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WO2021247042A1 - Revêtements imprégnés de nanoparticules d'argent pour dispositifs électroniques en vue de lutter contre des infections nosocomiales - Google Patents

Revêtements imprégnés de nanoparticules d'argent pour dispositifs électroniques en vue de lutter contre des infections nosocomiales Download PDF

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Publication number
WO2021247042A1
WO2021247042A1 PCT/US2020/036384 US2020036384W WO2021247042A1 WO 2021247042 A1 WO2021247042 A1 WO 2021247042A1 US 2020036384 W US2020036384 W US 2020036384W WO 2021247042 A1 WO2021247042 A1 WO 2021247042A1
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Prior art keywords
sheet
covering
recited
silver
nano
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Ceased
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PCT/US2020/036384
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English (en)
Inventor
Sumit Arora
Om Prakash JHA
Robert C. ROSS Jr.
J. Mark SWANZY
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Infection Sciences LLC
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Infection Sciences LLC
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Publication of WO2021247042A1 publication Critical patent/WO2021247042A1/fr
Anticipated expiration legal-status Critical
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    • 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
    • A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
    • A61L2/16—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor using chemical substances
    • A61L2/23—Solid substances, e.g. granules, powders, blocks, tablets
    • A61L2/238—Metals or alloys, e.g. oligodynamic metals
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y30/00—Nanotechnology for materials or surface science, e.g. nanocomposites

Definitions

  • the present invention relates generally to materials providing anti- microbial properties.
  • the invention relates to coverings for electronic devices integrated with an antimicrobial agent or compound.
  • the invention further relates to materials impregnated with silver based substances to combat microbial activity.
  • HAIs hospital-acquired infections
  • CDC Centers for Disease Control and prevention
  • ECDs electronic communication devices
  • ECDs electronic communication devices
  • MSRA Methicillin-Resistant Staphylococcus Aureus
  • MSRA Methicillin-Resistant Staphylococcus Aureus
  • Nanotechnology is the convergence of different sciences such as physics, chemistry, biology, material science and medicine, which finds large applications in multiple aspects of research and in everyday life.
  • the availability of new nanomaterials has caused a rapid expansion of the medical arts, often referred to as “nanomedicine,” and are now incorporated into a range of products and technologies. These applications can be in general useful for the management of various microbial infections and in particular for diagnostic and therapeutic uses.
  • metal nanoparticles have recently become known to be a promising antimicrobial agent that acts on a broad range of target sites on microorganisms, both extracellularly and intracellularly.
  • advances in reducing ions to nanoscale-sized particles have enabled the integration of metal nanoparticles into a large number of materials such as plastics, coating materials, foams and fibers, both natural and synthetic. These nanomaterials have proven their effectiveness for treating infectious diseases, including antibiotic resistance, in vitro as well as in animal models.
  • Silver is well known for its antimicrobial properties. Silver derives its broad spectrum antimicrobial effect from its ability to bind irreversibly to a variety of nucleophilic groups commonly found in or on the cells of bacteria, viruses, yeast, fungi, and protozoa. Binding to cellular components disrupts the normal reproduction and growth cycle resulting in the death of a cell. Capitalizing on this potent activity, silver in its various compounds and formulations has historically been incorporated into a variety of wound care preparations, such as ointments, hydrogels, hydrocolloids, creams, gels, and lotions.
  • silver nanoparticles are currently being used on the surfaces of various consumer medical products, wound care supplies, and medical treatment supplies, including bandages, dressings, catheters, and sutures, and such usages have proven the safety of silver nanoparticles for human use. After adjusting for the range of effectiveness, the benefits of such infection prevention is expected to be valued at more than $32 billion during the next decade.
  • ECDs electronic communication devices or electronic medical devices
  • ECDs electronic medical devices
  • ECDs electronic medical devices
  • ECDs electronic medical devices
  • Today, ECDs such as for example, mobile phones, pagers, conference phones, and electronic tablets such as iPads®, have become indispensable accessories of professional and social life among doctors and other health care workers in hospitals.
  • electronic tablets have quickly become an indispensable device for patient record reviews and updating of patient records during patient exams and procedures.
  • EMDs and ECDs are used for all types of activities and are present in every location of a hospital, including operating rooms and intensive care units.
  • EMDs and ECDs are seldom cleaned, but are frequently touched during or after the examination of patients without hand-washing, and have been proven to act as reservoirs for transmission of nosocomial infections. Colonization of potentially pathogenic organisms on EMDs and ECDs has been reported in the literature. Once colonized on the surface of these EMDs and ECDs, infectious microbes can survive for extended periods, unless, these are eliminated by disinfection or sterilization procedure.
  • the United States of America has one of the largest telecommunication networks in the world, and the medical community as with the rest of U.S. society is fully dependent on its telecommunication networks for efficiency.
