Polymer composition containing antimicrobial nanoparticles and method for producing it

Abstract

Disclosed are polymer compositions incorporating metal nanoparticles, and medical devices or other products made therefrom. The disclosed polymer compositions can be used to form medical devices, including implantable medical devices, that have effective antimicrobial properties. The disclosed polymer compositions incorporate metal nanoparticles that function without releasing metal (e.g., silver) ions. The polymer compositions may have anti-UV properties conferred by the metal nanoparticles.

Description

[Technical Field]

[0001] This disclosure relates to a polymer composition containing antimicrobial nanoparticles, a method for producing it, and a device formed therefrom. [Background technology]

[0002] Polymers used in medical and other applications are typically inexpensive and can be used for many different functions. Polymer products can be manufactured using injection molding processes. One challenge associated with injection-molded polymers is that the surface finish of the product can be spongy, with pores that can extend to a depth of several microns within the product. For example, Figure 1 is a scanning transmission electron microscope (STEM) image of a polystyrene surface from a thermally extruded pellet. Polymer surfaces are highly porous, making them a potential habitat for bacteria and other microorganisms. The growth of such microorganisms can be a concern in medical settings such as hospitals. Controlling polymers used in sensitive areas, including many medical applications, may require expensive and stringent sterilization and storage procedures. Even when sterilization guidelines are followed, infections can occur from polymer devices used to deliver substances to patients and / or polymer devices implanted in patients. Drug-resistant microbial infections can also result from the use of potentially infectious polymer products, leading to costly medical management and even death.

[0003] The overuse of antibiotics has, in some cases, contributed to antibiotic-resistant bacteria and other treatment-resistant microorganisms. There are concerns that the increase in antibiotic resistance could lead to microorganisms that cannot be treated with conventional technologies. Medical devices incorporating antibiotics may not reliably prevent biofilm formation and / or infection from antibiotic-resistant bacteria. In such cases, the use of antibiotics in polymer materials may not reliably protect patients from infection.

[0004] There have been attempts to introduce antimicrobial activity into polymer materials by incorporating ionic colloidal silver and silver nanoparticles. However, resistance to antimicrobial agents has now been discovered to both colloidal silver (i.e., silver nanoparticles typically produced by conventional chemical reduction processes with some form of capping agent, and known to release silver ions) and ionic silver. McNeilly et al., “Emerging Concern for Silver Nanoparticle Resistance in Acinetobacter baumannii and Other Bacteria,” Front. Microbiol., 16 April 2021, discusses the emergence of several antibiotic-resistant bacteria, including Acinetobacter baumannii, Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Enterobacter spp. Of these, A. baumannii was of particular concern, as it was found to have established resistance to colloidal silver nanoparticles, similar to Escherichia coli, Enterobacter cloacae, S. typhimurium, B. subtilis, S. aureus, P. erginosa, K. pneumoniae, Serratia marcescens, and Acinetobacter species.

[0005] Silver, “Bacterial silver resistance: molecular biology and uses and misuses of silver compounds,” FEMS Microbiology Reviews, Volume 27, Issue 2-3, June 2003, Pages 341-35 discusses silver-resistant Salmonella and Escherichia coli. Elkrewi, et al., “Cryptic silver resistance is prevalent and readily activated in certain Gram-negative pathogens,” J. Antimicrob. Chemother., 2017 Nov 1;72(11):3043-3046 discloses resistance to colloidal silver nanoparticles by Gram-negative pathogens such as Enterobacter species, Klebsiella species, Escherichia coli, Pseudomonas eruginosa, Acinetobacter species, Citrobacter species (Citrobacter spp.), and Proteus species (Proteus spp.). Hosney, “The increasing threat of silver-resistance in clinical isolates from wounds and burns,” Infect Drug Resist. 2019; 12: 1985-2001 discusses colloidal silver-resistant Klebsiella pneumoniae, Staphylococcus aureus, Escherichia coli, Enterobacter cloaca, Pseudomonas eruginosa, and Acinetobacter baumannii. Percival, et al., “Bacterial resistance to silver in wound care,” J. Hospital Infection, Vol. 60, Issue 1, May 2005, pp. 1-7 discusses the dangers and potential of colloidal silver-resistant microorganisms in wound care.Kedziora, et al., “Consequences Of Long-Term Bacteria's Exposure To Silver Nanoformulations With Different PhysicoChemical Properties,” Intl. J. of Nanomedicine, 2020:15 199-213 discusses Gram-positive and Gram-negative bacteria resistant to colloidal silver.

[0006] The paper with the following title, “Are Silver Nanoparticles a Silver Bullet Against Microbes?” July 13, 2021, https: / / news.engineering.pitt.edu / are-silver-nanoparticles-a-silver-bullet-against-microbes / (accessed October 12, 2022), discusses E. coli resistant to colloidal silver nanoparticles and states the following: "Initially, the bacteria could only survive at low concentrations of silver nanoparticles, but as the experiments continued, the authors found that the bacteria could survive at higher doses. (omitted) Interestingly, the authors found that the bacteria established resistance to silver nanoparticles, but not to silver ions released from the nanoparticles alone." This group sequenced the genome of E. coli exposed to silver nanoparticles and discovered mutations in genes corresponding to the efflux pump that pushes heavy metal ions out of the cell. "It's possible that some form of silver enters the cell, and once it reaches its target, the cell mutates to rapidly pump it out. (….) Further research is needed to determine whether researchers can overcome this resistance mechanism through particle design."

[0007] Silver nanoparticles produced by conventional chemical synthesis methods have external bond angles and edges that allow silver ions to be released even when the bulk nanoparticles are in the ground state. Adding ion-releasing metal nanoparticles to polymers results in nanoparticle-impregnated polymers and plastics that are sources of unwanted metal ions, such as silver ions, which can be toxic to human and animal tissues under excessive exposure. Furthermore, ion release can decrease over time. Even if there is a beneficial antimicrobial effect associated with the release of silver ions, such an effect decreases over time as the ions leach from the bulk polymer material. If the release of silver ions is the primary mode of antimicrobial activity, as in the case of polymer products treated with conventional colloidal silver, the antimicrobial activity of the polymer will similarly decrease over time.

[0008] In addition, exposure to solar radiation can cause weakening and other structural damage to polymers. When UV energy is absorbed by polymers, it can excite electrons and generate free radicals that can lead to plastic degradation. Polymers affected by UV radiation may develop a chalky appearance, their surfaces may become brittle, and noticeable discoloration may occur on the surface. UV-induced degradation can cause cracking in polymer products and may even lead to complete product failure. For example, UV radiation can activate tertiary carbon bonds in the structure of polypropylene and / or low-density polyethylene, which then interact with oxygen in the atmosphere. This can lead to the formation of carbonyl groups in the main chain of the structure, making plastic products more susceptible to cracking and / or discoloration.

[0009] Considering the above, there is still a need to find improved polymer materials that exhibit effective antimicrobial properties and / or resistance to degradation caused by UV light for use in medical devices, including implantable medical devices. [Overview of the Initiative]

[0010] Polymer compositions incorporating metal nanoparticles and medical devices fabricated therefrom are disclosed. Methods for incorporating metal nanoparticles into polymers are also disclosed. The disclosed polymer compositions can be used to form medical devices, including implantable medical devices, and other devices having effective antimicrobial properties. The disclosed polymer compositions incorporate metal nanoparticles having antimicrobial activity that does not release metal (e.g., silver) ions. Methods for incorporating metal nanoparticles into polymers are also disclosed.

[0011] In some embodiments, polymer compositions incorporating metal nanoparticles can also effectively withstand UV damage when exposed to sunlight and / or other UV light sources. For example, the disclosed polymer compositions may include wavelength-shifting metal nanoparticles that function to protect exposed surfaces from UV radiation. For instance, the polymer composition can downconvert incident UV light to longer wavelengths that cause less or no damage to polymer bonds.

