JP2023553954A - Nitride-based antipathogen compositions and devices, and methods of use thereof - Google Patents

Abstract

The present specification includes aluminum nitride, boron nitride, chromium nitride, cerium nitride, hafnium nitride, lanthanum nitride, phosphorus nitride, sulfur nitride, tantalum nitride, titanium nitride, vanadium nitride, yttrium nitride, zirconium nitride, silicon nitride, or Antipathogenic compositions comprising nitrides selected from combinations of nitrides are described, as well as methods of using the compositions described above to inactivate viruses, bacteria, and/or fungi. [Selection diagram] Figure 1A

Description

CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to and benefits from U.S. Provisional Patent Application No. 63/123,037, filed December 9, 2020, which is incorporated herein by reference in its entirety. .

TECHNICAL FIELD This disclosure relates generally to anti-pathogen compositions and devices, and specifically to systems and methods for nitride-based anti-pathogen compositions and devices.

It is well known that surface transmission of pathogenic organisms causes numerous diseases, disorders, and deaths. In recent years, the discovery of new pathogens such as the SARS-CoV-2 virus has emphasized this problem. Methods of killing or inactivating pathogens living on surfaces often involve the use of cleaning products, high heat or pressure, or electromagnetic radiation. These methods can be expensive and, in some cases, can present other risks to humans, such as exposure to toxic chemicals or intense ultraviolet radiation. Furthermore, over time, certain pathogens develop resistance to existing methods.

Therefore, there is a need for methods and compositions useful for inactivating or killing pathogenic organisms.

Provided herein are nitride-based compositions or devices for inactivating viruses, bacteria, and/or fungi. Nitride-based compositions include aluminum nitride, boron nitride, chromium nitride, cerium nitride, hafnium nitride, lanthanum nitride, phosphorus nitride, sulfur nitride, tantalum nitride, titanium nitride, vanadium nitride, yttrium nitride, zirconium nitride, and various forms of Contains silicon nitride, or combinations thereof.

Also provided herein are methods for inactivating pathogens by contacting viruses, bacteria, and/or fungi with the anti-pathogen nitride-based compositions or devices disclosed herein. provided.

2 is a graphical representation showing the inactivation of SARS-CoV-2 by nitride powder treated with 15 wt% Cu, AlN, and Si3N4 powder for 1 and 10 minutes at room temperature in aqueous medium, where the control virus was It was processed identically without adding any powder. After centrifugation, the supernatant was subjected to TCID50 assay. Viral titers were determined using the Reed-Muench method. TCID50/50 μL (FIGS. 1A and 1B) and % reduction FIGS. 1C and 1D are shown for virus inactivation times of 1 and 10 minutes, respectively. Statistics are shown in the inset according to an unpaired two-tailed Student's t-test (n=3). 1 is a graphical representation showing viral RNA undergoing severe degradation after exposure to copper or nitride particles. In Figures 2A and 2B, virus suspensions were exposed to Cu, AlN, and Si3N4 powders for 1 min, and viral RNA in the supernatant and on particles was isolated from viral N genes "Set 1" and "Set 2", respectively. It was evaluated using primers. Data collected on supernatant and pellet samples are shown in comparison to the amount of viral N gene RNA in suspensions left untreated. Figures 2C and 2D show the results of RT-PCR tests after exposing the supernatant to Cu, AlN, and Si3N4 powder for 10 minutes for the viral N gene "Set 1" and "Set 2" primers, respectively. Statistics are shown in the inset according to an unpaired two-tailed Student's t-test (n=3). 1 is a graphical representation showing viral RNA undergoing severe degradation after exposure to copper or nitride particles. In Figures 2A and 2B, virus suspensions were exposed to Cu, AlN, and Si3N4 powders for 1 min, and viral RNA in the supernatant and on particles was isolated from viral N genes "Set 1" and "Set 2", respectively. It was evaluated using primers. Data collected on supernatant and pellet samples are shown in comparison to the amount of viral N gene RNA in suspensions left untreated. Figures 2C and 2D show the results of RT-PCR tests after exposing the supernatant to Cu, AlN, and Si3N4 powder for 10 minutes for the viral N gene "Set 1" and "Set 2" primers, respectively. Statistics are shown in the inset according to an unpaired two-tailed Student's t-test (n=3). 1 is a graphical representation showing viral RNA undergoing severe degradation after exposure to copper or nitride particles. In Figures 2A and 2B, virus suspensions were exposed to Cu, AlN, and Si3N4 powders for 1 min, and viral RNA in the supernatant and on particles was isolated from viral N genes "Set 1" and "Set 2", respectively. It was evaluated using primers. Data collected on supernatant and pellet samples are shown in comparison to the amount of viral N gene RNA in suspensions left untreated. Figures 2C and 2D show the results of RT-PCR tests after exposing the supernatant to Cu, AlN, and Si3N4 powder for 10 minutes for the viral N gene "Set 1" and "Set 2" primers, respectively. Statistics are shown in the inset according to an unpaired two-tailed Student's t-test (n=3). 1 is a graphical representation showing viral RNA undergoing severe degradation after exposure to copper or nitride particles. In Figures 2A and 2B, virus suspensions were exposed to Cu, AlN, and Si3N4 powders for 1 min, and viral RNA in the supernatant and on particles was isolated from viral N genes "Set 1" and "Set 2", respectively. It was evaluated using primers. Data collected on supernatant and pellet samples are shown in comparison to the amount of viral N gene RNA in suspensions left untreated. Figures 2C and 2D show the results of RT-PCR tests after exposing the supernatant to Cu, AlN, and Si3N4 powder for 10 minutes for the viral N gene "Set 1" and "Set 2" primers, respectively. Statistics are shown in the inset according to an unpaired two-tailed Student's t-test (n=3). Figure 2 is an image showing that Si3N4 suppressed viral infection without affecting cell viability where Cu killed cells. VeroE6/TMPRSS2 cells were inoculated with unexposed virions (Fig. 3A) and virions exposed to UTE for 10 min on Si3N4 (Fig. 3B), AlN (Fig. 3C), and Cu (Fig. 3D). In Figure 3E, uninoculated cells (labeled "mock-infected" cells) were also prepared and imaged for comparison. After fixation, cells were stained with anti-SARS coronavirus envelope antibody (red), phalloidin (green) to visualize F-actin, and DAPI (blue) to stain the nucleus. Representative fluorescence micrographs of n=3 samples are shown. Figure 2 is an image showing that Si3N4 suppressed viral infection without affecting cell viability where Cu killed cells. VeroE6/TMPRSS2 cells were inoculated with unexposed virions (Fig. 3A) and virions exposed to UTE for 10 min on Si3N4 (Fig. 3B), AlN (Fig. 3C), and Cu (Fig. 3D). In Figure 3E, uninoculated cells (labeled "mock-infected" cells) were also prepared and imaged for comparison. After fixation, cells were stained with anti-SARS coronavirus envelope antibody (red), phalloidin (green) to visualize F-actin, and DAPI (blue) to stain the nucleus. Representative fluorescence micrographs of n=3 samples are shown. Figure 2 is an image showing that Si3N4 suppressed viral infection without affecting cell viability where Cu killed cells. VeroE6/TMPRSS2 cells were inoculated with unexposed virions (Fig. 3A) and virions exposed to UTE for 10 min on Si3N4 (Fig. 3B), AlN (Fig. 3C), and Cu (Fig. 3D). In Figure 3E, uninoculated cells (labeled "mock-infected" cells) were also prepared and imaged for comparison. After fixation, cells were stained with anti-SARS coronavirus envelope antibody (red), phalloidin (green) to visualize F-actin, and DAPI (blue) to stain the nucleus. Representative fluorescence micrographs of n=3 samples are shown. Figure 2 is an image showing that Si3N4 suppressed viral infection without affecting cell viability where Cu killed cells. VeroE6/TMPRSS2 cells were inoculated with unexposed virions (Fig. 3A) and virions exposed to UTE for 10 min on Si3N4 (Fig. 3B), AlN (Fig. 3C), and Cu (Fig. 3D). In Figure 3E, uninoculated cells (labeled "mock-infected" cells) were also prepared and imaged for comparison. After fixation, cells were stained with anti-SARS coronavirus envelope antibody (red), phalloidin (green) to visualize F-actin, and DAPI (blue) to stain the nucleus. Representative fluorescence micrographs of n=3 samples are shown. Figure 2 is an image showing that Si3N4 suppressed viral infection without affecting cell viability where Cu killed cells. VeroE6/TMPRSS2 cells were inoculated with unexposed virions (Fig. 3A) and virions exposed to UTE for 10 min on Si3N4 (Fig. 3B), AlN (Fig. 3C), and Cu (Fig. 3D). In Figure 3E, uninoculated cells (labeled "mock-infected" cells) were also prepared and imaged for comparison. After fixation, cells were stained with anti-SARS coronavirus envelope antibody (red), phalloidin (green) to visualize F-actin, and DAPI (blue) to stain the nucleus. Representative fluorescence micrographs of n=3 samples are shown. Figure 2 is a graphical representation showing that fluorescently labeled and unlabeled cells were counted on fluorescence micrographs and % infected cells and % viable cells were calculated as follows. % infected cells = (number of cells stained with anti-SARS coronavirus envelope antibody) / (number of cells stained with DAPI) × 100, and % viable cells = (number of cells stained with phalloidin) / ( Number of cells stained with DAPI) x 100. Data are representative of n=3 samples. * and ** p<0.05 and 0.01, respectively, by unpaired two-tailed Student's t-test (n=3), n. s. = Not significant. 1 is a graphical representation of a Raman spectrum for: (a) Uninfected cells (Fig. 5A) (i.e., not exposed to virions) and (b) Si3N4 (Fig. 5B), (c) AlN (Fig. 5C), and (d) Cu (Fig. 5D). ) cells infected with SARS-CoV-2 virions exposed for 10 minutes. In Figure 5E, Raman spectrum of cells infected with unexposed virions (negative control). Figure 5F shows the two tryptophan T1 and T2 bands (756 and 875 cm, respectively) as a function of the percentage of infected cells by unexposed virions and virions exposed for 10 min to different particles (see labels). 1) Plot of average intensity. Inset: Structure of N'-formylkynurenine, an intermediate in the catabolism of tryptophan during the enzymatic IDO reaction. In FIG. 5G, a graphical representation shows three possible conformations of a tyrosine-based peptide that may justify the disappearance of the ring vibration in tyrosine (Ty2 band) upon chelation of Cu(II) ions. 1 is a graphical representation of a Raman spectrum for: (a) Uninfected cells (Fig. 5A) (i.e., not exposed to virions) and (b) Si3N4 (Fig. 5B), (c) AlN (Fig. 5C), and (d) Cu (Fig. 5D). ) cells infected with SARS-CoV-2 virions exposed for 10 minutes. In Figure 5E, Raman spectrum of cells infected with unexposed virions (negative control). Figure 5F shows the two tryptophan T1 and T2 bands (756 and 875 cm, respectively) as a function of the percentage of infected cells by unexposed virions and virions exposed for 10 min to different particles (see labels). 1) Plot of average intensity. Inset: Structure of N'-formylkynurenine, an intermediate in the catabolism of tryptophan during the enzymatic IDO reaction. In FIG. 5G, a graphical representation shows three possible conformations of a tyrosine-based peptide that may justify the disappearance of the ring vibration in tyrosine (Ty2 band) upon chelation of Cu(II) ions. 1 is a graphical representation of a Raman spectrum for: (a) Uninfected cells (Fig. 5A) (i.e., not exposed to virions) and (b) Si3N4 (Fig. 5B), (c) AlN (Fig. 5C), and (d) Cu (Fig. 5D). ) cells infected with SARS-CoV-2 virions exposed for 10 minutes. In Figure 5E, Raman spectrum of cells infected with unexposed virions (negative control). Figure 5F shows the two tryptophan T1 and T2 bands (756 and 875 cm, respectively) as a function of the percentage of infected cells by unexposed virions and virions exposed for 10 min to different particles (see labels). 1) Plot of average intensity. Inset: Structure of N'-formylkynurenine, an intermediate in the catabolism of tryptophan during the enzymatic IDO reaction. In FIG. 5G, a graphical representation shows three possible conformations of a tyrosine-based peptide that may justify the disappearance of the ring vibration in tyrosine (Ty2 band) upon chelation of Cu(II) ions. 1 is a graphical representation of a Raman spectrum for: (a) Uninfected cells (Fig. 5A) (i.e., not exposed to virions) and (b) Si3N4 (Fig. 5B), (c) AlN (Fig. 5C), and (d) Cu (Fig. 5D). ) cells infected with SARS-CoV-2 virions exposed for 10 minutes. In Figure 5E, Raman spectrum of cells infected with unexposed virions (negative control). Figure 5F shows the two tryptophan T1 and T2 bands (756 and 875 cm, respectively) as a function of the percentage of infected cells by unexposed virions and virions exposed for 10 min to different particles (see labels). 1) Plot of average intensity. Inset: Structure of N'-formylkynurenine, an intermediate in the catabolism of tryptophan during the enzymatic IDO reaction. In FIG. 5G, a graphical representation shows three possible conformations of a tyrosine-based peptide that may justify the disappearance of the ring vibration in tyrosine (Ty2 band) upon chelation of Cu(II) ions. 1 is a graphical representation of a Raman spectrum for: (a) Uninfected cells (Fig. 5A) (i.e., not exposed to virions) and (b) Si3N4 (Fig. 5B), (c) AlN (Fig. 5C), and (d) Cu (Fig. 5D). ) cells infected with SARS-CoV-2 virions exposed for 10 minutes. In Figure 5E, Raman spectrum of cells infected with unexposed virions (negative control). Figure 5F shows the two tryptophan T1 and T2 bands (756 and 875 cm, respectively) as a function of the percentage of infected cells by unexposed virions and virions exposed for 10 min to different particles (see labels). 1) Plot of average intensity. Inset: Structure of N'-formylkynurenine, an intermediate in the catabolism of tryptophan during the enzymatic IDO reaction. In FIG. 5G, a graphical representation shows three possible conformations of a tyrosine-based peptide that may justify the disappearance of the ring vibration in tyrosine (Ty2 band) upon chelation of Cu(II) ions. 1 is a graphical representation of a Raman spectrum for: (a) Uninfected cells (Fig. 5A) (i.e., not exposed to virions) and (b) Si3N4 (Fig. 5B), (c) AlN (Fig. 5C), and (d) Cu (Fig. 5D). ) cells infected with SARS-CoV-2 virions exposed for 10 minutes. In Figure 5E, Raman spectrum of cells infected with unexposed virions (negative control). Figure 5F shows the two tryptophan T1 and T2 bands (756 and 875 cm, respectively) as a function of the percentage of infected cells by unexposed virions and virions exposed for 10 min to different particles (see labels). 1) Plot of average intensity. Inset: Structure of N'-formylkynurenine, an intermediate in the catabolism of tryptophan during the enzymatic IDO reaction. In FIG. 5G, a graphical representation shows three possible conformations of a tyrosine-based peptide that may justify the disappearance of the ring vibration in tyrosine (Ty2 band) upon chelation of Cu(II) ions. 1 is a graphical representation of a Raman spectrum for: (a) Uninfected cells (Fig. 5A) (i.e., not exposed to virions) and (b) Si3N4 (Fig. 5B), (c) AlN (Fig. 5C), and (d) Cu (Fig. 5D). ) cells infected with SARS-CoV-2 virions exposed for 10 minutes. In Figure 5E, Raman spectrum of cells infected with unexposed virions (negative control). Figure 5F shows the two tryptophan T1 and T2 bands (756 and 875 cm, respectively) as a function of the percentage of infected cells by unexposed virions and virions exposed for 10 min to different particles (see labels). 1) Plot of average intensity. Inset: Structure of N'-formylkynurenine, an intermediate in the catabolism of tryptophan during the enzymatic IDO reaction. In FIG. 5G, a graphical representation shows three possible conformations of a tyrosine-based peptide that may justify the disappearance of the ring vibration in tyrosine (Ty2 band) upon chelation of Cu(II) ions. Schematic model (left panel) showing the chemical and charge similarity between the protonated amine group Si-NH3+ on the surface of Si3N4 and the N-terminal C-NH3+ of lysine in cells, and the SARS-CoV-2 virus. Charged molecular species on the surface of Si3N4 (specifically adding charge of protonated amine) and interaction with eluted species NH3/NH4+ (middle panel). The eluted N leaves 3+ charged vacancies on the solid surface (purple areas), which are generated together with negatively charged silanol. eluted nitrogen species (i.e., deprotonation of 2'-hydroxyl groups, formation of transient pentaphosphates, and cleavage of phosphodiester bonds in the RNA backbone by hydrolytic alkaline transesterification) resulting in RNA backbone cleavage. The three-step process is shown in the right panel. The similarity between protonated amines and the N-terminus of lysine may trigger highly effective "competitive binding" for SARS-CoV-2 virion inactivation, while the eluted Note that ammonia fatally degrades virion RNA in a combined "catch and kill" effect. Figure 3 is a logarithmic comparison of mean bacterial growth for PEEK, boron nitride, aluminum nitride, Shapal (a combination of boron nitride and aluminum nitride), and silicon nitride materials at 24 and 48 hours. Figure 2 is a chart showing RT-qPCR genomic testing of the Washington state variant of the SARS-CoV-2 virus on α- and β-silicon nitride powders exposed at 15% wt/vol for 30 minutes. Figure 2 is a chart showing the results of plaque assay testing of the Washington state variant of the SARS-CoV-2 virus on α- and β-silicon nitride powders exposed at 15% wt/vol for 30 minutes. Figure 2 is a chart showing the results of a plaque assay test of the South African variant of the SARS-CoV-2 virus on α- and β-silicon nitride powders exposed at 15% wt/vol for 30 minutes. Figure 2 is a chart showing the results of a plaque assay test of the UK variant of the SARS-CoV-2 virus on α- and β-silicon nitride powders exposed for 30 minutes at 15% wt/vol.