  • One method of reducing the probability of infection in ECDs is to cover or enclose the device with sanitary or sterile coverings to contain any microbes already present or within a particular ECD to prevent them from contacting a patient or other person who may handle the device.
  • U.S patent application no. 2003/0012371 (“’371”) discloses a cover for a telephone receiver. Although designed to enclose a phone, the ‘371 invention discloses an open net configuration over the ear and mouth microphones and an open area in the handle portion of the “sock” through which the phone is inserted.
  • U.S. Patent No. 8,605,892 discloses a protective instrument cover which appears to cover the entire instrument. It teaches a tube having a continuous wall, an open proximal end, a closed distal end, and sealing means operatively associated with the tube. In another embodiment, ‘892 additionally discloses a continuous wall containing a reservoir formed therein.
  • the disadvantage of the ‘892 patent is the cover’s material is not integrated with any antimicrobial compound. Therefore, although the cover may prevent bacteria from contacting the instrument, the cover itself may be susceptible to bacterial growth and, thereby become its own microorganism reservoir.
  • the present invention is an anti-microbial covering for an electronic device used in a hospital environment.
  • a flexible thermoplastic sheet is impregnated during manufacturing with nano-sized silver particles and wrapped around the electronic device to stop the spread of nosocomial infections.
  • the silver particles vary in shape to maximize the anti-microbial effects of each sheet, and each particle is sized to be less than 60 nanometers in diameter.
  • the present invention includes a process for disrupting nosocomial infections in a healthcare facility by providing an anti-microbial covering to cover electronic devices in the facility.
  • the process includes a method for tailoring the anti-microbial covering to target specific pathogens present in the facility.
  • Figure 1 A is a perspective view of an anti-microbial sheet supported by a folded backing substrate and including perforations and tabs to allow for easy separation of the sheet from the backing substrate;
  • Figure IB is a perspective view of another anti-microbial sheet supported by a folded backing substrate and including concentric perforations;
  • Figure 2 a photo micrograph of silver nanoparticles having a rod shape
  • Figure 3 a photo micrograph of silver nanoparticles having an oval shape
  • Figure 4A a photo micrograph of silver nanoparticles having a flower shape
  • Figure 4B a photo micrograph of silver nanoparticles having a prism or triangle shape
  • Figure 5A is a process flow diagram showing an example process to prepare a seed quantity of silver nanoparticles for further use in the process of Fig. 5B;
  • Figure 5B is a process flow diagram showing an example process to prepare a quantity of rod shaped silver nanoparticles
  • Figure 6 is a process flow diagram showing a method of making an impregnated anti-microbial sheet
  • Figure 7A is an example of an apparatus for reducing the spread of nosocomial infections using a roller type sheet dispenser
  • Figure 7B is another example of an apparatus for reducing the spread of nosocomial infections using a box type dispenser
  • Figure 8 is an example of an anti-microbial covering in the shape of a bag.
  • Figure 9 shows an example of an electronic device (tablet) being covered by an anti-microbial covering incorporating the features of the invention.
  • Figs. 1A and IB show example anti-microbial sheets having substrate backings and folded (i.e. configured) to be utilized as a wrap over typical electronic devices used in a hospital environment.
  • the depictions 20,40 each show sheets 20,40 or “wraps” that include a thermoplastic sheet 21,41 impregnated with silver nanoparticles (not shown).
  • Target electronic devices suitable for use in the present invention includes, but are not limited to, smart phones, remote control devices, keyboards, personal computer, tablets, laptop touch-screens, ATM machine monitors, desktop monitors, digital camera screens, GPS navigation screens, mounted touch-screen monitors for factory floors, aviation touch-screen displays, interactive touch-screen displays, interactive white boards (e.g.
  • any modern hospital patient room today includes a multiplicity of electronic devices for assisting in the therapy of the patient.
  • patient and treatment rooms can include devices for dispensing medicines, heart monitors, TV control devices, nurse call devices, heart monitors, respiration monitors, and telephones.
  • patient and treatment rooms can include devices for dispensing medicines, heart monitors, TV control devices, nurse call devices, heart monitors, respiration monitors, and telephones.
  • tablet computing devices that have screens that range in size from 7 to 11 inches to record patient data and issued medical prescriptions.
  • thermoplastic also known as “thermos softening plastic” is a plastic material, typically comprised of a synthetic plastic polymer, which becomes pliable or moldable above a specific temperature and hardens upon cooling. Most thermoplastics have a high molecular weight. The polymer chains associate through intermolecular forces, which weaken rapidly with increased temperature, yielding a viscous liquid. Thus, thermoplastics may be reshaped by heating and are typically used to produce parts by various polymer processing techniques such as injection molding, compression molding, calendaring, and extrusion.