[0012] The disclosed polymer compositions containing metal nanoparticles advantageously possess antimicrobial properties that prevent microbial colonization on the composition, including preventing microbial colonization within the pores of the polymer material and the structures formed therefrom. Such nanoparticle-modified polymers are less prone to the establishment of microbial resistance to silver nanoparticles, as can occur with colloidal silver produced through chemical synthesis. Surprisingly and unexpectedly, nonionic silver nanoparticles formed by laser ablation were found not to induce microbial resistance to silver nanoparticles, as observed with colloidal silver and / or silver nanoparticles produced by chemical synthesis, which derive antimicrobial activity from the release of silver ions. Antimicrobial resistance may be a result of adaptation by bacteria expelling silver ions from their cell membranes via ion pumps or the like.

[0013] In some embodiments, spherical metal (e.g., silver) nanoparticles may have an average diameter and particle size distribution in which at least 99% of the spherical metal nanoparticles have a particle size within 30% of the average diameter, or within 20% of the average diameter, or within 10% of the average diameter, and / or at least 99% of the spherical metal nanoparticles have a diameter within ±3 nm of the average diameter, or within ±2 nm of the average diameter, or within ±1 nm of the average diameter.

[0014] Where used herein, unless otherwise specified, average diameter (i.e., average particle size) means the number average, which can be determined according to standard methods known in the art. For example, the average diameter can be determined by microscopy (e.g., scanning transmission electron microscopy (STEM)) and analysis of the resulting images. Another suitable method for determining the average diameter of a set of metal nanoparticles is dynamic light scattering (DLS), which is typically reported on a volume basis.

[0015] In some embodiments, the polymer composition may include coral-shaped metal nanoparticles instead of, or in addition to, spherical metal nanoparticles. Coral-shaped metal (e.g., gold) nanoparticles have a spherical structure and a heterogeneous cross-section formed by multiple non-linear strands joined together without right angles. In some cases, coral-shaped metal nanoparticles may be used to enhance the effect of spherical metal (e.g., silver) nanoparticles.

[0016] In some embodiments, the metal nanoparticles may include at least one metal selected from the group consisting of silver, gold, platinum, palladium, rhodium, osmium, ruthenium, rhenium, molybdenum, copper, iron, nickel, tin, beryllium, cobalt, antimony, chromium, manganese, zirconium, zinc, tungsten, titanium, vanadium, lanthanum, cerium, heterogeneous mixtures thereof, and alloys thereof. Nanoparticles containing silver, gold, and mixtures and alloys thereof may be particularly effective.

[0017] In some embodiments, the polymer composition can be made from a thermoplastic material incorporating metal nanoparticles, such as by coating polymer granules (which may be interchangeably referred to herein as "beads" or "pellets") that are later thermoplastically formed into a manufactured product of a desired structure. In some embodiments, the polymer composition can be a thermosetting composition made from a multi-component (e.g., two-component) type composition in which the metal nanoparticles are included in one or both components of the composition. In either case, the metal nanoparticles will be mixed throughout the polymer composition either in the molten state before molding and cooling or in the liquid state before molding and thermosetting.

[0018] To produce a product shaped from a thermoplastic polymer, the polymer granules used to form the polymer product may be treated (e.g., coated and / or impregnated) with metal (e.g., silver and / or gold) nanoparticles. For example, the metal nanoparticles are dispersed in a volatile solvent, the dispersion is applied to the polymer granules, the solvent and metal nanoparticles are allowed to penetrate the polymer granules as desired, and the solvent is evaporated to leave the metal nanoparticles on and / or impregnated in the polymer granules. When the metal nanoparticle-treated polymer granules are heated to a molten state in a shaping device such as an auger, extruder, or injection molding machine, the metal nanoparticles will be distributed throughout the molten thermoplastic polymer and the plastic materials and articles produced therefrom.

[0019] In the case of a multi-component (e.g., two-component) type curable resin used to produce a thermosetting polymer product, the metal nanoparticles may be included in one or both components of the system (e.g., in a monomeric and / or oligomeric resin). When the components are mixed together, the metal nanoparticles are blended throughout the mixture and solidify at a predetermined location in the product or article being shaped from the composition. In some embodiments, a first type of nanoparticles (e.g., spherical silver nanoparticles) may be included in the first component of a two-component thermosetting polymer system, and a second type (e.g., coral-shaped gold nanoparticles) may be included in the second component of the two-component thermosetting polymer system.

[0020] The portions of metal nanoparticles on the surface of a shaped polymer material or structure and / or the portions of metal nanoparticles embedded within pores communicating with the polymer surface can provide antibacterial activity for preventing microbial growth on the surface of the polymer material. Additionally, the metal nanoparticles can be selected to protect the polymer material from damage by UV radiation, such as by down-converting incident UV radiation into lower energy radiation (e.g., visible light) that causes less or no damage to the polymer material.

[0021] Advantageously, the polymer compositions disclosed herein can provide antibacterial and UV protection effects over a long period of time without nanoparticle depletion even after abrasion or machining. For example, since the embedded nanoparticles do not rely on ion release as the primary means of antibacterial activity, the polymer compositions disclosed herein can provide their antibacterial function for a longer period than polymer compositions incorporating conventional nanoparticles formed via chemical synthesis and releasing ions.

[0022] This summary is provided to introduce briefly a series of concepts further described in the detailed description below. This summary is not intended to identify key features or essential features of the claimed subject matter, nor is it intended to be used as an indication of the scope of the claimed subject matter.

[0023] All of the various objects, features, characteristics, and advantages of the present invention will become apparent and will be more readily understood from the following description of the embodiments in conjunction with the accompanying drawings and the appended claims, which form a part of this specification. In the drawings, like reference numerals may be used in some cases to designate corresponding or similar parts in the various figures, and the various elements shown are not necessarily drawn to scale.

Brief Description of the Drawings

[0024] [Figure 1]Figure 1 shows a scanning transmission electron microscope (STEM) image of the polystyrene surface from a thermally extruded pellet. [Figure 2] Figures 2A to 2C are STEM images showing thermoplastics containing silver (Ag) nanoparticles. [Figure 3] Figures 3A and 3B schematically show microorganisms after absorbing spherical metal nanoparticles from a substrate, and disulfide bonds that have been catalytically modified by the spherical nanoparticles. [Figure 4] Figure 4 shows a STEM image of silver (Ag) nanoparticles inside MRSA SA62 drug-resistant bacteria. [Figure 5] Figures 5A-5C show STEM images of Tecoflex EG-93A-B20 thermoplastic polymer (thermoplastic polyurethane or TPU) embedded with silver nanoparticles. [Figure 6] Figures 6A–6C show STEM images of Isoplast 2510 thermoplastic polymer (another TPU) embedded with silver nanoparticles. [Figure 7] Figure 7A shows thermoplastic pellets treated with silver (Ag) nanoparticles. Figure 7B shows extruded filaments from thermoplastic pellets, such as those shown in Figure 7A. [Figure 8] Figures 8A and 8B show magnified STEM images of spherical silver (Ag) nanoparticles embedded in a thermoplastic material. [Modes for carrying out the invention]

[0025] I. Introduction The term "nanoparticles" often refers to particles with a maximum dimension of less than 100 nm. While bulk materials typically have constant physical properties regardless of size, at the nanoscale, size-dependent properties are often dominant. Thus, the properties of a material change as its size approaches the nanoscale and as the proportion of atoms on the material surface increases. For bulk materials with a cross-section larger than 1 micrometer (or micron), the ratio of surface atoms to the number of atoms in the bulk material is not significant. Therefore, the interesting, and sometimes unexpected, properties of nanoparticles are primarily attributable to the large surface area of ​​the material, which outweighs the contribution from the relatively small bulk material.

[0026] In a surprising turn of events given the extensive data on conventional silver nanoparticles produced by chemical synthesis, it was found here that nonionic metal nanoparticles formed by laser ablation are less likely to develop antimicrobial resistance, meaning that the concentration of silver nanoparticles necessary to effectively kill microorganisms is essentially maintained over time. This is in contrast to colloidal silver and other silver nanoparticles produced by chemical synthesis, which have external bond angles and typically release silver ions to confer antimicrobial activity. If antimicrobial resistance develops to colloidal silver and other silver ion-releasing silver nanoparticles or compounds, the concentration of such nanoparticles needs to be increased to maintain their ability to kill microorganisms.

