GB2073024A - Antimicrobial Surgical Implants - Google Patents
Antimicrobial Surgical Implants Download PDFInfo
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- GB2073024A GB2073024A GB8109500A GB8109500A GB2073024A GB 2073024 A GB2073024 A GB 2073024A GB 8109500 A GB8109500 A GB 8109500A GB 8109500 A GB8109500 A GB 8109500A GB 2073024 A GB2073024 A GB 2073024A
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- silver
- implant
- surgical implant
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/18—Applying electric currents by contact electrodes
- A61N1/20—Applying electric currents by contact electrodes continuous direct currents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
- A61B17/56—Surgical instruments or methods for treatment of bones or joints; Devices specially adapted therefor
- A61B17/58—Surgical instruments or methods for treatment of bones or joints; Devices specially adapted therefor for osteosynthesis, e.g. bone plates, screws, setting implements or the like
- A61B17/68—Internal fixation devices, including fasteners and spinal fixators, even if a part thereof projects from the skin
- A61B17/80—Cortical plates, i.e. bone plates; Instruments for holding or positioning cortical plates, or for compressing bones attached to cortical plates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
- A61B17/56—Surgical instruments or methods for treatment of bones or joints; Devices specially adapted therefor
- A61B17/58—Surgical instruments or methods for treatment of bones or joints; Devices specially adapted therefor for osteosynthesis, e.g. bone plates, screws, setting implements or the like
- A61B17/68—Internal fixation devices, including fasteners and spinal fixators, even if a part thereof projects from the skin
- A61B17/84—Fasteners therefor or fasteners being internal fixation devices
- A61B17/86—Pins or screws or threaded wires; nuts therefor
- A61B17/866—Material or manufacture
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/30—Joints
- A61F2/30767—Special external or bone-contacting surface, e.g. coating for improving bone ingrowth
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/54—Biologically active materials, e.g. therapeutic substances
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
- A61B17/04—Surgical instruments, devices or methods, e.g. tourniquets for suturing wounds; Holders or packages for needles or suture materials
- A61B17/06—Needles ; Sutures; Needle-suture combinations; Holders or packages for needles or suture materials
- A61B17/06166—Sutures
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/30—Joints
- A61F2002/30001—Additional features of subject-matter classified in A61F2/28, A61F2/30 and subgroups thereof
- A61F2002/30003—Material related properties of the prosthesis or of a coating on the prosthesis
- A61F2002/3006—Properties of materials and coating materials
- A61F2002/30062—(bio)absorbable, biodegradable, bioerodable, (bio)resorbable, resorptive
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/30—Joints
- A61F2002/30001—Additional features of subject-matter classified in A61F2/28, A61F2/30 and subgroups thereof
- A61F2002/30667—Features concerning an interaction with the environment or a particular use of the prosthesis
- A61F2002/30677—Means for introducing or releasing pharmaceutical products, e.g. antibiotics, into the body
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/30—Joints
- A61F2/30767—Special external or bone-contacting surface, e.g. coating for improving bone ingrowth
- A61F2002/30934—Special articulating surfaces
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2210/00—Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
- A61F2210/0004—Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof bioabsorbable
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2310/00—Prostheses classified in A61F2/28 or A61F2/30 - A61F2/44 being constructed from or coated with a particular material
- A61F2310/00005—The prosthesis being constructed from a particular material
- A61F2310/00011—Metals or alloys
- A61F2310/00023—Titanium or titanium-based alloys, e.g. Ti-Ni alloys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2310/00—Prostheses classified in A61F2/28 or A61F2/30 - A61F2/44 being constructed from or coated with a particular material
- A61F2310/00389—The prosthesis being coated or covered with a particular material
- A61F2310/00395—Coating or prosthesis-covering structure made of metals or of alloys
- A61F2310/00419—Other metals
- A61F2310/0052—Coating made of silver or Ag-based alloys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/10—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing inorganic materials
- A61L2300/102—Metals or metal compounds, e.g. salts such as bicarbonates, carbonates, oxides, zeolites, silicates
- A61L2300/104—Silver, e.g. silver sulfadiazine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/602—Type of release, e.g. controlled, sustained, slow
- A61L2300/604—Biodegradation
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Surgery (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Heart & Thoracic Surgery (AREA)
- Molecular Biology (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Chemical & Material Sciences (AREA)
- Transplantation (AREA)
- Neurology (AREA)
- Medicinal Chemistry (AREA)
- Medical Informatics (AREA)
- Epidemiology (AREA)
- Dermatology (AREA)
- Radiology & Medical Imaging (AREA)
- Cardiology (AREA)
- Vascular Medicine (AREA)
- Materials For Medical Uses (AREA)
- Prostheses (AREA)
Abstract
Surgical implants, especially endoprosthetic orthopaedic implants and sutures, are rendered antimicrobial by the presence of a bioerodible metallic silver component, especially a surface coating, which provides in vivo a sustained release of silver ions in a concentration sufficient to provide a localized antimicrobial effect but insufficient to cause significant damage to connective tissue. Latently bioerodible silver components of an implant can be activated by, for example, abrasion, heating to above about 180 DEG C or, especially, contact with hydrogen peroxide. For example, an implant pin 2 of Ti alloy is coated at 1 with silver by film evaporation and subsequently placed in a culture plate 3 inoculated with Staphylococcus aureus, and incubated. A zone 4 of inhibition is apparent. <IMAGE>
Description
SPECIFICATION
Antimicrobial Surgical Implants
The present invention relates to surgical implants for the human or animal body and provides a manner of rendering such implants antimicrobial. The invention has particular, but not exclusive, application to endoprosthetic implants, especially orthopaedic implants.