  • the sheets in present invention are principally formed through sheet or balloon (i.e. blown) extrusion, but various techniques are available for sheet forming of thermoplastics.
  • Thermoplastic sheets which are suitable for use in the present invention includes, but are not limited to, any light weight or low density polyolefin polymer, preferably low density polyethylene (“LDPE”). Further, as will be described, LDPE may be combined with linear low density polyethylene (“LLDPE”) to allow for increased resiliency. Additives for such thermoplastic may include polyphthalamide (“PPA”) or polybutene (“PBT”), to increase stiffness, elevate softening temperature, and reduce sensitivity to moisture. The inventors are also utilizing polyvinyl chloride also known as polyvinyl or vinyl, and commonly abbreviated “PVC” as a suitable thermoplastic base. Generally, PVC may replace any other disclosed base thermoplastic utilized in any of the herein described sheet formation processes. The same is true for the unitary use of LLDPE as a thermoplastic.
  • thermoplastic sheet can be integrally attached to a substrate 22,48 with an adhesive component (not shown) and contains a plurality of perforations 23, 44, 46, integrated therein such that each sheet is capable of being detached along the perforations utilizing a plurality of tabs 24,47.
  • Substrates 22,48 suitable for use in the present invention include, but are not limited to, parchment paper, wax paper, polyethylene, polypropylene, polystyrene, polyester, and Glassine, as are known in the industry.
  • Adhesive components suitable for use in the present invention include, but are not limited to, acrylic resin adhesives and the like.
  • the thermoplastic sheet is constructed of polyethylene such as for example a mixture of the aforementioned LDPE and LLDPE, which is integrated with silver nanoparticles, with each thermoplastic sheet formed to have thickness range of 10 to 1000 microns.
  • Suitable methods of integrating the thermoplastic with silver nanoparticles include, but are not limited to combing particles during extrusion, as will be discussed, and spray coating such particles onto the hardened sheet exterior after cooling. Extrusion forming of the present invention is preferred because during usage a sheet may be deformed during an encapsulation process of an electronic device or simply through usage in and around a hospital environment.
  • an extrusion process impregnates the silver nanoparticles throughout the thermoplastic material, a deformation event will not diminish the effectiveness of the antimicrobial process of the silver nanoparticles since a deformation event would only uncover new particles to react with microorganisms.
  • an extrusion process inherently makes available silver nanoparticles to combat microorganisms on all sides of a thermoplastic sheet. So, for example, a bag holding an electronic device will kill microorganisms on both the inside and outside of the bag.
  • thermoplastic sheet 21 is integrally attached to a substrate 22 with an adhesive component (not shown) and contains a plurality of perforations 31 formed therein such that the thermoplastic sheet 21 is capable of being detached along the perforations 31 utilizing a plurality of tabs 24 formed within each thermoplastic sheet 21.
  • the substrate 22 can be bifurcated along a center fold 25 thereby creating a front substrate 26 above the center fold 25 and a back substrate 27 below the fold 25, the perforations 31 being positioned on the front substrate 26 such that a crossdike shape 23 is formed.
  • an electronic device such as a cell phone
  • a cell phone may be placed at the center of the cross shape formed by the perforations 31.
  • the portion of the sheet 21 inside the perforations 31 is lifted from the substrate 22 via tabs 24 and the sheet wrapped over an electronic device, with each arm of the cross shaped portion being folded over the device to cover all portions of its outer surface.
  • the removed portion of the sheet will cling to the outer surface of the device through static attraction, or from any residual adhesive remaining from the substrate 22.
  • Fig. IB shows another thermoplastic sheet 41 integrally attached to a substrate 48 with an adhesive component (not shown) and contains a plurality of perforations 44,46 integrated therein such that the thermoplastic sheet 41 is capable of being detached along such perforations utilizing a plurality of tabs 47.
  • Substrate 48 may be bifurcated along a center fold 49, thereby creating a front substrate 42 above the center fold 49 and a back substrate 43 below the center fold 49.
  • the perforations 44 supported on the back substrate 43 are configured into concentric shapes so that a user may separate the sheet 41 from the substrate 43 to accommodate various sized devices by selecting and lifting the sheet at an appropriate perforation perimeter.
  • the sheets on the back substrate 43 are shown without lifting tabs, and may be separated from substrate 43 by simple manual manipulation of the combined sheet and substrate. While rectangles with eased corners are shown, it will be understood that any shapes, whether concentric or not, may be formed in the sheets using common die-cutting methods.
  • a device may be placed on one of the outlined perforation shapes on substrate 43 and a user lifts the appropriate sheet shape in order to cover the entire surface of the device.