[0027] The metal nanoparticles used in the disclosed polymer composition may be in a nonionic ground state and lack external edges or bond angles that would cause the release of metal ions. Typically, spherical metal nanoparticles are used to kill microorganisms, but coral-shaped metal nanoparticles may be used in combination with typically spherical metal nanoparticles to provide antimicrobial activity.

[0028] The metal nanoparticles incorporated into polymers disclosed herein include, or essentially consist of, nonionic, ground-state metal nanoparticles that lack external edges or bond angles that would cause the release of metal ions. Examples include spherical metal nanoparticles, coral-shaped metal nanoparticles, and blends of spherical and coral-shaped metal nanoparticles.

[0029] Conventional silver nanoparticles, manufactured via chemical reduction (typically with a capping agent), tend to exhibit clustered, crystalline, faceted, or polyhedral shapes rather than true spherical shapes with round, smooth surfaces. Such nanoparticles typically form clusters and have a broad particle size distribution. In some cases, conventional silver nanoparticles form as silver shells on non-metallic seed materials.

[0030] In contrast, spherical nanoparticles contained in the polymer compositions disclosed herein may exhibit one or more of the following: (1) solid metal form, (2) unclustered state, (3) exposed / uncoated / uncapped surface (i.e., pure metal without organic capping or stabilizing molecules), (4) smooth surface form, and (5) narrow particle size distribution. In preferred embodiments, all five of these forms are present in metal nanoparticles. As used herein, “exposed” or “uncoated” surface means a surface having a fully exposed metal surface that is free from capping agents or other organic stabilizers and can instead react with the surrounding environment.

[0031] The metal nanoparticles of the disclosed polymer composition, which include spherical nanoparticles and coral-shaped nanoparticles, may include any desired metal, mixture of metals, or metal alloy, including at least one of silver, gold, platinum, palladium, rhodium, osmium, ruthenium, rhenium, molybdenum, copper, iron, nickel, tin, beryllium, cobalt, antimony, chromium, manganese, zirconium, tin, zinc, tungsten, titanium, vanadium, lanthanum, cerium, heterogeneous mixtures thereof, or alloys thereof. Nanoparticles containing silver, gold, and mixtures and alloys thereof may be particularly effective.

[0032] In some embodiments, gold (Au) nanoparticles are included in the polymer composition and can function to downshift incident UV radiation to lower energy wavelengths. Gold nanoparticles can downconvert high-energy wavelengths to longer wavelengths, lower-energy, and less harmful light. Gold nanoparticles can downconvert UV or other high-energy wavelengths to the red and / or infrared regions of the light spectrum. In some embodiments, the gold nanoparticles are spherical. In some embodiments, the gold nanoparticles have a particle size in the range of about 1 nm to about 40 nm in diameter.

[0033] In some embodiments, silver (Ag) nanoparticles are included in the polymer composition to impart or enhance antimicrobial properties to the polymer composition. In some embodiments, the silver nanoparticles are spherical. In some embodiments, the silver nanoparticles have a particle size in the range of about 1 nm to about 10 nm in diameter.

[0034] Examples of metal (e.g., silver and gold) nanoparticles and nanoparticle compositions that can be used herein are disclosed in U.S. Patents 9,849,512; 9,434,006; 9,919,363; 10,137,503; and 10,610,934, which are incorporated herein by reference.

[0035] II. Nanoparticles The metal nanoparticles used in the disclosed polymer compositions may include metal nanoparticles that are in a nonionic ground state and lack external edges or bond angles that could cause the release of undesirable metal ions. The metal nanoparticles may include spherical metal nanoparticles, coral-shaped metal nanoparticles, or a combination thereof. Typically, spherical metal nanoparticles have higher antimicrobial activity, but coral-shaped metal nanoparticles can also provide antimicrobial activity, and when combined, they can enhance the antimicrobial activity of spherical metal nanoparticles.

[0036] Nonionic, ground-state spherical metal nanoparticles without external edges or bond angles, and compositions containing such nanoparticles, can be prepared in accordance with the disclosures of U.S. Patents 9,849,512, 10,137,503, and 10,610,934. Nonionic, ground-state coral-shaped metal nanoparticles without external edges or bond angles, and compositions containing such nanoparticles, can be prepared in accordance with the disclosure of U.S. Patent 9,919,363. A composition containing a mixture of spherical metal nanoparticles and coral-shaped metal nanoparticles is disclosed in U.S. Patent 9,434,006. The aforementioned patents are incorporated herein by reference in their entirety.

[0037] In some embodiments, the liquid medium applied to the polymer composition (such as polymer granules) may contain nanoparticles at concentrations of about 50 ppb to about 100 ppm, or about 100 ppb to about 50 ppm, or about 200 ppb to about 20 ppm, or about 400 ppb to about 10 ppm, or about 600 ppb to about 6 ppm, or about 800 ppb to about 4 ppm, or about 1 ppm to 3 ppm, or about 2 ppm, based on the weight of the liquid medium applied to the polymer composition.

[0038] After the metal nanoparticles are incorporated into the polymer composition, the nanoparticles may have concentrations ranging from approximately 0.5 mg / kg to approximately 8 mg / kg, such as approximately 1 mg / kg, 2 mg / kg, 3 mg / kg, 4 mg / kg, 5 mg / kg, 6 mg / kg, and 7 mg / kg, or within a range ending at any combination of the aforementioned values.

[0039] In some embodiments, the spherical metal nanoparticles may have an average particle size (i.e., diameter) in the range of about 1 nm to about 20 nm, such as about 3 nm to about 14 nm, or about 4 nm to about 13 nm, or about 5 nm to about 12 nm, or about 6 nm to about 10 nm. In some embodiments, the spherical metal nanoparticles may have a particle size of about 40 nm or less, about 35 nm or less, about 30 nm or less, about 25 nm or less, about 20 nm or less, about 15 nm or less, about 10 nm or less, about 7.5 nm or less, or about 5 nm or less. The composition may contain nanoparticles within a concentration range having an endpoint determined by any two of the aforementioned values.

[0040] Spherical metal nanoparticles may have a particle size distribution in which at least 99% of the metal nanoparticles have a diameter within 30% of the average diameter, or within 20% of the average diameter, or within 10% of the average diameter, and / or at least 99% of the spherical nanoparticles may have a particle size distribution in which at least 99% of the spherical nanoparticles have a diameter within ±3 nm of the average diameter, or within ±2 nm of the average diameter, or within ±1 nm of the average diameter. Due to their nonionic nature and narrow particle size distribution, spherical nanoparticles may have a ξ potential of at least about ±10 mV (absolute value), or at least about ±15 mV, or at least about ±20 mV, or at least about ±25 mV, or at least about ±30 mV. Such a ξ potential may help maintain the dispersion of metal nanoparticles in a polar solvent without a dispersant.

[0041] In some embodiments, coral-shaped metal nanoparticles may be used in place of or in combination with spherical metal nanoparticles. Generally, spherical metal nanoparticles may be smaller than coral-shaped metal nanoparticles, and in this way they can provide a very high surface area for catalyzing a desired reaction or for providing other desired benefits. On the other hand, generally larger coral-shaped nanoparticles may exhibit a higher surface area per unit mass compared to spherical nanoparticles because they have internal spaces and surfaces as well as a solid core and outer surface.

[0042] In at least some cases, a synergistic effect can be obtained by providing a nanoparticle composition containing both spherical and coral-shaped nanoparticles. In addition to providing their own unique benefits, coral-shaped nanoparticles can also help maintain and / or enhance the activity of spherical metal nanoparticles. For example, smaller (e.g., spherical) metal nanoparticles may provide better protection against UVB radiation, while relatively larger (e.g., coral-shaped) metal nanoparticles may provide better protection against UVA radiation. In some embodiments, a combination of spherical and coral-shaped metal nanoparticles can result in synergistic broad-spectrum protection with a greater amount of protection per unit amount of active material component (e.g., amount of reflected UV radiation) compared to metal nanoparticles of a single size and / or shape.

