a hermetically sealed capsule and method for making same|
|US5984905 *||Mar 18, 1997||Nov 16, 1999||Southwest Research Institute||Non-irritating antimicrobial coating for medical implants and a process for preparing same|
|US6034295 *||Dec 2, 1996||Mar 7, 2000||Christoph Rehberg||Implantable device having an internal electrode for stimulating growth of tissue|
|US6087549 *||Sep 22, 1997||Jul 11, 2000||Argentum International||Multilayer laminate wound dressing|
|US6120502 *||May 27, 1994||Sep 19, 2000||Michelson; Gary Karlin||Apparatus and method for the delivery of electrical current for interbody spinal arthrodesis|
|US6143035 *||Jan 28, 1999||Nov 7, 2000||Depuy Orthopaedics, Inc.||Implanted bone stimulator and prosthesis system and method of enhancing bone growth|
|US6238686 *||Jun 25, 1997||May 29, 2001||Westaim Technologies||Anti-microbial coating for medical devices|
|US6267590 *||Nov 24, 1999||Jul 31, 2001||Agion Technologies, Llc||Antimicrobial dental products|
|US6393323 *||Jan 31, 2000||May 21, 2002||Mcgill University||Electronic stimulator implant for modulating and synchronizing bladder and sphincter function|
|US6500165 *||Nov 21, 2000||Dec 31, 2002||Steven R. Frank||Active antisepsis device|
|US6579539 *||Dec 22, 1999||Jun 17, 2003||C. R. Bard, Inc.||Dual mode antimicrobial compositions|
|US6582715 *||Apr 27, 1999||Jun 24, 2003||Agion Technologies, Inc.||Antimicrobial orthopedic implants|
|US6610096 *||Aug 22, 2001||Aug 26, 2003||Macdonald Stuart G.||Prosthetic implants having enhanced utility|
|US6663634 *||Aug 3, 2001||Dec 16, 2003||Synthes (U.S.A.)||Bone screw|
|US6778861 *||Jun 21, 2000||Aug 17, 2004||Geot Gesellschaft Fur Elektro-Osteo-Therapie G.M.B.H.||Bone screw comprising a device for electrostimulation|
|US20040243130 *||Apr 20, 2004||Dec 2, 2004||Spineco, Inc., An Ohio Corporation||Electro-stimulation and medical delivery device|
|Citing Patent||Filing date||Publication date||Applicant||Title|
|US7097662 *||Aug 25, 2004||Aug 29, 2006||Ut-Battelle, Llc||In-vivo orthopedic implant diagnostic device for sensing load, wear, and infection|
|US7837719||May 9, 2003||Nov 23, 2010||Daemen College||Electrical stimulation unit and waterbath system|
|US7875082||May 9, 2008||Jan 25, 2011||Remi Sciences, Inc.||Ulnar head prosthesis system|
|US7918887||Mar 29, 2006||Apr 5, 2011||Roche Martin W||Body parameter detecting sensor and method for detecting body parameters|
|US8029566||Jun 2, 2008||Oct 4, 2011||Zimmer, Inc.||Implant sensors|
|US8052755||Jan 29, 2009||Nov 8, 2011||Remi Sciences, Inc.||Ulnar head prosthesis system|
|US8135466||Jun 30, 2006||Mar 13, 2012||Argentumcidalelectrics, Inc.||Prophylactic bactericidal implant|
|US8162924 *||Dec 4, 2008||Apr 24, 2012||The Invention Science Fund I, Llc||System, devices, and methods including actively-controllable superoxide water generating systems|
|US8221396||Aug 27, 2010||Jul 17, 2012||Silver Bullet Therapeutics, Inc.||Bone implants for the treatment of infection|
|US8241296||Dec 23, 2008||Aug 14, 2012||Zimmer, Inc.||Use of micro and miniature position sensing devices for use in TKA and THA|
|US8372147||Jan 27, 2011||Feb 12, 2013||Martin W. Roche||Method for detecting body parameters|
|US8372153||Jan 27, 2011||Feb 12, 2013||Martin W. Roche||Method for detecting body parameters|
|US8414286||Dec 4, 2008||Apr 9, 2013||Zimmer Orthopaedic Surgical Products, Inc.||Spacer molds with releasable securement|
|US8444654||Jan 27, 2011||May 21, 2013||Martin W. Roche||Method for detecting body parameters|
|US8449556||Jan 28, 2011||May 28, 2013||Martin W. Roche||Method for detecting body parameters|
|US8480389||Jul 9, 2010||Jul 9, 2013||Zimmer Orthopedic Surgical Products, Inc.||Spacer mold and methods therefor|
|US8583224 *||Aug 3, 2007||Nov 12, 2013||Cardiac Pacemakers, Inc.||Implantable medical device and methods for automated detection of infection|
|US8609036||Dec 27, 2007||Dec 17, 2013||Agentumcidalelectrics, Inc.||Ex vivo antimicrobial devices and methods|