  • Silver nanoparticles are nanoparticles of silver of between 1 nm and 100 nm in size. Variations in shapes of nanoparticles in general are known to affect the chemical properties of different nanoparticle based substances. Silver nanoparticles have an extremely large surface area and produce a high quantity of “ligands,” ions or functional molecular groups, which bind to a central metal atom and form a coordination complex.
  • each shape has a different surface to volume ratio and thus each has different high-atom-density facets. These facets act as maximum reactivity sites leading to varying strength in antibacterial activity against bacteria.
  • Gram-positive and Gram-negative bacteria respond differently to specific shapes. Under this theory, silver nano-rods and nano-wires might be more effective against Gram-positive bacteria, whereas silver nano-prisms (i.e. nano-triangles) might be more effective against Gram-negative bacteria as antimicrobial agents.
  • the inventors conceptualized the idea of combining various crystal shapes of silver nanoparticles into a single preparation material to improve their antimicrobial properties.
  • the antimicrobial efficacy over a spectrum of microorganisms is increased over what a single crystal shape can achieve because each shape interacts differently with different microorganisms.
  • the inventors’ research indicates that certain shaped silver nano-particles appear to be more toxic to certain types of microorganisms. The inventors theorize that this is because ligand availability varies chemically in accordance with a potential chemical matching between a microorganism protein coating and the shape or availability of a nearby silver nanoparticle ligand. For example, a prism shaped nanoparticle may fit (i.e. react) better with the coating of a S. aureus bacteria, but a sphere shaped nanoparticle may react more toxically with E. coli.
  • the combination of the two shapes provides a synergistic effect because it not only provides an additive effect of toxicity by simply increasing the strength of a nanoparticle solution for a particular volume, but it also provides a synergistic effect by broadening the effectiveness of the antimicrobial effect against two or more microorganisms.
  • Prior silver coating preparations did not exploit this strategy to provide a broad spectrum of microorganism toxicity.
  • formulation F3 had the broadest efficacy across the eight (8) strains and was selected for product extrusion. Hence, formulation F3 is currently the preferred silver nanoparticle crystal shape combination.
  • synergistic toxicity effects Another study was also done to test for synergistic toxicity effects. As indicated above, the inventors had already observed a synergistic effect related to the ability for a combination of different silver nanoparticle crystal shapes to target different types of microorganisms as a group by exhibiting a higher level of toxicity between matched toxic susceptibility based on crystal shape to a type of microorganism. However, a different type of synergy would also be desirable — an effective toxicity beyond expected additive toxicity expectations when combining two or more silver nanoparticle crystal shapes with a single microorganism, irrespective of matched toxic susceptibility.
  • Table 4 shows synergistic effects against single strain of Gram positive and Gram-negative bacteria.
  • the Table represents the results of a study conducted by the inventors to determine the effects of combining silver nanoparticles of different crystal shapes (“SNPx”) on their antimicrobial activity against representative Gram-positive and Gram-negative bacterial pathogens.
  • the silver nanoparticles crystal shapes comprised nanowires (“Wires”), nanorods (“Rods”), and nanospheres (“Spheres”) tested against Staphylococcus aureus (Gram-positive), Streptococcus pneumoniae (Gram-positive), and Escherichia coli (Gram-negative) in one technical replicate assay.
  • the study employed a modified “checkerboard assay” strategy to test the inhibitory potential of the three different silver nanoparticles crystal shape combinations over a range of concentrations.
  • a checkerboard assay is a well known testing technique to determine if the combined effects of a plurality of substances provides a targeted result greater than an expected result.
  • the checkerboard assay setup used in this study simultaneously determined the minimum inhibitory concentration or “MIC” for each individual compound alone and the fractional inhibitory concentration or “FIC” for each silver nanoparticles crystal shape when tested in combination with another silver nanoparticles crystal shape.
  • FICSNPI MICSNPI in combination / MICSNPI alone
  • FICSNPI MICSNP2 in combination / MICSNP2 alone
  • the “Example Data” portion in Table 4 provides a key guide to the table. In the study, a FICI value is only reported where both the MIC and FIC could be determined simultaneously in the Checkerboard Assay.
  • the inventors have concluded that by varying combinations of silver nanoparticle crystal shapes, and by varying the percentage by weight of each shape relative to other shapes, the inventors are able to optimize a formulation of silver nanoparticles for impregnation into a thermoplastic sheet that maximizes an antimicrobial effect in the sheet. Moreover, a formulation may be created in which a quantity of one shape of crystal may be increased so that interstices observed via electro micrograph (e.g. Fig. 4B) between two or more other crystal shapes may be filled, essentially optimizing the formulation to minimize spatial interstices between each crystal.
  • Such formulation flexibility allows for various types of formulations to be created to optimize an impregnated thermoplastic sheet to resist or be more effective against a particular type of bacteria or virus.