[0043] In embodiments in which both spherical metal nanoparticles and coral-shaped metal nanoparticles are included in the polymer composition, the mass ratio of spherical nanoparticles to coral-shaped nanoparticles in the nanoparticle composition may be in the range of about 1:1 to about 50:1, or about 2.5:1 to about 25:1, or about 5:1 to about 20:1, or about 7.5:1 to about 15:1, or about 9:1 to about 11:1, or about 10:1. The particle number ratio of spherical nanoparticles to coral-shaped nanoparticles in the nanoparticle composition may be in the range of about 10:1 to about 500:1, or about 25:1 to about 250:1, or about 50:1 to about 200:1, or about 75:1 to about 150:1, or about 90:1 to about 110:1, or about 100:1.

[0044] In some embodiments, at least a portion of the metal nanoparticles are selected to selectively reflect, block, and / or scatter a specific range of solar radiation. For example, a first set of metal nanoparticles may be selected as spherical metal nanoparticles having a smaller relative particle size and therefore more strongly selectively reflecting, scattering, and / or blocking UVB radiation, while a second set of metal nanoparticles may be selected as coral-shaped metal nanoparticles having a larger relative particle size and therefore more strongly selectively reflecting, scattering, and / or blocking UVA radiation.

[0045] In some embodiments, the polymer composition includes at least one spherical antimicrobial metal nanoparticle component and a larger coral-shaped nanoparticle component. In some embodiments, compositions containing metal nanoparticles may be used in a plastic manufacturing process for producing plastic products in which nanoparticles are embedded.

[0046] III. Antibacterial properties of nanoparticles Figures 2A to 2C are STEM images showing thermoplastics containing silver (Ag) nanoparticles, which yield polymer compositions with antibacterial and / or wavelength-shifting properties.

[0047] Figures 3A and 3B schematically show microorganisms after absorbing spherical metal nanoparticles from a substrate, and disulfide bonds that have been catalytically modified by the spherical nanoparticles. Figure 3A schematically shows a microorganism 608 that has absorbed spherical nanoparticles 604 from a solid substrate 602 by active absorption or other transport mechanisms. The nanoparticles 604 can move freely throughout the interior 606 of the microorganism 608 and come into contact with one or more life-related proteins or enzymes 610 that, when denatured, will kill or incapacitate the microorganism.

[0048] One way in which metal nanoparticles can kill or denature microorganisms is by catalyzing the cleavage of disulfide (SS) bonds within life-sustaining proteins or enzymes. Figure 3B schematically shows how a microbial protein or enzyme 710 containing disulfide bonds is catalytically denatured by adjacent spherical nanoparticles 704 to become a denatured protein or enzyme 712. In bacteria or fungi, microorganisms can be killed in this way by the cleavage of disulfide bonds and / or other chemical bonds in life-sustaining proteins or enzymes occurring inside the cell. Such catalytic cleavage of disulfide (SS) bonds is facilitated by the generally simple protein structure of microorganisms, where many life-sustaining disulfide bonds are exposed and readily cleaved by catalysts.

[0049] Another possible mechanism by which metal (e.g., silver) nanoparticles can kill microorganisms is through the generation of reactive oxygen species, such as peroxides, that can oxidatively cleave protein bonds, including but not limited to amide bonds.

[0050] Nonionic metal nanoparticles, despite being lethal to microorganisms, have been shown to be harmless and non-toxic to humans, mammals, and other animals because they possess much more complex protein structures compared to simple microorganisms. In such higher organisms, most or all of the life-sustaining disulfide bonds are shielded by other, more stable regions of the protein. In many cases, nonionic nanoparticles do not interact with or adhere to human cells, other mammalian cells, or other animal cells, and can be rapidly and safely excreted in urine without damaging the kidneys or other cells, tissues, or organs. Furthermore, nonionic silver nanoparticles do not release silver ions, which means they become ineffective upon excretion.

[0051] In the case of spheroidal silver (Ag) nanoparticles, the interaction of silver (Ag) nanoparticles within microorganisms is not typical of that with conventional colloidal silver compositions, but rather similar to that with silver ions (Ag). + It has been demonstrated that silver (Ag) nanoparticles are particularly lethal, without the need to rely on the generation of toxic silver ions (Ag). + The ability to provide effective antimicrobial activity without significantly or actually releasing silver ions into the patient or the surrounding environment represents a substantial advance in this art. Silver ions released from silver nanoparticles, if present, are typically unmeasurable in any amount or concentration and are well below known or inherent toxicity levels to animals such as mammals, birds, reptiles, fish, and amphibians.

[0052] Figure 4 shows a STEM image of silver (Ag) nanoparticles inside MRSA SA62 drug-resistant bacteria. By combining the STEM image with electron diffraction spectroscopy, fission at the disulfide bond and ferredoxin sites was confirmed.

[0053] The use of non-ionic silver nanoparticles fabricated using laser ablation offers advantages compared to conventional silver nanoparticles, which are known to function primarily through the release of silver ions and have been shown to lead to resistance to antimicrobial silver nanoparticles. As discussed above, conventional silver nanoparticles fabricated using chemical reduction processes are known to lead to resistance to antimicrobial agents, meaning that their effectiveness in killing microorganisms decreases over time. In some studies, microbial resistance to ionic silver has been demonstrated in as little as six generations.

[0054] In contrast, the spherical nanoparticles contained in the polymer compositions disclosed herein have been shown to have stable antimicrobial activity even after 28 passages, without any decrease in antimicrobial activity, including a significant deterioration in MIC (minimum inhibitory concentration).

[0055] IV. UV protection function of nanoparticles Metal nanomaterials of the type disclosed herein, having a diameter or particle size in the range of about 10 nm to 40 nm, may have a loose dielectric field. When a large number of nanoparticles are present together, the dielectric effect on passing light waves may not attenuate but may cause a frequency shift toward either the red or blue edge of the electromagnetic spectrum. Polymer compositions containing a sufficient amount of such nanoparticles may influence incoming UV radiation, shifting it toward the red edge of the spectrum and reducing the penetration of light energy to a level that reduces or eliminates damage.

[0056] In some embodiments, the polymer composition may include metal nanoparticles having a high refractive index to reflect and / or scatter incident UV radiation. For example, metal nanoparticles used in the polymer composition of the present disclosure may have a refractive index for UVA and / or UVB radiation of about 1.5 to about 4.6, or about 2.0 to about 4.0, or about 2.5 to about 3.5. In some embodiments, the refractive index of the nanoparticles may be higher for UVB radiation than for UVA radiation (e.g., the refractive index increases as the wavelength decreases). In other embodiments, the refractive index of the metal nanoparticles may be lower for UVB radiation than for UVA radiation (e.g., the refractive index increases as the wavelength increases).

[0057] In some embodiments, the polymer composition may contain metal nanoparticles that have photostability such that, when exposed to solar radiation (e.g., in an environment with a relatively high UV index of about 15), the metal nanoparticles do not decrease or lose their protective effect against UV radiation over a given time (e.g., about 1 hour, or about 2-4 hours, or about 4-6 hours, about 6-12 hours or longer, or even indefinitely). (e.g., maintaining about 100% effectiveness, or about 95-100% effectiveness, or about 90-100% effectiveness, or about 80-100% effectiveness).

[0058] In some embodiments, metal nanoparticles can impart radiation-protective properties to polymer compositions. For example, some embodiments may include a plurality of metal nanoparticles (e.g., beryllium and / or gold) configured to absorb harmful radiation (e.g., alpha particles, beta particles, and / or gamma rays), thereby reducing or eliminating harmful radiation passing through the nanoparticle-treated polymer.

[0059] In some embodiments, gold nanoparticles dispersed throughout the polymer composition downconvert incident UV radiation to less harmful UV radiation. In some embodiments, gold nanoparticles can downshift incident UV radiation by at least about 50 nm, at least about 100 nm, or at least about 150 nm, such as about 200 nm. In some embodiments, gold nanoparticles can downshift incident UV radiation from UV light to visible light. In some embodiments, gold nanoparticles can downshift incident UV radiation from UV wavelengths toward red and / or green wavelengths.

[0060] In some embodiments, gold nanoparticles dispersed throughout the polymer can absorb incident UV radiation and downconvert it to lower energy wavelengths, thereby providing UV protection to the polymer composition and the products made therefrom. Unexpectedly, the ability of the gold nanoparticles to permanently downconvert high-energy radiation does not degrade with use. That is, the gold nanoparticles demonstrated that they retain their UV protection capability and did not undergo any apparent degradation due to incident UV radiation. Beneficially, this allows the effects of the polymer composition and the products made therefrom to be maintained for a longer period. This also means that lower concentrations of gold nanoparticles or other wavelength-shifting metal nanoparticles can be used, resulting in products that are cheaper to manufacture while maintaining integrity.

[0061] V. Overview of Plastics Manufacturing Common plastic manufacturing processes include extrusion molding and injection molding. Many medical thermoplastics are manufactured using one of these two processes.

[0062] In the extrusion process, polymer pellets or granules are fed into the extruder by a hopper. The polymer pellets or granules are heated and melted inside the barrel, sometimes with the assistance of an auger. The molten polymer is then extruded through a metal die by a screw auger to create a fixed, continuous shape. The resulting extruded polymer object can be cut or trimmed as desired. The extrusion process is commonly used in the manufacture of pipes, tubes, frames, symmetrical devices, pellets, and the like.

[0063] Injection molding involves injecting molten thermoplastic polymer into an existing mold. The molten thermoplastic polymer can be formed by heating polymer pellets or granules. Once injected into the mold, the polymer can be cooled and solidified into its final shape. Molten polymer can also be produced in a similar manner to the extrusion process, where polymer pellets or granules are fed by a hopper into a barrel or other chamber, where they are heated and melted. If hollow products are desired, a process combining extrusion and injection molding may be used.

[0064] Additives may be included in plastic pellets or granules that are melted and molded to produce the final product. Colorants, reinforcing agents, and other enhancers may be sprayed or coated onto the pellets before heating. For example, a colorant may be dissolved or dispersed in a volatile solvent and sprayed onto the polymer pellets. Upon heating, the volatile solvent evaporates, leaving the colorant uniformly dispersed on the pellets. When the treated pellets are heated, the colorant is uniformly dispersed in the molten plastic, resulting in a uniformly colored product. Other additives may also be incorporated into plastic products in a similar manner.

[0065] Thermosetting polymers are also useful materials that can be molded or shaped into desired objects. Thermosetting polymers are typically formed by mixing two or more initially separate components that are formulated to react together to form a fluid initial mixture, rather than by heating them above their melting point. The fluid mixture can be molded into the desired shape in a similar manner to thermoplastic materials. The components in a thermosetting composition react together, causing polymerization and / or crosslinking to form a solidified thermosetting polymer.

[0066] Examples of materials for manufacturing medical devices and other polymer objects or structures include silicone, polysiloxane, epoxy, polystyrene (PS), polyethylene (PE) (including low-density polyethylene (LDPE), linear low-density polyethylene (LLDPE), and high-density polyethylene (HDPE)), polypropylene (PP), ethylene-vinyl acetate copolymer (EVA), polycarbonate (PC), polyurethane (PU), polyether ether ketone (PEEK), polylactic acid (PLA), polyhydroxyalkanoate (PHA), polyester (PES), polyethylene terephthalate (PET), and polymethylmethic acid. Examples include relate (PMMA), polybutylene terephthalate (PBT), phenol-formaldehyde (PF), nylon / polyimide (PA), melamine-formaldehyde (MF), polytetrafluoroethylene (PTFE), polyvinyl chloride (PVC), polyvinylpyrrolidone (PVP), acrylonitrile butadiene styrene terpolymer (ABS), styrene block copolymer (SBC), rubber latex (natural or synthetic), nitriles such as nitrile-butadiene rubber (NBR), medical-grade thermoplastic elastomers (TPE), aramid fibers such as Kevlar, carbon fiber reinforced polymers, and combinations thereof. Thermoplastics such as PE and PVC can be melted and heated multiple times during plastic manufacturing. Thermosetting plastics such as PU and many silicones remain solid after the plastic hardens during the curing process. TPU is a thermosetting polyurethane polymer that retains the properties of thermoplastics and can be used as a thermoplastic. Some silicones can be thermoplastic.

[0067] VI. Incorporation of nanoparticles into polymer compositions, resins, prepolymers, and monomers a. Application of solvents to polymer granules Nonionic metal nanoparticles formed by laser ablation may be manufactured in a liquid (e.g., water and / or organic solvent) or dispersed after manufacture, and subsequently applied to polymer pellets / granules / beads. For example, metal nanoparticles may be formed and / or dispersed in water and / or organic solvents such as ethanol, isopropyl alcohol, or acetone, and applied to polymer granules before the extrusion or injection molding process. Water may be used in the nanoparticle solution, but many polymer granules are somewhat hygroscopic and readily absorb moisture, which is usually undesirable. In such cases, the nanoparticle-containing liquid may be applied using an organic solvent, excluding water.

[0068] The nanoparticle solution may be applied to the granules by any suitable method, such as by spray application or by adding both the liquid and polymer granules to the same container. In embodiments where the nanoparticle solution is sprayed onto polymer granules, the granules may be placed on a conveyor system to which the granules are sprayed. The spray application may be carried out using a cyclonic chamber, and thermal enhancements may be provided as desired to assist in the removal of the liquid solvent by evaporation.

[0069] After application, the nanoparticle solution may be removed from the granules by evaporation, thereby removing the solvent and leaving the nanoparticles deposited on and / or impregnated into the polymer granules. This can be facilitated by the application of heat (e.g., infrared radiation, microwaves, thermal convection using an inert gas (e.g., nitrogen or argon), or thermal conduction) and / or vacuum. This is preferably carried out in an inert gas if the solvent is flammable and / or if oxygen or other gases damage the polymer at high temperatures.

[0070] The resulting molten polymer, containing a substantially uniform dispersion of metal nanoparticles, can then be used in extrusion molding, injection molding, or other plastic manufacturing processes to produce polymer products. The final polymer product will contain nanoparticles dispersed throughout the entire polymer portion of the product. For example, a tube made from the molten polymer may contain uniformly distributed nanoparticles, thereby enabling antimicrobial and / or UV protective effects throughout the polymer bulk.

[0071] Centrifuge systems, including batch mode centrifuge systems and flow centrifuge systems, may be used to associate metal nanoparticles with polymer granules. At sufficient speeds (e.g., 10,000 rpm), the centrifuge can force the metal nanoparticles to move to the location of the polymer granules. Higher concentrations in the centrifuge region can increase the uptake of metal nanoparticles by the polymer granules, resulting in nanoparticle absorption in addition to surface adsorption. This may be beneficial in applications where it is desired to include metal nanoparticles in the subsurface layer of the resulting polymer material.

[0072] b. Application of solvents to liquid polymer compositions In addition, or as an alternative, metal nanoparticles may be incorporated into a polymer composition by directly mixing a solvent containing metal nanoparticles with a liquid polymer composition (e.g., a latex emulsion or other emulsion, polymer suspension, resin, or prepolymer) that is not fully cured or otherwise not formed into a solid product, provided that the solvent is not significantly destructive to the components of the liquid polymer composition (e.g., monomer / oligomer material) and is significantly more volatile than the liquid polymer composition. After mixing, the solvent can be removed by evaporation, leaving behind a liquid polymer containing metal nanoparticles.

[0073] c. Application to precursor components In addition, or as an alternative, metal nanoparticles may be incorporated into the polymer composition by mixing them with a precursor polymer component, such as polyethylene glycol (PEG), which is added to the liquid polymer composition to undergo further processing / shaping. One or more such precursor components may contain metal nanoparticles insofar as they are used in an amount sufficient to add the desired amount or concentration of metal nanoparticles and are capable of functioning as carriers for the metal nanoparticles before being mixed with the remaining polymer composition components.

[0074] d. Multi-component resin In the case of multi-component (e.g., two-component) curable resins used in the manufacture of thermosetting polymer products, metal nanoparticles may be included in one or both components of the system. When both components are mixed together, the metal nanoparticles are blended throughout the mixture and solidify in place in the product or article into which the composition is formed. In some embodiments, a first type of nanoparticle (e.g., spherical silver nanoparticles) may be included in the first component of the two-component thermosetting polymer system, and a second type (e.g., coral-shaped gold nanoparticles) may be included in the second component of the two-component system.

[0075] For example, metal nanoparticles may be dispersed in or mixed with monomers and oligomers used to produce polymers, including monomers and oligomers used to produce thermoplastic polymers and thermosetting polymers. Examples of monomers that can be blended with metal nanoparticles before being used to form polymers include diols (ethylene glycol, propylene glycol, 1,3-butanediol, 1,4-butanediol (BDO), 1,5-pentanediol, 1,6-hexanediol, polyether glycol, other glycols and diols, e.g., up to 20 or more carbon atoms in length), triols, other polyols (e.g., polyether polyols and polyester polyols), isocyanates (e.g., methylenediphenyl diisocyanate (MDI), toluene diisocyanate (TDI), hexamethylene diisocyanate (HDI), isophorone diisocyanate (IPDI), 1,6-hexamethylene diisocyanate (HDI)) used in the production of polyurethanes, and those used in the production of polyesters or polyamides. Examples of such materials include, but are not limited to, dicarboxylic acids (e.g., terephthalic acid; adipic acid, etc.), diamines (e.g., for the production of polyamides), alkenes (e.g., for the production of polyolefins) and derivatives (e.g., fluorinated alkenes for Teflon, vinyl chloride for polyvinyl chloride, styrene for polystyrene), dienes (e.g., butadiene, isoprene), epoxides (e.g., for the production of epoxy), bisphenol A (BPA) (e.g., for the production of polycarbonates), acrylates, methacrylates, acrylonitriles, silanes (e.g., for the production of polysiloxanes), ketones (e.g., for the production of polyetheretherketones), phosphazenes (e.g., for the production of polyphosphazenes), chain extenders (e.g., 1,4-butanediol, 1,6-hexanediol), aliphatic diamines (e.g., ethylenediamine (EDA)), aromatic diamines (e.g., 1,4-diaminobenzene, p-phenylenediamine), and crosslinking agents.

[0076] Other monomers that can incorporate metal nanoparticles are listed in the "Monomer Product Guide" published by Polysciences, Inc. (available at https: / / www.polysciences.com, referenced by reference). Further monomers that can incorporate metal nanoparticles are listed in "Monomers" published by TCI America (available at https: / / www.tcichemicals.com, referenced by reference).

[0077] Metal nanoparticles may be mixed with catalysts (e.g., dibutyltin dilaurate), stabilizers, antioxidants, UV stabilizers, and biocompatible additives used in the production of polymers. VII. Medical Devices Polymer-based products manufactured using one or more of the methods disclosed herein may include medical devices. Medical devices thus formed are beneficially protected from microbial growth. Metal nanoparticles incorporated into the medical device can inactivate or kill microorganisms, preventing microbial accumulation on or within the medical device. This beneficially extends the lifespan of the device in environments such as hospitals or clinics. This is also beneficial for product sterilization, leading to reduced costs for storage and sterilization procedures.

[0078] In some embodiments, metal nanoparticles incorporated into medical devices may also be capable of downconverting incident UV radiation to lower-energy radiation. This is beneficial in preventing overall degradation of polymer-based devices or articles due to UV radiation. Polymer-based devices or articles can then be used for longer periods without cracking, discoloration, clouding, leaking, and / or complete failure.

[0079] Examples of medical devices that may be formed at least in part using the methods disclosed herein include, but are not limited to, gloves (e.g., latex gloves), catheters, wound dressings, syringes and other drug delivery components, silicone products (e.g., breast implants), adhesives, tapes, and polymer portions of implantable devices (e.g., pacemakers, joint replacements, drug pumps, intrauterine devices (IUDs), cochlear implants, vascular access devices, and polymer portions of artificial heart valves). [Examples]

[0080] VII. Examples Example 1 Silver nanoparticles were suspended in 99.9% isopropyl alcohol. The nanoparticle concentration was confirmed using inductively coupled plasma atomic emission spectroscopy (ICPOES). The nanoparticle diameter was determined to be approximately 6–10 nm using DLS. Surface composition and short bond length were confirmed by STEM imaging using electron loss spectroscopy (ELS).

[0081] It was found that drug-resistant bacteria were killed at nanoparticle concentrations ranging from 0.5 mg / L (0.5 ppm) to 2 mg / L (2 ppm). The highest concentration found to kill drug-resistant bacteria was 8 mg / L (8 ppm). Using STEM imaging with a dark-field camera coated with 3 nm carbon, without the use of staining agents, nanoparticles within and around the bacteria could be tracked. By combining STEM imaging with electron diffraction spectroscopy (EDS), cell division at disulfide bonds and ferredoxin sites was confirmed.

[0082] Example 2 Polyethylene (PE) products embedded with silver nanoparticles were tested for antibacterial properties. Two polymers, Tecoflex FG-93A-B20 (W filament) and Isoplast 2510 (D filament), were prepared and treated with silver nanoparticles. Figures 5A-5C show STEM images of Tecoflex EG-93A-B20 thermoplastic with embedded nanoparticles. Figures 6A-6C show STEM images of Isoplast 2510 thermoplastic with embedded nanoparticles. Figures 8A-8B show silver nanoparticles embedded in the thermoplastic.

[0083] Silver nanoparticles were prepared in isopropyl alcohol at a concentration of 38 mg / L (38 ppm). This alcohol mixture was applied to polymer beads or granules. The polymer beads or granules were melted, and the final concentration in the resulting PE polymer was 6 mg / kg (6 ppm). This concentration of 6 mg / kg has been successfully tested in surface antibacterial tests to date.

[0084] After removing the alcohol using a nitrogen blowdown system, nanoparticles distributed on the surface of the plastic beads remained. The polymer beads were then passed through a 230°C extrusion melting system to form filaments. The nanoparticles on the polymer bead surface were mixed into the fabricated filaments. Next, the filaments were embedded in a toming polymer, thinned to a thickness of 80–100 nm, and mounted on a 200-mesh Formvar carbon B TEM grid for imaging.

[0085] Imaging was performed using a JEOL 2800 scanning transmission electron microscope (STEM) equipped with a dark-field camera, a bright-field camera, and a secondary surface camera. 1 nm 2 Elemental mapping was performed down to resolution, and nanoparticles and fine particles were identified using a dual EDS detector for triangulation and net count accuracy.

[0086] The Tecoflex FG-93A-B20 thermoplastic was pale purple and required a quenching or cooling step after melt extrusion at 230°C. As shown in Figures 5A-5C, large solid metal particles with a particle size of several hundred nanometers were observed under STEM. EDS mapping confirmed that these were barium sulfate.

[0087] The silver nanoparticles directly interacted with sulfurous chemicals, and it is thought that the overwhelming amount of barium sulfate (used as a filler and reinforcing agent in Tecoflex FG-93A-B20) encapsulated the silver nanoparticles. No direct nanoparticles were found on any grid from the STEM imaging. Background silver was detected in the barium sulfate particles. Thermal dissociation was observed on the filament surface, which was expected due to insufficient thermal control in the final filament formation.

[0088] The Isoplast 2510 thermoplastic was a darker purple and had a more glass-like surface finish. The Isoplast 2510 thermoplastic was melted at 230°C and cooled to room temperature (22.5°C). This thermoplastic used phosphate as a filler and reinforcing agent instead of barium sulfate. As shown in Figures 6A–6C, the phosphate did not interact with the Ag nanoparticles, making it easy to locate and elementally map the present silver nanoparticles. Isoplast 2510 is a more suitable candidate for uniformly distributing silver nanoparticles within the plastic. The surface did not undergo the same type of thermal dissociation.

[0089] Example 3 Surface antibacterial testing was performed using the standard penicylal method. A conventional penicylal has an outer diameter of 7.8 mm, an inner diameter of 5.8 mm, and a length of 9.9 mm. The surface area can be calculated as follows:

[0090] A s =(Outer surface area)+(Inner surface area)+2(Edge surface area) A s = 242.6 mm2 +180.4 mm 2 +42 mm 2 A s = 465 mm 2 Since both ends of the penicillin cylinder have a 45° taper, the overall surface area is slightly smaller than the calculated value, but the difference is not significant.

[0091] A 20-mm-long filament similar to the penicillin cylinder was used for the antibacterial test. The filament diameter was 1.2 mm, and it had an outer surface area of 7.5 mm per 1-mm length, and the surface area at both ends was 2.3 mm. 2 The total surface area of the 20-mm-long filament is A 2 = 152.3 mm f The total number of 20-mm-long filaments required to replace the penicillin cylinder is as follows. 2

[0092] A s / A f = 465 / 152.3 = 3.1 Three filaments were used for each test sample set so that the surface area was approximately equal to that of one penicillin cylinder. The metal nanoparticles were suspended throughout each filament.

[0093] The filaments were cut with a disposable straight-edge razor blade washed with 70% or more isopropyl alcohol. The filaments were measured against a continuous surface with two marks at 20-mm intervals, and the filaments were cut to that length. The cut filaments were transferred to a 50-mL sample tube containing 25 mL of isopropyl alcohol and vortexed for 1 minute. Then, using flame-sterilized / heat-sterilized tweezers, the filaments were removed to a 50-mL sample holding container.

[0094] The antibacterial test was performed at 10 5 6 7 ​​​The study was conducted using E. coli at the colony-forming unit (CFU) level. Each set of three filaments was introduced into E. coli in trypsin-containing soy broth and exposed to the E. coli for 1 hour. Two sample sets (three filaments) were used for each concentration of E. coli.

[0095] Filaments were removed from trypsin soy broth containing E. coli colonies, and liquid was added to the filaments until no liquid remained. Next, the filaments were introduced into purple Dey-Engley (DE) broth. If E. coli proliferated from the filaments in the DE broth, the broth would turn yellow.

[0096] DE broth samples were cultured in a trypsin soycan template for colony growth, and the first 10 5 , 10 6 , and 10 7 The culture was compared with the CFU culture. Subsequently, the number of colonies was counted 24 hours and 48 hours after growth. The CFU of E. coli was confirmed by the following agar count: 10 5 =23CFU;10 6 =256 CFU; and 10 7 = 1000 CFU.

[0097] 24 hours after the test, the CFU on the filament can template was 0 for all prepared concentrations of E. coli. 48 hours after the test, the CFU on the filament can template was 0 for all prepared concentrations of E. coli. DE broth showed no color change in all prepared concentrations of E. coli exposed to filaments at 24 and 48 hours. 10 5 , 10 6 , and 10 7 No viable bacteria were found on the surface of any filaments exposed to CFU concentrations of E. coli for one hour. Both sets of samples in the test showed the same result.

[0098] Example 4 We successfully used a method in which metal nanoparticles dispersed in a volatile solvent were sprayed onto industry-standard pellets, as shown in Figure 7A, and the solvent was removed by evaporation. The treated pellets were extruded into filaments through a hot mixer, as shown in Figure 7B. The filaments were wrapped in ECON polymer to protect them from damage, and then cut crosswise with a diamond edge cutter to a thickness of less than 100 nm. Thin slices of the filaments were used for STEM / EDS imaging. The metal nanoparticles integrated well with the plastic and showed an interesting, uniform distribution that was compatible with the plastic polymer chains. The nanoparticles appear to move freely within the plastic when hydrodynamic forces and temperature or energy gradients are present.

[0099] Example 5 Spherical silver nanoparticles, produced by laser ablation without external bond angles or edges, and being non-ionic and non-emitting of silver ions, were tested to determine whether they could induce silver nanoparticle-resistant bacteria. No such resistance was detected even after 28 passages.

[0100] The title of this experiment was "Mutant Generation Test for P. erginosa ATCC 15442 and Escherichia coli ATCC 25922". Two different types of spherical silver nanoparticles were tested: silver lot number desktop laser: Ag200917-104 (19 ppm) and silver lot number industrial laser: 171229-101 (16.8 ppm). Spherical silver nanoparticles produced using the desktop laser had an average diameter of 8–10 nm, while spherical silver nanoparticles produced using the industrial laser had an average diameter of 8–12 nm.

[0101] The general procedure for the experiment is as follows: Bacteria preparation: 1. Streak the bacteria onto a trypsin soy agar (TSA) plate and incubate overnight at 37°C. 2. The following day, inoculate one colony into 10 mL of silver mixed with Mueller-Hinton broth. a. Desktop laser: i. Prepare a 4.75 ppm silver nanoparticle mix in E. coli broth (2.5 mL of Ag+ + 7.5 mL of broth). ii. Prepare a 4.75 ppm silver nanoparticle mix in P. erginosa broth (2.5 mL of Ag + 7.5 mL of broth). b. Industrial lasers: i. Prepare a 2 ppm silver nanoparticle mix in E. coli broth (1.2 mL of Ag + 8.8 mL of broth). ii. Prepare a 2 ppm silver nanoparticle mix in P. erginosa broth (1.2 mL of Ag + 8.8 mL of broth). 3. Incubate at 37°C and 250 RPM for 24-36 hours. 4. Monitor the growth the following day. 5. Continue continuous subculturing in a new silver broth mixture by inserting the inoculation loop into the culture. 6. Every 5-7 days, streak the culture loop onto a TSA plate for subculturing, then perform an MIC test on the colonies to measure whether the bacteria have developed resistance to spheroidal silver nanoparticles.

[0102] The experimental results are as follows: MIC value: Escherichia coli - Industrial laser sample: MIC was maintained at 2 ppm up to 28 consecutive passages. DT laser sample: Culture regrowth stopped at passage 21. MIC was maintained in previous passages. P. erginosa - Industrial laser sample: MIC was maintained at 2 ppm up to 28 consecutive passages. DT laser sample: Culture regrowth stopped at passage 21. MIC was maintained in previous passages. All negative and positive controls passed.

[0103] Comparative Example Using conventional silver nanoparticles prepared using a chemical reduction process, the same tests as described in Example 5 were performed. These silver nanoparticles have external bond angles and edges and release silver ions in water. Silver resistance was evident from the increase in MIC value within 6 passages.

[0104] Example 6 Metal nanoparticles are formed by laser ablation in an isopropyl alcohol carrier. Subsequently, excess solvent is evaporated using warm nitrogen gas to increase the nanoparticle concentration in the carrier to 35 ppm. 400 ml of the carrier and metal nanoparticles are added together with 800 g of PE granules to a cylinder (e.g., glass, PTFE, or PET) with a surface that does not significantly attract nanoparticles. The cylinder and its contents are heated in a vacuum oven to promote solvent removal and deposition of metal nanoparticles onto the PE granules. The evaporated solvent is collected in a cooling trap for recycling as desired. Applying 400 ml of the carrier containing metal nanoparticles twice results in PE beads containing approximately 35 mg / kg of nanoparticles, assuming essentially complete migration.

[0105] After drying, the granules are extruded to form filaments. For ICP-OES and / or ICP-MS testing, the filaments are ashed and digested to determine the final amount of nanoparticles packed into the granules. Imaging of the filaments using a STEM equipped with a dark-field camera is also performed to confirm the distribution of nanoparticles on the filaments. The filaments are also tested for resistance to microbial colonization. Subsequently, for storage or distribution, the granules are subjected to further drying and packaged with a desiccant under vacuum.

[0106] Example 7 Spherical silver nanoparticles are dispersed in 1,4-butanediol at a concentration of 100 ppb to 100 ppm. The 1,4-butanediol silver nanoparticle composition is used to produce polymer compositions such as polyurethane by reaction with isocyanate or polyester by reaction with diacitates. Polyurethane is initially formed by thermosetting. In some cases, thermosetting polyurethane can also be thermoplastic (i.e., TPU).

[0107] IX. Additional Terms and Definitions While certain embodiments of this disclosure have been described in detail with reference to specific configurations, parameters, components, elements, etc., these descriptions are illustrative and should not be construed as limiting the scope of the claimed invention.

