Devices and methods for decontamination / disinfection

By using a binding agent that binds carbohydrate matrix polymer and covalent bonding, a device has been developed that can effectively remove and stabilize the resilient viruses and microorganisms on the surface, solving the problems of inefficient removal efficiency and insufficient safety in the prior art.

JP7676026B2Active Publication Date: 2025-05-14AQUILA BIOSCIENCE LTD
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Patent Information

Application Number
JP2021571512
Authority / Receiving Office
JP · JP
Patent Type
Patents
Current Assignee / Owner
Priority Date
2019-05-31
Filing Date
2020-05-29
Publication Date
2025-05-14
Estimated Expiration
2040-05-29

AI Technical Summary

Technical Problem

The prior art is difficult to effectively remove viruses, microorganisms and pathogens on the surface, especially those species that are resistant to conventional disinfection methods, and it is difficult to stably remove and retain these microorganisms from the surface.

Method used

An apparatus comprising a carbohydrate matrix polymer and a binding agent which binds to the carrier material by covalent bonds and has a high affinity for viruses, microorganisms and microbial components.

Benefits of technology

The stable removal and retention of adversarial microorganisms and viruses is achieved, avoiding the potential health risks and environmental pollution caused by conventional disinfection methods, while improving removal efficiency and safety.

✦ Generated by Eureka AI based on patent content.

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Abstract

Devices for the control and removal of viruses, microorganisms, and pathogens are provided. The devices include a carrier material comprising a carbohydrate-based polymer and a binding agent. The binding agent is attached to the carrier material by one or more covalent bonds, and the binding agent is capable of binding to a target, where the target is one or more of a biotoxin, a virus, a microorganism, and a microbial component. Also provided are methods of using such devices for removing biotoxins, viruses, microorganisms, and / or microbial components, and methods for making the devices, the methods including providing a carrier material comprising a carbohydrate-based polymer, treating the carrier with an oxidizing agent to generate acid and / or aldehyde groups, and contacting the treated carrier with a binding agent comprising one or more of a lectin, a glycoprotein, and a glycoconjugate, such that the binding agent is attached to the carbohydrate-based polymer by one or more covalent bonds.
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Description

[Technical field]

[0001] The present invention relates to the field of virus, microorganism and pathogen control and elimination. [Background technology]

[0002] In the modern world, how to prevent the spread of viruses, bacteria and other microorganisms and their components is a major issue, especially when such substances are harmful to the health of humans or other organisms. Because transmission of these substances often occurs by surviving on or between surfaces or by being transported through air or liquids, it is desirable to remove viruses, microorganisms and microbial components from these surfaces.

[0003] Pathogens must of course be particularly removed, but it may also be desirable to harvest or remove harmless microorganisms for a variety of purposes, such as maintaining a sterile environment or avoiding contamination of scientific or industrial processes.

[0004] Many of the techniques designed to remove microbial or viral attachments from surfaces attempt to denature or otherwise destroy the target. For example, alcohol and other disinfectants, strong chemical disinfectants (commonly oxidizing agents such as bleach, although reducing agents can be used), antibiotics, extreme heat, and radiation such as shortwave ultraviolet light or non-thermal (low-temperature) plasma are often used to destroy or denature viruses and microorganisms.

[0005] Such approaches have several major drawbacks, primarily their variable efficacy. Microorganisms can become or develop resistance to almost any method of sterilization. Some microbial species can produce spores that are highly resistant to heat, chemical, pharmaceutical, and ultraviolet attack, making them extremely difficult to destroy. Many viruses, by their very nature, are resistant to destruction by standard means, are immune to antibacterial drugs such as antibiotics, and lack the cellular processes to destroy them. Biotoxins and components of microorganisms and viruses can also be difficult to remove, as they are likely to be resistant to mechanisms designed to kill living organisms.

[0006] Furthermore, the means used for disinfection may themselves be harmful to the user. This is especially true for strong chemical disinfectants, while other means such as antibiotics may induce allergic reactions, and the use of ultraviolet light may damage the skin and cause cancer. Also, in many cases it may not be practical to apply such means. For example, heating surfaces to high temperatures for sterilization is not always feasible.

[0007] Even if the target microorganism or virus is destroyed, harmful substances may remain, such as protein-based bacterial toxins such as lipopolysaccharides (endotoxins) and non-protein-based enterotoxins produced by Vibrio cholerae. Other biotoxins, such as those produced by plants and animals, pose similar concerns.

[0008] Perhaps most importantly, chemical and antibiotic resistance can be evolved by microorganisms, retained by their offspring and even horizontally transmitted by gene transfer. Thus, the use of strong chemical disinfectants and sanitation products is an additional risk factor, promoting mutations and making eradication procedures less efficient. Many important antimicrobial agents, including the most powerful antibiotics and chemicals, will no longer be effective, resulting in increased human (and animal) mortality, the threat of global pandemics and increased healthcare costs. This is equally worrisome in the case of pathogens that pose a biological weapon threat; in the absence of appropriate control measures, they can cause widespread fear and damage to human and animal lives.

[0009] Thus, there is a need to produce methods and devices that are effective in removing biotoxins, viruses, microorganisms and microbial components, including those that may be resistant to standard removal and destruction methods, and effectively retaining these contaminants for later analysis and / or disposal.

[0010] Existing devices that aim to remove targeted biotoxins, viruses, microorganisms and microbial components by retaining them in a substance or carrier are unable to effectively retain these targets because the interactions between the biotoxins, viruses, microorganisms and microbial components and the substance or carrier are generally not strong enough. For example, the removed targets may simply be adsorbed to the substance or carrier, for example, by hydrogen bonding or similar interactions. These approaches result in inefficient uptake of targets or release of temporarily bound targets when the substance or carrier encounters another surface.

[0011] The present invention provides devices and methods for removing biotoxins, viruses, microorganisms and microbial components from contaminated surfaces and stably retaining them within a carrier material. Summary of the Invention

[0012] In a first aspect, the present invention provides a device (e.g. suitable for removing biotoxins, viruses, microorganisms and / or microbial components from surfaces and / or from gases or liquids) comprising a carrier material comprising at least one carbohydrate-based polymer and a binding agent, the binding agent being attached to the carrier material by one or more covalent bonds and capable of binding to a target, the target being one or more of a biotoxin, a virus, a microorganism and a microbial component.

[0013] The carrier material may include cellulose as the carbohydrate-based polymer and may include one or more of cotton and paper. When the carrier material includes cellulose, the binder may be attached to the cellulose by one or more covalent bonds.

[0014] The device may contain a fluid in which the carrier material is dissolved, suspended, dispersed, emulsified, or otherwise carried.

[0015] The binding agent may comprise one or more of an anti-thrombotic agent, an anti-inflammatory agent, an antibody, an antigen, an adhesin, an immunoglobulin, an enzyme, a hormone, a neurotransmitter, a cytokine, a protein, a globular protein, a cell attachment protein, a peptide, a cell attachment peptide, a proteoglycan, a toxin, a polysaccharide, a carbohydrate, a fatty acid, a drug, a vitamin, a DNA segment, an RNA segment, a nucleic acid, a dye, and a ligand. In some embodiments, the binding agent comprises one or more of a lectin, a glycoprotein, an oligosaccharide, and a glycoconjugate.

[0016] The binding agent may comprise a lectin, which may be one or more of AIA / Jacalin, RPbAI, AAL, ABL, ACA, AMA, BPA, CAA, Calcepa, CCA, ConA, CPA, DBA, DSA, ECA, EEA, GHA, GNA, GSL-I-B4, GSL-II, HHA, HPA, Lch-A, Lch-B, LEL, LTA, MAA, MOA, MPA, NPA, PA-I, PCA, PHA-E, PHA-L, PNA, PSA, RCA-I / 120, SBA, SJA, SNA-I, SNA-II, STA, UEA-I, VRA, VVA-B4, WFA, and WGA. Preferably, the lectin is one or more of VRA, Lch-B, EEA, PA-I, PNA, CAA, GSL-I-B4, AMA, RCA-I / 120, GNA.

[0017] In some embodiments, the binding agent may comprise a glycoprotein, which may be one or more of uromodulin (Tamm-Horsfall protein), fetuin, asialofetuin, invertase, fibrinogen, alpha-1-antitrypsin, alpha-crystallin, ceruloplasmin, alpha-1-acid glycoprotein, RNAse B, transferrin, beta-lactoglobulin, C.-lactalbumin, albumin, B-casein, C-casein, K-casein, lactoferrin, ovalbumin, ovomucoid, ovotransferrin, and derived glycomacropeptides. Typically, the glycoprotein may be one or more of fetuin, asialofetuin and α-crystallin.

[0018] In some embodiments, the binding agent is a glycoconjugate or a neoglycoconjugate. Glycoconjugates or neoglycoconjugates include Blood Group A-BSA, Blood Group B-BSA, Blood Group C-BSA, Blood Group D-BSA, Blood Group E-BSA, Blood Group F-BSA, Blood Group G-BSA, Blood Group H-BSA, Blood Group I ... B-HSA, Fuc-α-4AP-BSA, Fuc-β-4AP-BSA, 2´fucosyllactose-BSA, difucosyl-para-lacto-N-hexaose-APD-HSA(Lea / Lex), trifucosyl-Ley-heptasaccharide-APE-HSA, monofucosyl, monosialyllacto-N-neohexaose-APD-HSA, Gal-β-4AP-BSA, Galα1,3Gal-BSA, Gal-α-1,3Galb1, Gal‐β‐1,4Gal‐BSA, Gal‐α‐1,2Gal‐BSA, 4GlcNAc‐HSA, Gal‐α‐PITC‐BSA, Gal‐β‐ITC‐BSA, Glc‐β‐4AP‐BSA, Glc‐β‐ITC‐BSA, GlcNAc‐BSA, GlcNAc‐BSA, Botryose-HSA, Globo-N-tetraose-APD-HSA, Globotriose-APD-HSA, GM1-pentasaccharide-APD-HSA, Asialo-GM1-tetrasaccharide-APD-HSA, Globo-N-tetraose-APD-HSA, Globotriose APD-HSA, H-type II-APE-BSA, H-type 2-APE-HSA, Man-α-1,3 (Man-α-1,6), Man-BSA, Man-α-ITC-BSA, Man-b-4AP-BSA, LacNAc-BSA, LacNAc-α-4AP-BSA, LacNAc-β-4AP-BSA, Lac-β-4AP-BSA, Lac-N-tetraose-APD-HSA, Lacto-N-fucopentaose I-BSA, Lacto-N-Neotetraose-APD-HSA, Lacto-N-Fucopentaose II-BSA, Lacto-N-Fucopentaose III-BSA, Lacto-N-Difucohexaose I-BSA, Lewis a-BSA, Lewis x-BSA, Lewis y-Tetrasaccharide-APE-HSA, LNDI-BSA / Lewis b-BSA, Di-Lex-APE-BSA, Di-Lewisx-APE-HSA, Tri-Lex-APE-HSA, L-Rhamnose-Sp14-BSA,The lactose may be one or more of 3' sialyllactose-APD-HSA, 3' sialyllactose-3-fucosyllactose-BSA, 6'-sialyllactose-APD-HSA, Xyl-α-4AP-BSA, Xyl-β-4AP-BSA, 3' sialyll Lewis x-BSA, 3' sialyll Lewis a-BSA, 6-sulfo Lewis x-BSA, 6-sulfo Lewis a-BSA, 3-sulfo Lewis a-BSA, 3-sulfo Lewis x-BSA, sialyl-LNF V-APD-HSA, and sialyl-LNnT-penta-APD-HSA.