Corresponding reference numbers indicate elements in the figures of the drawings. The headings used in the drawings are not intended to limit the scope of the claims.

Various embodiments of the disclosure are discussed in detail below. Although specific implementations are discussed, it should be understood that this is done for illustrative purposes only. Those skilled in the art will recognize that other components and configurations may be used without departing from the spirit and scope of this disclosure. Accordingly, the following description and drawings are illustrative in nature and should not be construed as limiting. Numerous specific details are set forth to provide a thorough understanding of the disclosure. However, in certain instances, well-known or customary details have not been described in order to avoid obscuring the description. References to one or an embodiment in this disclosure may be references to the same embodiment or any embodiment, and such references mean at least one of the embodiments.

Reference to "an embodiment" or "an embodiment" means that a particular feature, structure, or characteristic described in connection with that embodiment is included in at least one embodiment of the present disclosure. . The appearances of the phrase "in one embodiment" in various places in this specification are not necessarily all referring to the same embodiment, but rather to separate or alternative embodiments that are mutually exclusive of other embodiments. Nor is it an embodiment. Additionally, various features are described that may be exhibited by some embodiments and not by other embodiments.

As used herein, the terms "comprising," "having," and "including" are used in their open, non-limiting sense. The terms "a," "an," and "the" are understood to include the plural and singular. Thus, the term "a mixture thereof" also relates to "mixtures thereof".

As used herein, "inactivate" or "inactivate" means that a virus contaminates a product or object, either by completely removing the virus or rendering it non-infectious. This refers to virus inactivation that stops the virus from doing anything.

The terms "object," "apparatus," or "component" as used herein include materials, compositions, devices, surface coatings, and/or composites. In some instances, the equipment may include various medical devices or instruments, examination tables, clothing, filters, personal protective equipment such as masks and gloves, catheters, endoscopic equipment, and other devices that may cause persistence of the virus to reduce the spread of the disease. This may include commonly touched surfaces that may be facilitated. The device may be metallic, polymeric, and/or ceramic (eg, silicon nitride and/or other ceramic materials).

As used herein, "contacting" is in physical contact with, or in close enough proximity to, a composition or device so as to be affected by the composition or device. It means that.

As used herein, "personal protective equipment" or "PPE" refers to equipment worn or otherwise worn by a person to minimize exposure to pathogens or other hazardous substances. means any device, article, or apparatus used. Non-limiting examples of PPE include body coverings, head coverings, shoe coverings, face masks, eye protectors, face and eye protectors, and gloves.