As used in this Specification (including the
Claims thereof), the term "surgical implant" means any inanimate article (including a device) which is to be surgically implanted in the human or animal body for a prolonged period. In particular, said term includes, for example, orthopaedic pins, plates and screws, tracheotomy tubes, artifical joints, artificial pacemakers, catheters, sutures and clips. References to "endoprosthetic implants" include the entire implant, parts thereof and fixing means therefor.
Thus, in this Specification (including the Claims thereof, fixing pins and screws for use with endoprosthetic devices are included within the term "endoprosthetic implant".
With few exceptions, it has been the established practice for many years to manufacture surgical implants from materials which induce minimal tissue response and effects and yet possess adequate mechanical properties for the particular application. in the particular case of endoprosthetic orthopaedic implants, structural materials have been sought which do not corrode in vivo and which do not cause bone reabsorption.
Materials used for orthopaedic implants have progressed from the early use of common metals and their alloys, especially mild steel, through the use of surgical stainless steel to the present day use of cobalt chromium molybdenum alloys and titanium and titanium alloys. Other materials which are used in endoprosthetic orthopaedic implants include ceramic and carbon-based materials and some synthetic plastics materials such as ultra-high molecular weight polyethylene, some forms of nylon, polymethylmethacrylate and silicone elastomers. None of these materials have fulfilled entirely the aim of bioinertness (i.e.
bioinactivity) in all circumstances, but in general the attempt has been towards the use of more fully inert materials to prevent as tar as possible any interaction in vivo. The search for materials of greater bioinertness for use in surgical implants continues without diminution.
In the early years of implant surgery, silver was employed in the manufacture of endoprosthetic implants. In particular, silver wire, silver plates and silver-plated screws were used in bone repair surgery and tracheotomy tubes were silver plated.
However, the use of silver and silver plated implants had generally ceased by about 1935 in the ever continuing search for greater bioinertness for implant materials. In the particular case of orthopaedic implants, silver was, and still is considered to be unacceptable as an implant material, because of poor mechanical properties, connective tissue reaction and excessive subperiosteal bone growth (see, for example, Venable eft at Ann. Surg. 105,917- 938,1937).
Silver was one of the first metals known to man. Silver artifacts have been found in tombs dating to 4,000 B.C. It is believed that in antiquity, silver was deliberately chosen for water receptacles to conserve the quality of drinking water. Silver needles have traditionally been used in acupuncture, which is one of the oldest forms of invasive medical treatment. The anitmicrobial properties of silver compounds have been recognized for about 100 years. The first report of silver compounds for pharmaceutical use is that of aqueous silver nitrate for preventing eye infection in new born babies. Since then a range of silver salts, colloids and complexes have been employed to prevent and control infection.
Colloidal metallic silver has been used topically for conjunctivitis, urethritis and vaginitis.
The antimicrobial activity of metallic silver had been exploited in filter elements for domestic and industrial use (see Disinfection, Sterilization, and
Preservation; Editor S. S. Block, Publishers Lea and Febiger, Philadelphia, 1977). For this purpose, silver has been deposited on porous carbon or used in the form of a wire, gauze or other physical shape. It is believed that the active agent is the silver ion and that impurities must be present in the metal to expedite oxidation and solution.
The bodys ability to counter infection in the immediate vicinity of an implant is reduced thereby increasing the risk of a localised infection around the implant. This risk persists beyond the immediate postoperative period and is a significant complication in implant surgery. It is usually difficult to treat such infection. Often additional surgery and sometimes removal of the implant is required in order to effectively treat the infection.
It has been proposed that inorganic silver compounds should be incorporated in bone cement to reduce the risk of postoperative infection following the insertion of an endoprosthetic orthopaedic implant. In particular,
J. A. Spadaro eft at (Clinical Orthopaedics and
Related Research, 143, 266-270, 1979) proposed that low concentrations of inorganic silver compounds should be incorporated in polymethylmethacrylate bone cement for this purpose. The compounds which they evaluated for this purpose were silver chloride (AgCI), silver oxide (Ag2O), silver sulphate (Ag2SO), silver phosphate (Ag3PO4) and chlorided silver (Ag
AgCI). They report that their proposal was based upon the known antibacterial effects of silver ions.
The least effective of the compounds evaluated was chlorided silver which at 0.5% concentration did not inhibit any of the three bacteria tested, viz
Staphylococcus aureus, Escherichia coli and
Pseudomonas aeruginosa. In contrast, each of the other compounds evaluated significantly inhibited the bacteria at 0.5% concentration except for silver chloride which did not inhibit Escherichia coil at that concentration.