[0019] When the binding agent is a glycoconjugate, neoglycoconjugate, or glycoprotein, it may have terminal sugar residues including one or more of the following moieties: mannose, N-acetylglucosamine, N-acetylgalactosamine, N-acetylneuraminic acid, N-glycolylneuraminic acid (sialic acid), galactose, glucose, and fucose.

[0020] The carrier material may further comprise an antimicrobial agent, which may be one or more of a disinfectant, an antibiotic, and a detergent. The antimicrobial agent may be silver, copper, or EDTA.

[0021] In any embodiment, the carrier material of the device may be in the form of a cloth, wipe, wound dressing, swab, filter, pad, blanket, mat, mask or coating.

[0022] In a second aspect, the present invention provides a method of removing biotoxins, viruses, microorganisms and / or microbial components from a surface, the method comprising providing a device according to any embodiment described herein and contacting the surface with the device.

[0023] In a third aspect, the present invention provides a method for removing biotoxins, viruses, microorganisms and / or microbial components from a gas or liquid, the method comprising providing a device according to any embodiment described herein and passing the gas or liquid through the device.

[0024] In any embodiment of the above-described methods, the binding agent may bind to the biotoxins, viruses, microorganisms and / or microbial components to be removed. The viruses, microorganisms and / or microbial components to be removed may be spores.

[0025] In a further aspect, the present invention provides a method for making a device, the method includes providing a carrier material comprising at least one carbohydrate-based polymer; treating the carrier with an oxidizing agent to generate acid and / or aldehyde groups; and contacting the treated carrier with a binder comprising one or more of lectins, glycoproteins, and glycoconjugates, such that the binder is linked to the carbohydrate-based polymer by one or more covalent bonds. The oxidizing agent is a periodate, preferably sodium periodate. The oxidizing agent can be selected from the group including 2,2,6,6-tetramethylpiperidine-1-oxyl radical (TEMPO), sodium nitrate or sodium nitrate in phosphoric acid; activating agent tosyl chloride in the presence of an organic solvent and a base; and combinations thereof.

[0026] Further potential features discussed in conjunction with device embodiments according to the present invention are believed to apply equally to devices manufactured by the above processes.

[0027] In certain embodiments, a device is provided, the device comprising a carrier material comprising cellulose and a binder comprising a glycoprotein, the glycoprotein being selected from one or more of uromodulin (Tamm-Horsfall protein), fetuin, asialofetuin, invertase, fibrinogen, alpha-1-antitrypsin, alpha-crystallin, ceruloplasmin, alpha-1-acid glycoprotein, RNAse B, transferrin, beta-lactoglobulin, C.-lactalbumin, albumin, B-casein, C-casein, K-casein, lactoferrin, ovalbumin, ovomucoid, ovotransferrin, and derivative glycomacropeptides. The binder is attached to the cellulose by one or more covalent bonds, the binder being capable of binding to a target, the target being one or more of a biotoxin, a virus, a microorganism, and a microbial component. [Brief description of the drawings]

[0028] The invention is further illustrated by reference to the accompanying drawings in which: [Figure 1A] FIG. 1A shows the results of efficacy testing of devices according to various embodiments of the present invention for use in removing F. tularensis from various surfaces. [Figure 1B] FIG. 1B shows the results of efficacy testing of devices according to various embodiments of the present invention in removing F. tularensis from various surfaces. [Figure 1C] FIG. 1C shows the results of efficacy testing of devices according to various embodiments of the present invention for use in removing F. tularensis from various surfaces. [Figure 2A] FIG. 2A shows the results of efficacy testing of devices according to various embodiments of the present invention for use in removing Clostridium botulinum from various surfaces. [Figure 2B] FIG. 2B shows the results of efficacy testing of devices according to various embodiments of the present invention for use in removing Clostridium botulinum from various surfaces. [Figure 2C]FIG. 2C shows the results of efficacy testing of devices according to various embodiments of the present invention for use in removing Clostridium botulinum from various surfaces. [Figure 2D] FIG. 2D shows the results of efficacy testing of devices according to various embodiments of the present invention for use in removing Clostridium botulinum from various surfaces. [Figure 3A] FIG. 3A shows the results of efficacy testing of devices according to various embodiments of the present invention in removing Bacillus anthracis in cellular (3A) or spore (3B) form from various surfaces. [Figure 3B] FIG. 3B shows the results of efficacy tests using devices according to various embodiments of the present invention to remove Bacillus anthracis in cellular (3A) or spore (3B) form from various surfaces. [Figure 4A] FIG. 4A shows the results of efficacy testing of devices according to various embodiments of the present invention in removing influenza virus from various surfaces. [Figure 4B] FIG. 4B shows the results of efficacy testing of devices according to various embodiments of the present invention in removing influenza virus from various surfaces. [Figure 4C] FIG. 4C shows the results of efficacy testing of devices according to various embodiments of the present invention in removing influenza virus from various surfaces. [Figure 5A] FIG. 5A shows the results of efficacy testing of devices according to various embodiments of the present invention in removing EHEC E. coli O157:H7 and Enterobacter cloacae from various surfaces. [Figure 5B] FIG. 5B shows the results of efficacy testing of devices according to various embodiments of the present invention in removing EHEC E. coli O157:H7 and Enterobacter cloacae from various surfaces. [Figure 6] FIG. 6 shows the results of efficacy testing of devices according to various embodiments of the present invention for removing Propionibacterium acnes from plastic surfaces. [Figure 7] FIG. 7 shows the results of efficacy testing of devices according to embodiments of the invention for removing Candida albicans from plastic surfaces at various pH levels. [Figure 8] FIG. 8 illustrates the method of testing a device according to an embodiment of the present invention on a model of skin inoculated with various microorganisms. [Figure 9A] FIG. 9A shows the results of an efficacy test in which a device according to an embodiment of the invention was used to remove E. coli from pig skin sections. [Figure 9B] FIG. 9B shows the results of an efficacy test in which a device according to an embodiment of the invention was used to remove E. coli from pig skin sections. [Figure 10] FIG. 10 shows the results of an efficacy study in which a device according to an embodiment of the invention was used to remove Candida albicans from a section of pig skin. [Figure 11] FIG. 11 shows the results of an efficacy study in which a device according to an embodiment of the invention was used to remove Aspergillus fumigatus from a section of pig skin. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0029] All references cited herein are incorporated by reference in their entirety. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

[0030] Before further describing the invention, definitions helpful to the understanding thereof are provided.

[0031] As used herein, the term "target" refers to something that is desired to be removed from a surface or to be incorporated or immobilized in / on the device of the present invention. Typically, the target is a biotoxin, a virus, a microorganism or a microbial component, which may be a pathogen. In some cases, the target may be an allergen, or a microbial component produced by non-microbial life, such as plant pollen, fungal spores, dust mite feces and other components, foods such as nuts and shellfish, animal or plant toxins or poisons, and potential allergens from animal products such as dander.

[0032] As used herein, the term "microorganism" refers to microorganisms, in particular bacteria, fungi, the so-called "protozoans" or any other prokaryotic or eukaryotic organisms of the microscopic level.

[0033] As used herein, the terms "microbial component", "microbial product" or "microbial material" refer to a product of a microorganism that one desires to remove from a surface or that is incorporated or immobilized in / on a device of the invention. A microbial component can be a toxin, i.e., a substance harmful to the body, e.g., a protein-based or non-protein-based bacterial toxin such as lipopolysaccharides (endotoxins), or an enterotoxin produced, e.g., by Vibrio cholerae.

[0034] As used herein, the term "toxin" or "biotoxin" refers to a substance of biological origin that is harmful to the body. Biotoxins may be produced by microorganisms, as described above, or may have other sources, such as plants or animals.

[0035] As used herein, the term "pathogen" means a virus or microorganism that can cause disease.

[0036] As used herein, the term "carbohydrate-based polymer" refers to a polymer that contains monosaccharide units (simple sugar molecules) as the main or only component of its repeating polymer units. Carbohydrate-based polymers include, but are not limited to, polysaccharides, dextran, starch, glycogen, fungal β-glucan, chitin, chitosan, cellulose and cellulose derivatives (e.g., cellulose acetate, celluloid, and nitrocellulose), laminarin, chrysolaminarin, xylan, arabinoxylan, mannan, fucoidan, and galactomannan, as further described below. Many such polymers consist only of monosaccharide units and their derivatives, but copolymers that contain monosaccharides and other units, such as sugar-peptide hybrid copolymers, exist. Furthermore, certain carbohydrate-based polymers, especially if they are non-fibrous, can be dissolved, suspended, dispersed, emulsified, or otherwise carried in a fluid carrier, such as a liquid or gas, as a spray, sol-aerosol, emulsion, or otherwise.

[0037] As used herein, the term "polysaccharide" refers to a carbohydrate-based polymer composed of chains of monosaccharide units (simple sugar molecules), where the chains can be linear or branched. Polysaccharides are often used to store sugars for later use, such as starch, glycogen, laminarin, and other polysaccharides. Other polysaccharides can be used for structural purposes, including cellulose, fungal β-glucan, chitin, pectin, xylan, arabinoxylan, and others. Bacteria often produce and secrete polysaccharides, for example to aid in adhesion to surfaces and to help evade the host's immune system.