As used herein, the term "silicon nitride" includes α-Si3N4, β-Si3N4, SiYAlON, β-SiYAlON, SiYON, SiAlON, or combinations thereof.

As used herein, the term "component" includes nitride-based materials, compounds, implants, devices, or the like that are useful for anti-pathogen purposes.

As used herein, the term "effective concentration" is defined as the concentration of material required to inactivate at least 90% of the pathogen in at least 30 minutes. As a non-limiting example, an effective concentration of α-Si3N4 may be a concentration that reduces the activity of the virus by at least 1-log10 within 30 minutes.

The terms used herein generally have their ordinary meanings in the art within the context of the disclosure and in the specific context in which each term is used. Alternative language and synonyms may be used for any one or more of the terms discussed herein, and specific terms may be used depending on whether a term is recited or discussed herein. no great importance should be attached to it. In some cases, synonyms for a particular term are provided. The recitation of one or more synonyms does not exclude the use of other synonyms. The use of any examples herein, including examples of any terms discussed herein, is merely exemplary and is not intended to further limit the scope and meaning of the disclosure or any exemplary term. It's not what I intend. Similarly, this disclosure is not limited to the various embodiments provided herein.

In the description that follows, additional features and advantages of the disclosure are set forth, in part, that are obvious from the description, or that can be learned by practicing the principles disclosed herein. The features and advantages of the disclosure may be realized and obtained by means of the instruments and combinations particularly pointed out in the appended claims. These and other features of the disclosure will be more fully apparent from the following description and appended claims, or can be learned by practicing the principles described herein.

I. Inactivation of SARS-CoV-2 Using Silicon Nitride and Aluminum Nitride The invention herein describes how to inactivate SARS-CoV-2 virus by contacting the virus with an object or composition comprising silicon nitride and/or aluminum nitride. A method is provided for inactivating. The silicon nitride and/or aluminum nitride sequentially binds (ie, captures) and then inactivates (eg, "captures and kills") the virus.

Silicon nitride has a unique surface chemistry, is biocompatible, and offers many biomedical applications, including: 1) simultaneous bone formation, osteoinduction, and osteoconduction, such as in spinal and dental implants; , and bacteriostasis, 2) killing of both gram-positive and gram-negative bacteria by different mechanisms, 3) inactivation of human and animal viruses, bacteria, and fungi, and 4) polymer or metal matrix composites, natural or Man-made fibers, polymers, or metals containing silicon nitride powder retain the important bone repair, bacteriostatic, antiviral, and antifungal properties of silicon nitride.

Silicon nitride (Si3N4) is a non-oxide ceramic compound that has been used in many industries since 1950. Formulation of Si3N4 is FDA approved for use as an intervertebral spacer in cervical and lumbar fusion procedures with proven long-term safety, efficacy, and biocompatibility. Clinical data for Si3N4 implants compare favorably with other spinal biomaterials such as allograft, titanium, and polyetheretherketone. An interesting finding is that Si3N4 implants have a low incidence of bacterial infection (ie, less than 0.006%) when compared to other implant materials (2.7% to 18%). This property reflects the complex surface biochemistry of Si3N4, which elutes small amounts of nitrogen, which is converted to ammonia, ammonium, and other reactive nitrogen species (RNS) that inhibit bacteria. Recent studies also showed that virus exposure to sintered Si3N4 powder in aqueous suspension neutralized H1N1 (influenza A/Puerto Rico/8/1934), feline calicivirus, and enterovirus (EV-A71). I discovered that. Based on these findings, Si3N4 may be able to inactivate SARS-CoV-2.

Silicon nitride may be anti-pathogenic due to the release of nitrogen-containing species upon contact with aqueous media or biological fluids and tissues. The surface chemistry of silicon nitride can be shown as follows.

Nitrogen elutes faster (within minutes) than silicon because the surface silanols are relatively stable. In the case of viruses, it has surprisingly been found that silicon nitride can lead to RNA cleavage by alkaline transesterification leading to loss of genome integrity and virus inactivation. Hemagglutinin activity may also be reduced. Elution of ammonia, with its attendant increase in pH, inactivates viruses, bacteria, and fungi. As shown in the Examples, it has surprisingly been found that silicon nitride and aluminum nitride each inactivate SARS-CoV-2.

The use of copper (Cu), a historically recognized virucide, is limited by its cytotoxicity. In contrast to Cu, ceramic devices or devices made of Si3N4 are biocompatible and non-toxic to humans. The advantage of Si3N4 is the versatility of the material. Therefore, Si3N4 can be incorporated into polymers, bioactive glasses, and even other ceramics to create composites and coatings that retain the favorable biocompatible and antiviral properties of Si3N4.

The present disclosure examines SARS-CoV-2 using an aqueous suspension of Si3N4 and aluminum nitride (AlN) particles, and two controls, namely, a suspension of copper (Cu) particles (positive control) and an antiviral agent. The effects of exposure to a mock suspension of SARS-CoV-2 virions without (negative control) are compared. Copper (Cu) was chosen as a positive control because of its well-known ability to inactivate various microorganisms, including viruses. Aluminum nitride, like Si3N4, was included in the test because it is a nitrogen-based compound whose surface hydrolysis in aqueous solution results in the elution of nitrogen with a concomitant increase in pH. Since comparable antiviral and antibacterial phenomena are believed to be effective for all nitride-based compounds, we investigated AlN to gain further insight into the antipathogenic mechanisms of nitrogen-containing inorganic materials. used.

The persistence of human coronaviruses on common materials (e.g., metals, plastics, paper, and textiles) and contact surfaces (e.g., knobs, handles, rails, desks, and desktops) has been linked to nosocomial and social spread of the disease. can contribute to Warnes et al. At room temperature and 30-40% humidity, pathogenic human coronavirus 229E (HuCoV-229E) can be grown on various materials such as Teflon, polyvinyl chloride, ceramic tiles, glass, stainless steel, and silicone rubber. reported that they remained infectious in a lung cell model after persistent survival for at least 5 days. These researchers also demonstrated rapid HuCoV-229E inactivation (within minutes) for simulated fingertip contamination on Cu surfaces. Cu ion release and generation of reactive oxygen species (ROS) were involved in virus inactivation. Increasing contact time with copper and brass surfaces caused greater non-specific fragmentation of viral RNA, indicating reversible virus inactivation. More recently, Doremalen et al. demonstrated surface stability of both SARS-CoV-1 and SARS-CoV-2 viruses on plastic, cardboard, stainless steel, and even Cu surfaces for 4 to 72 hours after application. Respiratory N95 grade masks can trap particulates before they can be inhaled, but SARS-CoV-2 virus particles remain active within the mask filter for up to seven days. Therefore, killing of viruses on contact, as observed on Cu surfaces, is gaining new interest as a strategy for disease mitigation.

Surprisingly, compounds capable of endogenous nitrogen release, such as Si3N4 and AlN, can inactivate the SARS-CoV-2 virus at least as effectively as Cu. Without being limited to any one theory, multiple antiviral mechanisms may be effective, including RNA fragmentation, direct metal ion toxicity in the case of Cu and AlN. However, while Cu and AlN supernatants showed cell lysis, Si3N4 may not cause metabolic changes. The Raman spectra of VeroE6 cells exposed to Si3N4 virus supernatant were similar to those of uninfected mocks. These findings indicate that Si3N4, Cu and AlN were all able to inactivate the SARS-CoV-2 virus, but Si3N4 was the safest.

Antiviral effects may be related to electrical attraction (in the case of influenza viruses, including "competitive binding" to the envelope glycoprotein hemagglutinin) and viral RNA fragmentation by reactive nitrogen species (RNS). These phenomena are due to the slow and controlled elution of nitrogen from the surface of Si3N4, which together with the release of free electrons and negatively charged silanols in aqueous solution, forms ammonia (NH3) and ammonium (NH4+) moieties. do.

In the context of SARS-CoV-2 virus inactivation, two important aspects of Si3N4 surface chemistry play a fundamental role. (i) the similarity between the protonated amino group Si-NH3+ on the surface of Si3N4 and the N-terminal C-NH3+ of lysine on the virus, and (ii) the elution of gaseous ammonia due to Si3N4 hydrolysis. A schematic diagram of the interaction between SARS-CoV-2 and the Si3N4 surface is shown in Figure 6 (middle panel). Similarities are shown in the left panel of this figure. This triggers a highly effective "competitive binding" approach to SARS-CoV-2 inactivation, derived from several other successful examples such as hepatitis B and influenza A. The strong antiviral effect of eluted (gaseous) NH3 is due to its penetration of virions and reaction with the RNA backbone. RNA undergoes alkaline transesterification via hydrolysis of its phosphodiester bonds. RNA phosphodiester bond cleavage is shown schematically in the right panel of FIG. The RT-PCR and fluorescence microscopy results of the present study suggest a contribution to SARS-CoV-2 inactivation from both mechanisms, consistent with previous studies. The TCID50 results shown in FIGS. 1A-1D and the RT-PCR data in FIGS. 2A-2D for viral RNA recovered from either the supernatant or the Si3N4 particles provide important information regarding these mechanisms. Although >99% inactivation was achieved after 1 minute exposure to Si3N4 (Fig. 1B), only partial viral RNA fragmentation was observed for the supernatant (Fig. 2A), whereas The recovered RNA (Figure 2B) was essentially completely fragmented. Note that the opposite effect was observed for Cu. This suggests that the mechanism of Si3N4 inactivation had a sequential event of "competitive binding" and ammonia toxicity (a kind of "catch and kill" scenario), as shown in the left panel of Figure 6. It suggests that. Complete RNA fragmentation upon 10 min exposure to Si3N4 suggests that nitrogen elution is a key process that triggers the cascade of reactions that lead to virus inactivation (see right panel of Figure 6). Please refer).

In some embodiments, an object, article, or composition comprising silicon nitride or aluminum nitride is manipulated to sequentially bind to a virus (e.g., SARS-Cov-2) and then inactivate the virus. It could be possible.

The antiviral effect of Si3N4 can be comparable to Cu. Cu is an essential trace element for human health and is an electron donor/acceptor for several important enzymes by changing the redox state between Cu+ and Cu2+, but these properties can also cause cell damage. Its use as an antiviral agent is limited by allergic dermatitis, hypersensitivity and multiorgan dysfunction. In contrast, the safety of Si3N4 as a permanently implanted material during spinal fusion surgery is well established by experimental and clinical data. Therefore, objects, articles, or compositions that include silicon nitride can be as effective as Cu in inactivating viruses without the negative effects of Cu.