It has also been reported by the same workers that electrically generated silver ions constitute a potent broad spectrum antibacterial agent of use as adjunctive treatment in the management of chronic osteomyelitis (Becker et al, J. Bone and
Joint Surg., 60A, 871-881, 1978). The silver iontophoresis was used after standard surgical treatment for osteomyelitis, including debridement and the opening of all pockets of infection. When the wound was to be surgically closed, silver wire electrodes were temporarily inserted for a period of about six weeks. Electrical current was applied to the electrode from an external power source.
It is specifically stated in Becker et al (supra) that the clinical utility of silver is limited and, in particular, that diffusion of silver ions from a metallic surface such as silver foil is negligible.
This statement is consistent with the absence, to the best of our knowledge, of any reported observation of significant antimicrobial activity when using the prior art silver or silver coated implants. Further, it is consistent with our own tests which have shown that commerically available 99.99% pure silver bar and foil do not inhibit the in vitro growth of Staphylococcus aureus.
Having regard to the above, the present state of the art can be summarized as being that, despite the reported antimicrobial activity of certain forms of metallic silver and its use before about 1935 in surgical implants, the use of metallic silver in surgical implants is contraindicated. Further, recant developments in the field of orthopaedic surgery teach the use of silver salts and electrically generated silver ions
but not metallic silver surfaces for the
prophylactic or adjunctive treatment of
postoperative infections following implant
surgery.
It is the object of the present invention to
provide a simple, effective and surgically
acceptable manner of rendering surgical implants
antimicrobial to provide a prophylactic treatment
of postoperative infection. Suprisingly, it has been
found that this object can be achieved by going
against the long-established teachings of the art
and using metallic (including alloyed) silver,
provided that two criteria are met. One criteria is
that the metallic silver should be activated in the
sense that it erodes in vivo to provide a sustained
release of silver ions at a concentration sufficient
to produce a localized antimicrobial effect but
insufficient to cause significant damage to
connective tissue.The other criteria is that the
structural material of the implant should be a
substantially bioinert material so that the
mechanical integrity of the implant is retained
despite the erosion of the metallic silver.
According to one aspect of the present
invention, there is provided a surgical implant
having a composite form comprising a
substantially bioinert structural material providing permanent mechanical integrity to the implant and a bioerodible metallic silver component providing in vivo a sustained release of silver ions
in a concentration sufficient to provide a localized antimicrobial effect but insufficient to cause significant damage to connective tissue.
In another aspect of the present invention, there is provided a method of rendering antimicrobial a surgical implant comprising a substantially bioinert structural material providing permanent mechanical integrity to the implant, said method comprising depositing on or in said implant a quantity of bioerodible metallic silver which will provide in vivo a sustained release of silver ions in a concentration sufficient to provide a localized antimicrobial effect but insufficient to cause significant damage to connective tissue.
In a further aspect of the present invention there is provided a method of rendering antimicrobial a surgical implant having a composite form comprising a substantially bioinert structural material providing permanent mechanical integrity to the implant and a latently bioerodible metallic silver component, said method comprising treating said implant to render said silver component bioerodible to provide in vivo a sustained release of silver ions in a concentration sufficient to provide a localized antimicrobial effect but insufficient to cause significant damage to connective tissue.
In yet another aspect of the present invention, there is provided a method of prophylactic treatment of postoperative infection following implant surgery, said method comprising selecting a surgical implant having a composite form comprising a substantially bioinert structural material providing permanent mechanical integrity to the implant and a latently bioerodible metallic silver component, treating said selected insert to render the metallic silver component thereof bioerodible to provide in vivo a sustained release of silver ions in a concentration sufficient to provide a localized antimicrobial effect but insufficient to cause significant damage to connective tissue, and surgically implanting the thus activated implant in the human or animal body.
As mentioned previously, the invention has particular, but not exclusive, application to endoprosthetic implants, especially orthopaedic implants. However, the invention is applicable to any implant which has permanent structural integrity. The implant can be made of any structural material which is substantially bioinert but usually will be made of titanium or titanium~ alloy, or cobalt chrome molybdenum alloy, or ceramic material, or non-toxic synthetic plastics material, or any combination of these materials.
Examples of implants to which the invention has particular application include orthopaedic plates, pins and screws, artificial joints and sutures.
The metallic silver component can be made of commercially pure (i.e. 99.99?/o) silver metal or of a silver alloy, for example a dental amalgam or silver solder. In order to promote galvanic action producing silver ions, there can be used an alloy of silver with a more noble metal such as gold or platinum.
Usually, but not necessarily, the silver component will be deposited in or on the permanent implant structure. Conveniently, the silver component is constituted by a surface coating on at least part of the implant structure.
However, the component can be constituted in other ways, for example as a deposit in one or more cavities provided in the permanent implant structure or as a permeant in a porous substrate in or on the permanent implant structure.
The location of the silver component in the implant will be selected having regard to the structure and intended application of the implant.
In the case of a silver coating, said coating can extend over all or only a selected part or parts of the implant structure. Similarly, in the case of cavity-deposited silver or permeant silver, the silver can be distributed over the implant structure or provided only at a selected part or parts thereof.
