News Column

Researchers Submit Patent Application, "Ultraviolet Activated Antimicrobial Surfaces", for Approval

May 27, 2014



By a News Reporter-Staff News Editor at Life Science Weekly -- From Washington, D.C., NewsRx journalists report that a patent application by the inventors MCGRATH, TERRENCE S. (WELLTON, AZ); SEWELL, DEIDRE (FORT COLLINS, CO); STOREY, DANIEL M. (LONGMONT, CO), filed on January 7, 2014, was made available online on May 15, 2014 (see also Metascape, Llc).

The patent's assignee is Metascape, Llc.

News editors obtained the following quote from the background information supplied by the inventors: "The invention relates to light induced activation of metal coated surfaces and in particular to the enhancement of antimicrobial properties of selected metal/metal oxide coated surfaces.

"Metallic silver, silver oxides, and silver salts are highly effective antimicrobials which control infection by killing bacteria and viruses at wound sites. Silver ions block infection by forming insoluble compounds within the cell walls, blocking respiratory chains, and binding and denaturing bacterial DNA, thereby preventing replication. Silver-based biocides have also shown activity against decay fungi, some common molds and some insects due to interference with microbes in the insect gut (Dorau, et al., 2004).

"Ionic silver is recognized as an effective bactericide at levels of about 0.1 .mu.g/L while fungicidal activity requires levels on the order of about 1.9 .mu.g/L (Joyce-Wohrmann and Mustedt, 1999). Silver ions disrupt microbial cell walls and can also damage cell receptors by binding metabolically ineffective compounds to cell pathways. To maintain effectiveness against bacterial growth, silver ions must be released continuously at effective levels in order to compensate for decrease in effective concentration due to these binding interactions. On the other hand, release of excessively high concentrations of silver can harm healthy mammalian cells so that release profiles need to be taken into consideration when antimicrobial coatings are manufactured.

"Silver exhibits antimicrobial activity against most pathogens and there do not appear to be any reports of allergic reactions by patients (Russell and Hugo, 1994). Silver based coatings thus would appear to be candidates for use on surfaces of implanted medical devices in view of the tendency of in vivo devices to harbor serious infections. Applications of silver/silver oxide coatings have included hydrogels imbedded with silver compounds, wet chemistry using silver salts and antimicrobial compounds, and plasma vapor deposited surfaces of silver, cast silver, and cryogenically applied silver.

"Unfortunately, medical devices and implants are ideal surfaces for primary bacterial adherence and biofilm formation. Valves and catheters for example provide hard surfaces in warm, moist, nutrient-rich environments. Biofilms, once formed, are very difficult to eradicate. Over 1,500-fold concentrations of an antimicrobial agent may be required to kill bacteria established in a biofilm compared to the amount required for treatment of free floating or planktonic forms of bacteria.

"A recent upsurge in antibiotic resistant bacteria has again focused attention on the antimicrobial properties of silver and silver oxide. While some studies suggest that silver-protected surfaces on medical devices and implants may well be a preferred method of fighting infection, practical and long-term effective coating methods have yet to be developed (Tobler and Warner, 2005).

"Most hospital-acquired bloodstream infections are associated with the use of an intravascular device, such as central venous catheters. Catheter-associated bloodstream infections occur more often in intensive care unit (ICU) patients than in ward patients. The mortality rate attributable to bloodstream infections in surgical ICUs has been estimated to be as high as 35%. ICU-acquired bloodstream infections account for an estimated $40,000 increase in costs per survivor and an estimated $6,000 increase in hospital costs. (CDC Publication, 2001)

"There are at least two important considerations in developing antibacterial coatings for use in medical implants. A recurring problem with silver-based coatings is flaking, peeling, or sloughing of silver from the surface of the coated substrate. Release of high levels of silver ions for an extended period of time can cause localized cell death, or necrosis. This particular problem, for example, caused St. Jude Medical to withdraw a sewn-in silver heart valve cuff from the market in 2001 when it appeared that a silver/silver oxide coating on a valve cuff prevented proper healing. [FDA Enforcement Report 000635, Mar. 29, 2000]

"Even when silver-based coatings on medical devices are sufficiently adherent to avoid causing cell damage, the antimicrobial effects may be weak and/or sustained for only short periods of time. Medical implants, for example, tend to be a focus for infections and therefore would benefit from antimicrobial coatings that maintain activity for long periods of time without toxicity to normal cells.