|US8709055||Jan 18, 2010||Apr 29, 2014||Carbofix Orthopedics Ltd.||Composite material bone implant|
|US8761859||Apr 8, 2013||Jun 24, 2014||Martin W. Roche||Method for detecting body parameters|
|US8771323||Sep 13, 2011||Jul 8, 2014||Silver Bullet Therapeutics, Inc.||Bone implant and systems that controllably releases silver|
|US8801983||Jun 11, 2013||Aug 12, 2014||Zimmer Orthopaedic Surgical Products, Inc.||Spacer mold and methods therefor|
|US8927004||Jun 11, 2014||Jan 6, 2015||Silver Bullet Therapeutics, Inc.||Bioabsorbable substrates and systems that controllably release antimicrobial metal ions|
|US8932294 *||Aug 29, 2012||Jan 13, 2015||The United States Of America As Represented By The Secretary Of The Navy||Antimicrobial electrostatic implantable medical device|
|US8999367||Dec 12, 2014||Apr 7, 2015||Silver Bullet Therapeutics, Inc.||Bioabsorbable substrates and systems that controllably release antimicrobial metal ions|
|US9101417||Apr 7, 2014||Aug 11, 2015||Carbofix Orthopedics Ltd.||Composite material bone implant|
|US9101427||Jul 4, 2013||Aug 11, 2015||Carbofix Orthopedics Ltd.||Self tapping insert|
|US9108051 *||Jan 23, 2013||Aug 18, 2015||Silver Bullet Therapeutics, Inc.||Bone implant and systems that controllably releases silver|
|US20050149124 *||May 9, 2003||Jul 7, 2005||Brogan Michael S.||Electrical stimulation unit and waterbath system|
|US20100204802 *||Sep 21, 2007||Aug 12, 2010||Wilson Darren||Medical device|
|US20130053903 *||Feb 28, 2013||David Fleischmann||Antimicrobial electrostatic implantable medical device|
|US20130166039 *||Dec 19, 2012||Jun 27, 2013||Micropen Technologies Corporation||Osseous implant and methods of its making and use|
|US20140379090 *||Aug 8, 2012||Dec 25, 2014||Ecole Polytechnique Federale De Lausanne (Epfl)||In-vivo condition monitoring of metallic implants by electrochemical techniques|
|EP1991284A1 *||Feb 1, 2007||Nov 19, 2008||Jake Barralet||Bioimplants for use in tissue growth|
|WO2008035089A1 *||Sep 21, 2007||Mar 27, 2008||Smith & Nephew||Medical device|
|WO2008082586A2 *||Dec 27, 2007||Jul 10, 2008||Thomas A Fuller||Ex vivo antimicrobial devices and methods|
|WO2010082183A3 *||Jan 18, 2010||Jan 6, 2011||N.M.B. Medical Applications Ltd.||Composite material bone implant|
|WO2011031548A2||Aug 27, 2010||Mar 17, 2011||Silver Bullet Therapeutics, Inc.||Bone implants for the treatment of infection|
|U.S. Classification||607/116, 606/907, 606/331, 606/300, 623/18.11|
|International Classification||A61F2/30, A61B17/86, A61N1/18|
|Cooperative Classification||A61N1/18, A61L27/54, A61L2/0082, A61F2310/00395, A61F2/0077, A61F2/28, A61F2220/0025, A61F2230/0069, A61B2017/00734, A61F2310/00065, A61F2002/30405, A61F2002/30604, A61F2/34, A61F2002/30795, A61F2002/30322, A61F2/30, A61B17/8685, A61F2/367, A61F2/30767, A61F2002/30535, A61F2/3662, A61F2250/0026, A61B17/866, A61F2310/00083, A61F2310/00449, A61L2300/404, A61F2220/0033, A61N1/20, A61F2310/00155, A61F2002/30932, A61F2310/0052, A61F2/36, A61F2002/3692, A61F2310/00059, A61F2310/00149, A61F2/3676, A61B17/86, A61F2310/00455, A61L2300/602, A61F2002/30677, A61F2310/00413, A61F2310/00461, A61F2002/3631, A61F2310/00562, A61F2310/00029, A61F2310/00473, A61F2002/3611, A61F2310/00077, A61F2250/0001, A61F2002/30235, A61F2310/00514, A61B17/60, A61F2002/368, A61F2002/009, A61F2310/00113, A61F2002/305, A61F2220/0041, A61F2250/0058, A61N1/205, A61F2310/00568, A61F2310/00107, A61F2/32, A61F2002/30718, A61F2002/30354, A61L2300/606, A61F2310/00467, A61F2310/00071, A61F2/0095, A61F2002/30329, A61F2/30744, A61F2002/2821, A61F2002/30589, A61F2002/3625, A61F2002/482, A61F2002/30438, A61L2300/102, A61L2300/104, A61F2002/30668, A61L27/30|
|European Classification||A61L27/30, A61F2/36D6, A61F2/30L, A61B17/86M, A61F2/02D, A61N1/20, A61L27/54, A61F2/36, A61F2/30, A61B17/86|
|Mar 24, 2008||AS||Assignment|
Owner name: ARGENTUMCIDALELECTRICS, INC., PENNSYLVANIA
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:FULLER, THOMAS A.;WYSK, RICHARD A.;SEBASTIANELLI, WAYNE;REEL/FRAME:020911/0542
Effective date: 20080220