The quality of silver in the composite implant and the rate of erosion in vivo is such as to provide a sustained release of silver ions in sufficient concentration to produce a localized antimicrobial effect but insufficient to produce significant damage to connective tissue. The required concentration balance readily can be achieved because antimicrobial activity is provided at a concentration of the order of nanogrammes/ml whereas connective tissue damage appears to require concentrations of six orders higher, i.e. milligrammes/ml. Nevertheless, the cumulative effects of sustained release of silver ions in the body must be considered when determining the quantity of silver to be used and the rate of erosion to avoid toxic effects in the human or animal body.Any osteogenesis produced by the antimicrobial concentrations of silver can be tolerated and in many cases actually can be advantageous in that, for example, an orthopaedic implant is more securely located and/or the bone thickened in an area of weakness where it is joined to the implant.
It has been found that the quantity of silver in the composite implant suitably is the amount corresponding to a surface coating of 10 to 1000
Angstroms applied over the entire surface of the implant. This corresponds in the case of a large implant such as an artificial hip joint to not more than about 2 mg silver with proportionally smaller amounts of silver for smaller implants. Usually, an amount corresponding to such a coating of 25 to 500 Angstroms thick will be used.
It is an essential feature of the invention that the metallic silver component should be bioerodible to provide in vivo the silver ions required for the desired antimicrobial activity. As previously stated, metallic silver surfaces such as silver bar, silver foil and silver coatings applied by conventional plating techniques are not significantly antimicrobial or at least lose any antimicrobial activity shortly after manufacture.
Moreover, the preoperative treatment of surgical implants at the time when silver or silver-plated implants were in use was such that the silver content of said implants would not have been suitably activated to become antimicrobial. In particular, sterilization would have been conducted using temperatures of no more than about 1 000C and/or sterilizing agents, such as alcohol, which do not activate the silver content of bioerode. However, there are a number of ways in which metallic silver can be rendered suitably bioerodible, including chemical, mechanical and/or thermal treatment as discussed below. It is expected that treatments additional to those discussed below will be apparent to those skilled in the metallurgical art.
An existing metallic silver surface can be activated by abrasion to freshly expose the metal surface. For example, the surface can be scratched with one or more pointed tools or, more usually, rubbed with an abrasive material or tool.
In a particular embodiment of the invention in which the implant is an artificial joint, the silver component can comprise a coating on or deposit at a wear surface of the joint so that movement of the joint continually abrades the silver coating or deposit. In another embodiment, the silver is deposited in or on a substrate of a more readily bioerodible material, for example iron, so that silver is released as the substrate erodes.
An existing metallic silver surface also can be activated thermally by heating to a temperature in excess of about 1806C. The duration of heating required to activate the surface will depend upon the temperature and the nature of the surface.
Usually a temperature in the range 2000 to 2700C will be used for a period of 16 to 60 mins.
It has been found suprisingly that the surface is activated either in a molecular oxygen-containing atmosphere such as gaseous oxygen or air, or in an inert atmosphere, such as gaseous argon or nitrogen.
The presently preferred manner of activating existing metallic silver surfaces is to treat the surface with hydrogen peroxide. Preferably, the implant is immersed in the hydrogen peroxide.
Suitably, 10 to 100 vols hydrogen peroxide is employed for a contact time of about 20 mins.
The preference for this method is based upon convenience of use especially in view of the ready availability of hydrogen peroxide in operating theatres, where it is used to irrigate wounds at the time of operation.
The silver component can be deposited in an activated form by use of modern techniques such as sputter coating, film evaporation and ion implantation. These techniques are well known per se in the metallurgical art and hence will not be discussed in detail. Selection of a particular technique can be made from the general knowledge of the properties of the deposit produced and/or by simple experiment to assess in vitro the antimicrobial activity of the deposit. It has been found, for example, that silk or terylene sutures can be satisfactorily coated with an active silver coating using sputter techniques.
The present invention affords many advantages over current proposals and methods of dealing with postoperative infection following implant surgery. In particular, it provides a prophylatic treatment which at least reduces the risk of postoperative infection and which can be regularly employed in implant surgery. The composite implant is self-contained requiring no energy source, such as electrical current, to produce the antimicrobial activity. Said activity is provided merely by bioerosion of the silver component.The silver ions so released are not accompanied by irritant and toxic cations such as those generated by freely dissociable salts such as silver nitrate, Further, it is less likely that the antimicrobial activity of silver ions will be circumvented by such relatively minor genetic mutation in a micro-organism as will often circumvent the anti-microbial activity of an antibiotic.
The following is a description, by way of example only and with reference to the accompanying drawings, of embodiments of the present invention. In the drawings:~
Figure 1 is a photograph of an incubated culture plate in which is located an implant pin which is partly coated with silver;
Figure 2 is a photograph of an incubated culture plate in which are located implant screws;
Figure 3 is a photograph of an incubated culture plate in which is located an implant screw
completely coated with silver;
Figures 4, 5 and 6 are photographs of incubated culture plates in which are located implant screws which are partly coated with silver;
Figure 7 is a photograph of an incubated culture plate in which a silver bar was located during incubation but was subsequently removed;
Figure 8 is a photograph of an incubated culture plate in which is located a silver bar;;
Figures 9, 10 and 1 1 are photographs of incubated culture plates in which are located silver foil discs.