Si3N4 is well known for its capabilities as an industrial material. Load-bearing Si3N4 prosthetic hip bearings and spinal fixation implants were first developed because of the superior strength and toughness of Si3N4. Later studies showed other properties of Si3N4 that make it desirable in orthopedic implant design, such as improved osteoconductivity, bacteriostasis, improved radiolucency, no implant subsidence, and wear resistance. Ta. Therefore, the surface chemistry, topography, and hydrophilicity of Si3N4 contribute to a dual effect (i.e., upregulation of osteogenic activity to promote spinal fusion while simultaneously preventing bacterial adhesion and biofilm formation). do. In addition to its proven track record as a bioimplant, the advantage of Si3N4 is its versatility in manufacturing. Sintered powders of Si3N4 have been incorporated into other materials such as polymers, other ceramics, bioglass, and metals to produce composite structures that maintain the exponential osteogenic and antimicrobial properties of monolithic Si3N4. . Three-dimensional layered deposition of Si3N4 may enable the production of protective surfaces in medicine that reduce vector-borne transmission of microbial diseases. Incorporating Si3N4 particles into the fabric of personal protective equipment such as face masks, protective gowns, and surgical drapes can contribute to the safety of healthcare workers and patients.

Si3N4 inactivates the SARS-CoV-2 virus within minutes of exposure. Without being limited to any one theory, the mechanism of action may be similar to other nitrogen-based compounds that exhibit trace levels of surface disinfectants, such as aluminum nitride.

In some embodiments, the object used to bind and inactivate the SARS-CoV-2 virus may include a device or apparatus that may include a silicon nitride and/or aluminum nitride composition on at least a portion of the object's surface. It is. Silicon nitride or aluminum nitride coatings may be applied to the surface of the object as a powder. In some examples, silicon nitride or aluminum nitride powder may be filled, embedded, or impregnated into at least a portion of the device. In some embodiments, the powder may have particles in the micron, submicron, or nanometer size range. The average particle size can range from about 100 nm to about 5 μm, about 300 nm to about 1.5 μm, or about 0.6 μm to about 1.0 μm. In other embodiments, silicon nitride or aluminum nitride may be incorporated into the device. For example, the object may incorporate silicon nitride and/or aluminum nitride powder within the body of the object. In one embodiment, the device may be made of silicon nitride. In another embodiment, the object may be made of aluminum nitride. In yet another embodiment, the object may include a slurry or suspension of aluminum nitride or silicon nitride particles.

In some embodiments, the object may further include other materials including, but not limited to, paper, cardboard, fabric, plastic, ceramic, polymer, stainless steel, metal, or combinations thereof. Some non-limiting examples of objects include surgical gowns, surgical drapes, shoe covers, cubicle curtains, tubing, clothing, gloves, eye protectors, masks and face shields including surgical masks, PPE, Tables such as hospital examination tables and operating tables, chairs, bed frames, bed trays, desks, fixtures, cabinets, equipment racks, carts, handles, knobs, rails, toys, water filters, as well as face mask filters, respirator filters, Air filters, such as air filtration filters and air ventilation filters, or air conditioning filters may be included. In some instances, the filter is attached to an anesthesia machine, ventilator, or CPAP machine so that an antimicrobial surface layer within the filter can trap lung pathogens as air moves in and out of infected lungs. It may be within a filtration device. In various embodiments, the object can be a medical device or apparatus. Non-limiting examples of medical devices or equipment include orthopedic implants, spinal implants, pedicle screws, dental implants, indwelling catheters, endotracheal tubes, colonoscopy scopes, and other similar Examples include devices.

In other embodiments, the object may be a composition incorporating silicon nitride or aluminum nitride powder therein, including but not limited to a slurry, suspension, gel, spray, paint, or toothpaste. good. For example, antibacterial, antifungal, and antiviral surfaces can be provided by adding silicon nitride or aluminum nitride to a slurry such as a paint that is then applied to the surface. In other embodiments, silicon nitride or aluminum nitride can be mixed with water along with any suitable dispersants and slurry stabilizers and then applied by spraying the slurry onto various surfaces. An example of a dispersant is Dolapix A88.

The silicon nitride or aluminum nitride coating may be present on the surface of the object at a concentration of about 1% to about 100% by weight. Silicon nitride and/or aluminum nitride may be coated onto the object or laminated within the object. In various embodiments, the coating comprises about 1%, 2%, 5%, 7.5%, 8.3%, 10%, 15%, 16.7%, 20% by weight. %, 25%, or about 30% by weight silicon nitride powder or aluminum nitride powder. In some examples, the coating may include about 10% to about 20% by weight silicon nitride or aluminum nitride. In at least one example, the coating includes about 15% by weight silicon nitride or aluminum nitride. In some embodiments, silicon nitride or aluminum nitride may be embedded within the object (as a filler) or on the surface of the object at a concentration of about 1% to about 100% by weight. In various embodiments, the object has about 1%, 2%, 5%, 7.5%, 8.3%, 10%, 15%, 16.7%, 20% by weight. %, 25 wt%, 30 wt%, 33.3 wt%, 35 wt%, 40 wt%, 50 wt%, 60 wt%, 70 wt%, 80 wt%, 90 wt% to 100 wt% It may include silicon nitride or aluminum nitride. In some examples, silicon nitride or aluminum nitride may be on the surface of the object at a concentration of about 10% to about 20% by weight. In at least one example, silicon nitride or aluminum nitride may be on the surface of the object at a concentration of about 15% by weight. In some embodiments, the concentration of silicon nitride or aluminum nitride may depend on the base material of the object, such as paper, cardboard, fabric, plastic, ceramic, polymer, stainless steel, and/or metal. In some embodiments, the base material of the object may be a polymer, and the polymer imposes a practical limit (i.e., percolation limit) on the amount of silicon nitride and/or aluminum nitride that can be incorporated into the object. may have.

In some embodiments, the object may be a monolithic component of silicon nitride or aluminum nitride. Such bodies may be completely dense with no internal voids, or porous with a porosity ranging from about 1% to about 80%. The monolithic object may be used as a medical device or in an apparatus where inactivation of viruses may be desired.

In some embodiments, the object may be in contact with the SARS-CoV-2 virus for a limited period of time. The object may be contacted with the SARS-CoV-2 virus for about 1 minute to about 2 hours to inactivate the virus. In various examples, the object is contacted with the SARS-CoV-2 virus for at least 30 seconds, at least 1 minute, at least 5 minutes, at least 30 minutes, at least 1 hour, at least 2 hours, at least 5 hours, or at least 1 day. It's okay. In at least one example, the object may be permanently implanted in the patient. In at least one example, the object may be worn externally by the user. In another example, the object may be permanently implanted in the patient. In yet another example, the object may be a high contact surface. In a further example, the object may be in continuous or persistent contact with the patient's bodily fluids. The body fluid may be blood or a gas (eg, inhaled or exhaled gas).

In some embodiments, the virus is at least 70% inactivated, at least 75% inactivated, at least 80% inactivated, at least 85% inactivated, at least 90% inactivated, at least 95% inactivated, or at least 99% inactivated. In at least one example, the virus is at least 85% inactivated after at least 1 minute of contact with the object. In another example, the virus is at least 99% inactivated after contact with the object for at least 30 minutes. In yet another example, the virus is at least 99% inactivated after at least 1 minute of contact with the object.

Also provided herein are articles of personal protective equipment having antiviral and antimicrobial properties. The article may include silicon nitride or aluminum nitride incorporated into the article, or the silicon nitride or aluminum nitride may be coated on the surface of the article.

The silicon nitride or aluminum nitride coating may be present on the surface of the article at a concentration of about 1% to about 100% by weight. In various embodiments, the coating comprises about 1%, 2%, 5%, 7.5%, 8.3%, 10%, 15%, 16.7%, 20% by weight. %, 25%, or about 30% by weight silicon nitride powder or aluminum nitride powder. In some examples, the coating may include about 10% to about 20% by weight silicon nitride or aluminum nitride. In at least one example, the coating includes about 15% by weight silicon nitride or aluminum nitride. In some embodiments, silicon nitride or aluminum nitride may be embedded within the article (as a filler) or on the surface of the article at a concentration of about 1% to about 100% by weight. In various embodiments, the object has about 1%, 2%, 5%, 7.5%, 8.3%, 10%, 15%, 16.7%, 20% by weight. %, 25 wt%, 30 wt%, 33.3 wt%, 35 wt%, 40 wt%, 50 wt%, 60 wt%, 70 wt%, 80 wt%, 90 wt% to 100 wt% It may include silicon nitride or aluminum nitride. In some examples, silicon nitride or aluminum nitride may be on the surface of the article at a concentration of about 10% to about 20% by weight. In at least one example, silicon nitride or aluminum nitride may be on the surface of the article at a concentration of about 15% by weight. In some embodiments, the concentration of silicon nitride or aluminum nitride may depend on the base material of the object.

In some embodiments, the article is PPE. In some embodiments, the article is a body covering, head covering, shoe covering, face mask, face and eye protector, or gloves. In some embodiments, the article is operable to inactivate the SARS-CoV-2 virus when the article comes into contact with the virus.

II. Nitride-Based Anti-Pathogen Compositions and Devices and Methods of Use Thereof Provided herein are nitride-containing anti-pathogen compositions and devices for the inactivation of viruses, bacteria, and fungi. As used herein, nitrides are compounds of nitrogen where nitrogen has a nominal oxidation state of -3 to +5. Non-limiting examples of suitable nitrides include silicon nitride, aluminum nitride, boron nitride, chromium nitride, cerium nitride, hafnium nitride, lanthanum nitride, phosphorous nitride, sulfur nitride, tantalum nitride, titanium nitride, vanadium nitride, nitride. Yttrium, zirconium nitride, or combinations thereof. Nitride can have a high inherent nitrogen content. For example, silicon nitride (Si3N4) contains about 40% nitrogen by weight, boron nitride (BN) has about 56% nitrogen by weight, and aluminum nitride (AlN) has 34% nitrogen by weight. However, titanium nitride (TiN) has about 22% nitrogen by weight.