[0038] The term "cellulose" as used herein refers to a bio-carbohydrate polymer made from chains of D-glucose units with β(1→4) linkages. Cellulose is also produced by other species, including green plants, some algae, and some bacteria, for use in cell walls. Finely divided cellulose or nanocellulose can be non-fibrous and therefore can be dissolved, suspended, dispersed, emulsified, or otherwise carried in a fluid carrier, such as a liquid or gas, as a spray, sol, aerosol, emulsion, or otherwise.

[0039] As used herein, the term "binding agent" refers to a biological molecule capable of binding to a biotoxin, virus, microorganism, or microbial component. Such molecules may include one or more of antithrombotic agents, anti-inflammatory agents, antibodies, antigens, adhesins, immunoglobulins, enzymes, hormones, neurotransmitters, cytokines, proteins, globular proteins, cell attachment proteins, peptides, cell attachment peptides, proteoglycans, toxins, polysaccharides, carbohydrates, fatty acids, drugs, vitamins, DNA segments, RNA segments, nucleic acids, dyes, and ligands. Typically, the binding agents discussed herein are one or more of glycoproteins, oligosaccharides, lectins, glycoconjugates, and derivatives thereof.

[0040] As used herein, the term "glycoprotein" refers to a protein having one or more oligosaccharide groups or glycans attached to it. Many secreted proteins are "glycosylated" in this manner, and transmembrane proteins with extracellular domains often have sugar groups attached to these domains.

[0041] As used herein, the term "glycoconjugates" refers to proteins and lipids having one or more glycan oligosaccharide groups attached to them. Examples include glycoproteins, glycolipids, glycosphingolipids, proteoglycans and glycosaminoglycans of natural or synthetic origin. "Neoglycoconjugates" or NGCs refer to artificial or synthetic glycoconjugates, particularly glycoproteins and glycolipids, in which a protein or lipid backbone is chemically linked to one or more sugar residues. Often, proteins such as bovine serum albumin (BSA) and human serum albumin (HSA) are used to prepare neoglycoconjugates.

[0042] As used herein, the term "lectin" refers to carbohydrate-binding proteins (the terms carbohydrate-binding protein or CBP are used interchangeably). Lectins are specific for carbohydrate moieties, such as those present on glycoproteins, glycolipids, or oligosaccharides. Some lectins are also called "agglutinins" because of their ability to agglutinate particles to which they bind. However, the term "agglutinin" can apply to any substance capable of such agglutination, such as an antibody.

[0043] As used herein, the term "adhesin" refers to a cell surface component involved in attaching cells to other cells or surfaces. They are used to adhere to host surfaces and are common in pathogenic, parasitic or symbiotic microorganisms.

[0044] As used herein, the term "antiseptic" refers to a chemical that has antimicrobial activity, particularly killing, denaturing or destroying, or preventing their growth or reproduction. In general, antiseptics are safe for use on skin and living tissue, including sites such as the oral cavity, but are not commonly used inside the body due to efficacy and safety concerns. Some, but not all, antiseptics are effective at denaturing or destroying viruses. There are many classes of antiseptics, including alcohols such as phenol, weak concentrations of antiseptics such as bleach and peroxide, iodine, and some specific chemicals such as chlorhexidine gluconate and quaternary ammonium compounds.

[0045] As used herein, the term "antibiotic" refers to a chemical substance that has an antimicrobial effect that is or can be used in the body. These substances often interfere with bacterial processes, causing the death or lysis of microbial cells, but generally have no effect on viruses or bacterial products. Many types of antibiotics are well known, including penicillins, cephalosporins, tetracyclines, and ansamycins.

[0046] The present invention describes devices and methods related to techniques for biotoxin, virus, microorganism and microbial derived components (proteins, peptides and carbohydrates) collection, decontamination / disinfection, preservation for peripheral diagnostic and forensic applications, and delivery. The approach targets the natural binding sites of viruses, microorganisms and / or their components, or biotoxins, providing a non-toxic, environmentally friendly alternative for biological decontamination used on physical surfaces and on the surfaces of human and animal skin and mucosal epithelia. The approach is intended to be broadly specific, i.e., target multiple types of pathogens for multiple purposes in multiple formats.

[0047] Interactions between cell surface proteins and carbohydrates are essential for cell-cell adhesion, which also applies to the adhesion of certain biotoxins, viruses, microorganisms and proteins of microbial origin to other surfaces, such as the cells of the host organism.

[0048] Microbial and viral attachment mechanisms to cells are a particularly important area of ​​evolution, especially when commensal, symbiotic or parasitic microorganisms bind to host cells. For example, host-bacterial interactions are mediated by bacterial adhesins to the host cell surface and their cognate glycan receptor epitopes. The majority of adhesins, both Gram-negative and Gram-positive, identify suitable hosts through glycan markers on the epithelial cell surface of the host organism (Kline et al., Cell Host and Microbe, 2009). Examples of bacterial species with their respective adhesins, target ligands and organization are shown in Table 1. Particularly for pathogens, the interaction of pathogen surface markers with those of the host is crucial for strong adhesion to the host, evasion of the immune system and (in the case of intracellular pathogens and toxins) access to the cell interior. Indeed, the ability of certain bacteria to specifically adhere to host cells (often by possession of specific surface proteins or other molecules) can represent a virulence factor, differentiating pathogenic and non-pathogenic strains. In nature, these substances are constantly bound, retained and removed from the surface of human and animal cells before pathogens can multiply or enter the cell and cause infection.

[0049] [Table 1]

[0050] Using similar principles of carbohydrate-protein conjugation technology, the device allows for a unique approach by utilizing natural and modified protein and carbohydrate epitopes that are chemically conjugated to carriers in a range of formats. The device provides a variety of "hooks" that can bind to biotoxins, viruses, microorganisms and / or their components that compete with the host's attachment surfaces and can quite effectively remove or capture these targets.

[0051] Thus, carbohydrates, proteins and protein fragments immobilized on physical materials can be used to remove microorganisms and proteins of microbial origin (bacteria, viruses, phage particles, fungi and proteins from these materials), collect samples of biotoxins, viruses, microorganisms and / or their components, reduce the microbial load on surfaces, decontaminate / disinfect surfaces and preserve samples collected on the device for diagnostic and forensic purposes.

[0052] Carrier material The carrier substance provides a surface to which the binding agent is attached and a substrate to which the virus, microorganism, microbial component and / or biotoxin may be immobilized. Suitably, the carrier material is capable of forming a covalent bond with the binding agent such that a strong and suitably irreversible linkage may be made.

[0053] Typically, the carrier may comprise a carbohydrate-based polymer, preferably a polysaccharide, such as starch, glycogen, chitin, cellulose, pectin, fungal β-glucan, xylan or arabinoxylan. The carrier may preferably comprise cellulose. For example, the carrier may comprise cellulose, hemicellulose or lignocellulose. The carrier may comprise a material that essentially contains cellulose, such as paper, cotton, viscose, linen or hemp, or may be blended or coated with cellulose from another source. The carrier may also comprise a blend of synthetic and cellulose-containing materials, such as a 50% blend of polyester material and cotton. Cellulose may also be produced by microorganisms such as bacteria. In particular, bacteria of the genera Acetobacter, Sarcinaventriculi and Agrobacterium have been used to produce bacterial cellulose.

[0054] Non-fibrous cellulose-based materials and carbohydrate-based polymers can be used as carriers. In particular, micronized cellulose and nanocellulose can be used as non-fibrous cellulose in this manner. Such non-fibrous cellulose or carbohydrate-based polymers can be dissolved, suspended, dispersed, emulsified, or otherwise carried in a fluid carrier, such as a liquid or gas. Thus, when combined with the binders described herein, such preparations can be applied to the receptor material in a non-solid form, such as a spray or paint.

[0055] Such non-solid formats of carbohydrate-based polymers linked to binders allow a range of applications that would not be possible otherwise. For example, such products / devices in suspension or soluble form can be sprayed or otherwise applied to a receptor material, such as a fabric, to impart protection to said material depending on the properties of the applied product. After application, the receptor material can be washed or treated, for example with a detergent or under low pH conditions, to remove the previously applied product. The receptor material can then be re-treated with fresh product to regenerate protection before its next use or exposure. Such an approach can be used, for example, in the treatment of personal masks or other personal protective equipment to impart protection against one or more of the targeted biotoxins, viruses, microorganisms, and / or microbial components depending on the specific purpose.

[0056] Further potential applications of non-solid formats of carbohydrate-based polymers linked to binders include use as cleaning compositions that can be sprayed or otherwise applied to a receptor material to be cleaned and then removed along with any bound target biotoxins, viruses, microorganisms, and / or microbial components. Particular applications of such techniques include cleaning large shipping containers, shipping hubs, and hospitals, sterilization of instruments for aseptic applications such as in hospitals or outer space, etc.

[0057] More generally, and for all possible formats, if it is desired to permanently kill, denature, or otherwise destroy the biotoxins, viruses, microorganisms, and / or microbial components incorporated into the device of the present invention, the carrier or device can further include suitable agents to accomplish this. For example, the carrier can be impregnated with or mixed with inherently antibacterial or antiviral chemicals such as antibiotics, preservatives, bleaching agents that may include hypochlorite, peroxide, and percarbonate, as well as other materials such as silver or copper that have antibacterial properties, other suitable metal ions, and metal chelators such as EDTA that have been shown to have antibacterial effects (Finnegan and Percival, Wound Healing Society, 2014). Other possibilities include benzoic acid, benzalkonium chloride, and other quaternary ammonium cations. Depending on the proposed use of the device, different additional materials can be selected. For example, if the device is intended to be used on the skin, a disinfectant that is safe for such use can be selected. Stabilizers and / or preservatives can also be used, examples of which are known in the art.

[0058] In some cases, it may be desirable to retain the target biotoxins, viruses, microorganisms and / or microbial components for subsequent analysis for research, diagnostic or forensic purposes. In such cases, the carrier may be substantially free of antimicrobial substances and may also be further treated to increase the likelihood that the target biotoxins, viruses, microorganisms and / or microbial components will remain intact for subsequent analysis, such as by including a buffer or other solution, or a particular pH level, to support the immobilized target. Buffers or other solutions may also be included to aid in the binding of the binding agent to the desired target, since most interactions depend on an aqueous environment, a particular pH level, and the like.