Referring first to Figure 1, the bottom half 1 of
an implant pin 2 of titanium alloy type 318 was coated with silver by film evaporation. The thus coated pin was autoclaved in a conventional modern operating theatre autoclave with steam at about 1 400C followed by a hot air drying cycle.
After cooling, it was then placed on a culture plate 3 which had been inoculated with
Staphylococcus aureus and the culture incubated for 24 hours. As can be seen in Figure 1, there was a clearly apparent zone 4 of inhibition around the silver coated bottom half 1 but no inhibition around the top half of the pin 2.
Referring now to Figure 2, three screws 5 of titanium alloy type 318 which had not been subjected to any special treatment were placed on a culture plate 23 which was inoculated and incubated as described above. As can be seen in
Figure 2, there was no inhibition of Staph. aureus.
A titanium alloy screw identical to the screws 5 of Figure 2 was completely coated with 35 nm layer of silver by sputter coating and shortly thereafter the coated screw 35 (see Figure 3) was placed on a culture plate 33, which was inoculated and incubated as described above. As can be seen in Figure 3, there was a clearly apparent zone 34 of inhibition completely around the silver coated screw 35.
Three titanium alloy screws identical to the screws 5 of Figure 2 were coated with a 35 nm layer of silver at their upper halves only by sputter coating. The partly coated screws 45 (see Figure 4) were heated in air for 1 hour at 2500C and then autoclaved with steam at 1200 C. After cooling, the autoclaved screws 45 were placed on a culture plate 43, which was inoculated and incubated as described above. As can be seen in
Figure 4, there were clearly apparent zones 44 of inhibition around the coated upper halves of the screws 45 but no inhibition around their bottom halves.
Two titanium alloy screws identical to the screws 5 of Figure 2 were sputter coated with a 35 nm layer of silver at their upper halves only and subsequently heated in air for 1 hour at 2500C. After cooling, the partly coated screws 55 (see Figure 5) were placed on a culture plate 53, which was inoculated and incubated as described above. As can be seen in Figure 5, inhibition occurred only in zones 54 around the silver coated top halves of the screws 55.
The titanium alloy screws identical to the screws 5 of Figure 2 were sputter coated with a 35 nm layer of silver at their upper halves only, subsequently heated in air for 1 hour at 2500C and then autoclaved in a theatre autoclave at 1 400C with steam followed by a hot air drying cycle. After cooling, the partly coated screws 65 (see Figure 6) were placed on a culture plate 63, which was inoculated and incubated as described above. As can be seen in Figure 6, inhibition occurred only in zones 64 around the silver coated top halves of the screws 65.
A commercially available silver bar (99.99% purity) was heated in air at 2250C for 1 hour and, after cooling, placed on an empty culture plate.
Culture medium was poured onto the plate and then inoculated with Staph. aureus (top half) and
E. coli (bottom half) and incubated as described above. As can be seen in Figure 7, there was a clearly apparent zone of inhibition surrounding the location of the silver bar (subsequently removed) in the culture plate 73.
The procedure described above with reference to Figure 7 was repeated except that the culture medium and bar 86 (see Figure 8) were refrigerated for 24 hours before inoculation. As can be seen in Figure 8 there was a clearly apparent zone 84 of inhibition in the culture plate 83 around the bar 86.
Four discs of silver foil (99.99% purity) 97 (see
Figure 9) were heated at 2700C for 20 mins in gaseous oxygen and, after cooling, placed on a culture plate 93, which was inoculated and
incubated as described above. As can be seen in
Figure 9, there were clearly apparent zones 94 of
inhibition surrounding the discs 97.
The procedure described above with reference
to Figure 9 was repeated except that the discs
107 (see Figure 10) were heated in gaseous
nitrogen instead of oxygen. As can be seen in
Figure 10, there were clearly apparent zones 104
of inhibition in the culture plate 103 surrounding
the discs 101.
Three discs of silver foil (99.99% purity) 117
(see Figure 11) were immersed in 100 vols
hydrogen peroxide for 20 mins. The discs were
thoroughly washed with water to remove all
traces of hydrogen peroxide and then placed on a
culture plate 11 3, which was inoculated and
incubated as described above. As can be seen in
Figure 11, there were clearly apparent zones 114
of inhibition around the discs 113.
Similar results to those reported above have
also been observed with Escherichia coli, with
black silk and terylene sutures onto which silver
has been sputter coated, and with hydrogen
peroxide activated silver alloy dental amalgam
which is at least 15 years old. Further, tests with
the activated foil discs 97, 107, and 11 7 show
that their antimicrobial activity is retained for at
least 8 weeks when stored in air at room
temperature.
Claims (48)
1. A surgical implant (as hereinbefore defined)
having a composite form comprising a
substantially bioinert structural material providing
permanent mechanical integrity to the implant
and bioerodible metallic silver compoent
providing in vivo a sustained release of silver ions
in a concentration sufficient to provide a localized
antimicrobial effect but insufficient to cause
significant damage to connective tissue.