  • a formulation may be designed therefore, after testing, to target a particular pandemic threat, such as for example the Covid-19 virus or seasonal influenza viruses.
  • a particular pandemic threat such as for example the Covid-19 virus or seasonal influenza viruses.
  • the inventors discovered that varying the shapes of silver particles, along with control of their sizes and concentrations, has a strong effect on antimicrobial efficacy. Hence, control and preparation of various shapes and sizes of silver nanoparticles is necessary to achieve a desired antimicrobial outcome.
  • various silver nanoparticle shapes may be realized, such as for example the following shapes: rod shaped, wire shaped, sphere shaped, oval or ellipsoid shaped, triangle or prism shaped, and flower shaped.
  • the most common methods for producing silver nanoparticles fall under the category of wet chemistry, or the nucleation of particles within a solution. This nucleation occurs when a silver ion complex, usually AgNCb or AgCICri, is reduced to colloidal silver in the presence of a reducing agent. When the concentration increases enough, dissolved metallic silver ions bind together to form a stable surface. The surface is energetically unfavorable when the cluster is small, because the energy gained by decreasing the concentration of dissolved particles is not as high as the energy lost from creating a new surface. When the cluster reaches a certain size, known as the critical radius, it becomes energetically favorable, and thus stable enough to continue to grow.
  • a certain size known as the critical radius
  • This nucleus then remains in the system and grows as more silver atoms diffuse through the solution and attach to the surface.
  • the dissolved concentration of atomic silver decreases enough, it is no longer possible for enough atoms to bind together to form a stable nucleus.
  • new nanoparticles stop being formed, and the remaining dissolved silver is absorbed by diffusion into the growing nanoparticles in the solution. Varying the rate and density of ions through various chemical agents and ambient conditions allows for the shape of the particles to be determined. For example, the attachment of a stabilizing agent will slow and eventually stop the growth of silver particles.
  • a common capping agent is trisodium citrate and polyvinylpyrrolidone (“PVP”), but others may be used to varying conditions and to control particle size and shape of the silver particles, along with surface properties.
  • PVP polyvinylpyrrolidone
  • Fig. 2 shows an electronic micrograph 50 of a grouping of silver particles having generally a rod like shape 51 and having a diameter of less than 60 nanometers.
  • Fig. 3 shows an electronic micrograph 60 of a grouping of silver particles having generally an oval shape 61 and having a diameter of less than 60 nanometers.
  • Fig. 4A shows an electronic micrograph 65 of a single silver particle 66 in a varied grouping of different shaped silver particles, such as rods 67.
  • the particle 66 has a generally flowered shape with many particle extensions or “arms” 68 emanating from a central index point. Each arm has a diameter of less than 10 nanometers.
  • Fig. 4B shows an electronic micrograph 70 of a plurality of silver particles having generally a triangle or “prism” shape 71 in a varied grouping of different sized triangle shaped particles.
  • the triangle shaped particles vary in size 72 of between 20 and 60 nanometers.
  • Figs. 5A-5B show an example process for synthesizing the rod shaped particles shown in Fig. 2.
  • a series of chemical steps 75 are taken to produce a “seed” solution of silver particles in a workable volume.
  • 20 mL of 2.5 mM AgNCh solution is combined with 20 mL of 2.5mM trisodium citrate 77 and stirred 78.
  • One hundred fifty mL of Ultra-pure (e.g. Milli-Q) water is added 81 to the mixture of 77 and stirred for 5 minutes 83.
  • Ultra-pure e.g. Milli-Q
  • a seed solution (A) 96 should be available to be use between 2 -5 hours after completion of the seed process of 75 and may be used to form specific shapes and sizes of silver nanoparticles with further chemical processing as will be described. This ends 95 seed solution process 75.
  • process 100 discloses a method to produce rod shaped silver nanoparticles using the seed solution formed in process 75.
  • process 100 starts 101 with the step of 22.5 mL of the seed solution (A) 96 being mixed with 22.5 mL of lOmM AgNo3 102 and stirred well for 5 minutes 103.
  • Twenty mL of 80mM CTAB (cetyl trimethylammonium bromide) solution is added 106 and mixed well 107.
  • 45.02 mL of 100 mM ascorbic acid solution is added 109 to the mixture of 106 and stirred well for 5 minutes 111.
  • the solution is then enlarged by adding 112 880 mL of 80 mM CTAB with continuous stirring 114.
  • 9 mL of 1M NaOH solution is added slowly 116 to the above mixture and the solution should turn a yellowish to red color 117.
  • the solution is then continuously stirred gently for an additional 30 minutes 119.
  • the above produces nano rods in solution and a centrifuge is used 121 to separate out the nano-rods.