[0059] It is envisioned that the carriers will be prepared in many different forms. For example, wipes, cloths, wound dressings, filters, pads, coatings, blankets, mats, masks and other articles can be constructed with the carrier material. In particular, it is envisioned to use wipe forms similar to tissues, towels or napkins, as they provide a convenient form for wiping on the surface to be decontaminated and then discarded. It is also envisioned that the device of the present invention can be used to remove target biotoxins, viruses, microorganisms and / or microbial components from gases or liquids, such as when removing suspended or aerosolized viral particles from the air. In this case, the carrier is designed to be permeable to gases or liquids so that the target can be removed. As mentioned above, it is also envisioned that certain carrier materials can be combined with binders and dissolved, suspended, dispersed, emulsified or otherwise carried in a fluid, and thus fluids containing such carrier materials are examples of devices of the present invention.

[0060] It may also be desirable for the device of the present invention to be suitable for general cleaning of biological surfaces, such as skin, or non-biological surfaces. As a result, it is contemplated that the carrier may contain additional components appropriate for the intended use, such as cleansers, moisturizers, deodorants or chemicals for makeup removal (e.g., when used for skin cleaning), and / or detergents, fragrances, or cleaning agents for removing dirt, grime, metal tarnish, etc. from non-biological surfaces. In this way, the device described herein can be used for therapeutic purposes, such as removing or killing pathogens from body surfaces and skin (e.g., to treat acne, diaper rash, and other skin conditions). In non-therapeutic applications, such as cosmetic applications, the device can be used for skin cleaning or moisturizing, baby care, hand washing, makeup removal, or deodorant application.

[0061] Incontinence pads incorporating or including the devices of the present invention are also contemplated and may be selected in configuration to provide protection against infectious agents that promote urinary tract disease.

[0062] Pads and / or wipes designed for breastfeeding and / or nipple care are also contemplated and can be designed to be effective in providing protection against infectious pathogens that cause mastitis.

[0063] Binder A binding agent capable of binding to a target biotoxin, virus, microorganism, and / or microbial component is attached to the carrier material. Any biologically derived molecule capable of binding to a biotoxin, virus, microorganism, or microbial component can be used in the device of the present invention. Such molecules may include one or more of antithrombotic agents, anti-inflammatory agents, antibodies, antigens, adhesins, immunoglobulins, enzymes, hormones, neurotransmitters, cytokines, proteins, globular proteins, cell attachment proteins, peptides, cell attachment peptides, proteoglycans, toxins, polysaccharides, carbohydrates, fatty acids, drugs, vitamins, DNA segments, RNA segments, nucleic acids, dyes, and ligands. Preferably, the one or more binding agents include glycoproteins, oligosaccharides, lectins, and glycoconjugates.

[0064] Binding agents suitable for use in the present invention have many origins, and many can be derived from naturally produced solutions such as milk, urine, mucus, saliva, eggs, fungi, algae, and plant extracts. Binding agents can also be produced synthetically (e.g., by in vitro translation) or genetically engineered (e.g., by recombinant engineering), or naturally produced binding agents can be treated or modified, for example, to display only the binding portion of a particular larger molecule, to make specific peptides, glycopeptides, fragments, glycans, or the like.

[0065] Another advantage of many of the binders discussed here is that they are non-toxic and environmentally friendly compared to commonly used antimicrobial or antiviral agents. For example, polyguanidine compounds, which are often used as biocides, are in a category of compounds restricted by the FDA due to their toxicity to humans and their potential to cause environmental damage. Another guanidine example is chlorhexidine gluconate, and there are plans to restrict this compound to prescription-only use in the future. Similarly, quaternary ammonium compounds such as polyionenes are often used in wipes and hand sanitizers, but the FDA is in the process of restricting their use.

[0066] While some potential binding agents can be expected to bind very specifically to only one target (especially antibodies), many have a broader range of potential binding targets and can be used to remove one or more target biotoxins, viruses, microorganisms and / or microbial components. However, to increase the number of potential targets and thereby improve the use of the device, multiple types of binding agents can be used in one device, which can be from the same class of molecules (e.g., multiple species of glycoproteins) or different classes (e.g., glycoproteins and lectins). As a result, depending on the desired application, the device according to the invention can be engineered to have very specific binding targets, for example in a research or forensic setting, or to have a more general use suitable for indoor or outdoor situations.

[0067] Many interactions between biotoxins, viruses, microorganisms and / or microbial components and host cells or surfaces to which they adhere are mediated by carbohydrates, glycoproteins and lectins (carbohydrate-binding proteins or CBPs, glycan-binding proteins or GBPs) and their fragments (e.g. peptides). For example, the type 1 fimbrial FimH adhesin carried by certain bacteria, such as certain strains of E. coli, can bind to host cell surface markers such as CD48, TLR4, or more commonly, to mannose residues via its lectin (carbohydrate-binding) domain.

[0068] Thus, glycoconjugates, including glycoproteins, glycolipids, glycosphingolipids, proteoglycans and glycosaminoglycans of natural or synthetic origin, are contemplated for use in providing binding sites for attachment of target biotoxins, viruses, microorganisms and / or microbial components to the device. Glycoconjugates for use in devices according to the invention have terminal residues that include one or more of mannose, N-acetylglucosamine, N-acetylgalactosamine, N-acetylneuraminic acid, and N-glycolylneuraminic acid (sialic acid), galactose, glucose, and fucose moieties.

[0069] Suitable glycoconjugates and neoglycoconjugates for use in the devices of the invention include Blood Group A-BSA, Blood Group B-HSA, Fuc-α-4AP-BSA, Fuc-β-4AP-BSA, 2′fucosyllactose-BSA, difucosyl-para-lacto-N-hexaose-APD-HSA(Lea / Lex), trifucosyl-Ley-heptasaccharide-APE-HSA, monofucosyl, monosialylacto-N-neohexaose-APD-HSA, Gal-b-4AP-BSA, Galα1,3Gal-BSA, Gala1,3Galb1, Gallb1,4Gal-BSA, Galα1,2Gal-BSA, 4GlcNAc-HSA, Gal- α‐PITC‐BSA, Gal‐β‐ITC‐BSA, Glc‐b‐4AP‐BSA, Glc‐β‐ITC‐BSA, GlcNAc‐BSA, globotriose‐HSA, globo‐N‐tetraose‐APD‐HSA, globotriose‐APD‐HSA, GM1‐pentasaccharide‐APD‐HSA, Asialo‐GM1‐tetrasaccharide‐APD‐HSA, globo‐N‐tetraose‐APD‐HSA, globotriose‐APD‐HSA, H‐type‐II‐APE‐BSA, H‐type 2‐APE‐HSA, Manα1,3 (Manα1,6), Man-BSA, Man-α-ITC-BSA, Man-b-4AP-BSA, LacNAc-BSA, LacNAc-α-4AP-BSA, LacNAc-β-4AP-BSA, Lac-β-4AP-BSA, lacto-N-tetraose-APD-HSA, lacto-N-fucopentaose I-BSA, lacto-N-neotetraose-APD-HSA, lacto-N-fucopentaose II-BSA, lacto-N-fucopentaose III-BSA, lacto-N-difucohexaose I-BSA, Lewis a-BSA, Lewis x-BSA, Lewis y-tetrasaccharide-APE-HSA, LNDI-BSA / Lewis b-BSA, Di-Lex-APE-BSA, Di-Lewisx-APE-HSA, Tri-Lex-APE-HSA, L-rhamnose-Sp14-BSA, 3'sialyllactose-APD-HSA, 3'sialyl-3-fucosyllactose-BSA, 6'-sialyllactose-APD-HSA, Xyl-α-4AP-BSA, Xyl-β-4AP-BSA, 3'sialyl Lewis x-BSA, 3'sialyl Lewis a-BSA, 6-sulfo Lewis x-BSA, 6-sulfo Lewis a-BSA, 3-sulfo Lewis a-BSA, 3-sulfo Lewis x-BSA, sialyl-LNF V-APD-HSA, and sialyl-LNnT-penta-APD-HSA.

[0070] Glycoproteins suitable for use in devices according to the invention may have terminal residues including one or more of mannose, N-acetylglucosamine, N-acetylgalactosamine, N-acetylneuraminic acid, N-glycolylneuraminic acid (sialic acid), galactose, glucose, and fucose moieties. Such glycoproteins and oligosaccharides may be derived from naturally occurring solutions such as milk, urine, mucus, saliva, eggs, fungi, algae, and plant extracts. Particular glycoproteins suitable for use in the device according to the invention include uromodulin (Tamm-Horsfall protein), fetuin, asialofetuin, invertase, fibrinogen, alpha-1-antitrypsin, a-crystallin, ceruloplasmin, alpha-1-acid glycoprotein, RNAse B, transferrin, B-lactoglobulin, C.-lactalbumin, albumin, B-casein, C-casein, K-casein, lactoferrin, ovalbumin, ovomucoid, ovotransferrin, and derivative glycomacropeptides. Mucins are high molecular weight proteins that are heavily glycosylated, and other glycoproteins found in mucus may also be used. These components of mucus are thought to reduce the risk of infection by interfering with microbial adhesion and preventing the formation of biofilms (Caldara et al., Current Biology, 2012).

[0071] Lectins, carbohydrate-binding proteins, are commonly involved in the binding of bacteria and viruses to their intended targets, as well as cell-cell interactions, and in innate and adaptive immune responses. Lectins are present in all organisms and play a variety of roles in cell adhesion, immune recognition, microbial recognition (e.g., for pathogens and symbionts), host recognition, toxin activity, and plant protection. In research, many lectins can be effectively isolated from plant and fungal species and can be engineered to change their specificity. Lectins are used to purify and characterize glycoconjugates, and in lectin-histochemistry to stain cells, tissues, and organs to understand differences in glycosylation on biological samples under different conditions.