2. A surgical implant as claimed in Claim 1 .which is an endoprosthetic implant.
3. A surgical implant as claimed in Claim 2
which is an endoprosthetic orthopaedic implant.
4. A surgical implant as claimed in Claim 1
which is a suture.
5. A surgical implant as claimed in any one of
the preceding Claims wherein the metallic silver is
commercially pure silver metal.
6. A surgical implant as claimed in any one of
Claims 1 to 5 wherein the metallic silver is a silver
alloy.
7. A surgical implant as claimed in any one of
the preceding Claims wherein the silver
component is deposited in or on the permanent
implant structure.
8. A surgical implant as claimed in Claim 7
wherein the silver component is constituted by a
surface coating on at least part of the implant
structure.
9. A surgical implant as claimed in Claim 7 or 8
which is an artificial joint and the silver
component comprises a coating or deposit at a
wear surface.
10. A surgical implant as claimed in Claim 7 wherein the silver is deposited in or on a substrate of more readily bioerodible material.
11. A surgical implant as claimed in any one of the preceding Claims wherein the amount of silver in the composite implant would be sufficient to provide a surface coating of 10 to 1000 Angstroms thick applied over the entire surface of the implant.
12. A surgical implant as claimed in Claim 11 wherein said amount of silver would be sufficient to provide a surface coating of 25 to 500
Angstroms thick applied over the entire surface of the implant.
13. A surgical implant as claimed in Claim 1 and substantially as hereinbefore described with reference to any one of Figures 1, 3, 4, 5 or 6 of the accompanying drawings.
14. A method of rendering antimicrobial a surgical implant (as hereinbefore defined) having a composite form comprising a substantially bioinert structural material providing permanent mechanical integrity to the implant and a latently bioerodible metallic silver component, said method comprising treating said implant to render said silver component bioerodible to provide in vivo a sustained release of silver ions in a concentration sufficient to provide a localized antimicrobial effect but insufficient to cause significant damage to connective tissue.
15. A method as claimed in Claim 14 wherein the surgical implant is an endoprosthetic implant.
16. A method as claimed in Claim 15 wherein the surgical implant is an endoprosthetic orthopaedic implant.
17. A method as claimed in Claim 14 wherein the surgical implant is a suture.
18. A method as claimed in any one of Claims 14 to 17 wherein the metallic silver is commercially pure silver metal.
19. A method as claimed in any one of Claims 14 to 17 wherein the metallic silver is a silver alloy.
20. A method as claimed in any one of Claims 14 to 19 wherein the silver component is deposited in or on the permanent implant structure.
21. A method as claimed in Clam 20 wherein the silver component is constituted by a surface coating on at least part of the implant structure.
22. A method as claimed in any one of Claims 14 to 21 wherein the amount of silver in the composite implant would be sufficient to provide a surface coating of 10 to 1000 Angstroms thick applied over the entire surface of the implant.
23. A method as claimed in Claim 22 wherein said amount of silver would be sufficient to provide a surface coating of 25 to 500 Angstoms thick applied over the entire surface of the implant.
24. A method as claimed in any one of Claims 14 to 23 wherein said treatment to activate the latently bioerodible metallic silver component comprises abrasion to freshly expose the metal surface.
25. A method as claimed in any one of Claims 14 to 23 wherein said treatment to activate the latently bioerodible metallic silver component comprising heating at a temperature in excess of about 18O0C.
26. A method as claimed in Claim 25 wherein the heating is carried out in a molecular oxygencontaining atmosphere.
27. A method as claimed in Claim 25 wherein the heating is carried out in an inert atmosphere.
28. A method as claimed in any one of Claims 14 to 23 wherein said treatment to activate the latently bioerodible metallic silver component comprises contact with hydrogen peroxide.
29. A method as claimed in Claim 28 wherein the implant is immersed in hydrogen peroxide.
30. A method as claimed in Claim 28 or Claim 29 wherein 10 to 100 vols hydrogen peroxide is used for a contact time of about 20 mins.
31. A method of rendering antimicrobial a surgical implant (as hereinbefore defined) comprising a substantially bioinert structural material providing permanent mechanical integrity to the implant, said method comprising depositing on or in said implant a quantity of bioerodible metallic silver which will provide in vivo a sustained release of silver ions in a concentration sufficient to provide a localized antimicrobial effect but insufficient to cause significant damage to connective tissue.
32. A method as claimed in Claim 31 wherein the surgical implant Is an endoprosthetic implant.
33. A method as claimed in Claim 32 wherein the surgical implant is an endoprosthetic surgical implant.
34. A method as claimed in Claim 31 wherein the surgical implant is a suture.
35. A method as claimed in any one of Claims 31 to 34 wherein the metallic silver is commerically pure silver metal.
36. A method as claimed in any one of Claims 31 to 34 wherein the metallic silver is a silver alloy.
37. A method as claimed in any one of Claims 31 to 36 wherein the silver is deposited as a surface coating on at least part of the permanent implant structure.