"Efforts have been made to produce medically acceptable antimicrobial coatings on medical devices. The most commonly used coating processes are sputtering, ion beam assisted deposition (IBAD), and dip processes. While there are other, less commonly employed techniques, none of these commercially used methods has provided a coating that is both stable and antimicrobially resistant for relatively long periods of time. The disadvantages of these processes are briefly summarized.

"Sputtering and IBAD methods are similar except that IBAD additionally employs an ion beam that provides a more dense coating. In the IBAD process, ions are accelerated toward a target of antimicrobial material such as silver. When the ions hit the target, individual silver atoms are 'knocked-off'. The silver atoms react with oxygen in the plasma and are directed to the substrate and deposited. Problems with this technique include controlling the percent reacted to form AgO (the antimicrobially active form of silver), scalability, and, of most concern, lack of good adhesion.

"Consistently good adhesion is one of the more frequently encountered difficulties when coatings are produced by sputtering. Sputtering is a low energy process compared to other methods such as ion plasma deposition. Because of this, incoming ions do not have sufficient energy to securely implant into the surface. In attempts to solve this issue, sputtering of an antimicrobial coating usually requires a seed layer on a substrate surface to achieve even moderate adhesion. Under static conditions, sputtering may produce an acceptably adherent film, but if the substrate is twisted, bent or exposed to bacteria in vivo, as encountered with soft tissue repair devices, the coating has a high probability of de-lamination and subsequent release of metal particles into the body. Silver particles are a serious problem because large amounts of silver concentrated in one area can cause necrosis.

"Controlling the actual percent of AgO can also pose a significant problem with sputtering methods because in order to act as an effective antimicrobial, coatings need to consist of a large percentage of AgO versus Ag.sub.2O. The generation of singlet oxygen is also thought to be important and has been known for years to provide antimicrobial activity due to it's free radical nature (Kumar, et al., 2005).

"Scalability is also a consideration with sputtering processes when commercial quantities of coated devices are manufactured. Even when adhesion is not a significant consideration, cost reduction can only be realized by way of scalability. The sputtering process does not lend itself to large scale production, which requires complex fixturing, small throwing power, because parts need to be in close proximity to the target, and because of limitations on target size. Sputtering is an extremely slow process that has a typical deposition rate of angstroms per minute. This leads to long processing times per deposition cycle, in addition to necessary post processing to convert the non-reactive Ag.sub.2O to AgO. The area that can be treated at any one time is typically limited to 20-100 square inches. For these reasons, it is not only economically inhibiting to scale up the sputtering process, it is in practical terms physically impossible.

"Dip processing is another method of depositing an antimicrobial, whether silver or non-silver based, onto the surface of medical devices. The process of depositing a liquid based coating onto a substrate is complicated. The major problems with this technique are identification of a soluble antimicrobial agent with long-lasting activity, and avoidance of uneven adherence of the agent to the substrate.

"Uneven coatings on a substrate surface are generally unacceptable. With dip processes, wetting of the surface is random and spotty at best. This leads to areas that lack any antimicrobial coating and are a breeding ground for infection and biofilm formation.

"Some attention has been devoted to modifying surfaces of antimicrobial coatings in the hope of increasing antimicrobial activity. Ion beams have been used to carve textures into surfaces on implants, hydrocephalic shunts, percutaneous connectors, and orthopedic prostheses. The patterns can be holes, columns, cones, or pyramids as small as one .mu.m. These added patterns have been described as increasing a device's surface area 20 times and therefore increasing antimicrobial activity of deposited coatings, as suggested in U.S. Pat. No. 5,383,934.

"Deficiencies in the Art

"Deposition of antimicrobial materials is commonly limited to only a few methods for producing silver and silver oxide coatings. Each of these methods has serious disadvantages and none has been developed to efficiently produce the highly adherent, and evenly distributed antimicrobial films required for use on surfaces of medical devices and instruments. Current state of the art processes, such as sputtering, dip and ion beam assisted deposition (IBAD), produce coatings with limited adhesion to flexible substrates. Multiple layers of base coatings added to provide adhesion not only increase processing time and costs but also increase thickness, which may not be desirable.

"The need for antimicrobial coatings in the medical device market is well known, especially for antimicrobial films that have broad activity over relatively long periods of time. Where medical devices are used, the coatings must also meet safety standards for in vivo use."

As a supplement to the background information on this patent application, NewsRx correspondents also obtained the inventors' summary information for this patent application: "The present invention particularly addresses the problem of low activity in antimicrobial coatings, in addition to related problems of inefficient coating processes, and poor substrate adhesion of antibacterial coatings. Highly antimicrobially active coatings that resist flaking and peeling from substrate surfaces can be produced by the disclosed process which utilizes ion plasma deposition (IPD) in combination with ultraviolet (UV) light.