Nitrides may generally be anti-pathogenic due to the release of nitrogen-containing species upon contact with aqueous media or biological fluids and tissues. For example, the surface hydrolysis chemistry of silicon nitride can be shown as follows.

Similarly, as a second example, the surface hydrolysis chemistry of boron nitride can be illustrated as follows.

Furthermore, in the presence of water, ammonia and ammonium exist in a pH-dependent equilibrium state as follows.

Elution of ammonia, its protonation to ammonium and hydroxide ions, and the associated increase in pH inactivates viruses, bacteria, and fungi. Similar to silicon nitride, other nitride materials can exhibit anti-pathogen properties due to surface hydrolysis of nitrogen and the resulting formation of ammonia and ammonium. Previously, it was believed that only β-silicon nitride exhibited antipathogenic properties. However, it was surprisingly found that other nitride materials exhibit similar surface chemistry. These results take into account the fact that all nitrides are essentially water-insoluble and their hydrolysis was previously thought to be insufficient to produce anti-pathogen properties. Then, something unexpected happened.

In certain embodiments, the anti-pathogen nitride-based compositions are characterized by (i) slow but continuous elution of ammonia from the solid state rather than from the normal gaseous state, (ii) damage or adverse effects on eukaryotic cells. and (iii) may exhibit elution kinetics showing excellent elution increasing with decreasing pH.

The antipathogenic compositions and devices disclosed herein include aluminum nitride, boron nitride, chromium nitride, cerium nitride, hafnium nitride, lanthanum nitride, phosphorous nitride, sulfur nitride, tantalum nitride, titanium nitride, vanadium nitride, nitride It may include one or more of yttrium and zirconium nitride. In some embodiments, the compositions and devices may further include silicon nitride, such as alpha-silicon nitride. In other embodiments, the nitride can be alpha-silicon nitride. In some embodiments, the nitride can be aluminum nitride. In yet other embodiments, anti-pathogenic compositions and devices can include nitride mixtures, such as mixtures of AlN and BN. Surprisingly, it has been found that these compositions are capable of inactivating viruses.

Nitride-based compositions can be powders, granules, slurries, suspensions, coatings, films, and/or composites. In some embodiments, the composition may include micrometer or nanometer particles of nitride. The average particle size of the nitride can range from about 100 nm to about 5 μm, about 300 nm to about 1.5 μm, or about 0.6 μm to about 1.0 μm. In another embodiment, the composition may include a slurry or suspension of nitride particles.

In some embodiments, the anti-pathogen composition can be a monolithic component consisting of a nitride. Such components may be completely dense with no internal voids or porous with a porosity ranging from about 1% to about 80%. The monolithic component may be used as a medical device or in an apparatus where inactivation of viruses, bacteria, and/or fungi may be desired.

In another embodiment, the anti-pathogen nitride-based composition may be incorporated into the device or into a coating on the surface of the device to inactivate viruses, bacteria, and fungi. At least a portion of the surface of the device may be coated with a coating that includes a nitride-based composition. Non-limiting examples of suitable devices include orthopedic implants, spinal implants, pedicle screws, dental implants, indwelling catheters, endotracheal tubes, colonoscopy scopes, and other similar devices. Can be mentioned. The device or apparatus may be metallic, polymeric, and/or ceramic.

In some embodiments, nitrides are used in polymers and fabrics, surgical gowns, gloves, tubing, clothing, air and water filters (e.g., anesthesia machines, ventilators, or CPAP machine filtration devices), masks, hospitals. Incorporated internally as a coating on tables, desks, fixtures, handles, knobs, toys, such as examination tables and operating tables, and filters such as jejunal filters, or materials or devices for anti-pathogenic properties such as toothbrushes. or may be applied.

Nitride-based coatings may be applied to the surface of the device as a powder. In some examples, nitride powder may be embedded or impregnated into at least a portion of the device. In some embodiments, the powder can be micrometer or nanometer sized. In other embodiments, silicon nitride may be incorporated into the device. For example, the device may incorporate nitride powder within the body of the device.

In some embodiments, the anti-pathogen nitride-based composition can be a slurry of nitride powder in an aqueous solution. The aqueous medium can be water, saline, buffered saline, or phosphate buffered saline. In other embodiments, the nitride-based composition can be a suspension or emulsion of nitride powder and a vehicle suitable for topical application, such as a cream, gel, or lotion. The nitride powder may be present in the composition at a concentration of about 0.1% to about 20% by volume. In various embodiments, the slurry contains about 0.1%, 0.5%, 1%, 1.5%, 2%, 5%, 10%, 15%, or 20% by volume. % silicon nitride by volume. In some embodiments, the concentration of nitride can be effective to inactivate pathogens.

In other embodiments, the nitride-based coating may be present on or within the device at a concentration of about 1% to about 100% by weight. In various embodiments, the coating comprises about 1%, 2%, 5%, 7.5%, 8.3%, 10%, 15%, 16.7%, 20% by weight. %, 25%, 30%, 33.3%, 35%, or 40% by weight of nitride powder. In at least one example, the coating includes about 15% by weight nitride. In some embodiments, the nitride may be present in or on the device or apparatus at a concentration of about 1% to about 100% by weight. In various embodiments, the device or apparatus contains about 1%, 2%, 5%, 7.5%, 8.3%, 10%, 15%, 16.7%, by weight, From 20% by weight, 25% by weight, 30% by weight, 33.3% by weight, 35% by weight, 40% by weight, 50% by weight, 60% by weight, 60% by weight, 70% by weight, 80% by weight, 90% by weight , may contain up to 100% by weight nitride. In some embodiments, the concentration of nitride can be effective to inactivate pathogens.

In some embodiments, the anti-pathogen nitride-based composition or device may inactivate or reduce the spread of viruses, bacteria, and/or fungi. Viruses, bacteria, and fungi can infect mammalian, animal, and/or plant cells. Non-limiting examples of viruses that can be inactivated by anti-pathogen nitride-based compositions include coronaviruses (e.g., SARS-CoV-2), rhinoviruses, influenza viruses (A, B, C, D), and feline calicivirus. Anti-pathogenic nitride-based compositions or devices can kill both Gram-positive and Gram-negative bacteria. Examples of fungi that can be lysed include, but are not limited to, downy mildew, powdery mildew, gray mold, Fusarium rot, rust, Rhizoctonia root rot, Sclerotinia rot, Sclerotinia rot ( Sclerotium rot), or those that cause other agriculture-related diseases.

In some embodiments, the pathogen may be on or within a human, animal, or plant. In other embodiments, the pathogen may be on the surface of or within the inanimate object.

Further provided herein are methods for inactivating pathogens by contacting viruses, bacteria, and/or fungi with the anti-pathogenic nitride-based compositions disclosed herein. Ru. In certain embodiments, the method may include coating a device or apparatus with a nitride-based composition and contacting the coated apparatus with a virus, bacteria, or fungus. In another embodiment, the method may include contacting a virus, bacteria, and/or fungus with a composition that includes a nitride-based composition. The composition can be a slurry containing nitride powder or particles. The composition can be a suspension or emulsion containing nitride powder.

Also provided herein are methods of treating or preventing pathogens at a location in a human patient. For example, a pathogen can be a virus, bacterium, or fungus. The method may include contacting a patient with a device, apparatus, or composition that includes a nitride-based composition. The device, apparatus, or composition may include from about 1% to about 100% nitride by weight. In some examples, the device or apparatus may include from about 1% to about 100% by weight nitride on the surface of the device or apparatus. In some embodiments, the device or apparatus may be a monolithic nitride-based ceramic. In another embodiment, the device or apparatus may include a nitride coating, such as a nitride powder coating. In another embodiment, the device or apparatus may incorporate nitride within the body of the device. For example, nitride powder may be embedded or impregnated into the body of the device or apparatus using methods known in the art.

In some embodiments, the device or apparatus may be in contact with the patient or user for at least 1 minute, at least 5 minutes, at least 30 minutes, at least 1 hour, at least 2 hours, at least 5 hours, or at least 1 day. . In at least one example, the device or apparatus may be permanently implanted in the patient. In at least one example, the device or apparatus may be worn externally by a user.

Exemplary Embodiments Embodiment 1: A method for inactivating a pathogen, comprising: inactivating the pathogen with boron nitride, chromium nitride, cerium nitride, hafnium nitride, lanthanum nitride, phosphorus nitride, sulfur nitride, tantalum nitride, titanium nitride. , contacting a composition comprising an effective concentration of a nitride selected from vanadium nitride, yttrium nitride, zirconium nitride, or a combination thereof, wherein the effective concentration of the nitride inactivates a pathogen.

Embodiment 2: The method of Embodiment 1, wherein the composition further comprises silicon nitride.

Embodiment 3: The method of Embodiment 1, wherein the composition further comprises aluminum nitride.

Embodiment 4: The method of Embodiment 1, wherein the nitride is boron nitride.

Embodiment 5: The method of Embodiment 1, wherein the composition comprises a slurry of nitride particles in an aqueous medium.

Embodiment 6: The method of Embodiment 5, wherein the effective concentration of nitride is from about 0.1% to about 20% by volume.

Embodiment 7: The method of Embodiment 1, wherein the composition comprises a nitride powder.

Embodiment 8: The method of embodiment 7, wherein the composition is coated over at least a portion of the surface of the device and/or incorporated into the device.

Embodiment 9: The method of Embodiment 8, wherein the effective concentration of nitride is from about 1% to about 100% by weight.

Embodiment 10: The device is an orthopedic implant, a spinal implant, a pedicle screw, a dental implant, an indwelling catheter, an endotracheal tube, a colonoscopy scope, a surgical gown, a mask, a filter, or tubing. , the method of embodiment 8 or 9.

Embodiment 11: The method of any one of embodiments 1-10, wherein the pathogen is a virus, bacteria, or fungus.

Embodiment 12: The method of embodiment 11, wherein the virus is a coronavirus.

Embodiment 13: The method of any one of embodiments 1-12, wherein the pathogen is on a surface or within a human, animal, or plant.

Embodiment 14: The method of any one of embodiments 1-12, wherein the pathogen is on the surface of an inanimate object.

Embodiment 15: A nitride-based composition for inactivating pathogens, the composition comprising a slurry of nitride particles in an aqueous medium, the nitride comprising from about 0.1% to about 20% by volume. % of the nitride-based composition, the concentration being effective to inactivate pathogens.