38. A method as claimed in any one of Claims 31 to 37 wherein the surgical implant is an artificial joint and the silver is deposited on or at a wear surface.
39. A method as claimed in any one of Claims 31 to 37 wherein the silver is deposited in or on a substrate of more readily bioerodible material.
40. A method as claimed in any one of Claims 31 to 37 wherein the amount of silver deposited would be sufficient to provide a surface coating of 10 to 1000 Angstroms thick applied over the entire surface of theimplant.
41. A method as claimed in Claim 40 wherein the amount of silver deposited would be sufficient to provide a surface coating of 25 to 500
Angstroms thick applied over the entire surface of the implant.
42. A method as claimed in any one of Claims 31 to 41 wherein the silver is deposited by sputter coating.
43. A method as claimed in any one of Claims 31 to 41 wherein the silver is deposited by film evaporation.
44. A method as claimed in any one of Claims 31 to 41 wherein the silver is deposited by ion implantation.
45. A method as claimed in Claim 14 and substantially as hereinbefore described with reference to any one of Figures 4, 5, 6, 9, 10 and 11.
46. A method as claimed in Claim 31 and substantially as hereinbefore described with reference to any one of Figures 2, 4, 5, 6 and 7.
47. A surgical implant whenever obtained by a method as claimed in any one of Claims 14 to 30 and 45.
48. a surgical implant whenever obtained by a method as claimed in any one of Claims 31 to 44 and 46.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB8109500A GB2073024B (en) | 1980-03-27 | 1981-03-26 | Antimicrobial surgical implants |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB8010362 | 1980-03-27 | ||
GB8109500A GB2073024B (en) | 1980-03-27 | 1981-03-26 | Antimicrobial surgical implants |
Publications (2)
Publication Number | Publication Date |
---|---|
GB2073024A true GB2073024A (en) | 1981-10-14 |
GB2073024B GB2073024B (en) | 1984-06-27 |
Family
ID=26274995
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
GB8109500A Expired GB2073024B (en) | 1980-03-27 | 1981-03-26 | Antimicrobial surgical implants |
Country Status (1)
Country | Link |
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GB (1) | GB2073024B (en) |
Cited By (22)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0124536A1 (en) * | 1982-11-05 | 1984-11-14 | BAXTER INTERNATIONAL INC. (a Delaware corporation) | Antimicrobial compositions |
EP0134340A1 (en) * | 1983-08-22 | 1985-03-20 | The University of Utah Research Foundation | Peritoneal injection catheter apparatus |
US4557724A (en) * | 1981-02-17 | 1985-12-10 | University Of Utah Research Foundation | Apparatus and methods for minimizing cellular adhesion on peritoneal injection catheters |
US4559033A (en) * | 1980-10-27 | 1985-12-17 | University Of Utah Research Foundation | Apparatus and methods for minimizing peritoneal injection catheter obstruction |
GB2194155A (en) * | 1986-08-22 | 1988-03-02 | Atomic Energy Authority Uk | Improvements in prostheses |
GB2203342A (en) * | 1987-04-07 | 1988-10-19 | Julian Garth Ellis | Radio-opaque tracer for surgical implants |
WO1993023092A1 (en) * | 1992-05-19 | 1993-11-25 | Westaim Technologies Inc. | Anti-microbial coating for medical devices |
WO1995013704A1 (en) * | 1993-11-18 | 1995-05-26 | Westaim Technologies Inc. | Anti-microbial materials |
US5454886A (en) * | 1993-11-18 | 1995-10-03 | Westaim Technologies Inc. | Process of activating anti-microbial materials |
US6017553A (en) * | 1992-05-19 | 2000-01-25 | Westaim Technologies, Inc. | Anti-microbial materials |
WO2001065937A1 (en) * | 2000-03-06 | 2001-09-13 | Porex Technologies Corporation | Porous plastic media with antiviral or antimicrobial properties and processes for making the same |
WO2001080920A3 (en) * | 2000-04-17 | 2002-04-11 | Nucryst Pharm Corp | Antimicrobial bioabsorbable materials |
US6989156B2 (en) | 2001-04-23 | 2006-01-24 | Nucryst Pharmaceuticals Corp. | Therapeutic treatments using the direct application of antimicrobial metal compositions |
US7201925B2 (en) | 2002-04-23 | 2007-04-10 | Nueryst Pharmaceuticals Corp. | Treatment of ungual and subungual diseases |
WO2007101267A1 (en) * | 2006-03-01 | 2007-09-07 | Warsaw Orthopedic, Inc. | Bone anchors and methods of forming the same |
US7695522B2 (en) | 2002-04-16 | 2010-04-13 | Accentus Plc | Metal implants |
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ATE282420T1 (en) | 2000-07-27 | 2004-12-15 | Nucryst Pharm Corp | USE OF PRECIOUS METALS FOR THE PRODUCTION OF A MEDICINAL PRODUCT FOR THE TREATMENT OF HYPERPROLIFERATIVE SKIN DISORDERS AND DISEASES |
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1981