"Coatings with surprisingly improved antimicrobial activities have been obtained by exposing the surface of controlled IPD deposited metal coatings to ultraviolet light. An entirely unexpected finding was that several highly adherent metal coatings which initially showed little or no antimicrobial activity could be activated when exposed to ultraviolet light in the 200-400 nm range; in some cases exhibiting antimicrobial activity only after exposure to ultraviolet light.

"The invention is in part based on the development of an IPD-based method that produces predictable coating structures that have excellent adhesion, making these coatings particularly desirable for use on implanted medical devices. The method provides antimicrobial coatings that can be deposited in multiple layers of antimicrobial or antimicrobially-activated materials on metal and non-metal substrates for use in implants such as valves and indwelling catheters. The layers can be relatively thin, for example in the 100 nm range, so that production cost is reduced without sacrificing desired antimicrobial activity.

"A modified IPD/UV method has been developed for preparing antimicrobial metal coatings that have significantly enhanced antimicrobial activity. The coatings are particularly adaptable for use on devices and materials used in medical applications. The coatings do not flake or peel, as is common with coatings produced by electrodeposition or magnetron sputtering. Antibacterial activity is maintained on coatings applied to polymers and various metals because flaking and peeling are not a problem. Moreover, the coatings exhibit significantly improved antibacterial activity compared with currently available antimicrobial coatings.

"The antimicrobial coatings of the present invention can be applied to metals, and to polymers, which are preferred materials for medical devices such as catheters, stents, and plastic implants.

"The invention provides coatings that are uniquely suitable for use on medical devices for use in the human body or veterinary applications. The IPD/UV method for producing the coatings is economical and provides high quality coatings.

"Definitions

"PVD is thin film deposition process in the gas phase in which source material is physically transferred in the vacuum to the substrate without any chemical reactions involved. This type of deposition includes thermal evaporation electron-beam deposition and sputtering deposition. The IPD process is a sub-segment of physical vapor deposition.

"Macros and macroparticles refer to particles larger than a single ion. Small macro-particles refer to particles from two atoms to approximately 100 nanometers (alternatively, nano-particles). Medium macro-particles refer to particles from 100 nanometers to about 1 micron. Large macro-particles refer to particles larger than 1 micron.

"Antimicrobial refers to the ability of a compound to destroy microbes, prevent their development, or inhibit their pathogenic action and as used herein is intended to apply to bacteria, yeast and other fungi.

"IPD, as used in the context of experiments and methods described herein, refers to an ionic plasma deposition process that uses a modified controlled cathodic arc discharge on a target material to create highly energized plasma. IPD differs from normal cathodic arc processes described by others in that the deposition of particle size is highly controlled.

"The term about as used herein is intended to indicate that a specified number is not necessarily exact but may be higher or lower within a 10% range as determined by the particular procedure or method used.

"The term 'a' as used in the claims is not intended to limit to a single species.

"As used herein, 'substantially free' does not necessarily mean entirely free; rather that the amount of material present will not significantly affect properties claimed for the absence of the material.

BRIEF DESCRIPTION OF THE DRAWINGS

"FIG. 1 is a sketch of the IPD apparatus. Target material (1), substrate being coated (2), mechanism for moving the substrate closer and further away from the target (3), vacuum chamber (4), power supply for the target (5).

"FIG. 2 is another embodiment of the IPD apparatus. Target material (1), substrate being coated (2), mechanism for moving the substrate closer and further away from the target (3), vacuum chamber (4), power supply for the target (5), device to control arc speed (6).

"FIG. 3 is an example of the setup for a modified IPD/UV apparatus for depositing an adherent highly antimicrobial coating on a substrate. The apparatus incorporates the features of FIG. 1 and/or FIG. 2 with a source (7) to input ultraviolet light at selected wavelengths."

For additional information on this patent application, see: MCGRATH, TERRENCE S.; SEWELL, DEIDRE; STOREY, DANIEL M. Ultraviolet Activated Antimicrobial Surfaces. Filed January 7, 2014 and posted May 15, 2014. Patent URL: http://appft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&u=%2Fnetahtml%2FPTO%2Fsearch-adv.html&r=2833&p=57&f=G&l=50&d=PG01&S1=20140508.PD.&OS=PD/20140508&RS=PD/20140508

Keywords for this news article include: Hospital, Metascape Llc.

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Source: Life Science Weekly


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