Embodiment 16: The nitride is selected from boron nitride, chromium nitride, cerium nitride, hafnium nitride, lanthanum nitride, phosphorous nitride, sulfur nitride, tantalum nitride, titanium nitride, vanadium nitride, yttrium nitride, zirconium nitride, or combinations thereof. The nitride-based composition of Embodiment 15.

Embodiment 17: The nitride-based composition of Embodiment 16, wherein the composition further comprises silicon nitride.

Embodiment 18: The nitride-based composition of Embodiment 16, wherein the composition further comprises aluminum nitride.

Embodiment 19: The nitride-based composition of Embodiment 16, wherein the nitride is boron nitride.

Embodiment 20: The nitride-based composition of Embodiment 15, wherein the pathogen is a virus, bacteria, or fungus.

Embodiment 21: The nitride-based composition of Embodiment 20, wherein the virus is a coronavirus.

Embodiment 22: The nitride-based composition of any one of embodiments 15-21, wherein the pathogen is on a surface or within a human, animal, or plant.

Embodiment 23: The nitride-based composition of any one of embodiments 15-21, wherein the pathogen is on the surface of an inanimate object.

Embodiment 24: A nitride-based device for inactivating pathogens, the device comprising a nitride powder coated over at least a portion of the surface of the device and/or incorporated into the device, wherein the nitride , in a concentration of about 10% to about 30% by weight, the concentration being effective to inactivate pathogens.

Embodiment 25: The nitride is selected from boron nitride, chromium nitride, cerium nitride, hafnium nitride, lanthanum nitride, phosphorous nitride, sulfur nitride, tantalum nitride, titanium nitride, vanadium nitride, yttrium nitride, zirconium nitride, or combinations thereof. The nitride-based device of Embodiment 24.

Embodiment 26: The nitride-based device of embodiment 25, wherein the device further comprises silicon nitride.

Embodiment 27: The nitride-based device of embodiment 25, wherein the device further comprises aluminum nitride.

Embodiment 28: The nitride-based device of Embodiment 25, wherein the nitride is boron nitride.

Embodiment 29: The nitride-based device of embodiment 24, wherein the pathogen is a virus, bacteria, or fungus.

Embodiment 30: The nitride-based device of Embodiment 29, wherein the virus is a coronavirus.

Embodiment 31: The nitride-based device of any one of embodiments 24-30, wherein the pathogen is on the surface or within the human, animal, or plant.

Embodiment 32: The nitride-based device of any one of embodiments 24-30, wherein the pathogen is on the surface of an inanimate object.

Embodiment 33: A method for inactivating a pathogen comprising contacting a pathogen with a slurry comprising an effective concentration of alpha-silicon nitride, wherein the effective concentration of nitride inactivates the pathogen and the slurry The effective concentration of alpha-silicon nitride in the method is about 15% w/v.

Embodiment 34: The slurry is selected from boron nitride, chromium nitride, cerium nitride, hafnium nitride, lanthanum nitride, phosphorous nitride, sulfur nitride, tantalum nitride, titanium nitride, vanadium nitride, yttrium nitride, zirconium nitride, or combinations thereof. 34. The method of embodiment 33, further comprising a nitride comprising:

Embodiment 35: A method for inactivating a pathogen comprising contacting a pathogen with a slurry comprising an effective concentration of aluminum nitride, wherein the effective concentration of nitride inactivates the pathogen and A method wherein the effective concentration of aluminum nitride is about 15% w/v.

Embodiment 36: The slurry is selected from boron nitride, chromium nitride, cerium nitride, hafnium nitride, lanthanum nitride, phosphorous nitride, sulfur nitride, tantalum nitride, titanium nitride, vanadium nitride, yttrium nitride, zirconium nitride, or combinations thereof. 36. The method of embodiment 35, further comprising a nitride comprising:

Example 1: Rapid inactivation of SARS-CoV-2 by silicon nitride and aluminum nitride This study inactivated the SARS-CoV-2 virus in an aqueous suspension of silicon nitride (Si3N4) particles, aluminum nitride (AlN) particles. , and two controls (i.e., a suspension of copper (Cu) particles (positive control) and one without antiviral agent (negative control)) were compared. Cu was chosen as a positive control due to its well-known ability to inactivate various microorganisms including viruses.

Preparation of Test Materials Si3N4, Cu, and AlN powders were obtained from commercial sources. Si3N4 powder (nominal composition of 90% by weight Si3N4, 6% by weight Y2O3, and 4% by weight Al2O3) was prepared by aqueous mixing of the inorganic components and spray drying, followed by sintering of the spray-dried granules (approximately 1700 °C (approximately 3 hours), hot isostatic pressing (approximately 1600° C., 2 hours, 140 MPa in N2), aqueous milling, and lyophilization. The average particle size of the obtained powder was 0.8±1.0 μm. As-received Cu powder (USP grade 99.5% purity) granules were milled to achieve a particle size comparable to Si3N4. The AlN powder had an average particle size of 1.2±0.6 μm as received, which was comparable to Si3N4.

Mammalian and Viral Cell Preparation VeroE6/TMPRSS2 mammalian cells were used in virus assays. Cells were grown in Dulbecco's modified Eagle's minimum essential medium (DMEM) supplemented with G418 disulfate (1 mg/ml), penicillin (100 units/ml), streptomycin (100 μg/ml), 5% fetal bovine serum, and humidified. The atmosphere was maintained at 37°C and 5% CO2/95%. SARS-CoV-2 virus stocks were grown for 2 days at 37°C using VeroE6/TMPRSS2 cells. Viral titers were assayed by tissue culture median infectious dose (TCID50).

Example 2:
Virus Assay Fifteen weight percent (15 wt%) of Si3N4, Cu, and AlN powders were separately dispersed in 1 mL of PBS(-), followed by the addition of virus suspension (TCID50 of 2 x 105 in 20 μL). . Due to the higher density of Cu powder, its volume fraction was approximately one third of that of Si3N4. Mixing was performed for 1 minute and 10 minutes by slow manual rotation at 4°C. After exposure, the powder was pelleted by centrifugation (2400 rpm for 2 minutes) followed by filtration through 0.1 μm media. The supernatant was collected and subjected to TCID50 assay, real-time RT-PCR test, and fluorescence imaging. Experiments were performed in triplicate including mock supernatants without antiviral powder. Confluent monolayers of VeroE6/TMPRSS2 cells in 96-well plates were inoculated with 50 μL/well of each virus suspension serially diluted 10-fold in 0.5% FBS DMEM (i.e., maintenance medium). Virus adsorption was performed at 37°C for 1 hour with tilting every 10 minutes. Then, 50 μL/well of maintenance medium was added. Plates were incubated for 4 days at 37°C in a 5% CO2/95% humidified atmosphere. Cytopathic effect (CPE) of infected cells was observed under a phase contrast microscope. Cells were then fixed by adding 10 μL/well of glutaraldehyde followed by staining with 0.5% crystal violet. TCID50 was calculated according to the Reed-Muench method.

Viral RNA assay After exposure to powder, 140 μL of supernatant was used for viral RNA extraction. RNA was also extracted from the surface of the centrifuged and filtered powder. RNA purification was performed using the QIAamp Viral RNA Mini kit. Aliquots of 16 μL of isolated RNA were reverse transcribed using ReverTra Ace® qPCR RT Master Mix. Quantitative real-time PCR was performed using Step-One Plus Real-Time PCR System primers/probes for two specific viral N gene sets. Each 20 μL reaction mixture contained 4 μL of cDNA, 8.8 pmol of each primer, 2.4 pmol of probe, and 10 μL of GoTaq Probe qPCR master mix. The amplification protocol consisted of 50 cycles of denaturation at 95°C for 3 seconds and annealing and extension at 60°C for 20 seconds.

Immunochemical Fluorescence Assay Vero E6/TMPRSS2 cells on coverslips were inoculated with 200 μL of viral supernatant. After virus adsorption for 1 hour at 37°C, cells were incubated with maintenance medium for 7 hours in a CO2 incubator. For detection of infected cells, these cells were washed with TBS (20mM Tris-HCl pH 7.5, 150mM NaCl), fixed with 4% PFA for 10 min at room temperature (RT), and then incubated at RT. Membranes were permeabilized with 0.1% Triton X in TBS for 5 minutes. Cells were blocked with 2% skim milk in TBS for 60 min at RT and stained with anti-SARS coronavirus envelope (rabbit) antibody (dilution = 1:100) for 60 min at RT. After washing with buffer, cells were incubated with Alexa 594 goat anti-rabbit IgG (H+L) (1:500) and Alexa 488 phalloidin (1:50) for 60 min at RT in the dark. ProLong™ Diamond Antifade Mount containing DAPI was used as the mounting medium. Staining was observed under a fluorescence microscope BZX710. Total and infected cell counts were obtained using a Keyence BZ-X Analyzer.

Raman spectroscopy assay Vero E6/TMPRSS2 cells were infected with 200 μL of each virus suspension in a glass place. After virus adsorption for 1 hour at 37°C, infected cells were incubated in maintenance medium in a CO2 incubator for 4 hours and fixed with 4% paraformaldehyde for 10 minutes at RT. After washing twice with distilled water, infected cells were air-dried and analyzed in situ using a Raman microprobe spectrometer. Raman spectra were collected using a high sensitivity spectrometer equipped with a 20x optical lens. It was operated in microscopic measurement mode with two-dimensional confocal imaging. A spectral resolution of 1.5 cm was efficiently achieved via a 532 nm excitation source operated at 10 mW using a holographic notch filter in the optical circuit. Raman emission was monitored using a single monochromator connected to an air-cooled charge-coupled device (CCD) detector (1024 x 256 pixels). The acquisition time was fixed at 10 seconds. Thirty spectra were collected and averaged for each analysis time point. Raman spectra were deconvolved to Gaussian-Lorentzian using commercially available software.

Statistical analysis Statistical significance was determined by Student's t-test using Prism software, n=3, and p-value 0.01.

Example 3:
Median Tissue Culture Infectious Dose The TCID50 assay results for 15 wt% Si3N4, Cu, and AlN powders are shown in Figures 1A-1D. Inactivation times of 1 minute and 10 minutes are shown in Figures 1A and 1B and Figures 1C and ID, respectively. Compared to the negative control, all three powders were effective (>99%) in inactivating SARS-CoV-2 virions for the two exposure times.