- 1981-03-26 GB GB8109500A patent/GB2073024B/en not_active Expired
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US4559033A (en) * | 1980-10-27 | 1985-12-17 | University Of Utah Research Foundation | Apparatus and methods for minimizing peritoneal injection catheter obstruction |
US4557724A (en) * | 1981-02-17 | 1985-12-10 | University Of Utah Research Foundation | Apparatus and methods for minimizing cellular adhesion on peritoneal injection catheters |
EP0124536A4 (en) * | 1982-11-05 | 1985-06-06 | Baxter Travenol Lab | Antimicrobial compositions. |
EP0124536A1 (en) * | 1982-11-05 | 1984-11-14 | BAXTER INTERNATIONAL INC. (a Delaware corporation) | Antimicrobial compositions |
EP0134340A1 (en) * | 1983-08-22 | 1985-03-20 | The University of Utah Research Foundation | Peritoneal injection catheter apparatus |
GB2194155B (en) * | 1986-08-22 | 1990-07-04 | Atomic Energy Authority Uk | Improvements in prostheses |
GB2194155A (en) * | 1986-08-22 | 1988-03-02 | Atomic Energy Authority Uk | Improvements in prostheses |
GB2203342B (en) * | 1987-04-07 | 1991-12-11 | Julian Garth Ellis | Radio-opaque tracer for surgical implants |
GB2203342A (en) * | 1987-04-07 | 1988-10-19 | Julian Garth Ellis | Radio-opaque tracer for surgical implants |
MD1728C2 (en) * | 1992-05-19 | 2002-03-31 | Westaim Technologies Inc | Modified material, modified anti-microbial material, method of preparing the modified material, method of forming the anti-microbial coating and medical device having on its surface the anti-microbial coating |
WO1993023092A1 (en) * | 1992-05-19 | 1993-11-25 | Westaim Technologies Inc. | Anti-microbial coating for medical devices |
AU673170B2 (en) * | 1992-05-19 | 1996-10-31 | Smith & Nephew (Overseas) Limited | Anti-microbial coating for medical devices |
US5681575A (en) * | 1992-05-19 | 1997-10-28 | Westaim Technologies Inc. | Anti-microbial coating for medical devices |
US5770255A (en) * | 1992-05-19 | 1998-06-23 | Westaim Technologies, Inc. | Anti-microbial coating for medical devices |
US6017553A (en) * | 1992-05-19 | 2000-01-25 | Westaim Technologies, Inc. | Anti-microbial materials |
CN1066783C (en) * | 1992-05-19 | 2001-06-06 | 韦斯泰姆生物医药公司 | Anti-microbial coating for medical devices |
WO1995013704A1 (en) * | 1993-11-18 | 1995-05-26 | Westaim Technologies Inc. | Anti-microbial materials |
US5454886A (en) * | 1993-11-18 | 1995-10-03 | Westaim Technologies Inc. | Process of activating anti-microbial materials |
US6551608B2 (en) | 2000-03-06 | 2003-04-22 | Porex Technologies Corporation | Porous plastic media with antiviral or antimicrobial properties and processes for making the same |
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US6719987B2 (en) * | 2000-04-17 | 2004-04-13 | Nucryst Pharmaceuticals Corp. | Antimicrobial bioabsorbable materials |
US6989156B2 (en) | 2001-04-23 | 2006-01-24 | Nucryst Pharmaceuticals Corp. | Therapeutic treatments using the direct application of antimicrobial metal compositions |
US7695522B2 (en) | 2002-04-16 | 2010-04-13 | Accentus Plc | Metal implants |
US9393349B2 (en) | 2002-04-16 | 2016-07-19 | Accentus Medical Limited | Metal implants |
US8945363B2 (en) | 2002-04-16 | 2015-02-03 | Accentus Medical Limited | Method of making metal implants |
US7201925B2 (en) | 2002-04-23 | 2007-04-10 | Nueryst Pharmaceuticals Corp. | Treatment of ungual and subungual diseases |
US9011665B2 (en) | 2004-03-13 | 2015-04-21 | Accentus Medical Limited | Metal implants |
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US7850717B2 (en) | 2006-03-01 | 2010-12-14 | Warsaw Orthopedic, Inc. | Bone anchors having two or more portions exhibiting different performance characteristics and method of forming the same |
US8858775B2 (en) | 2007-10-03 | 2014-10-14 | Accentus Medical Limited | Method of manufacturing metal with biocidal properties |
DE102009014771A1 (en) | 2009-03-25 | 2010-09-30 | Cochlear Ltd., Lane Cove | Percutaneous hearing aid implant for permanent anchoring in skull bone of patient, has counter bearing provided with outer surface, where antibacterial coating is applied on inner part of bearing and/or bone fastener and/or surface of screw |
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EP2637608A4 (en) * | 2010-11-12 | 2014-04-09 | Silver Bullet Therapeutics Inc | Bone implant and systems that controllably releases silver |
EP2637608A1 (en) * | 2010-11-12 | 2013-09-18 | Silver Bullet Therapeutics Inc. | Bone implant and systems that controllably releases silver |
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Legal Events
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PCNP | Patent ceased through non-payment of renewal fee |