[0072] Lectins contemplated for use in the present invention, and their sources, include, but are not limited to: AIA, jacalin, (Artocarpus integrifolia) jack fruit lectin; RPbAI, (Robinia pseudoacacia), false locust alectin; AAL, (Aleuria aurantia), orange peel fungus lectin; ABL (Agaricus bisporus), an edible mushroom lectin; ACA, (Amaranthus caudatus), amaranthin lectin; AMA, (Arum maculatum), Rose and Lady's Lectin; BPA, (Bauhinia purpurea), camel's foot tree lectin; CAA (Caragana arborescens), giant burdock lectin; Calsepa, (Calystegia sepium), bindweed olecutin; CCA, (Cancer antennarius), California crab; ConA, (Canavalia ensiformis), jack bean lectin; CPA, (Cicer arietinum), chickpea lectin; DBA, (Dolichos biflorus), horsegram lectin; DSA, (Datura stramonium), jimsonweed lectin; ECA, (Erythrina cristagalli), cockle kelp / coral tree lectin; EEA, (Euonymus europaeus), spindle tree lectin; GHA, (Glechoma hederacea) oyster lectin; GNA (Galanthus nivalis), snowdrop lectin; GSL-I-B4, (Griffonia simplicifolia), Griffonia / bandy bean lectin-I; GSL-II, (Griffonia simplicifolia), Griffonia / bandy bean lectin-II; HHA, (Hippeastrum hybrid), Amaryllis agglutinin; HPA, (Helix pomatia), small apple snail lectin; Lch-A, (Lens culinaris), lentil lectin A; Lch-B, (Lens culinaris), lentil lectin B; LEL, (Lycopersicum eculentum), tomato lectin; LTA, (Lotus tetragonolobus), Lotus lectin; MAA, (Maackia amurensis), dogwood agglutinin; MOA, (Marasmius oreades), fairy-ring mushroom lectin; MPA, (Maclura pomifera), American halibut lectin; NPA, (Narcissus pseudonarcissus), dahodyl lectin; PA-I, (Pseudomonas aeruginosa), Pseudomonas aeruginosa lectin; PCA (Phaseolus coccineus), scarlet runner bean lectin; PHA-E (Phaseolus vulgaris) kidney bean hemagglutinin; PHA-L (Phaseolus vulgaris) Phaseolus leukemia agglutinin; PNA, (Arachis hypogaea), peanut lectin; PSA, (Pisum sativum), Pea lectin; RCA-I / 120, (Ricinus communis), castor seed lectin I; SBA, (Glycine max), soybean lectin; SJA (Sophora japonica), pagoda tree lectin; SNA-I, (Sambucus nigra), elderberry lectin-I; SNA-II, (Sambucus nigra), elderberry lectin-II; STA, (Solanum tuberosum) potato lectin; UEA-I, (Ulex europaeus), gorse lectin-I; VRA (Vigna radiate), mungbean agglutinin; VVA-B4, (Vicia villosa), hairy vetch lectin; WFA, (Wisteria floribunda), Japanese wisteria lectin; and WGA, (Triticum vulgaris), wheat germ agglutinin

[0073] adjustment Although in theory the binder can be relatively simply impregnated into the carrier material, for example by immersing the carrier material in an aqueous solution containing the binder, so that it is absorbed or adsorbed by the carrier, the binding agent is suitably linked to the carrier material so that a chemical bond, particularly a covalent bond, is created between the two. Such a relatively strong and permanent bond is advantageous in that the binder will not be lost over time, and the targeted biotoxins, viruses, microorganisms and microbial components will be more strongly retained on the device / carrier material and less likely to migrate to the next surface. Without wishing to be limited by theory, it is also believed that the stronger the binder is attached to the carrier material, the more likely the target will be taken up and attached to the carrier, rather than the binder itself being removed from the carrier. Thus, the formation of a covalent bond between the binder and the carrier material improves the safety, efficacy, stability and lifespan of the device.

[0074] The binder attached to the carrier material can be provided or formulated in any suitable manner. For example, the binder can be combined with a diluent and / or excipient or stabilizer in a buffer solution. The binder can alternatively or additionally be provided in a form that includes a pharma- ceutically acceptable vehicle, which can include one or more of a solution, rinse, shampoo, spray, lotion, gel, foam, lubricant, cream, ointment, soap, non-soap bar, and powder.

[0075] To form a covalent bond between the binder and the carrier material, it may be convenient to chemically treat the carrier material to provide a binding site for the binder. For example, if the carrier material comprises cellulose, the cellulose may be treated to produce acid and / or aldehyde functional groups that can react with the amino groups of the protein to create a bond. In these carrier treatment reactions, carbohydrate rings in the cellulose are cleaved by an oxidizing agent. In particular, it is believed that the oxidizing agent used may be a perhalogenate such as periodate or perchlorate, a percarbonate, a permanganate, a hypochlorite, a perborate, or a peroxide. Other oxidation methods include oxidation of cellulose with TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl radical); oxidation with sodium nitrate and / or sodium nitrite in phosphoric acid; and / or treatment with the activating agent tosyl chloride (toluenesulfonyl chloride) in the presence of an organic solvent (such as acetone / dioxane) and a base (such as pyridine or triethylamine). Exemplary methods are discussed, for example, in US 5,516,673; Cumpstey I. "Chemical Modification of Polysaccharides" ISRN Org Chem. 2013 Sep 10;2013:417672; Saito T, Isogai A. "TEMPO-Mediated Oxidation of Native Cellulose" Effect of Oxidation Conditions on the Chemical and Crystalline Structure of the Water-Insoluble Fraction. 2004;5(5):1983-1989; and Kim UJ et al. "Periodate Oxidation of Crystalline Cellulose" Biomacromolecules. 2000;1(3):488-492.

[0076] The purpose of such treatment is to introduce reactive groups into the cellulose molecule, which can be, for example, one or more of aldehyde, ketone, N-hydroxysuccinimide, epoxide, imide ester, anhydride, or carbonate groups. Reactions 1 and 2 are examples of reactions in which sodium periodate creates active aldehyde groups by ring-opening the D-glucose units of cellulose β(1-4) linkages (reaction 1), followed by conjugation of proteins such as lectins, glycoproteins, and neoglycoconjugates (reaction 2). The reactions can be carried out in buffers ranging from pH 5 to 9 (Figure 7). [ka]

[0077] In the example shown below, a 'Schiff base' (-CH=NH-) is created between the cellulose unit and the attached protein. Optionally, to improve the permanence of the linkage, this double bond can be reduced to a single bond. This can be achieved by the use of a reducing agent such as sodium cyanoborohydride. Such a reaction will also reduce exposed CH=O moieties to CH2OH.

[0078] Such reactions form irreversible and highly stable bonds, allowing the desired carbohydrates and proteins to be embedded in cellulosic materials. Similar reactions can be used to attach sugar polymers, multimeric proteins and other biopolymers, where amide or carboxylic acid bonds are used for conjugation. Considering that these reactions target sugar monomers, it can be recognized that similar approaches can be used to attach binders to other sugar-containing carriers, such as polysaccharides including starch, glycogen, laminarin, fungal β-glucan, chitin, pectin, xylan, arabinoxylan, dextran or amylose. For example, dextran has been oxidized and subsequently conjugated with soybean peptides (Wang and Xiong, J Food Sci Technol, 2016). Other polymers containing sugars, such as peptidoglycans (such as those found in bacterial cell walls), can also be substrates to which binders can be attached.

[0079] It can also be appreciated that methods such as those described, which involve oxidation of cellulose to which binders are subsequently attached, are preferable over methods that involve modification of the attached reagents themselves, since such treatments can impair or destroy the binding potential of those reagents. In contrast, the methods described herein preserve the carbohydrate (or other) chemistry of the binders while ensuring that they are attached to the carrier material. Similarly, the long life of covalent bonds is advantageous over methods that rely on electrostatic attraction or other forces to bind chemicals to the carrier material, since such bonds can deteriorate over time.

[0080] To promote long-term stability and sterility of the devices of the invention, the carrier substance, carrier solution, produced materials and / or packaging materials may be treated before, during or after the above preparation steps with a combination of filtration, heat, chemicals, irradiation and high pressure, including, for example, pasteurization, autoclaving, gamma irradiation, ultraviolet irradiation, electron beam (eBeam irradiation), gas vapor sterilization (ozone, chlorine dioxide, ethylene oxide, oxides of nitrogen) or similar techniques.

[0081] Similarly, buffers such as borate, Tris and citrate buffers may be used to promote long term stability and sterility of the device, which have the added advantage of being ophthalmically safe.

[0082] Targeted biotoxins, viruses, microorganisms and microbial components The devices of the invention can target biotoxins, viruses, microorganisms and / or microbial components associated with biothreat hazards, i.e. potential dangers from biological weapons, synthetic biological products and / or weaponized microbial components, as in the case of bioterrorism, or potential pandemic pathogens, such as influenza variants, SARS, MERS, Hantavirus, Nipah virus, Ebola virus, Zika virus, etc. Devices for such targets include wipes and filters that can be used to defend against or remove these hazards. However, the devices of the invention can also be used in general research or in research into defenses against such substances, such as in the production of vaccines or antitoxins. Thus, the described devices can be used in the context of biosurveillance, for example to capture or screen for persistent biothreat pathogens after intended release or during natural outbreaks, or for prophylaxis against pandemic and food-borne pathogens. It is advantageous that the devices of the invention are not primarily intended to destroy targets, but rather to remove them, since it is often important to positively identify these substances for forensic, biosurveillance or other purposes. Examples of such biothreat hazards and the species believed to cause them include bacteria such as Francisella (tularemia), Bacillus anthracis (anthrax), Clostridium botulinum (botulism), Malariae (glanders) and Bacillus pseudomallei (melioidosis); viruses such as influenza virus, Ebola virus, Marburg virus, Variola major virus (smallpox), Foot and Mouth Disease virus (aphthovirus), SARS-associated coronavirus, Chapare / Lujo virus (Q fever caused by Coxiella genus of the Arenaviridae family); and toxins such as botulinum neurotoxin, ricin, abrin and Shiga-like toxin.In particular, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as 2019 novel coronavirus (2019-nCoV), the coronavirus strain that causes the pandemic coronavirus disease, COVID-19, is considered a biothreat hazard that may be targeted by embodiments of the present invention. Surrogate strains are species that resemble a biothreat pathogen in one or more ways and can be used as mimics to study various strategies to combat the biothreat. Examples of species that can be used as surrogates and also targeted by the devices as described herein include Bacillus spp. (Bacillus subtilis, Atrophaeus, Mycoides); Clostridium sporogenes, and Francisella tularensis, Francisella tularensis North American subspecies LVS.