RNA Gene Fragmentation To determine whether viral RNA was fragmented from exposure to both supernatant and powder, RT-PCR tests were performed on the N gene set of viral RNA. The results are shown in Figures 2A and 2B and Figures 2C and 2D for 1 minute and 10 minute exposures, respectively. Again, almost complete fragmentation of RNA was observed for Cu compared to the negative control upon 1 minute exposure to supernatant, but significantly less for AlN and to a lesser extent for Si3N4. severe damage was caused. After 10 minutes of exposure to the supernatant, substantial cleavage of RNA was seen for all three materials. Cu still showed the greatest fragmentation, but Si3N4 showed similar effectiveness and AlN was essentially identical to the 1 minute exposure condition. Viral RNA was virtually undetectable for all three materials based on RNA extracted from pelleted powder at 1 minute exposure (see Figures 2A and 2B). This result suggests that the reduction in viral RNA in the supernatant was not due to RNA attachment to the powder, but rather due to direct degradation.

Immunofluorescence testing. Immunofluorescence imaging was then used with anti-SARS coronavirus envelope antibody (red), phalloidin to stain F-actin in viable cells (green), and DAPI (blue) for cell nuclear staining. , confirmed the TCID50 assay and gene fragmentation results. Figures 3A-3D show VeroE6 cells inoculated with (a) unexposed virions (i.e., negative control) and (b) supernatants of virions exposed for 10 min to Si3N4, (c) AlN, and (d) Cu. /TMPRSS2 cell aggregates are shown in fluorescence micrographs. Figure 3E shows cells that were not inoculated with virus (labeled "mock-infected" cells). The red spot in the negative control (Fig. 3A) indicated that the virions invaded and hijacked the metabolism of Vero6E cells. This is in contrast to mock-infected cells (Fig. 3E), which showed normal metabolic function.

Remarkably, cells inoculated with supernatants from Si3N4 and, to a lesser extent, cells inoculated with supernatants from AlN exhibited near normal function with little infection. . In contrast, cells inoculated with Cu supernatant were essentially dead (i.e., complete loss of F-actin, Figure 3D), but with no bluish-red staining present in the nucleus. Based on this, the virion appears to have hijacked several nuclei, suggesting it may be alive but in a pre-death stage. This suggests that the cell lysis was not only a result of viral infection but also due to toxic effects from free Cu ions within the cells. Quantification of the colorimetric results from FIGS. 3A-3E is shown in FIG. 4. These data indicate that approximately 35% of viable VeroE6 cells from the negative control were infected with virions, whereas only 2% and 8% of cells inoculated with supernatants from Si3N4 and AlN were infected, respectively. It shows. Quantitative evaluation of cells inoculated with Cu supernatant could not be evaluated due to their premature death.

Raman spectroscopy VeroE6 cells exposed to various supernatants were examined by Raman spectroscopy to assess biochemical cellular changes due to infection and ionic (ie, Cu and Al) toxicity. Figures 5A-5G show (a) uninfected VeroE6/TMPRSS2 cells and (b) Si3N4, (c) AlN, (d) Cu (positive control), and (e) no antiviral compound (negative control). Raman spectra in the frequency range of 700-900 cm for cells inoculated with supernatant containing virions exposed to ) for 10 min. Of fundamental importance are the ring breathing and H-scissor vibrational bands of the indole ring of tryptophan (756 and 875 cm-1, respectively, labeled T1 and T2). Tryptophan plays an important role in protein synthesis and the production of molecules for various immunological functions. Its stereoisomers help anchor proteins within cell membranes, and its catabolic forms have immunosuppressive functions. Tryptophan catabolism is caused by viral infection. This occurs through the enzymatic activity of indoleamine-2,3-dioxygenase (IDO), which protects host cells from overreactive immune responses. IDO reduces tryptophan to kynurenine and then to N'-formyl-kynurenine. Increased IDO activity depletes tryptophan. Consequently, the intensity of tryptophan bands (T1 and T2) is an indicator of these biochemical changes. With the exception of the Cu-treated samples, the data shown in Figure 5F shows an exponential decrease in the tryptophan band combination that correlates with the fraction of infected cells. (For clarity, the chemical structure of N'-formyl-kynurenine is shown in the inset). Copper abnormalities provide further evidence of its toxicity. VeroE6 cells consumed tryptophan to reduce Cu2+ and stabilize it as Cu+.

Raman signals due to ring stretching vibrations of adenine, cytosine, guanine, and thymine are seen at 725, 795, 680, and 748 cm and are labeled A, Cy1, G, and Th, respectively, in Figures 5A-5E. ing). These bands were preserved after virus challenge. However, cells infected with Cu-exposed virions had abnormalities in the lineages representing tyrosines at 642 and 832 cm-1, labeled Ty1 and Ty2, respectively. The tyrosine ring breathing band Ty2 was very weak compared to other samples (see Figure 5D with Figure 5B). Conversely, the Ty1 signal associated with CC bonds remained strong. This suggests that the aromatic ring of tyrosine chelated Cu ions. This explains why only the tyrosine ring breathing mode decreased while the CC signal remained unchanged. Three possible Cu(II) chelation conformations in tyrosine are shown in Figure 5G.

For VeroE6 exposed to virions treated with AlN (Fig. 5C), the tryptophan T1 and T2 bands were preserved, but the bands at 615 and ~700 cm due to ring bends in the DNA cytosine (in Figs. 5A-5E) (labeled as Cy2 and Cy3, respectively) almost disappeared. Their disappearance is due to either progressive internucleosomal DNA cleavage or complex formation, both of which are associated with toxicity. The loss of cytosine signal is interpreted as a toxic effect by Al ions, which are much less important than copper. Al3+ interacts with the carbonyl O and/or N ring donors in the nucleotide base and binds selectively to the backbone of the PO2 group and/or to the guanine N-7 site of the G-C base by chelation. .

Unlike exposure of VeroE6 cells to Cu and AlN supernatants, which resulted in moderate to severe toxicity, Si3N4 did not cause tryptophan, tyrosine, and cytosine modifications. The spectral morphology of the Si3N4 virus supernatant closely matched that of the uninfected mock suspension (see Figures 5A and 5B).

Example 4: Biofilm Assay of Aluminum Nitride and Boron Nitride Materials This study was conducted to compare Staphylococcus epidermidis biofilm growth on biomaterial modifications of silicon nitride and other ceramic materials, with PEEK as a positive control. The ceramic materials under observation included azfire silicon nitride (AFSN), aluminum nitride (AlN), two grades of boron nitride (BN: AX05BN and PCBN1000), and Shapal (a mixture of AlN and BN). .

Three replicates were selected for each sample material at 24 and 48 hour time points for basic statistical analysis. The samples were washed in alcohol with ultrasonic agitation for 5 minutes, then rinsed with DI water using ultrasonic agitation for 5 minutes, and then the samples were sterilized by UV-C light exposure on each side for 30 minutes. The samples were prepared by allowing the samples to rest for at least 60 minutes before inoculation.

Bacterial medium was prepared by combining 7% glucose, 1×PBS, and 10% human plasma and then inoculating with a small aliquot of Staphylococcus epidermidis. Initial absorbance values were obtained using a spectrophotometer. The medium was then placed in a shaking incubator for 6 hours at 37°C and 175 rpm, and the bacteria were incubated until an absorbance value of 0.05 AU (corresponding to 105 cells/mL according to the previously generated growth curve) was achieved. Proliferated.

Each sterile sample was placed in a well plate and 7 mL of liquid medium was added. The well plate was placed in a shaking incubator for 24 hours at 37°C and 125 rpm. At t=24 hours, the liquid medium was removed and 7 mL of fresh medium was added. The well plate was returned to the shaking incubator for an additional 24 hours.

Samples were removed at appropriate time points (24 or 48 hours) and washed with 5 mL of 1x PBS in a fresh well plate in a shaking incubator for 2 minutes at 125 rpm. Each sample was soak washed in fresh 1x PBS. Samples were placed in 10 mL of 1× PBS in a 50 mL centrifuge tube and vortexed vigorously for 2 minutes.

Surface area measurements were obtained using disc diameter, width, and weight. The number of colonies on each Petrifilm was counted, recorded and compared.

The biofilm solution of each sample was serially diluted with 1x PBS to 1x, 1/10x, 1/100x, 1/1,000x, and 1/10,000x of the original sample. Obtained the concentration. Each dilution was placed on Petrifilm so that the lowest countable dilution could be used in data comparisons for each sample. After growing in an incubation environment for 24 hours at 37°C, the bacteria formed colonies, referred to as colony forming units (CFU). Once the CFU counts were obtained, the counts were multiplied by the appropriate dilution factor to calculate the CFU per sample. The total CFU was then divided by the surface area to accurately compare samples of different sizes, so the final data reported is in units of CFU/mm2. Statistical analysis was performed and graphed. Table 1 and Figure 7 show the averages for each material at both 24 and 48 hours. Statistical analysis was performed by applying a heteroskedastic two-tailed t-test with 95% confidence intervals on all samples.

At 24 hours, bacterial growth on PEEK was more than an order of magnitude greater than Azfire β-Si3N4 (AFSN), AlN, and Shapal, all p<0.05. Statistical differences were found between PEEK and all materials except AX05BN. AX05BN was also found to have a statistically significant difference in biofilm growth compared to all other materials. Comparisons of biofilm growth between AlN, Shapal, AFSN, and PCBN1000 were not significantly different overall. For the 24 hour time point, it can be concluded that AlN, Shapal, PCBN1000 and AFSN have the most efficient antibacterial properties.

At 48 hours, the serial dilution and plating procedure described in paragraph 0093 (Embodiment 25) was performed on the remaining samples. Biofilm growth on PEEK was consistent with the results found at the 24 hour time point, as CFU counts remained at least an order of magnitude greater than either of the ceramic materials. The representative p-value for this comparison did not reflect any visual difference due to one PEEK sample outlier. Due to expected biological variation, this outlier does not change the conclusions drawn from the overall results. Significant differences were found for both AX05BN and PCBN1000 compared to AFSN, Shapal, and AlN. The p-values for AFSN, AlN, and Shapal were p=0.032, p=0.031, and p=0.033, respectively, when compared to AX05BN. The 48 hour results are consistent with the trend from the 24 hour period. All materials had a consistent increase in biofilm growth over time.