  • a centrifuge run at 11,000 RPM is typically suitable for such separation.
  • the resulting separated nano rods are left suspended in ultra-pure water 122 until needed for impregnation with a thermoplastic (B) 123 in an extrusion process.
  • Seed solution A 96 may be further chemically processed to create other shapes and sizes of silver nanoparticles, such as sphere shaped nanoparticles and wire shaped nanoparticles.
  • the same process may be used as for forming rod shaped nano particles except that 155.65 mL of silver seed solution is used instead of 22.5 mL in step 102, and 750 mL of 80mM CTAB is used instead of 880mL in step 106 of process 100. All other steps are identical in process 100.
  • prism shaped silver nanoparticles To form prism shaped silver nanoparticles, the following steps are satisfactory. As will be observed, no seed solution is utilized in making prism shaped nanoparticles:
  • Step 1 Combine 885 mL of 0.1 mM AgNo3 in a beaker and stir.
  • Step 2 Add 53.4 mL of 30 mM trisodium citrate to the above solution via a dropwise process.
  • Step 3. Add 53.4 mL of 0.7 mM Polyvinyl Pyrilidone via a dropwise process to above mixture formed in step 2.
  • Step 4. Add 30% by weight (i.e 2.12 mL) of hydrogen peroxide to the above mixture resulting from step 3 immediately after completion of step 3.
  • Step 5 Add 884.01 mL of lOOmM sodium borohydrite dropwise to above mixture formed in step 4 and continue stirring.
  • Step 6 Continue stirring the mixture formed in step 5 for 30 minutes until the solution changes to a brownish red color. A centrifuge may then be utilized on the mixture to separate out the prism nanoparticles. Sphere shaped silver nanoparticles are formed during the seed production procedure 75 shown in Fig. 5A and hence no additional processing is required except to apply a centrifuge to the seed solution to extract the sphere shaped silver nanoparticles.
  • process 130 is a suitable process for making an antimicrobial sheet.
  • the process starts 131 and pellets of LLDPE and LDPE are combined 132 in a ratio of approximately 80% LDPE and 20% LLDPE by weight.
  • a preferred method to make a batch of approximately 10kg of antimicrobial sheets includes combining of the polyethylene pellets with other additives in dry quantities pursuant to the following component amounts by weight:
  • UV protection agents 200 gm
  • Plastic brightener 100 gm
  • Antistatic agent 100 gm
  • Silver nanoparticles 900 microgram
  • Items 1-6 are combined via dry mixing 132 in a tray or other suitable vessel.
  • the silver nanoparticles (B) 123 from the processes (75,100) in Figs. 5A and 5B are then combined with the plastic ingredients 134 and dry mixed 136 in the presence of polyethylene glycol to facilitate the removal of water.
  • the silver nanoparticles that are added may include one or more shapes and sizes produced in the above described processes.
  • a preferred concentration ratio of shapes and sizes of silver nanoparticles are 2: 1:1:1 for the following shapes, respectively: rods (2); prisms (1); spheres (1); and wires (1).
  • Each of the aforementioned particle shapes may have varying concentrations resulting from the above formation steps.
  • concentrations of each shape must be known and normalized with respect to the concentrations of the other shapes in order to properly combine all of the shapes pursuant to the above stated concentration ratio. So, for example, if a supply source for each of the above preferred shapes was available at a concentration level of 1.0 microgram per mL, and a desired total volume of 5 mL of silver nanoparticles was desired, then in order to meet the above preferred combination ratio, the following quantities shown in Table 6 would be needed.
  • All silver nanoparticles should be less than or equal to 60 nanometers at their widest diameter, with a preferred range of between 10 and 50 nanometers. While a quantity of 900 micrograms is utilized in the preferred present method for the disclosed quantity, the inventors have seen satisfactory results using a range 500 micrograms to 50 mg of silver nanoparticles in such a process.
  • thermoplastic 137 The combination of silver nanoparticles with the other thermoplastic ingredients are dry -mixed in a heated mechanical mixer 136 at approximately 300-500 RPM, a temperature of 70°-90°C, and a time duration of 30 minutes. This removes moisture from the silver nanoparticles and thoroughly mixes and impregnates the silver nanoparticles (via absorption) into the thermoplastic. Sheet or balloon extrusion then occurs at 250°C to produce a thin sheet of silver nanoparticle impregnated thermoplastic 137. The resulting antimicrobial sheet has superior antimicrobial characteristic, is highly flexible, resilient, and transparent. Additional additives may be included to add color to the formed antimicrobial sheets, or increase optical light scattering so that the sheets are translucent.
  • a suitable sheet thickness for the herein described invention is any thickness less than 100 microns.
  • a preferred thickness is 30 microns where the tensile strength is sufficient to cover devices such as medical instruments while withstanding regular use by medical personnel. Nevertheless, sheets having a thickness of 10-30 microns are possible and would be satisfactory for many medical environments.
  • the herein described sheets may be dispensed in convenient rolls of non-adhesive applied sheets without backing sheets holding a separate adhesive layer.
  • the sheets must surround and adhere to the exterior of the targeted electronic device, such as EMDs and ECDs, and/or adhere to itself by wrapping the targeted device until surrounded.
  • an important functional property that preferably should be exhibited by an extruded sheet is a “cling” force property sufficient for it to adhere satisfactorily to itself and other targeted surfaces, such as the exterior to an electronic device like a cell phone or tablet.
  • Thermoplastic resin films do not generally possess inherent cling characteristics but must be obtained through the use of so-called cling agents or adhesives within the base sheet.
  • Adhesives are chosen for their ability to produce a surface on a thermoplastic sheet (or film) that can be sealed, opened and resealed, and are selected with due care in consideration of the use of thermoplastic film.
  • the adhesives are referred to in the industry as “tackifiers” since they make the surface of the film “tacky” or sticky. Examples of preferred tackifiers include mixtures of rosin esters and styrene-isoprene-styrene block copolymers.
  • Tackifiers are mixed with the thermoplastic sheet base such as, for example, polyolefins like LDPE and LLDPE during the sheet extrusion process and may include one or more of the following: a resin such as ethylene vinyl acetate 40 (“EVA”), a resin of ethylene methyl acrylate (“EMA”), or styrene-isoprenestyrene (SIS) block copolymer in combination with a rosin ester tackifier.
  • EVA ethylene vinyl acetate 40
  • EMA ethylene methyl acrylate
  • SIS styrene-isoprenestyrene
  • rosin ester tackifiers examples include SylvarosTM PR R85 and SylvarosTM PR 295 which are available from Arizona Chemical located in Panama City, Fla.
  • SIS and rosin ester tackifiers may be combined with a base polyolefin, in varying weight proportions, to cause a desired level of tackiness.
  • a tackifier provides the cling property necessary for a thermoplastic sheet to surround and stick to a computing or electronic device.
  • a minimum degree of cling property must be exhibited by the sheet to sustain an effective covering of the electronic device during daily use.
  • the strength of the cling property is referred to in the industry as the “cling force” exhibited by the sheet or film, and is measured by various ASTM tests such as ASTM D4649 or ASTM D5458.
  • a typical cling force of a plastic film to cling to the same or a similar film should be approximately between 300 and 500 grams as measured in accordance with ASTM D4649.
  • a pattern of perforations, or shaped perforations may be made using die cutters 139.
  • a backing substrate along with tabs may also be added 141 using industry known techniques.
  • Manufactured sheets may be cut into individual sheets and dispensed, or placed on a roller for dispensing by tearing along perforations.
  • Fig. 7A shows a paper towel type dispenser 150 holding a roll 153 of antimicrobial sheets suspended by a roller 154 and positioned in conveniently accessed location in a hospital or clinic environment.
  • Each antimicrobial sheet is rectangular in shape having right angle corners 152 and may include a backing substrate 158 so that a user may grasp the sheet 151 from its lower edge 157 and separate it from roll 153 via perforations 156. They may then remove the antimicrobial sheet using manual manipulation or place an electronic device upon the upper surface of the sheet and lift the sheet from its backing to cover the entire surface of the electronic device, as described above in the description for Figs. 1 A-1B.
  • a minimum inhibitory concentration or MIC of silver nanoparticles solution may be tested against a targeted specific microorganism in a laboratory applicable to a present healthcare facility. Testing may be done with silver nanoparticles in solution against such a targeted microorganism to establish minimum concentration level of silver nanoparticles having varying shapes and sizes. Using those results, a standard of 10 times the minimum effective concentration level may be established as a MIC per square meter of area of a produced antimicrobial sheet.
  • any organization can target and establish a MIC for its antimicrobial sheets tailored to be used in their medical operations, and a manufacturer can produce and supply such sheets meeting those established minimums.
  • a broad MIC of 0.02 to 2 microgram per mL is preferred to achieve a broad spectrum of antimicrobial efficacy in the described antimicrobial sheets produced.
  • tailored formulations may be created to maximize a toxicity effect against a targeted pathogen by varying proportions of volumes of a selected shape of silver nanoparticles known to have a higher degree of toxicity against the target.
  • Fig. 7B shows a dispensing box 160 holding a set of stacked, pre separated sheets 168 accessible via opening 167.
  • a door or lid 166 is hinged from rear upper surface 171 and biased downward to seal the opening 167 and keep dust or debris from settling on the sheets or inside the dispensing box.
  • Opening 167 is defined by the upper edges of front upstanding portion 169 and a pair of lateral upstanding side panels 163. The dimensions of the dispensing box determine how many sheets may be stored within it.
  • rear portion 162 may be affixed in a conventional manner to a wall or stand so that the dispenser 160 may be positioned in convenient locations within a hospital or clinic in order for medical personnel to easily access the antimicrobial sheets.
  • a companion platform may also be provided adjacent to the dispensing box (not shown) in order to facilitate the wrapping of the antimicrobial sheet around an electronic device.
  • FIG. 8 shows such a bag 180 that is formed by thermo-sealing a bi-folded antimicrobial sheet at edges 182 to form an opening 184.
  • An elongated edge 181 includes a resealing edge 187 holding an adhesive strip 188, or similar sealing device.
  • a device may simply be placed through opening 184 in direction 189 and the top edge of the bag turned over to engage a lower portion of the bag to seal it.
  • a re-sealable zipper type edge similar to that used in Ziploc® container bags, may also be used to seal each bag resulting in a bag-type antimicrobial container.
  • bag-type antimicrobial containers may be more practical in some environments, especially where response time is limited as in a hospital emergency room. Further, a bag-type antimicrobial container may be simply more convenient for workers to access and utilize.
  • Antimicrobial sheets used to make such a bag are slightly thicker than a nominal single sheet, optimally 40 to 60 microns in thickness, and would vary in size to form bags suitable for enclosing electronic devices of varying sizes and shapes. Referring now to Fig.
  • an antimicrobial sheet 192 has been placed over an electronic tablet 191 covering around all edges 194, 196, 197, and 198, and including margin area 201 surrounding screen 199.
  • the antimicrobial sheet exhibits transparent optical properties so that the screen 199 of the tablet 191 may be freely viewed by a user through sheet 192.
  • the inherent thin, flexible nature of any antimicrobial sheet allows for a user to access all buttons or levers necessary on the device without interference with the haptics of the touchscreen. This allows for the normal operation of the tablet by a medical practitioner.
  • the combination 190 allows for the full functionality of a tablet for hospital use, while interrupting the spread of communicative microorganisms that cause nosocomial infection

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  • Medicinal Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
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  • Agricultural Chemicals And Associated Chemicals (AREA)
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Abstract

L'invention concerne un revêtement antimicrobien destiné à être utilisé avec des dispositifs électroniques utilisés dans un environnement de soins de santé. Le revêtement est imprégné, lors de la fabrication, de particules d'argent de taille nanométrique et enroulé autour du dispositif électronique pour arrêter la propagation d'infections nosocomiales. Les particules d'argent varient en forme et en taille pour maximiser les effets antimicrobiens de chaque feuille, et chaque particule est dimensionnée façon à avoir un diamètre inférieur à 60 nanomètres. Le revêtement peut être utilisé dans un procédé pour perturber des infections nosocomiales dans une installation de soins de santé, des employés utilisant le revêtement pour recouvrir des dispositifs électroniques dans l'installation. Le procédé comprend un processus pour personnaliser le revêtement antimicrobien pour cibler des agents pathogènes spécifiques présents dans l'installation ou, en variante, personnaliser le revêtement pour cibler des menaces de niveau pandémique, telles que le virus du Covid-19 ou les virus de la grippe saisonnière.
PCT/US2020/036384 2020-06-05 2020-06-05 Revêtements imprégnés de nanoparticules d'argent pour dispositifs électroniques en vue de lutter contre des infections nosocomiales Ceased WO2021247042A1 (fr)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20120213665A1 (en) * 2011-02-23 2012-08-23 Applied Silver Llc Anti-microbial Device
US20160144350A1 (en) * 2013-06-28 2016-05-26 President And Fellows Of Harvard College High-surface area functional material coated structures
US20180236118A1 (en) * 2017-02-22 2018-08-23 Infection Sciences, LLC Silver nanoparticles impregnated covers for electronic devices to combat nosocomial infections

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20120213665A1 (en) * 2011-02-23 2012-08-23 Applied Silver Llc Anti-microbial Device
US20160144350A1 (en) * 2013-06-28 2016-05-26 President And Fellows Of Harvard College High-surface area functional material coated structures
US20180236118A1 (en) * 2017-02-22 2018-08-23 Infection Sciences, LLC Silver nanoparticles impregnated covers for electronic devices to combat nosocomial infections

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
XU ZHAOYANG, XU ZHAOYANG, XU NING, WANG HAIBO: "Effects of Particle Shapes and Sizes on the Minimum Void Ratios of Sand", ADVANCES IN CIVIL ENGINEERING, vol. 2019, 14 April 2019 (2019-04-14), pages 1 - 12, XP055883489, ISSN: 1687-8086, DOI: 10.1155/2019/5732656 *

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