[0083] The target bacteria may also be pathogens causing healthcare associated infections (HAI), healthcare associated infections (HCAI), hospital acquired infections, and / or antibiotic resistant bacteria that resist destruction by common antibiotics. Examples of such bacteria include Clostridium difficile, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Staphylococcus aureus (VRSA), Escherichia coli (STEC, VTEC, EHEC), Clostridium difficile. Klebsiella pneumoniae, Acinetobacter spp., Pseudomonas aeruginosa, Enterococcus faecalis, nontuberculous mycobacteria, Mycobacterium fortuitum, Proteus mirabilis, and the like. An advantage of the present invention for such bacteria is that adhesion is not affected by the mechanisms used by these bacteria to destroy or evade antibiotics.

[0084] A further advantage of the present invention is that it can be effective in eliminating bacterial spores. As already mentioned, the spores produced by certain microorganisms prove to be very difficult to destroy, as they are extremely resistant to heat, chemical, pharmaceutical and ultraviolet attack. However, since direct destruction of the spores is not always attempted, the adhesion method used by the present invention has proven to be effective in eliminating such targets.

[0085] Targets may include biotoxins, viruses, microorganisms and microbial components associated with food poisoning. Many such targets are bacteria such as Campylobacter, Clostridium, Escherichia, Listeria, Salmonella, Shigella, Staphylococcus, Vibrio, Helicobacter pylori, etc. Viruses such as Norwalk Virus, Rotavirus, Foot and Mouth Disease Virus, etc. In such cases, the device of the present invention may be used to decontaminate food preparation surfaces and utensils, or may be used as mats, napkins, etc.

[0086] It is also contemplated that microbial components such as bacterial toxins may be targeted by the device of the present invention. Such toxins include, for example, cholera toxin, botulinum, pertussis toxin, enterotoxin, tetanus toxin, and staphylococcal enterotoxin. Similarly, plant or animal derived biotoxins such as tetrodotoxin, ricin, and abrin are contemplated as targets for the device of the present invention. As an example, the highly toxic ricin protein is a heterodimer, with an A chain that acts as an N-glycoside hydrolase, which is the basis of its toxicity, and a B chain that is a lectin that can bind to galactose residues on the surface of target cells, allowing cell entry. Use of the device of the present invention, which has a specific binder that can interact with the B chain lectin, is effective in removing or otherwise capturing these proteins. Some other toxic proteins, such as abrin, have similar lectin components and therefore can also be targeted. In this context, the present invention is advantageous compared to existing antimicrobial approaches, since toxins cannot be killed like microorganisms and can often be resistant to denaturation by chemical or other means. The adhesion approach of the present invention allows for the removal of toxins without these problems.

[0087] Tables 2 and 3 show the different bacterial toxins and their known specific interactions with the top 10 lectins (Table 2) and glycoproteins / neoglycoconjugates determined based on binding analysis (Table 3). These analyses were performed by glycan microarrays evaluating selected toxins against different lectins and glycoproteins / neoglycoconjugates. These techniques are tools to evaluate protein-carbohydrate interactions in vitro, which can increase the number of experiments possible with limited sample amounts and facilitate profiling or screening before subsequent focused investigations (Kilcoyne, Gerlach, Kane and Joshi, Analytical Methods, 2012).

[0088] [Table 2]

[0089] [Table 3]

[0090] The devices of the invention are intended for use in a variety of applications, e.g., prophylactically, therapeutically, and topically. Potential uses include decontamination, cleaning, sample collection, sample retention, sample concentration, sample forensic analysis, wound care and healing, prevention of disease transmission and spread, prevention of cross-contamination, prevention of biofilm formation, personal hygiene, and / or reduction of stress and fear associated with risks associated with infectious pathogens.

[0091] Also provided are methods for treating or preventing certain conditions and diseases using the devices of the present invention. These include human, animal and plant diseases that may be mediated by bacteria, fungi, viruses or toxins, or eukaryotic microorganisms such as malarial parasites, trypanosomes such as leishmania and sleep parasites, etc. For example, the target microorganisms or microbial components may cause skin diseases and disorders.

[0092] Examples of skin diseases and disorders caused by fungal pathogens, and the species believed to be the underlying cause, include candidiasis (Candida albicans), tinea pedis or ringworm (Malassezia fur or Pityrosporum orbiculare), seborrheic dermatitis (Malassezia spp.), and athlete's foot (tinea pedis, which can be caused by fungal species including Trichophyton, Epidermophyton, and Microsporum fungi). Other infectious diseases and pathogens believed to be caused or involved include acne vulgaris (Propionibacterium acnes, Propionibacterium granulosum and Pseudomonas aeruginosa), staphylococcal scalded skin syndrome, impetigo, ecthyma, folliculitis, furuncles, carbuncle pyoderma (Staphylococcus aureus, Streptococcus pyogenes, Pseudomonas aeruginosa) and general body odor (Propionibacterium avidum). Treatment of inflammation of the mammary tissue (mastitis) such as that mediated by Staphylococcus aureus, Propionibacterium agalactiae, Streptococcus bovis, Escherichia coli, Pseudomonas aeruginosa, Streptococcus uberis and Staphylococcus aureus (Staphylococcus chromogenem) is also contemplated. Devices can be manufactured that aim to remove these pathogens from the skin to aid in treatment or from surfaces to reduce transmission. These conditions may be treated or prevented by applying the device of the present invention to infected or at-risk skin to remove the targeted biotoxins, viruses, microorganisms, or components thereof. A method of protection against wound infection is also contemplated; removal of the targeted virus, microorganism, or microbial pathogen from wounded skin or the skin surrounding it, or from a future wound site (such as at surgery), may prevent colonization of the wound by opportunistic infectious agents.

[0093] It is also contemplated that the target of the device as described may be present within a body cavity. For example, the target biotoxin, virus, microorganism or microbial component may cause oral cavity deficiency, disease or disorder, such as gingivitis, periodontitis, dental caries, or halitosis (bad breath). The target biotoxin, virus, microorganism or microbial component may cause vaginal infection. The device of the present invention may be applied in and around such cavities to treat or prevent infection.

[0094] Pathogens involved in causing sexually transmitted diseases that may be targeted by the devices of the present invention include Neisseria gonorrhoeae, Chlamydia trachomatis, Treponema pallidum, Ureaplasma urealyticum, and Haemophilus ducreyi.

[0095] Pathogens involved in causing eye infections that may be targeted by the device according to the present invention include Staphylococcus aureus, Neisseria gonorrhoeae, and Chlamydia trachomatis.

[0096] Pathogens involved in causing upper respiratory tract infections that may be targeted by the devices of the present invention include Aspergillus, Streptococcus pneumoniae and other Streptococcus species, Pseudomonas aeruginosa, Bordetella pertussis, Moraxella catarrhalis, Mycoplasma pneumoniae, Mycobacterium tuberculosis, Coxiella burnetii, Klebsiella pneumoniae, Staphylococcus aureus, Legionnaires' disease, and Escherichia coli, Proteobacteria such as Proteus and Serratia, Haemophilus influenzae, influenza viruses, rhinoviruses, and coronaviruses such as SARS, MERS, and pandemic SARS-CoV-2.

[0097] The device of the present invention is also intended for use in removing biofilms from target surfaces, i.e., conglomerates of microorganisms that adhere to each other and to a surface. Such biofilms can be difficult to remove by conventional means due to the number of organisms and the presence of extracellular factors that may protect the microorganisms from attack.

[0098] The described devices are also intended to be used to deliver beneficial, commensal, probiotic, non-harmful and symbiotic bacteria and / or microbial components, and / or controlled doses of biotoxins for therapeutic and cosmetic purposes between surfaces, including the skin. In such cases, a binder capable of binding to a probiotic target is attached to a carrier material and used to bind and release multiple layers of probiotic microorganisms or microbial components onto a selected surface. In this way, the device can be used to collect and / or concentrate beneficial microorganisms (such as commensal and probiotic organisms) and transfer, implant and / or deliver them to other sites or surfaces, including, for example, internal delivery to the gastrointestinal tract. Although the transferred microorganisms themselves may be bound to the device of the invention by the binder, replication may still occur and the microorganisms produced later may not be bound and may be freely transported to the target surface. A similar approach may allow for the collection and / or storage of beneficial bacteria for later use. For this purpose or other purposes (such as forensic analysis or laboratory use), it may even be possible to separate the bound biotoxins, viruses, microorganisms or microbial components from the device using buffers, for example by changing the pH, or ionic strength, or by using weak acids. Mono- or disaccharide solutions can also be used to disrupt sugar-protein interactions, thereby releasing the bound biotoxins, viruses, microorganisms or microbial components.

[0099] Additionally, the device of the present invention can also be used to capture or remove targets that are not strictly biotoxins, viruses, microorganisms or microbial components, provided that they can be bound by a binding agent as contemplated herein. For example, allergens and other microcomponents produced by non-microbial life may have surface components such as lectins or glycoconjugates that can be bound by a binding agent as described. Examples include plant pollen, fungal spores, dust mite feces and other components, potential allergens from foods such as nuts and shellfish, animal or plant venoms or poisons, and animal products such as dander. Such targets may cause allergic reactions or otherwise be harmful to humans or animals. Since allergic reactions are often mediated by cell-surface interactions, and some allergens include or consist of glycoconjugates, the device of the present invention may be effective in binding such targets. Advantageously, this may allow for the removal of such targets from surfaces, liquids or gases, or from the face or skin of a subject. For example, a device prepared to provide binding sites for plant pollen may be used to remove pollen from a surface or from the eyes or skin of a human or animal.

[0100] In epidemic or pandemic situations, the present invention may have a variety of uses, including but not limited to: decontamination of exposed skin to reduce the risk of transfer upon removal of personal protective equipment (PPE); sampling and clean-up of the PPE itself; and collection of samples from the public (e.g. during screening at transport hubs / vehicles) to aid in future decision-making (e.g. enforcing lockdowns, eliminating public access and transport units).

[0101] The provision of devices for delivering inhibitory compounds / anti-adhesion molecules (anti-bacterial, anti-viral, anti-fungal, anti-toxins, etc.) is also contemplated.

[0102] In the laboratory context or elsewhere, embodiments of the invention can also be used to capture glycan- and lectin-containing components in purification fractions during biopharmaceutical and pharmaceutical processes, such as removing LPS / endotoxins, microbial residues and contaminants produced during manufacturing processes or non-product fractions. This can also be applied in recombinant protein / vaccine production to remove host components and concentrate the desired product.

[0103] The devices and methods of the present invention may also be used in conjunction with surgical gloves or other surgical or medical equipment, for example, a device according to the present invention may be applied to the surface of a surgical glove, reducing the possibility of spreading infection during surgery or other care, which is a major source of biocontamination of surgically implanted devices. One example is the use of surgical gloves during catheter implantation. Working Example

[0104] The following non-limiting examples illustrate some embodiments of the present invention.

[0105] Example 1 - Device Fabrication

[0106] Periodate oxidation reaction was carried out to generate active aldehyde groups on the cellulose chain for subsequent attachment of binders. 33 gms of cellulose backbone of 100% cotton material was chemically treated with sodium periodate (Sigma-Aldrich 311448) by immersing it in sodium periodate solution at a concentration of 5.0 mg / ml in 0.1 M acetate buffer (1:50 ratio, w / v). The mixture was kept in the absence of light with gentle shaking at 50 rpm at room temperature for 6 hours for efficient reaction. It is believed that the reaction occurs at the C2-C3 bond of the glucopyranoside ring, resulting in two aldehyde groups at the C2 and C3 positions. The resulting compound is 2,3 dialdehyde cellulose (DAC).

[0107] The material was then washed thoroughly with ice-cold distilled water (three washes, 10 times the absorption volume each time) to remove the periodate oxidant from the treated material. For the addition of binders (lectins, glycoproteins, glycoconjugates, neoglycoconjugates) after chemical treatment, it is believed that the active ingredient chemically attaches to the DAC residues on the cellulose backbone. Binder solutions (1 mg / ml) were prepared by dissolving in PBS at pH 7.4. The above treated cotton material was immersed in the protein solution at a ratio of 1:25 (w / v). The material was incubated at 4°C for 16 hours and then washed three times with 10 times the absorption volume in PBS at pH 7.4.

[0108] Example 2 - Biothreat Pathogens

[0109] Biothreat pathogens (Tularemia tularensis, Clostridium botulinum, Bacillus anthracis (cells and spores)) were harvested and grown to stationary phase and stained for targets. After careful analysis of binding data generated by glycan microarrays as described above and based on comparison with model organisms, glycoproteins / glycoconjugates and lectins were selected for preparation of antibacterial cellulose-based devices. Efficacy testing of activated cellulose-based wipes (manufactured according to Example 1) was performed on plastic / metal / glass surfaces contaminated with the above biothreat pathogens, in comparison with dry wipes and wipes treated with relevant buffers (dH2O, PBS).

[0110] Contaminants were detected at an OD of 2.0 stained with 0.5% crystal violet. 600 The wipes were prepared from overnight cultures of each of the contaminants. 100 μl of each contaminant was placed on each selected test area, 5 cm in diameter, and allowed to dry for 60 minutes. For each of the following experiments, a wipe was placed in the center of the contaminated area and allowed to sit for 10 minutes. After removal of the wipe, the "residual contaminant" on each surface was collected by washing with 0.5 ml of pH 7.4 PBS and analyzed using a series of quantitative methods for enumeration of bacteria remaining on the surface (optical density measurements, colony count PCR).

[0111] For Francisella tularensis (Figure 1), efficacy tests were performed as described above using activated wipes containing fetuin glycoprotein (Figure 1A), asialofetuin glycoprotein (Figure 1B) or lectin GNA (Figure 1C). Residual contamination was monitored with the addition of recovery solutions in appropriate buffers and measurements of absorbance / optical density at 600 nm (OD600). Raw values ​​without surface adjustment are shown. Asterisks indicate data points that are statistically different compared to the "no wipe" condition based on Student's t-test (p<0.05). Error bars represent standard deviation from triplicate experiments. It can be seen that in all cases, the use of "activated" wipes treated with glycoprotein or lectin resulted in significantly less residual bacteria.

[0112] For Clostridium botulinum (Figure 2), efficacy tests were performed with activated wipes containing fetuin glycoprotein (Figure 2A), asialofetuin glycoprotein (Figure 2B) or lectin GNA (Figure 2C). Residual contamination was monitored by adding a recovery solution of the appropriate buffer and measuring the absorbance / optical density at 600 nm (OD600). Raw values ​​without surface adjustment are shown. Asterisks indicate data points that are statistically different compared to the "no wipe" condition based on Student's t-test (p<0.05). Error bars represent standard deviation from triplicate experiments. It can be seen that in all cases except one, the use of "activated" wipes treated with glycoprotein or lectin resulted in significantly less residual bacteria. Figure 2D shows that the 7.32x10 8 Residual bacteria present on the surface after wipe treatment is shown as measured by recovery of colony forming units (cfu) against a reference strain in cfu / ml. For the measurements, the recovered contaminant was serially diluted and 100 μl of each was spread onto agar plates to grow the bacteria. Plates with 30-300 colonies were considered an appropriate range for the calculation.

[0113] For B. anthracis (Figure 3 and Table 4), efficacy tests were performed using activated wipes containing fetuin glycoprotein, asialofetuin glycoprotein, GNA lectin, GSL-I-B4 lectin, PA-I lectin, AMA lectin, or RCA-1 lectin against B. anthracis cells (Figure 3A) or spores (Figure 3B). Residual contaminants after wipe treatment were determined to be 1.21x10 7 cfu / ml (vegetative cells) or 1.31x10 7 The recovery was measured by the recovery of colony forming units (cfu) against a reference strain in cfu / ml (spores). The recovered contaminants were serially diluted and 100 μl of each was spread on agar plates to grow the bacteria. Plates with 30-300 colonies were considered an appropriate range for the calculations. Raw values ​​without surface adjustment are shown. Asterisks indicate data points that are statistically different compared to surfaces without wipes based on Student's t-test (p<0.05). Error bars represent standard deviations from triplicate experiments. These data are also presented in Table 4 (Table 4-1, Table 4-2), which shows the percentage of residual contaminants detected compared to surfaces treated with dry wipes (FET-fetuin, ASF-asialofetuin).

[0114] [Table 4-1]

[0115] [Table 4-2]

[0116] The device of the present invention was also used for influenza virus contamination on glass, plastic and metal surfaces. Briefly, the surfaces were contaminated with 500 μl of virus solution. The supernatant was spread on the surface and allowed to dry for 3 hours. Wipes with fetuin glycoprotein or asialofetuin glycoprotein were used. All surfaces were contaminated three times for each type of wipe. For the wipe test, the wipe was placed in the center of the contaminated area (static). The wipe was left to interact for 10 minutes. After incubation, the wipe was removed and the residues recovered in the contaminated area were evaluated. Each surface was washed with 1 ml of PBS and the recovered liquid was transferred to a sterile Eppendorf tube for viral RNA isolation and quantification of residues from glass (Figure 4A), plastic (Figure 4B) and metal (Figure 4C). The figure shows the amount of virus isolated from the surface compared to the amount detected using only dry wipes. Error bars represent standard deviation from triplicate experiments. Results showed that only 2-28% of the virus particles remained on the fetuin-conjugated wipes after static capture (Table 5), which appeared to reduce residual virus, whereas the asialofetuin-conjugated wipes appeared to have no effect compared to the PBS-treated wipes.

[0117] [Table 5]

[0118] Example 3 - Foodborne Pathogens:

[0119] The device of the invention (manufactured according to Example 1) was also used against bacteria associated with food poisoning on glass, plastic and metal surfaces. Table 6 shows the bacteria tested (E. coli O157:H7 and Enterobacter cloacae) and the lectin bound to the carrier material in each case.

[0120] [Table 6]

[0121] Figures 5A and 5B show the results of efficacy testing for these bacteria. Contaminants were prepared from overnight cultures stained with crystal violet as in the previous examples. 100 μl of contaminant was placed on each selected test area and allowed to dry for 60 minutes. For each of the following experiments, a wipe was placed in the center of the contaminated area and allowed to sit for 10 minutes. Residual contaminant was monitored by measuring fluorescence after SYTO82 (Figures 5A, 5B) staining. Raw values ​​without surface adjustment are shown. Error bars represent standard deviation from triplicate experiments. A contaminated surface that was not wiped was used as a reference. Based on measurements of residual fluorescence after 10 minutes of static testing, the WGA lectin-activated wipes left only 1% of the E. coli O157:H7, while the GSI-B4-activated wipes left 4% of the Enterobacter cloacae. Results showing the efficacy of the control and activated wipes are also shown in Table 7.

[0122] [Table 7]

[0123] Example 4 - Other Skin Pathogens (Bacteria / Fungi):

[0124] Other microorganisms known to colonize the skin are potential targets for the devices of the present invention, including Propionibacterium, Malassezia (formerly known as Pityrosporum), Candida, Aspergillus, Staphylococcus, Streptococcus, Pseudomonas, and Haemophilus influenzae. For illustration purposes, the exemplary device (manufactured according to Example 1) was also used against Propionibacterium acnes and Candida albicans associated with skin diseases and disorders.

[0125] Wipes conjugated with the glycoprotein asialofetuin (ASF) and the lectin WGA were used on a plastic surface contaminated with Propionibacterium acnes (Figure 6) as in the previous example. After 10 min, again performing the static wipe test as in the previous example, 33% of the residual contaminant was observed on the PBS wipe, compared with 15.8% on the ASF wipe and only 9.5% on the WGA wipe, indicating that the WGA wipe was able to capture 90.5% of the contaminant by contact alone (static).

[0126] Wipes conjugated with the lectin ConA were used against plastic surfaces contaminated with C. albicans (Figure 7), and the contamination and wipe tests were performed as described previously. To compare the capture efficacy at various pH levels, wipes with and without the active ingredient (ConA) were prepared using buffers at pH 5, 7, and 9 and a standard pH 7.4. The efficacy of capture by the active ingredient was observed to be similar over a wide range of pH from 5 to 9. Thus, the wipes had comparable efficacy under the selected conditions, and pH changes did not affect the potency of the active ingredient.

[0127] Example 5 - Wound decontamination and care

[0128] A porcine skin model was used to evaluate the device and its effectiveness for capture from biological surfaces. Over the past 20 years, porcine skin has dominated as a human skin model used in human skin disease research. This is due to the similarity of anatomical structure between pigs and humans compared to any other laboratory animal. For example, porcine dermal collagen is more similar to human than other common laboratory animals. Pig skin is well established and studied for use in wound care and infection research of human diseases. The epidermal thickness and structure of porcine skin have strong similarities to human skin. Vascular characteristics and hair follicle types are highly relevant. Strains of E. coli and C. albicans were used as target organisms.

[0129] This method is illustrated in FIG. 8. Briefly, to remove natural contaminants of the pig skin, the section samples were placed in 60°C water for 30 seconds. 100 μl of E. coli (crystal violet stain) or Candida albicans (trypan blue fungal stain) culture at OD 2.0 was pipetted onto each pig sample and left on the skin sample for 30 minutes to dry. After performing the wipe capture test with a device manufactured according to Example 1 with 10 minutes of static contact as described above, 1 ml of LB or yeast medium was added to each pig skin sample and the contaminant mixture was collected. The growth of this mixture was monitored and the remaining E. coli (FIGS. 9A and B) and C. albicans (FIG. 10) were quantified. FIGS. 9A and 9B show E. coli recovered from pig skin after the cotton-based wipe capture test process, and active wipes contained WGA lectin as measured by absorbance at 595 nm (FIG. 9A) or colony forming units (FIG. 9B). FIG. 10 shows C. albicans DSM 6659 recovered from pig skin following a cotton-based wipe capture test process, where active wipes contained ConA lectin or GNA lectin as measured by absorbance after a 15 hour growth period.

[0130] Wipes conjugated with the lectin ConA were used on pig skin sections contaminated with Aspergillus fumigatus. The contamination protocol and wipe test were as previously described. A. fumigatus was recovered from pig skin after the cotton-based wipe capture test process. Active wipes were measured in colony forming units after plating of 1:10 serial dilutions of the remaining contaminants on potato-dextrose agar (Figure 11) and contained ConA lectin. Colony count analysis was performed after 24 hours of incubation at 30°C. Figure 11 shows A. fumigatus Fresenius 819 strain recovered from pig skin after the cotton-based wipe capture test process. Active wipes contained ConA lectin.

Claims

1. a carrier material comprising a carbohydrate-based polymer; i) glycoproteins selected from one or more of the group consisting of uromodulin (Tamm-Horsfall protein), fetuin, asialofetuin, invertase, fibrinogen, alpha-1-antitrypsin, alpha-crystallin, ceruloplasmin, alpha-1-acid glycoprotein, RNAse B, transferrin, beta-lactoglobulin, C.-lactalbumin, B-casein, C-casein, K-casein, lactoferrin, and ovotransferrin; and ii) lectins selected from one or more of the group consisting of AIA / Jacalin, RPbAI, AAL, ABL, ACA, AMA, BPA, CAA, Calcepa, CCA, ConA, CPA, DBA, DSA, ECA, EEA, GHA, GNA, GSL-I-B4, GSL-II, HHA, HPA, Lch-A, Lch-B, LEL, LTA, MAA, MOA, MPA, NPA, PA-I, PCA, PHA-E, PHA-L, PNA, PSA, RCA-I / 120, SBA, SJA, SNA-I, SNA-II, STA, UEA-I, VRA, VVA-B4, WFA, and WGA; and a binder comprising: the binding agent is attached to the carrier material by one or more covalent bonds; said binding agent being capable of binding to a target; The device, wherein the target is one or more of a biotoxin, a virus, an allergen, a microorganism, and a microbial component.

2. i) the carrier material comprises cellulose; and / or ii) the carrier material comprises one or more of cotton and paper; and / or iii) the carrier material is in the form of a cloth, wipe, wound dressing, swab, filter, pad, blanket, mat, mask or coating; and / or iv) The device of claim 1, wherein the carrier material further comprises a buffer.

3. The device of claim 1 or 2, wherein the carrier material comprises a fluid in which it is carried in solution, suspension, dispersion, or emulsion.

4. 4. The device of claim 2 or 3, wherein the carrier material comprises cellulose and the binder is bound to the cellulose by one or more covalent bonds.

5. The device of any one of claims 1 to 4, wherein the binding agent further comprises one or more of an anti-thrombotic agent, an anti-inflammatory agent, an antibody, an antigen, an adhesin, an immunoglobulin, an enzyme, a hormone, a neurotransmitter, a cytokine, a protein, a globular protein, a cell attachment protein, a peptide, a cell attachment peptide, a proteoglycan, a toxin, a polysaccharide, a carbohydrate, a fatty acid, a drug, a vitamin, a DNA segment, an RNA segment, a nucleic acid, a dye, and a ligand.

6. The device of any one of claims 1 to 5, wherein the glycoprotein is one or more of lactoferrin, fetuin, asialofetuin and α-crystallin.

7. The binder may further comprise any one of Blood Group A-BSA, Blood Group B-HSA, Fuc-α-4AP-BSA, Fuc-β-4AP-BSA, 2′fucosyllactose-BSA, difucosyl-para-lacto-N-hexaose-APD-HSA (Lea / Lex), trifucosyl-Ley-heptasaccharide-APE-HSA, monofucosyl, monosialylacto-N-neohexaose-APD-HSA, Gal-β-4AP-BSA, Galα1,3Gal-BSA, Gal-α-1,3Galb1, Gal-β-1,4Gal-BSA, Gal-α-1,2Gal-BSA, 4GlcNAc-HSA, Gal -α-PITC-BSA, Gal-β-ITC-BSA, Glc-β-4AP-BSA, Glc-β-ITC-BSA, GlcNAc-BSA, globotriose-HSA, globo-N-tetraose-APD-HSA, globotriose-APD-HSA, GM1-pentasaccharide-APD-HSA, Asialo-GM1-tetrasaccharide-APD-HSA, globo-N-tetraose-APD-HSA, globotriose-APD-HSA, H-type-II-APE-BSA, H-type-2-APE-HSA, Man-α-1,3 ...6), Man-BSA, Man-α-ITC-BSA, Man-b-4AP-BSA, LacNAc-BSA, LacNAc-α-4AP-BSA, LacNAc-β-4AP-BSA, Lac-β-4AP-BSA, Lac-N-tetraose-APD-HSA, Lacto-N-fucopentaose I-BSA, Lacto-N-neotetraose-APD-HSA, Lacto-N-fucopentaose II-BSA, Lacto-N-fucopentaose III-BSA, Lacto-N-difucohexaose I-BSA, Lewis a-BSA, Lewis x-BSA, Lewis y-tetrasaccharide-APE-HSA, LNDI-BSA / Lewis b-BSA, Di-Lex-APE-BSA, Di-Lewisx-APE-HSA, Tri-Lex-APE-HSA, L-rhamnose-Sp14-BSA, 3'sialyllactose-APD-HSA, 3'sialyllactose-3-fucosyllactose-BSA, 6'sialyllactose-APD-HSA, Xyl-α-4AP-BSA, Xyl-β-4AP-BSA, 3'sialyll Lewis x-BSA, 3'sialyll Lewis a-BSA, 6-sulfo Lewis x-BSA, 6-sulfo Lewis a-BSA, 3-sulfo Lewis a-BSA, 3-sulfo Lewis x-BSA, sialyl-LNF The device according to any one of claims 1 to 6, comprising a glycoconjugate or neoglycoconjugate selected from one or more of the group consisting of V-APD-HSA, and sialyl-LNnT-penta-APD-HSA.

8. 8. The device of claim 7, wherein when the binding agent is a glycoconjugate, neoglycoconjugate, or glycoprotein, the binding agent has terminal residues comprising one or more of mannose, N-acetylglucosamine, N-acetylgalactosamine, N-acetylneuraminic acid, N-glycolylneuraminic acid (sialic acid), galactose, glucose, and fucose moieties.

9. The device of any one of claims 1 to 8, wherein the device further comprises an antimicrobial agent.

10. 10. The device of claim 9, wherein the antimicrobial substance is one or more of a disinfectant, an antibiotic and a detergent, or is silver, copper, or EDTA.

11. 1. A method for removing biotoxins, viruses, allergens, microorganisms and / or microbial components from a surface, gas or liquid, comprising: Providing a device according to any one of claims 1 to 10, and contacting said surface with said device or passing said gas or liquid through said device; The method includes:

12. i) the binding agent binds to the biotoxins, viruses, allergens, microorganisms and / or microbial components to be removed; and / or ii) The method of claim 11, wherein the biotoxin, virus, allergen, microorganism and / or microbial component is a spore.

13. 1. A process for manufacturing a device, the method comprising: Providing a carrier material comprising a carbohydrate-based polymer; treating the support with an oxidizing agent to generate acid and / or aldehyde groups; and the treated support such that the binder is attached to the carbohydrate-based polymer by one or more covalent bonds; i) glycoproteins selected from one or more of the group consisting of uromodulin (Tamm-Horsfall protein), fetuin, asialofetuin, invertase, fibrinogen, alpha-1-antitrypsin, alpha-crystallin, ceruloplasmin, alpha-1-acid glycoprotein, RNAse B, transferrin, beta-lactoglobulin, C.-lactalbumin, B-casein, C-casein, K-casein, lactoferrin, and ovotransferrin; and ii) lectins selected from one or more of the group consisting of AIA / Jacalin, RPbAI, AAL, ABL, ACA, AMA, BPA, CAA, Calcepa, CCA, ConA, CPA, DBA, DSA, ECA, EEA, GHA, GNA, GSL-I-B4, GSL-II, HHA, HPA, Lch-A, Lch-B, LEL, LTA, MAA, MOA, MPA, NPA, PA-I, PCA, PHA-E, PHA-L, PNA, PSA, RCA-I / 120, SBA, SJA, SNA-I, SNA-II, STA, UEA-I, VRA, VVA-B4, WFA, and WGA; with a binder comprising The method, wherein the binding agent further comprises a complex carbohydrate.

14. The oxidizing agent is i) periodate, ii) sodium periodate, or iii) selected from the group comprising 2,2,6,6-tetramethylpiperidine-1-oxyl radical (TEMPO), sodium nitrate or sodium nitrite in phosphoric acid, activator tosyl chloride in the presence of an organic solvent and a base, and combinations thereof; The method of claim 13.

Citation Information

Patent Citations

  • Washing soap

    JP1994505248A

  • antimicrobial composition

    JP1996500588A

  • Immobilized lactoferrin (im-lf) antimicrobial agents and uses thereof

    JP2003500425A

  • Method for removing virus from blood by lectin affinity hemodialysis

    JP2007525232A

  • Methods for extracorporeal removal of pathogenic microorganisms, inflammatory cells or inflammatory proteins from blood

    JP2009521413A