[0108] Furthermore, it should be understood that, for any given element of the components of the described embodiments, unless otherwise implicitly or explicitly stated, any of the enumerated possible alternatives for that element or component may be used individually or in combination with each other.

[0109] In addition, numerical values ​​representing quantities, components, distances, or other measurements used herein and in the claims should be understood to be modified, as desired, by the term “approximately.” When terms such as “approximately,” “about,” or “substantially” are used in conjunction with a stated quantity, value, or condition, it may be interpreted that the quantity, value, or condition deviates by less than 20%, less than 10%, less than 5%, less than 1%, less than 0.1%, or less than 0.01% from the stated quantity, value, or condition. At the very least, and not intended to limit the application of the doctrine of equivalents to the claims, each numerical parameter should be interpreted using the usual rounding method, taking into account the number of significant figures reported.

[0110] The headings and subheadings used herein are for structural purposes only and are not intended to limit this specification or the claims. Furthermore, it should be noted that, as used herein and in the appended claims, the singular forms “a,” “an,” and “the” do not exclude multiple referents unless the context clearly indicates otherwise. Therefore, for example, embodiments referring to a singular referent (e.g., “medical device”) may also include two or more such referents.

[0111] The embodiments disclosed herein should be understood to comprise / contain the disclosed components and, therefore, may include additional components not specifically described. If desired, the embodiments disclosed herein may essentially or completely omit components not specifically described. That is, components not disclosed may, if desired, be completely or essentially omitted from the disclosed embodiments. For example, undisclosed nanoparticle conjugates or undisclosed solvents may, if desired, be completely or essentially omitted from the polymer compositions and / or finished medical products disclosed herein.

[0112] Embodiments that "essentially omit" or "essentially do not contain" a certain component may contain that component in trace and / or non-functional amounts. For example, an "essentially omitted" component may be present in amounts of 2.5% or less, 1% or less, 0.1% or less, or 0.01% or less of the total weight of the composition. This also applies to other negative modifiers, including but not limited to similar phrases using other synonyms for "essentially omitted," "essentially without," "substantially," or "essentially."

[0113] A composition that "completely omits" or "completely does not contain" a certain component does not contain any detectable amount of that component when analyzed using standard coating composition analysis techniques such as chromatography (e.g., thin-layer chromatography (TLC), gas chromatography (GC), liquid chromatography (LC)) or spectroscopy (e.g., Fourier transform infrared (FTIR) spectroscopy) (i.e., does not contain an amount exceeding the inherent background signal associated with the test equipment).

[0114] Furthermore, the embodiments described herein may also include characteristics and / or features (e.g., raw material components, components, members, elements, parts, and / or parts) described in one or more distinct embodiments, and are not necessarily strictly limited to the features explicitly described for that particular embodiment. Accordingly, various features of a given embodiment may be combined with and / or incorporated into other embodiments of the Disclosure. Therefore, the disclosure of certain features relating to a particular embodiment of the Disclosure should not be interpreted as limiting the application or inclusion of such features to that particular embodiment. Rather, it is understood that other embodiments may also include such features.

Claims

1. Applying a nanoparticle solution containing nonionic metal nanoparticles formed by laser ablation to a polymer composition; and The polymer composition is molded into a polymer product into which the metal nanoparticles are incorporated. A method for manufacturing polymer products, including

2. The nanoparticle solution comprises a volatile solvent, and the polymer composition comprises polymer granules, and the method further comprises The aforementioned nanoparticle solution is applied to polymer granules; The volatile solvent is removed by evaporation, thereby leaving the metal nanoparticles on the polymer granules and / or impregnating them into the polymer granules. The polymer granules are heated to form a melted polymer, and the metal nanoparticles are dispersed in the melted polymer; and Molding the molten polymer into the polymer product, The method according to claim 1, including the method described in claim 1.

3. The method according to claim 2, wherein the nanoparticle solution is applied to the polymer granules by adding both the nanoparticle solution and the polymer granules to a container.

4. The method according to claim 2 or 3, wherein the nanoparticle solution is applied to the polymer granules by spraying the nanoparticle solution onto the polymer granules.

5. The method according to any one of claims 2 to 4, wherein the nanoparticle solution is applied to the polymer granules using a centrifuge.

6. The method according to any one of claims 1 to 5, wherein the nanoparticle solution comprises a volatile solvent, the polymer composition is a liquid polymer composition, and the method comprises removing the volatile solvent by evaporation after applying the nanoparticle solution to the polymer composition and before forming the polymer composition into the polymer product.

7. The method according to any one of claims 1 to 6, wherein the nanoparticle solution comprises a precursor polymer component, and the polymer composition is a liquid, and the method further comprises mixing the precursor polymer component with the nanoparticle solution.

8. The method according to claim 7, wherein the precursor polymer component comprises polyethylene glycol (PEG) or 1,4-butanediol.

9. The method according to any one of claims 1 to 8, wherein the metal nanoparticles include silver nanoparticles.

10. The method according to any one of claims 1 to 9, wherein the metal nanoparticles include gold nanoparticles.

11. The method according to any one of claims 1 to 10, wherein the metal nanoparticles include a combination of gold nanoparticles and silver nanoparticles.

12. The method according to claim 11, wherein the ratio of silver nanoparticles to gold nanoparticles is 1:1 to about 50:1, or about 2.5:1 to about 25:1, or about 5:1 to about 20:1, or about 7.5:1 to about 15:1, or about 9:1 to about 11:1, or about 10:

1.

13. The method according to any one of claims 1 to 12, wherein the metal nanoparticles include spherical nanoparticles.

14. The method according to claim 13, wherein the spherical metal nanoparticles have an average diameter in the range of about 1 nm to about 40 nm, or about 2 nm to about 20 nm, or about 3 nm to about 14 nm, or about 4 nm to about 13 nm, or about 5 nm to about 12 nm, or about 6 nm to about 10 nm.

15. The method according to claim 13 or 14, wherein the metal nanoparticles have a particle size distribution in which at least 99% of the metal nanoparticles have a particle size within 30% of the average diameter, or within 20% of the average diameter, or within 10% of the average diameter, and / or at least 99% of the spherical nanoparticles have a particle size distribution in which the diameter is within ±3 nm of the average diameter, or within ±2 nm of the average diameter, or within ±1 nm of the average diameter.

16. The method according to any one of claims 1 to 15, wherein the metal nanoparticles have a ξ potential of at least about ±10 mV (absolute value), or at least about ±15 mV, or at least about ±20 mV, or at least about ±25 mV, or at least about ±30 mV.

17. The method according to any one of claims 1 to 16, wherein the metal nanoparticles include coral-shaped nanoparticles.

18. The method according to any one of claims 1 to 17, wherein the metal nanoparticles include both spherical nanoparticles and coral-shaped nanoparticles, and optionally the mass ratio of spherical nanoparticles to coral-shaped nanoparticles in the nanoparticle solution is 1:1 to 50:

1.

19. Applying a nanoparticle solution containing nonionic metal nanoparticles formed by laser ablation and a volatile solvent to thermoplastic polymer granules; Removing the volatile solvent by evaporation, thereby leaving the metal nanoparticles on the thermoplastic polymer granules and / or impregnating them into the thermoplastic polymer granules; The thermoplastic polymer granules are heated to form a melted polymer, and the metal nanoparticles are dispersed in the melted polymer; and The polymer composition is molded into a polymer product into which the metal nanoparticles are incorporated. A method for manufacturing polymer products, including

20. A method for producing thermosetting polymer products, Adding metal nanoparticles to the liquid component of a multi-component thermosetting polymer composition; Mixing multiple components of the thermosetting polymer composition to disperse the metal nanoparticles in the thermosetting polymer composition; Molding the thermosetting polymer composition into a desired shape; and The thermosetting polymer composition is solidified or made solidifiable in the desired shape of the thermosetting polymer product, wherein the metal nanoparticles are dispersed in the thermosetting polymer product. Methods that include...

21. A polymer product formed by the method described in any one of claims 1 to 20.

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