At both 24 and 48 hour time points, Staphylococcus epidermidis was found to form significantly denser biofilms on PEEK than either of the ceramic variants, as expected. . AX05BN did not perform as efficiently as the other ceramic materials evaluated in this experiment, as the CFU counts obtained were not significantly different from PEEK. Shapal, AlN, and AFSN have similar biofilm growth and S. highlighted its ability to resist surface attachment and colonization. Although their bacterial resistance was very similar, AlN outperformed PEEK, AX05BN, PCBN1000, Shapal, and AFSN in resistance to biofilm formation at both the 24-hour and 48-hour evaluations. Shapal and AFSN closely followed AlN in their antibacterial properties.

These results support previous conclusions that ceramic materials significantly exceed PEEK in biofilm resistance. Comparisons within the ceramic samples show that AX05BN is significantly less efficient at resisting bacterial adhesion than other ceramic compositions. No significant differences were found between Shapal, AlN, and AFSN, although AlN had slightly less biofilm formation at both time points.

Example 5: Rapid inactivation of SARS-CoV-2 by alpha-silicon nitride and beta-silicon nitride Two silicon nitride powders were prepared. The β-silicon nitride powder had a nominal composition of 90% by weight β-Si3N4, 6% by weight yttira (Y2O3), and 4% by weight alumina (Al2O3). Each powder was prepared by aqueous mixing of the organic components and spray drying followed by sintering of the spray dried granules at about 1700° C. for about 3 hours. The sintered granules were then hot isostatically pressed at 140 MPa in nitrogen for 2 hours at approximately 1600°C. Pressing was followed by aqueous grinding and freeze drying.

The α-silicon nitride powder was 98 wt% pure Si3N4 with about 2 wt% SiO2. Commercially available high purity α-silicon nitride was prepared by heating in air at about 300° C. for about 1 hour and then cooling to room temperature.

To perform antiviral testing, the Washington variant of the SARS-CoV-2 virus was diluted in DMEM growth medium to a concentration of 2 x 104 virions/mL. 4 mL of diluted virus solution was then added to tubes containing either α- or β-silicon nitride powder at 15% weight/volume (w/v). A virus without Si3N4 was processed in parallel as a control. The tube was vortexed for 30 seconds to ensure good contact and then placed in a tube revolver for 30 minutes. The samples were centrifuged and the supernatant was collected and filtered through a 0.2 μm filter. RNA in the remaining infectious virus in the clarified supernatant was isolated along with the pellet and quantified by RT-qPCR.

The supernatant was also subjected to the plaque assay test method. The results provided in Figure 8 show that the virus-only control genome copies have a concentration of approximately 1 x 10/mL, while the β-silicon nitride powder has a concentration of approximately 4.3 x 10/mL. (95.9%) and two different lots of α-silicon nitride showed a virion reduction of approximately 1×10 3 /mL (99.9%). In this same series of tests, pelleted samples from two α-silicon nitrides were found to contain no viable virions.

Plaque assay test results are provided in Figure 9A. These data show a reduction in viral activity for β-silicon nitride powders ranging from 1.25 to 3.5 log10 (approximately 93% to 99.97%), whereas α-silicon nitride powders showed a reduction of more than .5 log10 (more than 99.997%). It is believed that variations in the surface hydrolysis of the β-silicon nitride powders led to the range of results observed. However, comparing RT-qPCR and plaque assays suggests that SARS-CoV-2 virions are not pelleted with silicon nitride and their RNA structure is damaged when incubated with silicon nitride. are doing.

Plaque assay testing was performed on the efficacy of α- and β-silicon nitride powders against the South African variant of the SARS-CoV-2 virus using the same powders and methods described above. The results are shown in Figure 9B. α-Silicon nitride was found to be highly effective, reducing viruses by more than 4.5 log10 (99.9997%), while β-silicon nitride powder reduced viruses by approximately 1-log10 (approximately 90 %).

Similarly, plaque assays were performed for the efficacy of α- and β-silicon nitride powders against the UK variant of the SARS-CoV-2 virus using the same materials and procedures given above. The results are provided in Figure 9C. α-Silicon nitride powder reduced the virus count by about 4-log10 (99.99%) and β-silicon nitride by about 1-log10 (about 90%).

Although several embodiments have been described, those skilled in the art will recognize that various modifications, alternative configurations, and equivalents may be used without departing from the spirit of the invention. Furthermore, some well-known processes and elements have not been described to avoid unnecessarily obscuring the present invention. Therefore, the above description should not be construed as limiting the scope of the invention.

Those skilled in the art will understand that the embodiments disclosed herein teach by way of example and not limitation. Accordingly, the matter contained in the above description or shown in the accompanying drawings is to be interpreted in an illustrative manner and not in a limiting sense. The following claims are intended to encompass all general and specific features recited herein and all statements of the scope of the methods and systems, which are intended to include all general and specific features recited herein and all statements of the scope of the methods and systems, which are The problem may be said to lie between them.

Claims (36)

A method for inactivating pathogens, the pathogens being inactivated using boron nitride, chromium nitride, cerium nitride, hafnium nitride, lanthanum nitride, phosphorus nitride, sulfur nitride, tantalum nitride, titanium nitride, vanadium nitride, yttrium nitride, nitride. A method comprising contacting a composition comprising an effective concentration of a nitride selected from zirconium, or a combination thereof, wherein the effective concentration of the nitride inactivates the pathogen. 2. The method of claim 1, wherein the composition further comprises silicon nitride. 2. The method of claim 1, wherein the composition further comprises aluminum nitride. 2. The method of claim 1, wherein the nitride is boron nitride. 2. The method of claim 1, wherein the composition comprises a slurry of nitride particles in an aqueous medium. 6. The method of claim 5, wherein the effective concentration of the nitride is from about 0.1% to about 20% by volume. 2. The method of claim 1, wherein the composition comprises a powder of the nitride. 8. The method of claim 7, wherein the composition is coated over at least a portion of a surface of a device and/or incorporated into the device. 9. The method of claim 8, wherein the effective concentration of the nitride is from about 1% to about 100% by weight. 12. The device is an orthopedic implant, a spinal implant, a pedicle screw, a dental implant, an indwelling catheter, an endotracheal tube, a colonoscopy scope, a surgical gown, a mask, a filter, or tubing. 9. The method according to 8 or 9. The method according to any one of claims 1 to 10, wherein the pathogen is a virus, a bacterium, or a fungus. 12. The method of claim 11, wherein the virus is a coronavirus. 13. A method according to any one of claims 1 to 12, wherein the pathogen is on a surface or within a human, animal or plant. A method according to any one of claims 1 to 12, wherein the pathogen is on the surface of an inanimate object. A nitride-based composition for inactivating pathogens, the composition comprising a slurry of nitride particles in an aqueous medium, the nitride comprising about 0.1% to about 20% by volume. A nitride-based composition present in a concentration, said concentration being effective to inactivate said pathogen. the nitride is selected from boron nitride, chromium nitride, cerium nitride, hafnium nitride, lanthanum nitride, phosphorous nitride, sulfur nitride, tantalum nitride, titanium nitride, vanadium nitride, yttrium nitride, zirconium nitride, or combinations thereof; The nitride composition according to claim 15. 17. The nitride-based composition of claim 16, wherein the composition further comprises silicon nitride. 17. The nitride-based composition of claim 16, wherein the composition further comprises aluminum nitride. The nitride-based composition according to claim 16, wherein the nitride is boron nitride. The nitride-based composition according to claim 15, wherein the pathogen is a virus, bacteria, or fungus. The nitride-based composition according to claim 20, wherein the virus is a coronavirus. Nitride-based composition according to any one of claims 15 to 21, wherein the pathogen is on a surface or in a human, animal or plant. A nitride-based composition according to any one of claims 15 to 21, wherein the pathogen is on the surface of an inanimate object. A nitride-based device for inactivating pathogens, the device comprising a nitride powder coated over at least a portion of the surface of the device and/or incorporated into the device, the nitride comprising: , in a concentration of about 10% to about 30% by weight, said concentration being effective to inactivate said pathogen. the nitride is selected from boron nitride, chromium nitride, cerium nitride, hafnium nitride, lanthanum nitride, phosphorus nitride, sulfur nitride, tantalum nitride, titanium nitride, vanadium nitride, yttrium nitride, zirconium nitride, or combinations thereof; A nitride-based device according to claim 24. 26. The nitride-based device of claim 25, wherein the device further comprises silicon nitride. 26. The nitride-based device of claim 25, wherein the device further comprises aluminum nitride. Nitride boron nitride, the nitride-based device of claim 25. 25. The nitride-based device of claim 24, wherein the pathogen is a virus, bacteria, or fungus. 30. The nitride-based device of claim 29, wherein the virus is a coronavirus. A nitride-based device according to any one of claims 24 to 30, wherein the pathogen is on a surface or within a human, animal or plant. A nitride-based device according to any one of claims 24 to 30, wherein the pathogen is on the surface of an inanimate object. A method for inactivating a pathogen, the method comprising contacting the pathogen with a slurry comprising an effective concentration of alpha-silicon nitride, the effective concentration of nitride inactivating the pathogen, The effective concentration of α-silicon nitride in the method is about 15% w/v. The slurry is a nitride selected from boron nitride, chromium nitride, cerium nitride, hafnium nitride, lanthanum nitride, phosphorous nitride, sulfur nitride, tantalum nitride, titanium nitride, vanadium nitride, yttrium nitride, zirconium nitride, or combinations thereof. 34. The method of claim 33, further comprising: A method for inactivating a pathogen, the method comprising contacting the pathogen with a slurry comprising an effective concentration of aluminum nitride, the effective concentration of nitride inactivating the pathogen and reducing the amount of aluminum in the slurry. The method wherein the effective concentration of aluminum nitride is about 15% w/v. The slurry is a nitride selected from boron nitride, chromium nitride, cerium nitride, hafnium nitride, lanthanum nitride, phosphorous nitride, sulfur nitride, tantalum nitride, titanium nitride, vanadium nitride, yttrium nitride, zirconium nitride, or combinations thereof. 36. The method of claim 35, further comprising: