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WO2025198753A1 - Appareil antipathogène à base de poly(2-alkyle-2-oxazoline) et procédé d'utilisation associé - Google Patents

Appareil antipathogène à base de poly(2-alkyle-2-oxazoline) et procédé d'utilisation associé

Info

Publication number
WO2025198753A1
WO2025198753A1 PCT/US2025/015785 US2025015785W WO2025198753A1 WO 2025198753 A1 WO2025198753 A1 WO 2025198753A1 US 2025015785 W US2025015785 W US 2025015785W WO 2025198753 A1 WO2025198753 A1 WO 2025198753A1
Authority
WO
WIPO (PCT)
Prior art keywords
formulation
polymer
percent
monomers
oxazoline
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
PCT/US2025/015785
Other languages
English (en)
Inventor
Mark Oman
Marion L. CHIATTELLO
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Exion Labs Inc
Original Assignee
Exion Labs Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from US18/637,668 external-priority patent/US20240260572A1/en
Priority claimed from US18/638,981 external-priority patent/US20240269333A1/en
Priority claimed from US18/641,922 external-priority patent/US20240268382A1/en
Priority claimed from US18/645,880 external-priority patent/US20240276984A1/en
Priority claimed from US18/663,414 external-priority patent/US20240298629A1/en
Priority claimed from US18/742,592 external-priority patent/US20240324591A1/en
Priority claimed from US18/889,131 external-priority patent/US20250024827A1/en
Priority claimed from US18/940,362 external-priority patent/US20250351822A1/en
Priority claimed from US18/950,493 external-priority patent/US20250073153A1/en
Priority claimed from US18/953,361 external-priority patent/US20250082562A1/en
Priority claimed from US18/964,384 external-priority patent/US20250090446A1/en
Priority claimed from US18/973,785 external-priority patent/US20250099362A1/en
Priority claimed from US18/980,530 external-priority patent/US20250114291A1/en
Application filed by Exion Labs Inc filed Critical Exion Labs Inc
Publication of WO2025198753A1 publication Critical patent/WO2025198753A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N33/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic nitrogen compounds
    • A01N33/02—Amines; Quaternary ammonium compounds
    • A01N33/04—Nitrogen directly attached to aliphatic or cycloaliphatic carbon atoms
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N33/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic nitrogen compounds
    • A01N33/02—Amines; Quaternary ammonium compounds
    • A01N33/12—Quaternary ammonium compounds
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/74—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,3
    • A01N43/76—1,3-Oxazoles; Hydrogenated 1,3-oxazoles
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P1/00—Disinfectants; Antimicrobial compounds or mixtures thereof
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B32—LAYERED PRODUCTS
    • B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
    • B32B33/00—Layered products characterised by particular properties or particular surface features, e.g. particular surface coatings; Layered products designed for particular purposes not covered by another single class
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G73/00—Macromolecular compounds obtained by reactions forming a linkage containing nitrogen with or without oxygen or carbon in the main chain of the macromolecule, not provided for in groups C08G12/00 - C08G71/00
    • C08G73/02—Polyamines
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J5/00—Manufacture of articles or shaped materials containing macromolecular substances
    • C08J5/18—Manufacture of films or sheets
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L39/00—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a single or double bond to nitrogen or by a heterocyclic ring containing nitrogen; Compositions of derivatives of such polymers
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L79/00—Compositions of macromolecular compounds obtained by reactions forming in the main chain of the macromolecule a linkage containing nitrogen with or without oxygen or carbon only, not provided for in groups C08L61/00 - C08L77/00
    • C08L79/02—Polyamines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/54—Biologically active materials, e.g. therapeutic substances
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/16—Biologically active materials, e.g. therapeutic substances
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
    • C08K5/00—Use of organic ingredients

Definitions

  • the invention relates generally to antibacterial / antimicrobial / antiviral / antifungal formulations, solutions, films, coatings, and/or compositions and/or the method of manufacture/use thereof.
  • DISCUSSION OF THE PRIOR ART Bacteria / Virus / Fungus Treatment A number of compositions acting as biocides have been reported. Patents / publications related to the current invention are summarized here. Purschwitz, et. al., “Enhancing the Antimicrobial Activity of Biocides with Polymers”, U.S. patent no.11,666,050 (June 6, 2023), and corresponding U.S. patent application publication no.
  • 2015/0342984 describe antimicrobial, non-hemolytic cationic polyamines. 180030844.1 2 Attorney Docket no. EXNI0001 Hedrick, J. L., et. al., “Cationic Polyamines for Treatment of Viruses”, U.S. patent no. 10,485,824 and corresponding U.S. patent application publication no.2017/0266224 describe antiviral cationic polyamines. Hedrick, J. L., et. al., “Cationic Polyamines for Treatment of Viruses”, U.S. patent no.9,682,100 and corresponding U.S. patent application publication no.
  • 2016/0213707 each describe antiviral cationic polyamines, such as cationic polyamines comprising pendant monosaccharide groups.
  • Hedrick, J. L., et. al. “Therapeutic Compositions Comprising n-alkyl-hydroxy Polymers”
  • U.S. patent application publication no. 2017/0056513 describe polymers modified with n-alkyl-hydroxy groups comprising one or more carbon atoms for antiviral activity.
  • patent application publication no.2023/0108533 describe aqueous coating compositions capable of forming residual antimicrobial coatings comprising non-silane quaternary compounds and quaternary silanes.
  • Gibney, K. “Polymeric Antibacterial Agents: Cytotoxicity and Antimicrobial Properties of Amphiphilic Polymers”, Honors Thesis, Department of Chemistry, University of Michigan, April 28, 2009 describes modifying synthesized polymer structures and observing the effect on antimicrobial activity.
  • U.S. patent application publication no. 2008/0045491 describes an antimicrobial surface sanitizer composition comprising a water-miscible alcohol, water, a weak acid, and a multivalent cation.
  • Figure 1 illustrates a method of tuning a polymer as an antimicrobial agent
  • Figure 2 illustrates tuned charged polymers and tuned counterions
  • Figure 3A and Figure 3B each illustrate tuned cationic polymers
  • Figure 4 illustrates polymer properties/states
  • 180030844.1 5 Attorney Docket no.
  • Figure 5A illustrates a set of polymers
  • Figure 5B illustrates polyethylenimine and polyDADMAC
  • Figure 5C illustrates a copolymer
  • Figure 5D provides an example of a copolymer
  • Figure 6 illustrates polymer protonation tuning
  • Figure 7 illustrates polymer counterion tuning
  • Figure 8 illustrates polymer acidification/alkalization processes
  • Figure 9A illustrates acidification of a polymer
  • Figure 9B illustrates unprotonated and protonated monomers
  • Figure 10 illustrates alkalization of a polymer
  • Figure 11 illustrates a first alkalization polymer tuning process
  • Figure 12 illustrates a second alkalization polymer tuning process
  • Figure 13 illustrates a third alkalization polymer tuning process
  • Figure 14 illustrates a first acidification polymer tuning process
  • Figure 15 illustrates a conjugate base polymer tuning process
  • Figure 16 illustrates a polymer slurry acid reduction process
  • 180030844.1 6 Attorney Docket no.
  • FIG. 17 illustrates a polymer - salt pair salt reduction process
  • Figure 18 illustrates polymer tuning with a weak acid
  • Figure 19A and Figure 19B each illustrate polymer tuning with a weak acid and salt/counterion production
  • Figure 20, illustrates relative concentration of conjugate base tuning
  • Figure 21 illustrates first conjugate base availability determination
  • Figure 22 illustrates second conjugate base availability determination
  • Figure 23 illustrates adjusting conjugate base concentration
  • Figure 24 illustrates relative tuning of two conjugate bases
  • Figure 25A and Figure 25B illustrate two counterion ratios
  • Figure 26 illustrates relative concentration of conjugate base tuning with three counterion types
  • Figure 27 illustrates relative concentration of conjugate base tuning with polyanionic compounds
  • Figure 28 illustrates relative tuning of multiple conjugate bases/counterions
  • 180030844.1 7 Attorney Docket no.
  • Figure 29 illustrates charged chemical backbone structures
  • Figure 30A illustrates a primary amine
  • Figure 30B illustrates a secondary amine
  • Figure 30C illustrates a tertiary amine
  • Figure 30D illustrates a quaternary amine
  • Figure 31A and Figure 31B illustrate deprotonated and protonated repeating units, respectively
  • Figure 31C illustrates a polypropylenimine
  • Figure 31D illustrates a generalized amine polymer
  • Figure 31E illustrates a nitrogen containing repeating backbone monomer of a polymer
  • Figure 32 illustrates conjugate acid formation from a base
  • Figure 33A, Figure 33B, Figure 33C, and Figure 33D illustrate progressively basic to acidic forms of polyethylenimine
  • Figure 34A and Figure 34B illustrate branched polyethylenimine in unprotonated and protonated forms, respectively
  • Figure 35 illustrates a backbone using amino acids
  • Figure 36 illustrates a generic backbone structure
  • Figure 37 illustrates tuning a poly
  • Figure 40A and Figure 40B illustrate two polymer protonation states, respectively;
  • Figure 41 illustrates first and second levels of protonation at a fixed pH;
  • Figure 42 illustrates effective charge of the polymer as a function of activity;
  • Figure 43A illustrates a non-enveloped virus and
  • Figure 43B illustrates an enveloped virus;
  • Figure 44A and Figure 44B illustrate a wrapped and partially wrapped virus;
  • Figure 45 illustrates polymer conglomerations of viruses;
  • Figure 46A illustrates high activity attraction between polyethylenimine and a virus and
  • Figure 46B illustrates attraction between polyethylenimine and a virus at lower activity;
  • Figure 47 illustrates charge control of a liquid biocide and/or a biocidal film;
  • Figure 48A, Figure 48B, and Figure 48C illustrate delivery of a biocide with a spray bottle, a spray canister, and a wipe, respectively;
  • Figure 49 illustrates treating a substrate with a biocide; 180030844.1 9 Attorney Docke
  • Figure 50A and Figure 50B illustrates liquid and solid films, respectively;
  • Figures 50C and Figure 50D illustrate an adhesion promoter in the film and settled out of the film, respectively;
  • Figure 51 illustrates a process of forming polyethylenimine;
  • Figure 52 illustrates a process 5200 of forming a poly(2-alkyl-2-oxazoline);
  • Figure 53A illustrates oxazolines and cationic ring opening polymerization and
  • Figure 53B illustrates a copolymer derived from removal of an acyl group;
  • Figure 54A and Figure 54B illustrate deacylation of poly(2-alkyl-2-oxazoline) and poly(2-ethyl-2-oxazoline), respectively;
  • Figure 55 illustrates purification of a polyalkylenimine;
  • Figure 56 illustrates generation of a formulation;
  • Figure 57 illustrates additive inactivation of bacteria;
  • Figure 58 illustrates preparation/use of a formulation;
  • Figure 59 illustrates adhesion of
  • the method optionally and preferably controls salts/anions of the solution, to enhance the inactivating step, such as measured by conductivity, activity, sodium concentration, organic acid/base types, and/or counterion concentrations/types.
  • the formulation optionally sprayed to form a film, has antivirion, antiviral, antibacterial, and/or antifungal properties that persist through time.
  • the copolymer has monomers in equilibrium with other chemical forms, where the equilibrium is a function of pH of the formulation/process of making the formulation. Any additive to the formulation is optionally used, such as an addition of a quaternary ammonium, a polydiallyldimethylammonium salt, and/or a partially protonated polyethylenimine.
  • the formulation is generally an antipathogen, such as finding applications in a washing machine additive, a hand sanitizer, and/or in at least partial coating of a fabric/garment.
  • the deacylation step optionally and preferably forms an at least partially protonated polyethylenimine. 180030844.1 11 Attorney Docket no.
  • the method optionally and preferably controls salts/anions of the solution, to enhance the inactivating step, such as measured by conductivity, activity, sodium concentration, organic acid/base types, and/or counterion concentrations/types.
  • the formulation optionally sprayed to form a film, has antivirion, antiviral, antibacterial, and/or antifungal properties that persist through time.
  • the copolymer has monomers in equilibrium with other chemical forms, where the equilibrium is a function of pH of the formulation/process of making the formulation. Any additive to the formulation is optionally used, such as an addition of a quaternary ammonium, a polydiallyldimethylammonium salt, and/or a partially protonated polyethylenimine.
  • the formulation is generally an antipathogen, such as finding applications in a washing machine additive, a hand sanitizer, and/or in at least partial coating of a fabric/garment.
  • the deacylation step optionally and preferably forms an at least partially protonated polyethylenimine. 180030844.1 12 Attorney Docket no. EXNI0001
  • EPA refers to the United States Environmental Protection Agency and ISO stands for the International Organization for Standardization. Overview Microbes exist everywhere. While many are beneficial, many have negative consequences.
  • Industries and environments where microbes are optionally and preferably controlled include at least: hospitals, food service areas, public areas, and in the home.
  • PAS2424 The PAS2424 specification is briefly summarized herein for clarity of presentation; however, the entirety of the PAS2424 specification is incorporated in its entirety herein by this reference thereto.
  • the PAS2424:2014 standard quantifies surface testing for the evaluation of residual antimicrobial efficacy of liquid chemical disinfectants on hard/non-porous surfaces.
  • the PAS standard specifies a test method for residual bactericidal and/or yeasticidal activity of liquid, chemical disinfectant products that are applied to hard, non- porous surfaces which are likely to undergo abrasive action. The method described is intended to determine the activity of commercial formulations or active substances under the conditions in which they are used in accordance with BS EN 13697:2001.
  • the entirety of the EPA 01-1A requirements and guidelines are incorporated herein by this reference thereto.
  • the EPA01-1A residual sanitization test method guidelines are: ⁇ the product or products (test substance) being evaluated for efficacy along with the method-specified control substance, are tested in quadruple replicate on 1 x 1 inch glass carriers or stainless-steel carriers.
  • Abrasion of the test surface is done using a standardized Gardco abrasion machine; 180030844.1 14 Attorney Docket no. EXNI0001 ⁇ a residual sanitization test requires a total of 12 alternating wet-dry abrasion cycles and a total of 5 re-inoculations, with a minimum of 15- minute rest times after each abrasion and a minimum of 30-minute dry times after each re-inoculation; ⁇ after the abrasion and re-inoculation wear regimen is complete, the carriers undergo a sanitization (RSS) test (performed at least 24 hours after application of the test product); ⁇ the sanitization test includes inoculating each treated and abraded carrier with test culture, allowing it to sit for the Study Sponsor’s requested contact time, and then neutralizing it in the appropriate neutralizer.
  • RSS sanitization
  • the parallel control carriers are treated in the same manner as in the test carriers; and/or ⁇
  • the product(s) should achieve ⁇ 3-log reduction in ⁇ 5 minutes when compared to the control- treated test surfaces.
  • a testing time is optionally less than or equal to 5, 10, 20, 50, 90, 100, 120, 300, 600, or 720 minutes.
  • a testing time is an elapsed time from inoculating a substrate, coated with an antipathogen, and/or from a time of contacting a pathogen with the antipathogen, until the testing period is terminated, such as with a wash off of the inoculum, a filtering step that separates the antipathogen polymers from the pathogens, and/or neutralization of the antipathogen, such as by altering/neutralizing charged site of the antipathogen polymer and/or by neutralizing the pH, such as by bringing the pH toward neutral by greater than 0.5, 1, 1.5, 2, 2.5 or 3 pH units.
  • the EPA 01-1A procedures for testing against bacteria is modified herein for testing against viruses.
  • ISO 21702 durability test against viruses in summarized here. However, the entirety of the ISO 21702 standard is incorporated herein by this reference thereto. Generally, the International Standard (ISO 21702 : 2019) is 180030844.1 15 Attorney Docket no. EXNI0001 a method for measuring antiviral activity on plastics and other non-porous surfaces of antiviral-treated products against viruses.
  • the ISO 21702 Test Method guidelines are: ⁇ control and treated samples are placed separately in sterile plates; ⁇ 400 ⁇ L of test inoculum is spread over the surface of the samples; ⁇ a 40 mm X 40 mm cover slip is placed on the inoculum and pressed gently such that the inoculum spreads to the edges but does not leak outside the edges ⁇ immediately after inoculation, 10 mL of either the SCDLP broth or other neutralizer is added to the petri dishes comprising 3 untreated test specimens; and/or ⁇ after a contact period of 24 hours, 10 ml of either the SCDLP broth or other neutralizer is added to treated and untreated samples to recover the remaining virus.
  • this neutralizing solution is serially diluted up to 10 dilutions and the infectious titre of the recovered virus is determined either by Plaque assay or by TCID50 assay. Other assays can also be used based on the virus strain.
  • the measuring test method of antiviral activity on porous product, such as textiles, is described in ISO 18184, which is incorporated herein in its entirety by this reference thereto.
  • the JIS : 1922 test method is summarized here. However, the entirety of the JIS 1922 test method is incorporated herein by this reference thereto.
  • the JIS : 1922 test is an antiviral textile test, where: ⁇ control (untreated) and test (treated) fabric samples are placed in the vial containers; ⁇ all vial containers are further kept in the autoclave for sterilization for 15 minutes at a temperature of 121 °C and pressure of 15 psi; 180030844.1 16 Attorney Docket no. EXNI0001 ⁇ immediately after the virus inoculation, 20 ml of Soya Casein Digest Lecithin Polysorbate Broth (SCDLP) is added to 3 control samples; to verify the cell sensitivity and cytotoxic activity, 3 control and 3 treated samples are put in sterilized vial containers.
  • SCDLP Soya Casein Digest Lecithin Polysorbate Broth
  • Vials are agitated using a vortex mixer to extract the remaining virus particles from the sample; and/or ⁇ wash-out viral suspension is further used to make serial dilutions and the infectivity titre of virus is determined either using Plaque assay or TCID50 assay.
  • Parameters for forming and implementing various polymers, such as cationic polymers; techniques for protonating the cationic polymers to achieving maximum charge; and formulation with various counter ions are provided herein.
  • the high performance and safety of products described herein are derived from the inventive use of charged polymers, such as cationic polymers, and their concomitant counter ions, which is starkly different than the current use of toxic small molecule antimicrobial chemicals in the art.
  • the cationic polymer technology is optionally implemented in antimicrobial films capable of inactivating: bacteria, viruses, and/or fungi as demonstrated in ISO 22196 testing resulting in reduction in microbial population by a factor of 10,000 or more (referred to herein as “ > log-4 inactivation”) against a wide range of bacteria and fungus in ten minutes. 5.
  • Antimicrobial films incorporating the cationic polymer technology kill both enveloped and non-enveloped viruses.
  • the cationic polymers, such as described herein show a continuous (additive) killing action against a large population of bacteria, with inactivating > log 7 population, on a 5-day old film, as tested with ISO 22196. 7.
  • Antimicrobial films created with the cationic polymers described herein pass both the EPA 01-1A durability test and the PAS2424 international durability test against, bacteria, virus, and fungi.
  • the protocol of EPA 01-1A is incorporated in its entirety herein as published at: https://www.epa.gov /sites/default/files/2015-09/documents/cloroxpcol_final.pdf.
  • the polymeric antimicrobial films reported herein provide an ongoing continuous killing action, such as for days and/or weeks.
  • the methods and processes taught herein are flexible and adaptable allowing for the creative implementation of new products, all to the benefit of humankind. 180030844.1 18 Attorney Docket no.
  • ISO 22196 is a standard that pertains to the measurement of antibacterial activity on plastics and other non-porous surfaces, which specifies a test method to evaluate the antibacterial activity of such surfaces by measuring the ability of bacteria to survive and multiply on them. Stated again, if a material undergoes ISO 22196 testing and achieves log-4 inactivation, it means that it has demonstrated a strong ability to inhibit or kill bacteria, making it suitable for applications where maintaining a hygienic environment is essential, such as in healthcare facilities, food processing areas, or public spaces.
  • Antimicrobial Action The antimicrobial cationic polymers films described herein provide antimicrobial action in at least one and optionally in all of several ways: 1.
  • a virion comprises a virus.
  • a virion includes the virus elements of an outer protein shell called a capsid and an inner core of nucleic acid.
  • a residual hand sanitizer such as using the cationic polymers described herein, is a beneficial application because hands are the major object of transmission. When contaminated surfaces are touched the transmission is two-fold: first to the individual as he or she touches their face and second to other surfaces, which in turn exposes others. Perhaps the next most important application to offer residual protection is textile clothing. This is because individual’s hand touches their clothing and then they continue to carry the disease-causing germs with them, which exposes others.
  • Protecting surfaces is important but in general it is limited, because there are so many surfaces to be protected. Still, protecting surfaces is important, especially key surfaces such as in healthcare settings and/or in food preparation. Since most viruses are transmitted as an aerosol spray, a truly antiviral face mask could significantly mitigate the transmission of viruses.
  • the polymeric antiviral coatings described herein are optionally and preferably used in an aerosol spray and/or a coating to achieve this. Small molecule germicidal chemical are generally poor at / not capable of creating durable residual antimicrobial films. However, the cationic polymers described herein are applicable to durable applications of residual antimicrobial films.
  • Regulators require that for a residual claim to be made, antimicrobial films must pass in the USA the EPA (01-1A) and internationally the PAS2424 durability protocols; the cationic polymer films described herein more than adequately meet the standards of these tests.
  • the antiviral inactivity of a virus exceeds 10, 20, 30, 40, 50, 60, 70, 80, 90, 99, 99.9, and/or 99.99 percent 180030844.1 21
  • Applications Stakeholders and the EPA are asking for disinfectants that leave a residual antimicrobial coating that "kill" / block disease causing pathogens into the future.
  • the EPA is seeking new disinfectant technologies to offer essentially two things. First, a residual antimicrobial action against a wide spectrum of pathogens, but particularly against viruses; and second, a new technology not based on toxic biocides and that provides residual longer-term protection on surfaces and skin.
  • the methods and processes taught herein meet these standards as they are based on non-toxic polymeric coatings, are applicable to coating a range of surfaces, and leave residual antimicrobial coatings.
  • some examples include of applications of the tuned polymers, described infra, are: (1) consumer and health care products, (2) medical applications, (3) industrial applications, and/or (4) agricultural applications, as further described herein.
  • Consumer and health care products 1.
  • a residual kill hand sanitizer is a preferred application for this new technology.
  • the EPA and other regulators have not approved residual "killing" hand sanitizers due to safety and effectiveness. 180030844.1 22 Attorney Docket no. EXNI0001 Based on methods described herein, an extremely low toxicity, durable, and high killing action residual, polymer-based hand sanitizer has been produced.
  • the viability of such a residual hand sanitizer was demonstrated with a > log-3 kill of bacteria and enveloped virus on artificial skin exposed to a 24 hour durability test as per the PAS2424 international durability protocol.
  • the tuned polymer is optionally used as a textile residual protective film on rinse additives, band-aids, and/or dryer sheets and/or is applied as an aerosol spray.
  • the tuned polymer is optionally used as a spray or wipe disinfectant that inactivates pathogens faster than traditional disinfectants and then forms a self- sanitizing antimicrobial coating on nonporous surfaces.
  • Medical applications of the tuned polymer include, but are not limited to, antiviral face masks, medical device sterilant, medical device hoses, surgical handwash, wound dressings, antimicrobial ointments, and/or reducing biofilms on implants.
  • the highly durable and remarkably non-toxic coatings offered by this technology reduce biofilm accumulation on various implanted medical devices.
  • Agricultural Applications Agricultural examples of applications of the tuned polymer optionally include animal skin care or antimicrobial protection in large feeding operations, which 180030844.1 23 Attorney Docket no.
  • EXNI0001 reduces healthcare acquired infections (HAI) that stem largely from bacteria and or individual illnesses due to viruses.
  • HAI healthcare acquired infections
  • the continuous killing action of the antimicrobial polymeric films/compositions produced by the processes taught herein are a novel approach to acting on bacteria and also, over time, a surface can remain virtually bacteria-free, which reduces the potential for residual (self-generating) bacteria to mutate and become antibiotic-resistant.
  • Tuned Polymer Generally, the polymers described herein are “tuned” in one or more ways as illustrated and described in Figures 1-20. Referring now to Figure 1, polymer tuning 100 is described. Generally, in a first process, a polymer is provided 110. In a second process, the polymer is tuned 120.
  • the process of tuning a polymer is detailed infra; however, generally, repeating units of the polymer are charged 121 and/or repeating unit counter ions are incorporated 122 to, separately and/or in combination, yield an antimicrobial component 123, an antibacterial component 124, an antiviral component 125, and/or an antifungal component 126.
  • the physical state of the tuned polymer is changed 130, such as from a liquid, to a gel, to a solid or vice versa.
  • the resulting tuned polymer is optionally used to treat a substance 140 and/or to treat a material or condition.
  • Optional and preferably methods of tuning the polymer are further described, infra.
  • a protein is substituted for a polymer in any embodiment herein.
  • any backbone chain is substituted for the polymer in any embodiment herein.
  • any organic molecule having a chain of carbons at least 3, 5, 10, 15, 20, 100, 500, or 1000 carbons long is optionally used in place of the polymer as described herein.
  • a backbone molecule is used in place of the polymer 200.
  • a chain of any combination of carbons, oxygens, and nitrogens of any length greater than 2, 5, 10, 20, or 50 atoms is used as a backbone where the backbone is 180030844.1 24 Attorney Docket no.
  • EXNI0001 optionally protonated, has counterions, and/or is tuned according to any of the approaches described herein for tuning a polymer.
  • the tuned polymer is optionally and preferably used in a formulation with other agents, as further described infra.
  • the formulation alters physical and/or chemical properties of the tuned polymer, such as tackiness, film thickness, total charge, total cationic charge, viscosity, porosity, charge density, pH, stability, and the like.
  • a polymer 200 such as provided in the polymer tuning 100 process, is further described.
  • the polymer 200 is optionally tuned to form a tuned polymer 210 having a state of cationic charge, a tuned pH, tuned charge, tuned salts/counterions, tuned combinations of polymers, tuned molecular weight, tuned solubility, tuned viscosity, tuned durability, and/or a tuned surface tension, which are each further described, infra.
  • any one or more of the tuning steps are optionally performed in any order and/or are performed simultaneously, as further described infra.
  • a polymer with repeating cationic units is used as an example herein to describe the chemistry, apparatus, methods, and processes and in particular a specific polymer of polyethylenimine is used to illustrate any polymer with repeating units/monomers that are charged and/or are chargeable.
  • the polymer 200 is optionally a copolymer, where a copolymer is a polymer formed by linking two or more different types of monomers into a single polymeric chain. The process of creating a copolymer is called copolymerization.
  • An example of a copolymer comprising two monomer types is a copolymer comprising: acylated monomers comprising a -COR 1 group attached to a nitrogen of a -N-CH 2 -CH 2 - element, wherein R1 comprises an alkyl group, and protonated monomers comprising a -NH 2 + -CH 2 -CH 2 - group, the acylated monomers and the protonated monomers comprising any order in the copolymer. 180030844.1 25 Attorney Docket no.
  • the polymer is still a copolymer, as the copolymer can optionally have more than two monomer types by definition.
  • the copolymer is a cationic polyamine.
  • Polyethylenimine is also referred to as polyethyleneimine and/or polyaziridine. Polyethylenimine is a polymer with repeating units composed of the amine group and two carbon aliphatic CH2CH2 spacers.
  • any number of the nitrogens in polyethylenimine are protonated to yield a localized positive cationic charge, which is typically associated with an anionic counterion.
  • polyethylenimine is optionally protonated at any number of sites.
  • the tuned polymer 210 is optionally and preferably cationic 211 and/or has repeating cationic polymer units; however, the polymer 200 is optionally anionic and/or has repeating anionic polymer units; and/or has a functional group that is optionally subjected to a chemical reaction to form a cationic, anionic, and/or zwitterionic repeating group on repeating sections of the polymer 200.
  • An anionic polymer comprises a long chain of carbon atoms with negatively charged groups of ions attached along the chain.
  • the negatively charged spots act like hooks that attract positively charged particles.
  • the polymer 200 is optionally and preferably tuned; optionally and preferably the formulation that contains the polymer is optionally tuned to any of the below described levels of the tuned polymer 210, such as in terms 180030844.1 26 Attorney Docket no. EXNI0001 of viscosity, durability, surface tension, and/or in terms of effectiveness against any microbe, bacteria, virus, and/or fungus.
  • the polymer 200 is optionally and preferably pH tuned 212 to a desired pH, such as: in a range with a pH greater than 2, 3, 4, or 5; to a pH less than 14, 12, 10, 8, 7, or 6; in a pH range of 2-10, 3-9, 3-8, 3-7, and/or 4-6; to a pH within any of ⁇ 0.25, 0.5, 0.75, 1.0, or 2 of any of 3, 4, 5, 6, or 7; and/or any combination of these pH ranges.
  • a desired pH such as: in a range with a pH greater than 2, 3, 4, or 5; to a pH less than 14, 12, 10, 8, 7, or 6; in a pH range of 2-10, 3-9, 3-8, 3-7, and/or 4-6; to a pH within any of ⁇ 0.25, 0.5, 0.75, 1.0, or 2 of any of 3, 4, 5, 6, or 7; and/or any combination of these pH ranges.
  • the polymer 200 is optionally and preferably tuned to a charge, such as in a range of 1*10 -20 to 1*10 -12 coulombs/molecule and more preferably in a range of 1*10 -18 to 1*10 -14 coulombs/molecule; coulombs abbreviated as C.
  • a charge such as in a range of 1*10 -20 to 1*10 -12 coulombs/molecule and more preferably in a range of 1*10 -18 to 1*10 -14 coulombs/molecule; coulombs abbreviated as C.
  • C coulombs abbreviated as C.
  • between 10 and 90 percent of the secondary amines of polyethylenimine 250 are positively charged or the same percentage of any protonatable group of the polymer 200. More preferably, greater than 15, 20, 25, or 30 percent of the nitrogens, or protonatable groups, are positively charged and/or less than 80, 70, 60, 50, or 40 percent of the protonatable groups are charged.
  • a total cationic charge is a charge of all of the positively charged groups, such as cationic sites, which does not include anionic charge from any counterion and/or any anion on the polymer.
  • cationic sites in a dose of dispensed contents from a container comprise a total cationic charge and anionic sites in the dose of dispensed contents comprise a total anionic charge, which are optionally equal or nearly equal in terms of absolute charge.
  • a total cationic charge such as a total cationic charge from present cationic sites, is used in a biocide treatment, such as in a unit of liquid dispensed and/or in a film formed is greater than 0.2, 0.4, 0.6, 0.8, 1, 1.2, 1.4, or 1.8 coulombs and/or is less than 100, 75, 50, 25, 10, or 5 coulombs, such as where a unit of fluid delivered is within 10, 25, or 50% of any of 0.1, 0.2, 0.5, 1, 2, 3, 5, or 10 mL.
  • the total cationic charge per spray is optionally and preferably greater than 0.1, 0.2, 0.3, or 0.5 C and/or less than 8, 7, 6, 5, or 4, 3, or 2 C.
  • a preferred total cationic charge per polymer is optionally tuned, such as in a range of 1 to 5000, 5 to 3000, and/or 1000 to 2500 positively charged sites per polymer chain.
  • any of the charges per molecule are optionally reduced by 10, 20, 30, 40, 50, 60, 70, 80, 90, or more percent as the total chain lengths of polymer decreases from thousands to hundreds to tens.
  • a percentage of a total cationic charge from cationic sites in an aliquot of sample/product in a composition and/or on/in a film from a cationic polymer is optionally greater than 1, 2, 5, 10, 25, 50, or 75 percent and/or is less than 100, 99, 95, 90, or 80 percent.
  • a concentration of salt in the composition is optionally greater than or less than 0, 10, 100, 250, 500, 1000, 2000, 5000, or 10,000 ppm. Charges, total charges, and effective charges are further described, infra.
  • the polymer 200 is optionally salt/counterion tuned 214 with one or more salt anions in solution; salt cations in solution, and/or counterions, which are optionally anionic or cationic; electrostatically and/or attracted via charge to charges, such as protons on monomers of the polymer 200, as further described infra. Still referring to Figure 2, the polymer 200 optionally has a tuned combination of polymers 215, such as a mix of molecular weights, polymer types, and/or types of counterions associated with each individual polymer or set of polymers.
  • the tuned combination of polymers 215 optionally contains a polymer or a group of polymers where one or both are antimicrobial, antibacterial, antiviral, a biocide, and/or antifungal.
  • the polymer 200 optionally has a tuned molecular weight 216. Longer chains have advantages like higher charge and/or complexing more than one object, such as a virus. Shorter chains have advantages, such as more precise charge. In general, the molecular weight of the polymer is greater than 100, 1000, 10,000, or 100,000 g/mol; less than 5,000,000, 1,000,000, or 500,000 g/mol; and/or within 5, 10, 25, or 50 percent 180030844.1 28 Attorney Docket no.
  • viscosity of a formulation is tuned with molecular weight of the polymer with or without a traditional viscosity/thickening tuning substance.
  • the polymer 200 is optionally solubility tuned 217, such as by adjusting pH of the solution, monomer size, monomer functional groups, length of the polymer 200, size of counterions, degree of salt, activity of the solution, and/or through use/application of any agent designed to complex the polymer 200 and/or attract the polymer 200 to a surface, such as the surface of a treated product, any of which may be expressed at solubility of the polymer 200 in g/L.
  • the solution optionally and preferably contains greater than or less than 0, 1, 2, 3, 5, 10, 15, 20, 25, 50, 75, or 95 percent water and/or any solvent such as ethanol and/or isopropanol.
  • the polymer 200 and/or polymer formulation is optionally viscosity tuned 218, such as in a range of centipoise units.
  • centipoise is expressed in units of poise, m 2 /s, Newton-second per square meter, and equivalents thereof.
  • Optional ranges of viscosities of the polymer 200 and/or a formulation containing the polymer in centipoise is near water in a range of 1-5, that of blood or 15 centipoise, that of corn syrup or 50- 100 centipoise, that of motor oil 150 to 500 centipoise, than of syrup or 1000- 3000 centipoise, that of molasses to peanut butter or 5000 to 200,000 centipoise, or higher in a more solid state, such as lard to window putty or 1,000,000 to 100,000,000 centipoise, and/or within 10, 25, 50, 75, or 100% of any of these levels.
  • an additional component in a formulation is optionally used to tune viscosity, such as a polyDADMAC.
  • the polymer 200 and/or polymer formulation is optionally durability tuned 219 according to any metric, such as durability metrics in PAS2424 and/or in the more rigorous U.S. 01-1A tests, referenced supra.
  • a durability test is to whether or not a treated substance still passes an EPA test, such as effectiveness against a microbe, bacteria, 180030844.1 29 Attorney Docket no. EXNI0001 virus, and/or fungus after a series of web rub then dry cycles, such as 6 to 12 cycles, at a testing pressure, such as about 5, 10, 15, or 20 pounds of pressure plus or minus 25 or 50 percent.
  • Optional tests for determining effectiveness of antimicrobial and/or antiviral agents include: (i) a germicidal spray test according to American Society for Testing and Materials (ASTM) international method E1153 that meets the Environmental Protection Agency (EPA) requirement of log 3 reduction for viruses and log 5 reduction for bacteria, (ii) a spray or film killing at least one of: (ii-a) at least 95% of log 5 population, in 30 minutes, of at least one of a gram positive bacteria and a gram negative bacteria; (ii-b) at least 95% of log 4 population of an enveloped virus within 30 minutes of contact; (ii-c) at least 95% of a non-enveloped virus within 30 minutes of contact; and (ii-d) at least 94% of a log 4 population of Clostridium difficile bacteria within 24 hours of contact, in accordance with Japanese Industrial Standard (JIS) Z 2801 (2006) test for antimicrobial activity, or a modified version of such test, and (iii) a durability test comprising at least one of: (
  • Test (i) refers to ASTM E1153, the entire contents of which are incorporated herein by this reference thereto, which is a germicidal spray test that is used to evaluate the antimicrobial efficacy of one-step cleaner-sanitizer formulations recommended for use on lightly soiled, inanimate, nonporous, and/or non-food contact surfaces.
  • Test (ii) is a suspension test in accordance with ASTM E1052-96 (2002) or ASTM E2315 (2016), included in its entirety by this reference thereto, to determine effectiveness of an antimicrobial solution that is in the form of a suspension against specific viruses, such as adenovirus, coronavirus, influenza viruses, rhinovirus, and/or rotavirus.
  • test (iii) the ability for a film formed from the antimicrobial composition to kill gram positive and gram negative bacteria, an enveloped virus, a non- enveloped virus, and/or Clostridium difficile bacteria can be tested in accordance with the conditions set forth in JIS Z 2801, which is known as the Japanese Industrial Test for Antimicrobial Activity and Efficacy in Antimicrobial Products, and identical ISO 22196, the entire contents of which are incorporated herein by this reference thereto.
  • JIS Z 2801 test method is used to assess the antibacterial effectiveness on materials such as plastics, ceramics, glass, and other non-porous materials.
  • a film formed from an antimicrobial composition of at least one embodiment of the present invention kills: (iii-a) at least 95% of a log 5 population of a gram positive and/or a gram negative bacteria in 30 minutes, (iii-b) at least 95% of a log 4 population of an enveloped virus within 30 minutes of contact, (iii-c) at least 95% of a non- 180030844.1 31 Attorney Docket no. EXNI0001 enveloped virus within 30 minutes of contact, and/or (iii-d) at least 94% of a log 4 population of Clostridium difficile bacteria within 24 hours of contact.
  • a film formed from an antimicrobial composition meets 1, 2, 3, or 4 of the requirements (iii-a)-(iii-d).
  • the polymer 200 and/or polymer formulation is optionally surface tension tuned 220 to a range of 0.001 to 0.3 N/m; to greater than 0.01, 0.02, 0.03, 0.04 N/m; less than 0.3, 0.2, 0.1 N/m; and/or to within 10, 25, 50, 75, or 100% of 0.01, 0.02, 0.03, 0.04, 0.06, 0.08, or 1.0 N/m.
  • a starch, slurry, paste, and/or binding agent is optionally used to increase the surface tension of the polymer 200.
  • the polymer 200 is optionally tuned to form a tuned polymer counterion 230, where each of one or more counterions have antimicrobial 231, antibacterial 232, antiviral 233, and/or antifungal 234 properties.
  • antimicrobial 231 is one or more of antibacterial 232, antiviral 233, and/or antifungal 234.
  • a biocide is antimicrobial 231, antibacterial 232, antiviral 233, and/or antifungal 234.
  • a tuned cationic polymer 300 is described, which is an example of a polymer 200.
  • linear polyethylenimine 250 (PEI) or polyaziridine is used as an example of a polymer 200, a polyalkylenimine, and/or a protonated polymer 240.
  • polyethylenimine 250 is used as a general case of linear polyethylenimine and/or branched polyethylenimine, which are further 180030844.1 32 Attorney Docket no.
  • polyethylenimine 250 refers to any unprotonated, partially protonate, or fully protonated version of polyethylenimine.
  • the polymer 200 includes any derivative of polyethylenimine 250 and/or any derivative of a polyalkylenimine.
  • an alkyl group such as in polyalkylenimine, is an alkane missing one hydrogen.
  • polyethylenimine is optionally and preferably protonated at any number of sites, such as at any given or any given set of secondary amine sites.
  • the protonated sites are optionally and preferably associated with anionic counterions; however, the total cationic charge of the protonated sites is determined by looking at only the cationic sites.
  • the polyalkylenimine is optionally polyethylenimine and/or is a mixture comprising at least 1, 2, 5, or 10 percent polyethylenimine, less than 1, 2, 5, or 10 percent polyethylenimine, and/or no polyethylenimine.
  • a suitable cationic polymers include a polydiallyl- dialkylammonium salt an acryloxyalkyltrialkylammonium salt, (e.g.
  • acryl- oxyethyltrimethylammonium halide and methacryloxyethyltrimethylammonium halide a vinylphenalkyltrialkylammonium salt (e.g. vinylbenzyltrimethyl-ammonium halide), an acrylamidoalkyltrialkylammonium salt (e.g., 3-acrylamido-3- methylbutyltrimethylammonium halide), a poly(acrylamide-co- diallyldialkylammonium salt) (e.g., poly(acrylamide-co- diallyldimethylammonium chloride)), a polyethylenimine-based polymer, chitosan, or a combination thereof.
  • a vinylphenalkyltrialkylammonium salt e.g. vinylbenzyltrimethyl-ammonium halide
  • an acrylamidoalkyltrialkylammonium salt e.g., 3-acrylamido-3- methylbuty
  • each alkyl group is the same or different and is a straight chain c1-6 or branched c3-6 (e.g., methyl, ethyl, t-butyl) group
  • the salt is an anion, such as a halide (e.g., chloride, fluoride, bromide), a halide-containing anion (e.g., bis(trifluoro- methane)sulfonimide, trifluoroacetate), a sulfate, and/or a phosphate.
  • the cationic polymer is a polydiallyldialkylammonium salt (e.g., polydiallyldimethylammonium halide), a poly(acrylamide-co- diallyldialkylammonium halide) (e.g., poly(acrylamide-co- diallyldimethylammonium chloride)), and/or a polyethylenimine-based 180030844.1 33 Attorney Docket no. EXNI0001 polymer (e.g., linear, non-chemically modified PEl).
  • a polydiallyldialkylammonium salt e.g., polydiallyldimethylammonium halide
  • a poly(acrylamide-co- diallyldialkylammonium halide) e.g., poly(acrylamide-co- diallyldimethylammonium chloride)
  • a polyethylenimine-based 180030844.1 33 Attorney Docket no. EXNI0001 polymer (e.g.,
  • the composition does not contain a bridged polycyclic compound (e.g., a cavitand structure), including a polymer-bound bridged polycyclic compound (e.g., a polymer-bound cavitand).
  • a bridged polycyclic compound e.g., a cavitand structure
  • the cationic polymer is not a hybrid material that comprises one or more divalent metals and siloxane bridges.
  • an alkyl group is an alkane missing one hydrogen.
  • a combination of two or more cationic polymers are used in a composition, such as selected from a polydiallyldialkylammonium salt (e.g., polydiallyldimethylammonium halide), an acryloxyalkyltrialkylammonium salt, a vinylphenalkyltrialkylammonium salt, an acrylamidoalkyltrialkylammonium salt, a poly (acrylamide-co- diallyldialkylammonium halide), a polyethylenimine-based polymer, and/or chitosan are used in the composition.
  • a polydiallyldialkylammonium salt e.g., polydiallyldimethylammonium halide
  • an acryloxyalkyltrialkylammonium salt e.g., polydiallyldimethylammonium halide
  • an acryloxyalkyltrialkylammonium salt e.g., polydiallyldi
  • a polydiallyldialkylammonium salt such as a polydiallyl-dimethylammonium halide
  • a polyethylenimine based polymer e.g., a linear or branched polyethylenimine (PEl)
  • PEl polyethylenimine
  • polydiallyl-dimethylammonium chloride or poly(acrylamide-co- diallyldialkylammonium chloride) is used in combination with a non-chemically modified linear PEI and/or a polyethylenimine only chemically modified to adjust protonation.
  • the cationic polymer is a polydiallyldialkylammonium salt, such as a polydiallyldialkylammonium halide (e.g., a halide or halide- containing anion), a polydiallyldialkylammonium sulfate, or polydiallyl- dialkylammonium phosphate.
  • a polydiallyldialkylammonium salt such as a polydiallyldialkylammonium halide (e.g., a halide or halide- containing anion), a polydiallyldialkylammonium sulfate, or polydiallyl- dialkylammonium phosphate.
  • the halide can be any suitable compound in which the anion is a halide or includes a halide (e.g., bis(triflouromethane)sulfonimide, trifluoroacetate), such as, polydiallyldimethylammonium fluoride, polydiallyldimethylammonium chloride, polydiallyldimethylammonium bromide, polydiallyldimethylammonium iodide, polydiallyldimethylammonium bis(triflouromethane)sulfonimide or a combination thereof.
  • a halide e.g., bis(triflouromethane)sulfonimide, trifluoroacetate
  • the polydiallyldimethyl-ammonium halide is polydiallyldimethylammonium fluoride, polydiallyldimethyl-ammonium chloride (polyDADMAC), or a mixture of polydiallyldimethyl-ammonium chloride and polydiallyldimethylammonium fluoride and/or polydiallyldimethylammonium bis(triflouromethane)sulfonimide.
  • Preferred polydiallyldialkylammonium salts are those polymers made from polymerization of diallyldialkylammonium compounds, which can be represented by the following formula: in which R1 and R2 are the same or different and each is hydrogen or C1-C6 alkyl; R 3 and R 4 are, independently, hydrogen or an alkyl, hydroxyalkyl, carboxyalkyl, carboxyamidalkyl or alkoxyalkyl group with 1 to 12 carbon atoms; and Y- represents an anion such as a halide, a halide-containing anion (e.g., bis(triflouromethane)sulfonimide), a sulfate, or a phosphate.
  • R1 and R2 are the same or different and each is hydrogen or C1-C6 alkyl
  • R 3 and R 4 are, independently, hydrogen or an alkyl, hydroxyalkyl, carboxyalkyl, carboxyamidalkyl or alkoxyalkyl
  • diallydialkylammonium monomer examples include diallyldimethyl-ammonium chloride (DADMAC), diallyldimethylammonium fluoride, diallyl-dimethylammonium bis(triflouromethane)sulfonimide, diallyldimethyl-ammonium bromide, diallyldimethylammonium sulfate, diallyldimethyl-ammonium phosphate, dimethyallyldimethylammonium chloride, dimethyallyl-dimethylammonium fluoride, dimethyallyldimethylammonium bis(triflouromethane)sulfonimide, diethylallyldimethylammonium chloride, diethyIallyldimethylammonium fluoride, diethylallyldimethylammonium bis(triflouromethane)sulfonimide, diallyldi(beta-hydroxyethyl) ammonium
  • the cationic polymer is polyDADMAC.
  • the polyethylenimine 250 or protonated polymer 240 is illustrated with repeating monomers, which have a carbon-carbon-nitrogen backbone, which are representative of any repeating background and/or monomer, dimer, or trimer of the polymer 200.
  • the nitrogens are optionally protonated 310, where protonation increases with decreasing pH and decreases with increasing pH.
  • protonation of the polyethylenimine 250 is about 60 ⁇ 5 percent; however, protonation is variable with treatment of the polyethylenimine 250, as further described infra.
  • any protonation 310 level of the polymer 200 is optionally used, such as within 1, 2, 5, or 10% of 30, 40, 50, 60, or 65 percent.
  • the protonation 310 sites of the protonated polymer 240 are associated with counterions 320.
  • polyethylenimine 250 is manufactured, polyethylenimine 250 is provided in hydrochloric acid, so the far dominant conjugate base counterion is the chloride ion 322, such as at greater than 98, 99, 99.5, or 99.9 percent of the counterions. Methods of exchanging the chloride counterion 322 with another counterion are described infra.
  • polyethylenimine 250 is manufactured in a “free base” form, such as a solid with a pH greater than 9, 10, 11, 12, or 13, where protonation 310 is very low, such as less than 20, 10, 5, 3, 2, 1, or 0.1 percent.
  • Another counterion is optionally formate 324, which has at least antibacterial and/or antiviral properties, such as in combination with the protonated polymer 240, such as polyethylenimine 250.
  • Still another counterion is optionally acetate 326, which has at least antiviral properties, such as with the protonated nitrogen and/or a protonated amine, such as in the repeating monomer of the polymer 180030844.1 36 Attorney Docket no. EXNI0001 200.
  • Formate 324, acetate 326, citrate- and citrate 2- 327 are all examples of weak acids, organic acids, and conjugate bases, such as of carboxylic acids 321.
  • sulfonate 328 which is at least antimicrobial in combination with polyethylenimine 250 and/or with a cationic polymer.
  • any anion conjugate base is optionally used as the counterion 320, such as: iodide, I-, bromide, Br-, a form of citrate- or citrate 2- , nitrate ion, NO3-, sulfate ion, SO4 2- , nitrite, NO2-, hydrogen carbonate, HCO3-, hydroxide ion, OH-, sulfide ion, and S 2- .
  • any combination of 1, 2, 3, or more counterions are optionally and preferably associated with the polymer 200, such as at a charged site of the repeating monomers, such as at the protonated sites 310, and/or as functional groups that are chargeable with a reaction, such as a secondary amine in polyethylenimine 250.
  • the ratio of the 1, 2, 3, or more counterions are optionally controlled at any ratio. For instance, two different counterions are optionally controlled at a ratio of greater than 1:0, such as greater than 1:0.01, 1:0.05, 1:0.1, 1:0.2, 1:0.3, 1:0.4, or 1:0.5 and/or at a ratio of less than 0:1.
  • n counterions are optionally held/produced at any ratio 0:1 to 0:1 to 0:1 for the relative concentrations of the three, or indeed n, counterions, where n is a positive integer greater than 1, 2, 3, 4, or 5.
  • the ratio of three counterions is 0.1 to 0.3 to 0.6; 0.33 to 0.33 to 0.33; or any set of ratios.
  • any of the n counterions optionally and preferably are selected for one or more of the properties of being antimicrobial 231, antibacterial 232, antiviral 233, and/or antifungal 234.
  • the additional counterions 320 of iodide 325, I-, and citrate 327 in an optional basic form of citrate 2- are illustrated.
  • the tuned polymer 210 is optionally dried into a film, is a semi-solid, and/or contains a level of salt, in solid and/or ionic form about the tuned polymer 210.
  • a salt solution 330 about the tuned polymer 210 optionally contains a set of ions 332, a set of one or more cations, represented as X + 332, and/or a set of one or more anions, represented as Y- 334.
  • Tuning the type and concentration of each member of the sets the cations 332 and anions 334 tunes the chemical activity coefficient, ⁇ , such as according to any version of the Debye-Hückel equation. Tuning the activity coefficient to 180030844.1 37 Attorney Docket no.
  • EXNI0001 a value less than 0, 0.1, 0.2, 0.3, 0.4, 0.5; to greater than 1, 0.9, 0.8, 0.7, or 0.6; and/or in a range of within 1, 2, 5, 10, 20, or 30% of 0.7, 0.8, 0.9, 0.92, or 0.95 alters the ability of the ability of the charges on the polymer repeating units and/or their associated counterions to kill, bind with, react with, hold onto, block, and/or hinder function of the antimicrobial 231, antibacterial 232, antiviral 233, and/or antifungal 234.
  • control of salt about the polymer 200 and/or the at least partially protonated repeating units of the polymer 200 tunes the antimicrobial 231 and/or biocide function of the tuned polymer 210.
  • Preferred activity coefficients are greater than 0.7, 0.8, 0.85, 0.9, 0.95, 0.97, 0.98, 0.99 and/or less than 1.000, 0.999, 0.998, or 0.996. Referring now to Figure 4, the polymer 200 is further described.
  • the polymer 200 is in a state comprising one or more of: a charged repeating unit 402; an uncharged repeating unit 404 and/or section; is cationic 406; is anionic 408; is a zwitterion; has a cationic repeating unit 410, has an anionic repeating unit 412; has a repeating amine 414; has a repeating chargeable monomer or polymer section; has a repeating unit with a pKa in a range of three to six 416; is in a basic form 418, such as at a pH >7; is in a pH neutral form; is in an acidic form 420, such as at a pH ⁇ 7; has a fixed charge 422, such as per unit length of the polymer 200; and/or is partially protonated 424, such as on average every 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more sets of repeating monomers.
  • a charge of a monomer and by extension a polymer is optionally measured and/or is preferably calculated using the Faraday constant, which is a quotient of the electric charge, such as in Coulombs, per amount, such as per mole.
  • the Faraday constant is often expressed in C/mol and/or is 96,485 C/mol.
  • charges of the solution, formulation, and/by extension dried films are optionally calculated using the Faraday constant, concentrations of the formulation components, and/or a mass/volume of the formulation elements used in a volume of the formulation.
  • the polymer 200 is optionally a group of polymers 500, such as a first polymer 502, a second polymer 504, a third polymer 506, or n polymers 508, where each of the n polymers differ by any state property, such as any of the polymer states described above.
  • the polymers 200 in a formulation comprise a set of polymers 510.
  • PolyDADMAC is also referred to as poly(diallyldimethylammonium chloride), a poly(diallyldimethylammonium Y-), where Y- is an anion, a poly(diallyldimethylammonium salt), where the salt is a chloride, fluoride, and/or an anion, and/or is referred to as a polydiallyldimethylammonium chloride, which contains a homopolymer of diallyldimethylammonium chloride.
  • Molecular weights of polyDADMAC are optionally hundreds to millions, but are preferably in a range of 1, 2, 3, 4, 5, 6, 7, 8, or 9 hundreds of thousands of grams/mol.
  • a copolymer 520 is described.
  • a copolymer has two or more different types of monomers linked into a single polymeric chain.
  • the copolymer 520 has a first copolymer monomer 522, a second copolymer monomer 524, and optionally a third copolymer monomer 526.
  • any number, n, of monomers 528 are optionally present in the copolymer 520, where n is a positive integer of two or more.
  • the monomers are optionally arranged in any repeating and/or random order in the copolymer.
  • any polymer such as the first polymer 502 is optionally a copolymer. 180030844.1 39 Attorney Docket no. EXNI0001
  • the copolymer 520 comprises a first copolymer monomer 5260 that includes an acyl group with an ethyl hydrocarbon chain 5261 linked/attached to a nitrogen in a polymer backbone group comprising - NCH2CH2-.
  • the copolymer 520 also comprises a second copolymer monomer comprising a -NHCH2CH2- group 5270 and a third copolymer monomer comprising a -NH 2 + CH 2 CH 2 - group 5280.
  • the second and third monomers in this example are acid base pairs, and as such are pH dependent in terms of relative concentration.
  • any one or more elements/steps of one of the processes is optionally used in combination with any one or more elements/steps of another one of the processes to form the tuned polymer 210.
  • the tuned polymer 210 is formed, such as by controlling/adjusting pH 610.
  • the polymer is provided 110.
  • polyethylenimine 250 also referred to as polyethyleneimine and/or polyaziridine, is used to illustrate any polymer 200.
  • the pH is adjusted 610.
  • the pH of the polymer 200 is adjusted, the pH of an aqueous solution containing the polymer is adjusted, and/or a pH of the polymer in any physical state, such as in a gel state, is pH adjusted.
  • a base is added 620, such as by addition of sodium hydroxide 622 in any form or concentration. Any base is optionally used in this case to reduce protonation of the polyethylenimine 250.
  • an acid is added 630, such as by addition of hydrochloric acid 632 in any form or concentration. Any acid is 180030844.1 40 Attorney Docket no. EXNI0001 optionally used in this case to increase protonation of the polyethylenimine 250.
  • an acid/conjugated base 640 and/or linked pair of acid and conjugate base is used to adjust the pH 610.
  • formic acid also referred to as methanoic acid
  • methanoic acid to an acidic solution below the pKa of formic acid will increase the pH of the solution, deprotonate the polyethylenimine 250, and add a counterion of formate.
  • addition of formic acid to a basic solution above the pKa of formic acid will decrease the pH of the solution, protonate the polyethylenimine 250 and/or add a counterion of formate. Adjustment of pH to tune protonation of the polyethylenimine 250 is further described, infra.
  • protonation is tuned 650.
  • protonation of the polyethylenimine 250 is tuned to less than one hundred percent 662, to a protonation range 664, and/or to greater than ten percent protonation 666.
  • Preferred protonation ranges are: greater than 0.1, 1, 5, 10, 15, 20, or 30 percent; less than 100, 99, 90, 80, 70, 60, or 50 percent; and/or in a range of ⁇ 0, 1, 5, 10, 15, 20, 25, or 50 percent of any of 30, 35, 40, 45, 50, 55, 60, 65, or 70 percent, where any combination of ranges described herein are optionally used, such as 35-45 percent and/or 30-40 ⁇ 5 percent on either end.
  • a protonation range of 20-65 percent is the preferred state of the tuned protonation 650.
  • a step of drying 660 is optionally used.
  • the drying step 660 forms an at least partially dried substance/product 670, such as a where a film is formed 672, a form or semi- crystalline solid is formed 674, a semi-solid 676 / gel is formed, a wet film, a dry film, and/or an antimicrobial substance 678 is formed/concentrated.
  • the drying step 660 increases the concentration of the polyethylenimine 250, the counterions 320, and/or the salt solution 330.
  • the drying step 660 is optionally used to remove a product, such as propionic acid, as further described infra.
  • a product such as propionic acid, as further described infra.
  • greater than 1, 2, 3 and/or less than 99, 98, or 97 percent of the propionic acid is removed. 180030844.1 41 Attorney Docket no. EXNI0001
  • the tuned polymer 210 is formed by controlling and/or adjusting pH 610 to yield a tuned counterion solution 700 / formulation.
  • the steps of tuning the protonation 650, illustrated in Figure 6, are optionally and preferably performed in combination with the steps of tuning the counterion solution 710.
  • a process of tuning the counterion 710 optionally includes any process of controlling one or more counterion types, counterion concentrations, ions, and/or molecules associated with cations or charges on the repeating units of the polymer 200.
  • Exemplary methods of tuning the counterion 710 comprise: (1) adding sodium hydroxide 622, in any concentration, for replacing chloride counterions with hydroxide counterions 623 on the polyethylenimine 250; (2) adding hydrochloric acid 632, in any concentration, to protonate the polyethylenimine 250, a secondary amine, and/or any protonatable functional group of the polymer 200; (3) adding a conjugate base of an organic acid 642 to replace the chloride counterion with the conjugate base anion 643, where more generally the conjugate base anion optionally displaces any counter anion associated with the polyethylenimine 250; (4) adding salt, such as where the chloride ion, the anion 334, Y-, or indeed any counter anion is replaced with one or more added salt anions; (5) adding an anion 740 where the counterion associated with polyethylenimine 250 is replaced by the anion 334, Y-, and/or (6) using any substitution method(s) of anions, such as via
  • the resulting solution / compound / formulation is optionally dried 660 to form at least a partially dried product 670, as described supra.
  • the added formate anion is used to replace a counterion associated with polyethylenimine 250, such as the chloride ion, such as when starting with a protonated form of polyethylenimine 250 in hydrochloric acid, as further described infra.
  • a carboxylic acid and/or a conjugate base of a carboxylic acid 321 is optionally used to displace the chloride ion, such as in step three of the previous paragraph, and/or more generally to supply a counterion.
  • formic acid a carboxylic acid
  • acetic acid also a carboxylic acid
  • acetate a conjugate base of acetic acid
  • Additional carboxylic acids that are optionally used to supply counterions and/or other counterions isolated from carboxylic acid include any of: acetic acid (ethanoic acid); formic acid (methanoic acid); citric acid; propionic acid (propanoic acid); butyric acid (butanoic acid); benzoic acid; lactic acid; tartaric acid; malic acid; oxalic acid; succinic acid; palmitic acid; stearic acid; oleic acid; and/or linoleic acid.
  • the propionic acid is optionally generated in-situ in the formation of the polypropylenimine, such as from a oxazoline.
  • an initial polymer 110 such as polyethylenimine 250
  • an acidic pH form 216 of the polyethylenimine 250 is pH adjusted 610 along a first path to form an acidic pH form 216 of the polyethylenimine 250 and/or along a second path to form a basic pH form 218 of the polyethylenimine 250.
  • a first process of alkalization polymer tuning 1100 that raises pH of the polyethylenimine 250, forms a salt, removes the formed salt, and lowers the pH to tune the polyethylenimine 250
  • a second process of alkalization polymer tuning 1200 that uses ion exchange to raise the pH about the polyethylenimine 250 to tune the polyethylenimine 250
  • a third process of alkalization polymer tuning 1300 that raises the pH about the polyethylenimine 250 through linear and/or sequential addition of a base and ion exchange, in either order of addition, to tune the polyethylenimine 180030844.1 43 Attorney Docket no.
  • EXNI0001 250 and associated counterions One process using the basic form 218 is illustrated: (4) a fourth acidification polymer tuning process 1400 of lowering the pH of the polyethylenimine 250 through a combination of adding acid and/or use of ion exchange to yield a tuned polyethylenimine 250 in terms of protonation, counterions, and/or salt solution.
  • the fourth process 1400 optionally has sub-parts associated with each of processes I-III, albeit in reverse direction of pH adjustment.
  • Each of the four processes are further described in the following examples. However, first generic processes of tuning with a conjugate base are illustrated in two subprocesses.
  • a basic form of polyethylenimine 252 is interacted/reacted with an acid 910 – conjugate base 920 pair or indeed with just the acid 910 or with just the conjugate base 920, where an equilibrium between the acid 910 and the conjugate base 920 suffices to continue to provide each of the acid 910 and/or the conjugate base in the reaction / counterion supply.
  • the acid or H + protonates the polyethylenimine 250 to form a tuned protonation level of the polyethylenimine 254 and the salt anions, Y-, provide the counterions 320.
  • a weak acid such as formate, acetate, citrate, any monoprotic acid, and/or any dibasic acid
  • no salt is formed in the strict case of a pure weak acid with no impurities.
  • salt concentrations are typically held to less than 20, 10, 5, 4, 3, 2, 1, 0.5 or 0.1 percent with this approach, such as due to presence of impurities in the reagents/solvent(s), such as the presence of sodium carbonate in the water.
  • unprotonated monomers 255 and protonated monomers 257 of polyethylenimine 250 are illustrated.
  • polyethylenimine 250 generally is at least partially protonated.
  • the unprotonated monomers 255 and protonated monomers 257 are attached 180030844.1 44 Attorney Docket no. EXNI0001 together in any sequence and in any length to form the polyethylenimine polymer.
  • a second subprocess of using a conjugate base to alkalize 1000 the polymer 200, such as polyethylenimine 250, is illustrated.
  • an acidic form of polyethylenimine 256 interacts with an acid 910 – conjugate base 920 pair or indeed with just the acid 910 and/or with just the conjugate base 920, where an equilibrium between the acid 910 and the conjugate base 920 suffices to continue to provide each of the acid 910 and the conjugate base in the reaction / counterion supply.
  • the conjugate base 920 deprotonates the acidic form of the polyethylenimine 256 to form a tuned protonation level of the polyethylenimine 254 and the salt anions, Y-, provide the counterions 320.
  • a weak acid such as formate, acetate, or citrate
  • salt is formed.
  • the first process has an advantage of limiting to eliminating production of the salt solution 330 about the tuned protonation level of the polyethylenimine 254 and/or the second process has an advantage of yielding salt and optionally a controlled amount of salt in the tuned protonation level of the polyethylenimine 254, which affects the antimicrobial 231 properties of the composition.
  • the resulting tuned cationic polymer 300 differs using the first process compared to using the second process without use of an additional optional salt control step, such as further described infra.
  • different processes such as forming or not forming a salt, yield different formulations, where efficacy, such as killing bacteria, differs from formulation to formulation.
  • changes in temperature, pressure, or reaction times yield differing formulations, which again differ in efficacy. 180030844.1 45 Attorney Docket no. EXNI0001 Example I (Process I) Referring now to Figure 11, the first alkalization polymer tuning process 1100 is further described.
  • the first alkalization polymer tuning process 1100 provides a polymer 110, such as polyethylenimine 250, such as in an acidic pH form 216; adds a base 620 to raise the pH, which yields a salt; in a subsequent and/or concurrent step removes at least a portion of the formed salt 1140; and adds an acid to bring the pH back down.
  • a polymer 110 such as polyethylenimine 250, such as in an acidic pH form 216
  • a subsequent and/or concurrent step removes at least a portion of the formed salt 1140; and adds an acid to bring the pH back down.
  • the process of raising the pH raises the pH of the formulation containing polyethylenimine 250 to a level where salt is formed, such as to a raised pH level of 4.51110, which yields a salty product 1120 containing polyethylenimine 250 or raises the pH even further 1130, such as to a pH greater than 4, 5, 6, 7, 8, or 9, which generates even more salt.
  • a level where salt such as to a raised pH level of 4.51110, which yields a salty product 1120 containing polyethylenimine 250 or raises the pH even further 1130, such as to a pH greater than 4, 5, 6, 7, 8, or 9, which generates even more salt.
  • forming the salt which precipitates, allows for an easy removal of the salt, whether in a precipitate form or in solution, through the process of removing the salt 1140.
  • the salt removal step 1140 optionally includes one or more of the steps of drying 1150, filtering 1160, and/or separating 1170 the salt with any salt removal technique, such as centrifugation, washing, rinsing, decanting, and the like.
  • the polyethylenimine 250 is brought back down in pH 1180, such as to a target pH of less than 6, 5.5, 5, 4.5, 4, 3.5, or 3 and/or to greater than 2, 3, or 4, which reprotonates the polyethylenimine 250 – yielding the antimicrobial 231, antibacterial 232, antiviral 233, and/or antifungal 234 properties, described supra, associated with the more protonated form of polyethylenimine 250 at the lower pH and with a reduced salt concentration 1190 / chemical activity allowing better interaction with bacteria and especially viruses, in any form.
  • formulation methods alter efficacy, such as antibacterial, antifungal, and/or antiviral efficacy.
  • Example II 180030844.1 46 Attorney Docket no. EXNI0001
  • the second alkalization polymer tuning process 1200 is further described.
  • the polymer is provided 110, such as the polyethylenimine 250, in a solution, such as in acidic pH form 216 and ion exchange 1210 is used to increase the pH of the polyethylenimine 250 formulation.
  • an ion exchange material 1220 such as ion exchange beads 1222 and/or an in exchange resin 1224 is used in an ion exchange column 1226, a container, and/or in ion exchange chemistry 1228 to exchange ions/counterions in/on the polyethylenimine 250 for anions on the anion exchange material.
  • anions on the ion exchange material 1220 are exchanged for counterions associated with positively charged sites on the polymer 200, such as for chloride anions functioning as counterions to protonated secondary amines of the polyethylenimine 250.
  • counterions / counter-anions such as chloride anions functioning as counterions to the polymer 200 are adsorbed onto and/or are bound to the ion exchange material 1220.
  • the percentage of counterions to protonated sites on the polymer is reduced to less than 99, 95, 90, 80, 70, 60, 50, 40, 30, 20, 10, or 5 percent of a total number of counterions, such as at a fixed point in time.
  • the ion exchange material 1220 is optionally used to provide any anion to the polymer solution, such formate, acetate, iodide, and/or any anion described herein.
  • the ion exchange material 1220 exchanges hydroxide anion, OH-, for the chloride anions.
  • the hydroxide anions and protons of the acidic solution combine to form water, which raises the pH of the solution, such as to a pH greater than 2, 3, 4, 5, or any pH described herein.
  • the ion exchange process 1210 achieves a task of raising the pH of the polyethylenimine 250 to a tuned pH level.
  • the salt concentration of the polymer and/or a concentration of anions/counterions in the solution containing the polymer 200 is reduced, is not increased, and/or is raised by less than 10, 5, 2, 1, or 0.1 percent.
  • the ion exchange process 1210 yields a target pH based on concentration and pKas and/or binding/exchange coefficients of the exchange material. For instance, a formate exchange, a formic acid/formate ion mix, naturally brings 180030844.1 47 Attorney Docket no. EXNI0001 the pH to within a pH unit or two of a pKa of formate of 3.75 or when using acetate to a pH of 4.75.
  • Combinations of conjugate bases are optionally used in the ion exchange process, as further described infra.
  • commercially available polyethylenimine 250 is in either a fully protonated form with a pH of about 1 with greater than 90, 95, or 99% of the counterions to the protonated amines being chloride anions or is available in a fully deprotonated state with no charges amines at a pH greater than about 12.
  • Commercially available polyethylenimine with a pH of less than six is not available in any form except where greater than 99% of the counterions, to protonated amines of the polyethylenimine, are chloride. Production of polyethylenimine 250 is further described infra.
  • Example III Process III
  • the third alkalization polymer tuning process 1300 combines elements of the first alkalization polymer tuning process 1100 and the second alkalization polymer tuning process 1200 to use both ion exchange 1320 and addition of a base 620 to raise the pH 612 to a tuned pH / protonation level of the polyethylenimine 250.
  • the third alkalization polymer tuning process 1300 provides a polymer 110, such as the polyethylenimine 250 in an acidic form 216 and raises the pH 612 of the formulation, such as through one and preferably two or more of: (1) ion exchange 1320, which tunes the counter ions 1360; (2) addition of sodium hydroxide 622, which yields sodium hydroxide ions 624; and/or (3) adding a base 620, which tunes the salt 1370 / counterions.
  • a polymer 110 such as the polyethylenimine 250 in an acidic form 216
  • raises the pH 612 of the formulation such as through one and preferably two or more of: (1) ion exchange 1320, which tunes the counter ions 1360; (2) addition of sodium hydroxide 622, which yields sodium hydroxide ions 624; and/or (3) adding a base 620, which tunes the salt 1370 / counterions.
  • the formate anion 324 is generated in the aqueous salt solution in the formulation about the polyethylenimine 250 and/or the formate anion 324 is provided as the counterion to the polyethylenimine 250, such as replacing, with an equilibrium coefficient, the chloride ion 322.
  • any acid/conjugate base molecule or acid/base pair 180030844.1 48 Attorney Docket no.
  • EXNI0001 is optionally used in place of and/or in combination with the formic acid : formate acid/base pair, which allows tuning of at least one of: (1) the salt type and/or salt concentration in the formulation about the polyethylenimine 250 and/or (2) the type and/or concentration of the counterions associated with the protonated sites 310 of the polyethylenimine 250.
  • Example IV Process IV
  • the acidification polymer tuning process 1400 is essentially any combination of the first alkalization polymer tuning process 1100, the second alkalization polymer tuning process 1200, and the third alkalization polymer tuning process 1300, where the pH is lowered rather than raised.
  • the acidification polymer tuning process 1400 provides a polymer 110, such as polyethylenimine 250, in the basic pH form 218; the pH is lowered 614; and the counterions and/or salts in solution are tuned 1350 in serial and/or parallel steps.
  • a polymer 110 such as polyethylenimine 250
  • the counterions and/or salts in solution are tuned 1350 in serial and/or parallel steps.
  • the lowering pH step 614 one and preferably two or more pH lowering processes are used, such as: (1) using ion exchange 1320 to tune the counterions 1360; (2) adding hydrochloric acid 632 to yield H + and Cl- in the formulation; and/or (3) adding acid 630 to tune the salt 1370 formed in solution.
  • addition of an acid-conjugate base pair tunes the counterion 320, such as associated with the protonated sites 310 of the polyethylenimine 250.
  • the pKa of the acid- conjugate base pair buffers the formulation. For instance, addition of the formic acid-formate acid/base pair results in lowering of the pH 614 while providing a buffer capacity, related to the amount of the acid/base pair added, about the pKa of the formic acid-formate pka of 3.75.
  • the tuned counterions-salts 1350 are an equilibrium of tuned counterions 1360 with tuned salts 1370, as further described infra.
  • the acidification polymer tuning process 1400 (1) lowers the pH with ion exchange and/or addition of an acid; (2) optionally provides the proton for the protonation 310 via the use of a weak acid-conjugate base acid/base pair, such as the use of formic acid; (3) tunes availability of the type and/or concentration of the counterion 320 via choice of the weak acid/base pairs or choice of strong acid type; (4) is optionally used in a process of creating no or limited salt, such as described in the process of using a conjugate base to acidify 900 the polymer 200, as described supra; (5) provides a buffer related to the pKas of the added acids; and/or (6) optionally and preferably removes a filtering step associated with removing excess salt in the formulation, such as resulting from either use of the initial fully acidic form of polyethylenimine 256 and/or the second subprocess of using a conjugate base to alkalize 1000 the polymer 200, which yields a salt, as described supra.
  • the salts in the salt solution 330 are in equilibrium with the counterions 320 associated with the polymer 200 in terms of position. That is, a first counterion and a first salt in solution optionally swap positions, such as relative to a protonation site 310 of the cationic 211 polymer.
  • the first counterion type and the second counterion type have preferred locations. For instance, chemically the formate 324 will tend to displace the chloride ion 322 as the counterion.
  • the polyethylenimine 250 preferably has thousands of protonated sites 310, the probability is great that the counterion type with the greater attraction to the protonated site 310 will be associated with the polymer 200.
  • Example V Referring now to Figure 15 and referring again to Figure 9, a conjugate base polymer tuning process 1500 is illustrated.
  • two or more stock solutions are optionally mixed to form the tuned polymer 210, which is particularly beneficial when starting with the basic form of polyethylenimine 252 or any polymer 200.
  • a polymer is provided 110, such as polyethylenimine 250 in the basic pH form 218 and the pH is lowered 614, such as with an ion exchange conjugate acid/base pair 1322, which tunes the counterions 1360 and tunes the salt 1370.
  • An example is provided for clarity of presentation and without loss of generality.
  • the basic form of polyethylenimine 252 such as in a first stock solution, is mixed with an acid/base pair or simply an acid, such as formic acid, in a second stock solution the basic form of polyethylenimine 252 is provided with an proton, from the acid, to yield a tuned protonation level of the polyethylenimine 254 and the counterion 320 is provided as the conjugate base.
  • the formic acid concentration quantitatively yields an amount of the protonation sites 310 and yields the counterion 320 of formate 324 at a quantitative level, such as according to the interaction illustrated in the first subprocess of using a conjugate base to acidify 900 the polymer 200 illustrated in Figure 9.
  • this allows for direct quantitative measurement and/or comparison of the efficacy of differing counterions 320 associated with the polymer 200.
  • a first formulation is made with a controlled amount of protonation 310 and a controlled amount of the counterion formate 324, which is tested against a bacteria or virus, such as using a government regulated process, as described supra.
  • a second formulation is made with a controlled amount of protonation 310 and a controlled amount of the counterion acetate 326, which is tested against a bacteria or virus, such as using a government regulated process, as described supra.
  • each protonation level 310 and each controlled amount of counterion 320 is thus optionally and preferably controlled and quantitatively 180030844.1 51 Attorney Docket no. EXNI0001 tested, as further described infra. Further, combinations of counterions 320 are optionally tested.
  • a controlled amount of formate is added and tested yielding a first efficacy measure and in a second test, 100 ppm iodide anion is added, tested, and a second efficacy is measured, yielding, by difference, the effectiveness of the iodide anion.
  • the conjugate base polymer tuning process 1500 described herein combines with and/or is used as a step in any of the first general process 600, the second general process yielding a tuned counterion solution 700 / formulation, the first alkalization polymer tuning process 1100, the second alkalization polymer tuning process 1200, the third alkalization polymer tuning process 1300, and/or the acidification polymer tuning process 1400, such as where a change in pH step is used, a counterion 320 is introduced, and/or a salt solution 330 is controlled. Still referring to Figure 15, the tuned counterions 1360, the tuned salts 1370, no formed salt state 1380, and/or the added salt state 1390 are all in equilibrium with each other.
  • Example VI Preprocessing
  • the polymer slurry acid reduction process 1600 is optionally used in conjunction with any of the above described methods; however, a preferred use of the polymer slurry acid reduction process 1600 is to concentrate the polymer 200 and/or reduce the overall acid molarity, which results in less salt production, where too much salt may interfere with efficacy of the tuned polymer 210 in terms of being antimicrobial 231, antibacterial 232, antiviral 233, and/or antifungal 234.
  • an acidic form of the polymer is provided 216, such as the acidic form of polyethylenimine 256.
  • EXNI0001 of polyethylenimine 256 is concentrated or simply the polymer is concentrated 1610, such as by one or more of: reducing the acid concentration 1611, filtering the acidic form of polyethylenimine 256 in hydrochloric acid to yield a slurry of polymer 1612, filtering 1613, decanting 1614, centrifuging 1615, or any process that reduces the overall molarity of the hydrochloric acid in any intermediate or final formulation of the tuned polymer 210.
  • removal of a portion of the hydrochloric acid results in a reduction of the amount of the chloride ion 322 and hence the reduction of the salt sodium chloride when the above described processes are implemented, where some of the processes exchange the chloride counterion 322 for another ion and/or alter the pH to form sodium chloride salt, such as by addition of a base, such as sodium hydroxide where the sodium cation combines with the chloride anion to form sodium chloride in any physical state, such as in solution and/or as a precipitate.
  • the resulting polymer/slurry is optionally dried 1620, as described supra, and/or is pH adjusted up to a target pH 1630, as described supra.
  • the filtering step 1613 and/or the step of concentrating the polymer 1610 reduces the total base molarity needed adjust the pH, so less salt is generated with the use of the polymer slurry acid reduction process 1600, especially when raising the pH of the formulation from a very acidic pH, such as less than 3, 2, 1.7, 1.6, 1.5, or 1.
  • a very acidic pH such as less than 3, 2, 1.7, 1.6, 1.5, or 1.
  • the polymer - salt pair salt reduction process 1700 optionally uses any one of more steps of the polymer slurry acid reduction process 1600, described infra, such as the step of concentrating the polymer 1610 and/or drying the slurry 1620, which may result in formation of a solid salt layer 1622.
  • the initial acidic form of the polymer 216 such as the acidic form of polyethylenimine 256
  • the pH is adjusted upward 1630 at the same or 180030844.1 53 Attorney Docket no.
  • Example I Referring now to Figure 18, a polymer tuning with a weak acid process 1800 is illustrated. In this example, any strong or weak acid is optionally substituted for the illustrated process of adding the counter ion formate 324 to the polymer 200 or as illustrated to the polyethylenimine 250.
  • linear PEI + formic acid ⁇ protonated linear PEI + formate ion (eq.1) is repeated with chemical illustrations in equations 1B and equation 1C.
  • the formate counter ion 324 from the formic acid equilibrium with formate is added to a proton on the secondary amine 1912 of the repeating unit 1910 and/or a proton from the formic acid protonates 310 the secondary amine 1912 to form a cationic polymer repeating unit.
  • Example I Referring now to Figure 19, a polymer tuning with a weak acid and salt production process 1900 is illustrated.
  • the weak acid and salt production process 1900 is the polymer tuning with a weak acid process 1800 with the addition of another acid, such as a strong acid, such as hydrochloric 180030844.1 54 Attorney Docket no. EXNI0001 acid at any concentration and/or in any state.
  • a strong acid such as hydrochloric 180030844.1 54 Attorney Docket no. EXNI0001 acid at any concentration and/or in any state.
  • any strong or weak acid is optionally substituted for either of the illustrated processes of adding hydrochloric acid or the counter ion formate 324 to the polymer 200 or as illustrated to the polyethylenimine 250.
  • equation 2 in Figure 19 the reaction of: PEI + HCl + formic acid ⁇ protonated PEI + chloride ion + formate ion (eq.
  • n monomers of polyethylenimine are associated with any number a and b of the chloride and formate anion, where n, a, and b are positive integers Tuning Counterion Availability
  • Figure 20 and Figures 21-28 relative concentration of conjugate base tuning 2000 is illustrated.
  • a process of relative concentration of conjugate base tuning 2000 includes one or more of the steps of: (1) determining availability of the conjugate bases 2010 / anions / counterions, such as the availability of a first conjugate base 2012, a second conjugate base 2014, or n conjugate bases, where n is a positive integer greater than 0, 1, 2, 3, 4, or 5; (2) adjusting concentration of the conjugate 180030844.1 55 Attorney Docket no.
  • EXNI0001 bases such as a first conjugate base concentration 2022, a second conjugate base concentration 2024, or n conjugate base concentrations, where n is a positive integer greater than 0, 1, 2, 3, 4, or 5; and/or (3) optionally adjusting for electronegativity and/or equilibrium coefficients 2030, such as determining/using an equilibrium between a conjugate base associated with the polymer 2032 and the conjugate base being a salt in solution 2034 and/or the affect of electronegativity on an activity coefficient for the protonated site 310 / counterion 320, which combined and/or separately allow for tuning a ratio of counterion types 2040, such as a concentration of first conjugate base on the polymer association 2042, a concentration of a second conjugate base on the polymer association 2044; or concentrations of n conjugate bases on the polymer associations, where n is a positive integer greater than 0, 1, 2, 3, 4, or 5.
  • a ratio of counterion types 2040 such as a concentration of first conjugate base on the polymer
  • Example I a process of determining a first conjugate base availability 2100 is illustrated.
  • the amount of any counterion 320 associated with the polymer 200 in a formulation of the tuned polymer 210 is optionally and preferably controlled.
  • control of the counterion formate 324 is illustrated, which again is optionally repeated for any counterion and/or two or more counterions 320.
  • the counterion concentrations and/or availabilities are optionally independently quantitatively controlled, such as through implementation of any one or more of the processes described herein.
  • formate 324 In the case of formate 324, formate has a pKa of 3.774. Based upon the pKa, the fraction percentage of any form or any monoprotic, diprotic, and/or triprotic acid is calculable.
  • the fraction percentage of formic acid and formate are illustrated as a function of pH. As indicated, if a fraction percentage of formate of 85.1 percent is desired, then the pH is adjusted to pH 4.5. Conversely, the pH is selected and the fraction percent of the conjugate base(s) are known.
  • the formate concentration is 85.1 180030844.1 56 Attorney Docket no. EXNI0001 percent of the total molarity of the formic acid-formate acid/base pair at pH 4.5.
  • the overall formate and/or conjugate base concentration is optionally raised or lowered to alter the total amount/concentration of formate 324 / conjugate base available as a counterion 320 in a formulation of the tuned polymer 210, as further described in the following example.
  • Example II Referring now to Figure 22, second conjugate base availability determination 2200 is illustrated.
  • availability of acetate 326 is determined just as described for the determination of formate 324 in the prior example, only using a pKa of acetate of 4.76. While formate 324 had an availability of 85.1 percent at pH 4.5, as described in the preceding paragraph, acetate 326 only has an availability of 35.5 percent at the same pH of 4.5.
  • Example III Referring now to Figure 23, adjusting a conjugate base concentration 2300 is illustrated. Generally, any counterion 320 concentration is raised / lowered by altering the total mass in a formulation of the polymer 200.
  • acetate 326 is illustrated at a first acetate concentration 2310 and at a second acetate concentration 2320 that is two times the first concentration.
  • the ratio of formate-to-acetate is controlled, as illustrated in the next example.
  • the fraction of acetate to total acetate + acetic acid is still 35.5 percent at pH 4.5, as illustrated in the prior example, the amount of acetate available is controllably altered by changing the total mass of acetate + acetic acid in the formulation and/or in a formulation step. For instance, doubling or halving the total mass of acetate + acetic acid, the amount of acetate double or halves, respectively. 180030844.1 57 Attorney Docket no. EXNI0001 Example IV Referring now to Figure 24, relative tuning of two conjugate bases 2400 is illustrated.
  • the relative concentration ratio of formate-to-acetate is made to be one-to-one (1:1).
  • the formate concentration is raised or lowered to alter the total amount of formate 324 available as a counterion 320 in a formulation of the tuned polymer 210.
  • the concentration of any conjugate base or first counterion is optionally and preferably tunable to any level, such as greater than 0, 0.1, 0.5, 1, 5, 10, 20, 30, 40, or 50 percent of the counterions 320 and/or a second counterion; less than 100, 90, 80, 70, 60, or 50 percent of the counterions 320 and/or a second counterion; and/or within ⁇ 1, 2, 5, 10, 25, or 50 percent of a fractional percentage of a given counterion to all counterions and/or to a second counterion of 10, 20, 30, 40, 50, 60, 70, 80, or 90 percent, as is further illustrated in the next example.
  • Example V Referring now to Figure 25A, a first counterion ratio 2500 on the polymer 200 with a backbone 2510 of atoms and/or monomers 253 is illustrated with a first conjugate base 2520 (CB 1 )-to-a second conjugate base 2530 (CB 2 ) ratio. As illustrated the first conjugate base-to-second conjugate base ratio is three to one, 3:1.
  • a second counterion ratio 2505 on the polymer 200 is illustrated after tuning the conjugate base ratios / counterion ratios, as described supra. Particularly, as illustrated the first conjugate base- to-second conjugate base ratio is now tuned to one to one, 1:1, where any tuning ratio is optionally formulated, as described supra.
  • ratios of three base pairs are optionally controlled with a ratio of zero-to-one for the first conjugate base to zero-to-one for the second conjugate base to zero-to-one for the third conjugate base (0 to 1 : 0 to 1 : 0 to 1) at any analog step interval, such as within ⁇ 0.05 of 0.1, 0.2, 0.25, or 0.5.
  • the same process optionally uses a polyprotic acid 2700 with multiple conjugate bases, such as illustrated for the fractions of citrate 2640, such as citrate 3- 2642, citrate 2- 2644, and citrate 1- 2646 with or without mixing with another conjugate base, such as the illustrated formate fraction 2610.
  • relative tuning of multiple conjugate bases/counterions 2800 is illustrated.
  • the polymer 200 which a chemical backbone 2510, is associated with the first conjugate base 2520 (CB 1 ), the second conjugate base 2530, a third conjugate base 2540, and a fourth conjugate base 2550 at a ratio of five to four to two to one (5:4:2:1), where any ratios of conjugate bases are optionally and preferably formulated.
  • CB 1 first conjugate base 2520
  • second conjugate base 2530 second conjugate base 2530
  • a third conjugate base 2540 a third conjugate base 2540
  • a fourth conjugate base 2550 at a ratio of five to four to two to one (5:4:2:1), where any ratios of conjugate bases are optionally and preferably formulated.
  • de-chlorinating / de-salting / tuning counterion availability decreases toxicity to humans, vertebrates, and invertebrates.
  • polyethylenimine 250 is protonated with traditional means of combining with concentrated hydrochloric acid, essentially all of the
  • the Environmental Protection Agency states that the National Aquatic Life Criteria for chloride is 860 mg/L for an acute exposure and 230 mg/L for a chronic exposure. Even with removal of all excess hydrochloric acid from formed protonated polyethylenimine, the concentration of chloride counterions, for a pH 4.5 / twenty-eight percent protonated polyethylenimine, is 1120 mg/L (1120 ppm). Generally, the chloride counterion concentration, with manufacturing with hydrochloric acid, exceeds the Environmental Protection Agency requirements 180030844.1 59 Attorney Docket no. EXNI0001 for any protonated polyethylenimine in a pH range of 1 to 9.
  • replacing chloride counterions with other, less toxic, counterions is optionally and preferably performed to meet the U.S. Environmental Protection Agency standards. Any of the methods described herein are optionally and preferably implemented to meet the U.S. Environmental Protection Agency standards.
  • ANTIBACTERIAL, ANTIVIRAL, AND ANTIFUNGAL TESTING The inventors have determined that formate/formic acid, acetate/acetic acid, citrate/citric acid, and iodide/iodine each have antibacterial properties in combination with linear PEI, where the PEI is in solution and/or a solid film. Linear PEI with both chloride and formate counterions yielded 99.9999 percent activation using the EPA 01-1A test protocol for durability testing for both MRSA and E.
  • Table 1A Linear PEI, Chloride, and Formate Antibacterial Film Testing Non-durability Substrate Contact Chloride Test Percent Testing Time and Protocol Inactivation Formate Gram-positive 99.99 MRSA Plastic 2 min X IS022196 Gram-negative E. coli Plastic 2 min X IS022196 99.99 Gram-negative E. coli Textile 10 min X JIS 1902 99.4 C. diff Glass 24 hours X IS022196 99.4 Gram-negative E. coli. Stainless 5 min X PAS 2424 99.99 Gram-negative P. Aeruginosa Stainless 5 min X PAS 2424 99.93 180030844.1 60 Attorney Docket no.
  • linear PEI with chloride and formate counterions yielded 99.6 to 99.9 percent inactivation of enveloped viruses
  • linear PEI with chloride and acetate counterions yielded 99.95 to 99.99 inactivation of enveloped and non-enveloped viruses
  • linear PEI with chloride and iodide counterions yielded 89.7 percent inactivation of the very difficult non-enveloped polio virus, where the tests were performed on a variety of substrates with contact times ranging from 5 to 10 minutes.
  • Table 2A Linear PEI, Chloride, and Formate Antiviral Testing Durability Substrate Contact Chloride Test Protocol Percent Testing Time and Inactivation Formate Vaccinia enveloped Plastic 5 min IS022702 99.96 Virus X Beta Corona enveloped Stainless 5 min IS022702 99.9 Virus X Polio Non- enveloped Plastic 10 min EN 14476 99.6 Virus X Vaccinia enveloped Stainless 10 min X PAS 2424 99.96 virus Beta Corona enveloped Artificial Sk 10 min X PAS 2424 99.9 virus in Table 2B: Linear PEI, Chloride, and Acetate Antiviral Testing 180030844.1 62 Attorney Docket no.
  • the polymer 200 is used as an example of a chemical backbone 2510 180030844.1 63 Attorney Docket no. EXNI0001 of a charged chemical structure 2910.
  • the polymers 200 described herein are used to carry a plurality of charges, such as cationic charges, along a chemical backbone 2510.
  • the chemical backbone 2510, of which the polymer 200 is an example is optionally any sequence of covalently bonded atoms, such as described infra.
  • Figure 29 a process of treating a substance with a charged chemical structure 2900 is illustrated. For clarity of presentation and without loss of generality, a polymer 200 is used herein to represent the charged chemical structure 2910.
  • the charged chemical structure is optionally a protein 202 or more generically any chemical backbone 2510.
  • the chemical backbone 2510 is a series of covalently bonded atoms, amino acids, monomers, and/or functional groups that optionally and preferably carry multiple charges, as further described in Figures 30-36.
  • the protein 202 and/or the chemical backbone 2510 are optionally and preferably tuned, such as by any process described herein for tuning the polymer 200.
  • the now multi-charged / polycationic protein and/or multi-charged / polycationic chemical backbone is optionally and preferably used to treat a substance 140, such as after an optional change in dominant state 130, where the treatment yields antimicrobial 231, antibacterial 232, antiviral 233, and/or antifungal 234 properties.
  • a substance 140 such as after an optional change in dominant state 130, where the treatment yields antimicrobial 231, antibacterial 232, antiviral 233, and/or antifungal 234 properties.
  • reference to the more generic chemical backbone 2510 is optionally and preferably inferred.
  • the charged chemical backbone 2510 optionally and preferably contains charged sites, such as a charged nitrogen.
  • a primary amine 3002 is illustrated, where, in a positively charged state, a nitrogen is bonded to three hydrogens and one additional molecular fragment, referred to here as a first molecular fragment, R 1 .
  • R 1 one additional molecular fragment
  • the primary amine 3002 is illustrated as protonated 310 and is illustrated with a counterion 320.
  • a secondary amine 3004 is illustrated, where, in a positively charged state, the nitrogen is bonded to two hydrogens and two additional molecular fragments, referred to here as a first molecular fragment, R 1 , and a second molecular fragment, R 2 .
  • the second molecular fragment and/or is any molecular fragment and optionally terminates in a carbon bound to the nitrogen.
  • a tertiary amine 3006 is illustrated, where, in a positively charged state, the nitrogen is bonded to a single hydrogen and three additional molecular fragments, referred to here as a first molecular fragment, R 1 ; a second molecular fragment, R 2 ; and a third molecular fragment, R 3 .
  • a quaternary amine 3008 is illustrated, where the nitrogen is bonded to four molecular fragments, designated R 1 , R 2 , R 3 , and R 4 .
  • the polymers illustrated herein such as the polyethylenimine 250, linear polyethylenimine 3300, and/or the branched polyethylenimine 3400 contain primary amines 3002, secondary amines 3004, and/or tertiary amines 3006, optionally and preferably in the absence of quaternary amines 3004, which are relatively toxic in comparison.
  • Quaternary ammonium compounds, or quats are a group of positively charged ions that are often used as disinfectants, surfactants, and fabric softeners.
  • any one or more quaternary ammonium compounds/molecules are optionally used in combination with any of the polymers 200, the polyethylenimine 250, and/or the multi-charged chemical backbones 2510 described herein. 180030844.1 65 Attorney Docket no. EXNI0001
  • Figure 31A and Figure 31B an exemplary repeating group, such as found in the polymer 200, the polyethylenimine 250, and in some cases the chemical backbone 2510 is illustrated.
  • the illustrated repeating monomer 253 is the repeating unit of polyethylenimine 250 in a basic form 3100.
  • the repeating unit of polyethylenimine 250 in an acidic form 3105 is illustrated.
  • polyethylenimine 250 has any number of unprotonated monomers 3110 and any number of protonated monomers 3105, such as based on pH and/or formulation methodologies, such as pH, temperature, and/or time of reaction, as further described infra.
  • the repeating unit includes a chain of covalently bonded atoms in a repeating sequence of carbon-carbon-nitrogen.
  • the acidic form of the nitrogen is protonated and has a counterion and is referred to as a protonated amine and more specifically a protonated secondary amine.
  • the repeating monomer is optionally of any structure.
  • a repeating carbon-carbon-nitrogen group of polypropylenimine 3110 is illustrated in Figure 31C.
  • the repeating group is optionally of any structure bonded to the nitrogen referred to here as R1-nitrogen, or simply a repeating unit of a nitrogen containing backbone 3120.
  • the polyethylenimine polymer has a repeating carbon-carbon-nitrogen backbone
  • the polypropylenimine polymer has a repeating carbon-carbon-carbon-nitrogen backbone
  • the polymer 200 has a repeating nitrogen containing backbone, such as R 1 -nitrogen, or R 1 -nitrogen-R 2 , where R 1 and R 2 are each independently any organic molecular fragment, such as of any length of carbons, and/or of any length of carbons covalently bonded to and/or interspersed with any other atoms, such as carbon-oxygen-carbon-carbon- carbon-, which is bonded to the nitrogen.
  • the nitrogen is not in the backbone structure, but is rather attached to the backbone structure of the repeating group, such as an -NH 2 or -NH 3 group attached to a carbon in the backbone structure.
  • the nitrogen is indirectly covalently bonded to the backbone structure.
  • the nitrogen, which is optionally protonated is attached in any manner to the backbone structure of the 180030844.1 66 Attorney Docket no. EXNI0001 repeating unit
  • the combined nitrogen containing fragment and the backbone fragment of the polymer is referred to as a nitrogen containing repeating backbone monomer 3130 / fragment of the polymer.
  • acidification of a base 3200 is illustrated.
  • linear polyethylenimine 3300 referred to as linear PEI, is sequentially illustrated in a base form, a slightly acidified form, a more acidified form, and an acidified form, respectively.
  • polyethylenimine 250 is illustrated with primary amines 3002 at the polymer termini and a multitude of secondary amines 3004, such in the repeating monomer 253.
  • the linear polyethylenimine 3300 contains a chemical backbone 2510 of repeating units of carbon-carbon-nitrogen.
  • the partially acidified polyethylenimine 250 is illustrated as partially protonated 310 with a counterion 320, in the illustrated case a chloride ion 322 / chloride counterion.
  • a dimer is present of one charged nitrogen monomer unit and one uncharged nitrogen monomer unit 413.
  • the frequency of the charged nitrogen monomer is every monomer unit, every second, third, fourth monomer unit, and/or at random intervals along the length of the polyethylenimine 250.
  • the polymer is optionally referred to a percent protonated, such as greater than 1, 2, 5, 10, 30, or 50 percent protonated and/or as less than 99, 98, 95, 90, 70, or 50 percent protonated.
  • a fully protonated version of the polyethylenimine 250 is illustrated.
  • the percentage of protonated sites on the polyethylenimine 250 generally increases and vice-versa.
  • branched polyethylenimine 3400 is illustrated, which is an example of another chemical backbone 2510.
  • the branched polyethylenimine 3400 contains the primary amines 3002 and the secondary amines 3004 of linear polyethylenimine 3300 and contains tertiary amines 3006.
  • any number of the primary amines 3002, secondary amines 3004, and/or tertiary amines 3006 are protonated, as illustrated in Figure 34B.
  • at least some of the nitrogens in the tertiary amines are covalently bonded to three carbon-carbon-nitrogen fragments.
  • linear polyethylenimine 3300 and branched polyethylenimine 3400 contain no quaternary amines 3008, but quaternary amines 3008 are optionally added to a formulation of the polyethylenimines 250 or any polymer 200 to enhance antimicrobial 231, antibacterial 232, antiviral 233, and/or antifungal 234 properties.
  • quaternary amines 3008 are optionally added to a formulation of the polyethylenimines 250 or any polymer 200 to enhance antimicrobial 231, antibacterial 232, antiviral 233, and/or antifungal 234 properties.
  • Figure 35 and Figure 36 for clarity of presentation and without loss of generality, two exemplary chemical backbones 2510 are illustrated.
  • Example I Referring now to Figure 35, a first example of a chemical backbone 3500 is illustrated with amino acids / protein sections in place of the polymer 200.
  • the chemical backbone 2510 has a first optional section 3510 of a set of amino acids, which form the chemical backbone 2510 and/or are covalently bonded, directly or indirectly, to the chemical backbone.
  • the amino acids include one or more of: glycine 3511, alanine 3512, serine 3513, and/or asparagine 3514, which are each protonatable, which yields a chemical backbone 2510 with multiple cationic charges, in a manner related to the multiple cationic charged of the polymer 200 / tuned polymer 210.
  • the first optional section 3510 of the chemical backbone 3500 contains and/or is bonded directly/indirectly to one or more amino acids 3515 180030844.1 68 Attorney Docket no.
  • the chemical backbone 2510 has a second optional section 3520 that intermixes one or more nitrogen groups 3517, such as a secondary amine 3004 and/or a tertiary amine 3006, into the chemical backbone 2510 and/or as molecule fragments bonded directly and/or indirectly to the chemical backbone 2510. More generally, the chemical backbone 2510 includes and/or is bonded directly/indirectly with a series of one or more amino acids, protein fragments, RNA fragments, DNA fragments, and/or peptides.
  • the chemical backbone 2510 contains/carries a plurality of protonatable sites, such as one or more secondary amines 3004; one or more tertiary amines 3006; one or more protonatable amino acids; and/or one or more protonatable sites.
  • the chemical backbone is of any length of greater than 10, 20, 50, or 100 covalent bonds in series.
  • Example II Referring now to Figure 36, a second example of a chemical backbone 3600 is illustrated with a series of covalent bonds in the chemical backbone 2510 from a first terminus 3610 to a second terminus 3620 of an optional number of n termini in a branched molecule, where n is a positive integer of at least two.
  • the chemical backbone 2510 contains, directly/indirectly, any number of protonatable groups 310.
  • the chemical backbone 2510 contains any combination of carbon, oxygen, sulfur, and nitrogen atoms covalently bonded in a series of greater than 5, 10, 15, 20, 50, 100, 500, or 1000 covalent bonds, where any of the covalent bonds are optionally double bonds.
  • the illustrated series of covalently bonded atoms is illustrative in nature only and is non-limiting.
  • the chemical backbone 2510 and/or any side chain/group bonded directly/indirectly to the chemical backbone 2510 contains greater than 3, 4, 5, 10, 20, 50, 100, 200, 500, 1000, 5000, 10,000, or 50,000 protonatable sites, which are tunable in any manner set forth herein for polymer tuning 210.
  • the chemical backbone 2510 optionally contains a set of one or more side chains 3610, such as a first side chain 3612, a second side chain 3614, and a third side chain 3616, where any of the side chains optionally contain, are bonded to, and/or are indirectly bonded to any number of protonatable groups, which are optionally tuned by any manner set forth 180030844.1 69 Attorney Docket no.
  • EXNI0001 herein for tuning the polymer 210.
  • a set of anions are optionally used in place of and/or in combination with the set of cations / protonatable groups set forth herein.
  • POLYMER TUNING Referring now to Figure 37, polymer tuning 100 is further described. As described in Figure 1, a polymer is provided 110, such as any of the polymer types described, supra. Herein, control parameters 3710 that yield a tuned polymer state 3740, of the polymer tuning 100 process, are described.
  • control parameters 3710 in polymer tuning includes a process 3712, such as the first general process 600, the second general process yielding a tuned counterion solution 700 / formulation, the first alkalization polymer tuning process 1100, the second alkalization polymer tuning process 1200, the third alkalization polymer tuning process 1300, the acidification polymer tuning process 1400, the conjugate base polymer tuning process 1500, and/or any process that yields a tuned polymer state.
  • the process 3712 optionally includes controlling: concentration 3714 of the polymer, the solvent 3716, temperature 3718, pressure 3720, time of any step 3722, mixing 3724, pH 3726, an acid type 3728, a counterion type 3730, solvent evaporation 3732, a delivery process 3734, and/or any chemical, mechanical, electrical, and/or physical parameter to yield the tuned polymer state 3740.
  • the solvent 3716 is optionally water, ethanol, isopropanol, and/or any organic solvent.
  • the tuned polymer state 3740 includes any one or more of: a tuned charge 3800; additive killing 3741 properties; an activity 3742, such as an activity coefficient, ⁇ , of a surrounding solvent and/or solution; 180030844.1 70 Attorney Docket no.
  • the tuned protonation 3815 and/or the tuned cationic charge 3810 is simultaneously and/or subsequently tuned for charge effectiveness 3820.
  • Charge effectiveness 3820 is dependent on one or more of salt concentration 3750, ionic strength 3751, de-salting 3753, and activity 3742.
  • Tuning cation charge 3810 is further described, infra, in reference to Figures 39-41 and tuning charge effectiveness is further described, infra, in reference to Figures 42-46.
  • EXNI0001 hydrochloric acid for 96 hours instead of 8 hours, a measured percent chlorination on the resulting polymer increases from 38 to 43 percent by weight, which is a protonation increase from 65 to 100 percent or a 54 percent increase in protonation.
  • a first explanation of increased protonation with reaction time at a temperature of 130 degrees is provided.
  • a cationic polymer 300 is illustrated at a first time with protonated sites 241 and a first region 3910 and a second region 3920 that are not readily accessed for protonation.
  • the degree of protonation 241 increases to differing total protonation levels as a function of time/temperature, as described supra.
  • an elevated temperature such as at greater than 30, 50, 75, 100, or 125 degrees Celsius
  • the cationic polymer 300 at least partially unfolds into a more elongated form 3930, which allows the acidic solution to more completely react with the polymer 200 at difficult to access sites, such as a first hindered site 3910 and/or a second hindered site 3920 that are sterically sheltered by the cationic polymer 300 from surrounding solution, to form more cationic sites 241.
  • the additional protonated sites 241 are stable when the temperature of the solution is subsequently reduced.
  • increasing a reaction time at an elevated temperature in a protonation step of the polymer 200, such as polyethylenimine 250 results in an increase of protonation of the polyethylenimine 250 by 54 percent, such as when protonated with hydrochloric acid at a pH of 1.2, which may be due to increase accessibility of secondary amines on the polyethylenimine 250 with a change in structure / unfolding / unwrapping 3930 of the polyethylenimine 250 at the elevated increased temperature for the longer elapsed time period.
  • a second explanation of increased protonation with reaction time at a temperature of 130 degrees is provided.
  • FIG. 40A three 180030844.1 72 Attorney Docket no. EXNI0001 chains of polyethylenimine 250 are illustrated with a first distance, d 1 , between chains.
  • the first distance between chains results in a physical obstacle for access to sterically blocked sites 2010 of some of the internal secondary amines, which limits protonation of the sterically blocked sites 2010 by the protonating acid.
  • the three chains of polyethylenimine 250 are illustrated with an increased temperature, which results in a second distance, d 2 , between chains, where the second distance is greater than the first distance, such as greater than 1, 2, 5, 10, 25, 50, 100, or 200 percent greater.
  • the increased distance between chains results in increased protonation sites 243 with treatment by the concentrated acid.
  • a preferred protonation level of the polyethylenimine is with 1, 2, 4, 6, or 8 percent of any of 25, 30, 35, 40, 45, 50, 55, 60, and 65 percent protonated.
  • the method of forming polyethylenimine 250 also affects protonation. Still referring to Figure 41, the inventors have determined that the percent protonation of the polyethylenimine is dependent upon the method of protonation / deprotonation of the polyethylenimine, such as being a function of time at given temperatures and pressures and/or the presence of one or more additional components in the formulation.
  • an initial effective charge of 100 units is illustrated with an activity coefficient, ⁇ , of 0.5.
  • the effective charge of the protonated sites on the polyethylenimine 250 increases.
  • the effective charge increases by 20, 40, 60, 80, and 100 percent as the activity coefficient of the polyethylenimine solution increases to 0.6, 0.7, 0.8, 0.9, and 1.0, respectively, through removal of ions in the solution.
  • viruses 4300 are illustrated. Particularly, a non-enveloped virus 4302 is illustrated in Figure 43A and an enveloped virus 4304 is illustrated in Figure 43B.
  • non-enveloped viruses 4302 include: hepatitis A, hepatitis E, norovirus, rhinovirus, and astrovirus.
  • enveloped viruses 4304 include: SARS, MERS, alphaviruses, hepatitis C, and zika virus.
  • the tuned polyethylenimine / tuned polymer 210 is demonstrated as being effective against both non-enveloped viruses 4302 and enveloped viruses 4304, as described in reference to Figures 2(A-C), supra.
  • a virus 4300 includes an inner region of a nucleic acid 4320, such as an RNA strand, that is circumferentially (spherically) encapsulated within a capsid shell 4310 or a set of capsids / nucleocapsid proteins.
  • the capsid shell 4310 contains positive charges facing the negatively charged areas of the nucleic acid 4320.
  • arginine and/or lysine in the capsid shell 4310, each have a positively charged NH2 end that faces inward.
  • the arginine and/or the lysine also contains a negatively charged COO- end, which can face outward.
  • the virus 4300 has an outer surface that is zwitterionic and/or in many cases has a plurality of local negatively charged locations 4312, which may interact with the positively charged protonated sites 310 of the cationic polymer 300. Possible interactions of the negative charges of the outer surface of the virus 300 interact with the cationic polymer 300 are further described, infra.
  • features of the non-enveloped virus 4302 are present in the enveloped virus 4304, while the enveloped virus further includes an encapsulating lipid bilayer 4360, such as derived from a host, where the lipid bilayer typically has additional features, such as glycoproteins 4370.
  • Example I 180030844.1 75 Attorney Docket no. EXNI0001
  • Figure 44A a first example of interaction between a tuned cationic polymer 300 and/or any charged polymer with a virus 4300 is illustrated. As illustrated, the positively charged protonated sites 241 of the polymer 200 are electrically attracted 4410 to the negatively charged locations 4312 of the virus 4300.
  • the electrical attraction 4410 optionally occurs many times as both the polymer 200 and the virus 4300 have multiple charged sites, which in this first example causes the tuned cationic polymer 300 to circumferentially encompass the virus 300, thus blocking interaction of the virus with a host, which effectively inactivates the virus 300.
  • Example II Referring now to Figure 44B, a second example of interaction between a tuned cationic polymer 300 and/or any charged polymer with a virus 4300 is illustrated. As illustrated, the positively charged protonated sites 241 of the polymer 200 are electrically attracted 4410 to the negatively charged locations 4312 of the virus 4300.
  • the electrical attraction 4410 optionally occurs many times as both the polymer 200 and the virus 4300 have multiple charged sites, which in this second example causes the tuned cationic polymer 300 to be electrically attracted to multiple sites of the virus, such as around greater than 10, 20, 30, 40, 50, 60, or 70 percent of a circumference of the virus 4300.
  • the polymer 200 sterically blocks part of the virus, which may result in partial inactivation of the virus.
  • Example III Referring now to Figure 45, a third example of interaction between a tuned cationic polymer 300 and/or any charged polymer with multiple viruses 4300 is illustrated.
  • the positively charged protonated sites 241 of the polymer 200 are electrically attracted 4410, as described above, to the negatively charged locations 4312 of more than one virus 4300.
  • the electrical attraction 4410 optionally occurs many times on a single virus 4300.
  • a first cationic polymer 4511 is optionally electrically 180030844.1 76 Attorney Docket no. EXNI0001 attracted simultaneously to a set of viruses 4520, such as to a first virus 4521, a second virus 4522, and a third virus 4523.
  • a second cationic polymer 4512, of a set of cationic polymers 4510 is optionally attracted to a common virus attracted to the first cationic polymer 4511, such as the second virus 4522, while simultaneously being attracted to a fourth virus 4524, where the fourth virus 4524 is not interacting with the first cationic polymer 4511.
  • any number of cationic polymers optionally interact with any number of viruses to form a virus-polymer conglomerate 4500, such as where the number of cationic polymers in the virus-polymer conglomerate 4500 is greater than 1, 2, 5, 10, 50, 100, 500, 1000, 10,000, or 100,000.
  • the virus-polymer conglomerate 4510 is also optionally referred to herein as a virus globule and/or a virus-polymer globule, which may be large enough to settle out of solution and/or form a solid.
  • the conglomerate optionally functions to inactivate a percentage of the virus, such as greater than 50, 60, 70, 80, 90, 99, 99.9, or 99.99% of the viral activity.
  • Activity Now that electrically driven virus-protein attractions have been discussed, the importance of the activity, ⁇ , and/or the activity coefficient, ⁇ , of a solution containing the tuned cationic polymer 300 is further addressed.
  • a virus 4300 having negatively charged locations 4312 and a tuned cationic polymer 300 having positively charged protonated sites 241 is illustrated with a high activity 4610 and a corresponding large ionic attractive force 4620 between the virus 4300 and the tuned cationic polymer 300.
  • a second lower activity case 4650 in a second lower activity case 4650, the virus 4300 and the tuned cationic polymer 300 are again illustrated, but with additional ions in solution, which leads to a lower activity coefficient 4660 and a correspondingly weaker ionic attractive force 4670 between the virus 4300 and the tuned cationic polymer 300.
  • the high activity is optionally an activity coefficient, for a given protonated site of the polymer, of greater than 0.2, 0.3, 0.4 and optionally and preferably greater than 0.5, 0.6, 0.7, 0.8, 0.9, 0.95. or 0.98 and less than 0.9999.
  • the greater the activity coefficient the stronger the large ionic attractive force 4620.
  • the high activity coefficient 4610 is greater than 0.05, 0.1, or 0.2 larger than the low activity coefficient 4660.
  • An example of the low activity coefficient is the activity of the charged polyethylenimine 250 after reaction with a strong acid, such as hydrochloric acid, in a protonation step of protonating the polymer, such as at a pH less than three.
  • An example of the high activity coefficient is the activity after any de-salting, chloride reduction step, and or a step of using an anion exchange bead, as described supra.
  • a higher activity coefficient and/or lower conductivity of a formulation aids in maintaining an actual ionic attractive force between the polymer 200 and the virus 4300, which is optionally measured as a percent inactivation / percent kill of the virus, such as in the above described government tests.
  • reducing salt to increase the activity coefficient, ⁇ to greater than 0.8, 0.9, 0.95, 0.96, 0.97, 0.98, 0.99, 0.995 and/or less than 0.9999 or 0.9995 increases the effectiveness of the formulation (as described herein) against viruses and/or encapsulated viruses.
  • lowering a conductivity of the formulation to 0.1 to 10 mS/cm, to less than 10, 100, 500, 1000, or 10,000 mS/cm, and/or to within a range of greater than 0.5, 1, or 2 mS/cm and less than 50, 25, 10, 8, 6, 4, or 3 mS/cm is used to increase effectiveness of the charged sites of the polymer interacting with charged sites of the virus, which increases inactivation of the virus rates, as described herein.
  • Liquid/Film Biocide Referring now to Figures 47-50, delivery of a biocide with a controlled total charge is described.
  • a method of charge control 4700 / control of delivery of tuned cationic polymer 300 and/or the tuned cationic polymer 300 in a formulation is illustrated.
  • a biocide of known charge density is delivered in 180030844.1 78
  • Attorney Docket no. EXNI0001 a solvent with a known volume, which yields a total cationic charge, such as at a pH with an activity, so that a calculable / controlled charge is delivered to a microbe / bacteria / virus / fungus / surface.
  • a liquid biocide 4710 such as any of the polymers 200 described herein, is contained in a delivery container 4720 along with a solvent 4730.
  • the solvent contains water and/or any organic solvent, such as a solvent that readily evaporates at room temperature and pressure.
  • an activity 3742 / activity coefficient of a polymer–solvent combination is controlled, such as described supra.
  • the tuned polymer 210 is at least one of the polymers 200 in the delivery container 4720.
  • the tuned polymer 210 has a charge density 4730, such as total cationic charge per milliliter of solution and the pH 3722 is known, buffered, and/or controlled.
  • the tuned polymer 210 and/or the tuned polymer 210 in a formulation is used in a step of coating a substance 4740, such as with a mist / spray 4742 and/or in any delivery manner, such as with a wipe.
  • the step of coating a substance 4740 delivers a controlled volume 4744, such as within 1, 2, 5, 10, 25, or 50 percent of 1, 2, 5, 10, 15, 20, 25, 50, 100, 250, 500, 1000, 2000, or 5000 ⁇ L. Delivery of a controlled volume 4744 is optionally and preferably used to deliver a total charge 4732, such as a total cationic charge per delivery dose.
  • the tuned polymer 210 is used to form a film 4750, such as through the coating a substance 4740 step.
  • the step of forming the film 4750 optionally delivers a solvent with a known evaporation rate 4752 and/or a known evaporation percentage 4754 as a function of time and/or temperature to form a film with a film state 4760, such as a charged density 4762, such as a total cationic charge per gram or liter, which is often expressed in total cationic charge / mg and/or total cationic charge / ⁇ L.
  • the formed film state 4760 optionally and preferably has a film durability 4764, such as meeting any of the above described durability measures.
  • the tuned polymer 210 is optionally delivered in any manner that: (1) delivers a known volume, total charge, and/or total cationic charge and/or (2) covers a surface or object over a given surface area, such in a delivery manner and/or delivery volume that delivers any of the above described parameters per sq. inch and/or per cubic inch. For clarity of presentation and without loss of generality, examples of delivery methods are provided here.
  • Example I Referring now to Figure 48(A-C), a first treatment method is illustrated. Referring still to Figure 48A, a spray bottle 4800 is illustrated for delivery of the tuned polymer 210, such as in a formulation solution.
  • the spray bottle 4800 includes a container 4720.
  • Contents 4820 of the container 4720 include at least a solvent 4730 and the tuned cationic polymer 302, which is optionally suspended and/or dissolved in the solvent 4730.
  • Contents 4820 optionally include any number of formulation components, such as a buffer, scent, an inactive ingredient, an emulsifier, a stabilizer, a thickener, and/or an antioxidant.
  • any formulation described herein contains more than one antibacterial and/or antiviral component, such as via inclusion of a quaternar4y amine and/or any form of a polyDADMAC.
  • any dispenser 4840 is used to dispense the contents 4820 of the container 4720, such as into the air and/or onto a substrate as a spray / mist / liquid / foam.
  • Common dispensers 4840 include trigger spray dispensers, pump spray dispensers, aerosol spray dispensers, airless spray dispensers, and/or foam spray dispensers.
  • the dispenser 4840 includes a nozzle 4844 and a trigger pump 4842.
  • the container 4720 is pressurized, such as with a compressed gas 4740 / expansion fluid, and is operated with a spray nozzle 4840.
  • the dispenser is a wipe 4860, which dispenses the tuned cationic polymer 302 onto a surface / substrate.
  • the wipe 4860 optionally and preferably contains the solvent 4730, which optionally and preferably rapidly evaporates after application to the 180030844.1 80 Attorney Docket no. EXNI0001 surface, such as greater than 50, 75, or 90 percent evaporation in less than 60, 30, 20, or 10 seconds. Still referring to Figure 48A and Figure 48B, optionally and preferably the charge density, referring to the total cationic charge, of the contents 4820 is 0.001 to 0.999 meq/g. An equivalent (eq) is the amount of a substance needed to react with or supply one mole of hydrogen ions (H + ) in an acid–base reaction.
  • the total cationic charge of the contents 4820 is greater than 0.001, 0.005, 0.01, 0.02, or 0.03 meq/g or meq/mL and less than 100, 50, 25, 10, 7, 5, 3, 1, 0.9, 0.8, 0.5, 0.2, 0.1, 0.07, or 0.05 meq/g or meq/mL.
  • Lysol TM (Parsippany, New Jersey, United States) has a charge of 0.003 meq/mL, but the charges in Lysol TM are from toxic quaternary ammonium molecules as opposed to the relatively non-toxic polymers described herein.
  • a charge, referring to the total cationic charge, of the contents 4820 is controlled per application, dose, delivery time, and/or delivery volume.
  • a preferable dose of total cationic charge of the contents is optionally and preferably within 10, 20, 50, or 100 percent of 1.45 C/mL or 1.45 C/g.
  • the total cationic charge of the contents per dose is greater than 0.05, 0.1, 0.5, or 1 C/mL or C/g and less than 50, 20, 10, 5, 4, 3, or 2 C/mL or C/g.
  • Example II Referring now to Figure 49, a second treatment method 4900 is illustrated.
  • a substrate is treated 4910 with a method, such as coating 4912, spraying 4914, dipping 4916, and/or electrocoating 4918, to form a film 4750, such as a liquid film 4751, which optionally at least partially evaporates to form a semi-solid film 4753 and/or a solid film 4755.
  • a semi-solid film has properties of both solids and liquids, such as viscosity and the ability to flow 180030844.1 81 Attorney Docket no. EXNI0001 under stress while still maintaining some structural integrity.
  • a semi-solid film offers a versatile and adaptable material for a wide range of applications where a balance between the properties of liquids and solids is desired.
  • Example III Referring now to Figure 50A and Figure 50B, a third treatment method 5000 is illustrated where a liquid film 4751 and a solid film 4755, respectively, are formed on a substrate 5010.
  • a substrate is optionally and preferably any material or surface upon which the tuned cationic polymer 302 is applied or deposited.
  • Figures 50C and 50D illustrate an adhesion promoter 5020 interspersed in the film 4750, such as the liquid 4751 and/or solid films 7542, and between the film 4750 and the substrate 5010 respectively.
  • the adhesion promoter 5020 is not a separate glue layer; rather, the adhesion promoter 5020 is added to the solution/formulation and aids bonding to the substrate 5010 and/or physically and/or chemically at least partially separates from the solution/formulation, such as to form a bonding layer as illustrated in Figure 50D.
  • An example of an adhesion promoter 5020 is polyDADMAC 554.
  • Optional and preferred concentrations of the polyDADMAC 554 / adhesion promoter 5020 are percentages of a concentration of the charged polymer, such as the polyethylenimine 552.
  • the adhesion promoter concentration such as by mass or parts per million, is greater than 5, 10, 20, 25, or 30 percent that of the charged polymer and/or less than 150, 100, 75, or 50 percent that of the charged polymer.
  • the adhesion promoter 5020 in a solution and/or a formulation is further described infra.
  • Film As described herein, without wishing to be bound to any particular theory, one theory is cationic charges of the polymer 200 bind to, penetrate into, and/or disrupt function of a bacteria, a virus, and/or a fungus.
  • a total cationic charge is a charge of all of the positively charged groups, which does not include anionic charge from any counterion and/or any anion on the polymer.
  • a total cationic charge of the formulation and/or a total 180030844.1 82 Attorney Docket no. EXNI0001 cationic charge of a film is a charge of all of the positively charged groups in the formulation, such as in the contents 4820 of the container or the total cationic charge of the film, such as the solid film 4755, which does not include anionic charges, such as from any counterion and/or any anions in the contents in the delivery container 4720.
  • a tuned total cationic charge is delivered to a surface, such as to a unit area of a surface and/or in a volume.
  • a surface such as to a unit area of a surface and/or in a volume.
  • the total cationic charge of the film per square inch is in the range of 0.001 C/sq. in. to 20 C/sq. in. and is optionally and preferably greater than 0.001, 0.003, or 0.1 C/sq. in. and less than 10, 5, 4, 3, 2, or 1 C/sq.
  • cationic charges in the solvent and/or additional elements in the contents 4820 of the container 4720, such as protons, cationic metals, Mg 2+ , Ca 2+ , Na + , K + , iron cations, ammonium ions, and/or cations.
  • Exemplary effective doses of polyethylenimine (LPEI) and/or polyDADMAC are provided in Table 3, where the effective doses pass one or more of the government tests described supra. Table 3: Total Cationic Film Charge Concentration Ionization Volume Film (ppm) (Percent) ( ⁇ L) Charge (C/sq.
  • a total cationic charge used in a biocide treatment such as in a unit of liquid dispensed and/or in a film formed is greater than 0.2, 0.4, 0.6, 0.8, 1, 1.2, 1.4, or 1.8 coulombs and/or is less than 100, 75, 50, 25, 10, 5, 4, 3, 2, or 1 coulombs, such as where a unit of fluid delivered is within 10, 25, or 50% of any of 0.1, 0.2, 0.5, 1, 2, 3, 5, or 10 mL.
  • the cationic charge in the film from the solvent used to form the film and/or from a salt present in the film is optionally greater or less than 0, 0.01, 0.03, 0.05, 0.1, 0.5, 1, 2, or 5 coulombs per square inch.
  • a general process 5100 of forming polyethylenimine 5110; purifying polyethylenimine 5120; tuning polyethylenimine 5130; generating a formulation 5140, such as containing polyethylenimine and/or any quaternary amine; and forming a film 4750, such as containing polyethylenimine is illustrated.
  • a production process 5200 of forming a poly(2- alkyl-2-oxazoline) is illustrated.
  • an oxazoline 5210 is used as a starting material, where oxazoline is a five membered ring with the formula 180030844.1 84 Attorney Docket no. EXNI0001 C3H5NO.
  • Oxazolines 5220 with an emphasis on the plural, are a family of compounds.
  • 2-alkyl-2-oxazoline 5230 refers to oxazoline 5210 with an alkyl group, such as attached to a carbon between the nitrogen and the oxygen in oxazoline 5210.
  • the alkyl group is a methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, hexyl, heptyl, octyl, nonyl, phenyl, or benzyl group, to name but a few potential alkyl groups.
  • alkyl group contains 1, 2, or more than 2, 3, 4, 5, or 6 carbons.
  • an oxazoline with an attached alkyl group such as 2-alkyl-2-oxazoline, is subjected to ring opening polymerization 5240 to form a polymer, particularly a poly(2-alkyl-2-oxazoline) 5250.
  • acyl group is optionally removed from any 1 or more monomers to form deacylated monomers and/or protonated and deacylated monomers 5280, such as with reaction with an acid, as further described infra.
  • deacylated monomers and/or protonated and deacylated monomers 5280 such as with reaction with an acid, as further described infra.
  • any amount of a 2- alkyl-2-oxazoline is added to and/or maintained in any formulation described herein.
  • an acylated monomer 5260 of the poly(2-ethyl-2- oxazoline) 5252 and/or the poly(2-alkyl-2-oxazoline) 5250 is optionally deacylated to form a second monomer type, where the second monomer type is optionally protonated, thus forming a first copolymer 5290.
  • a first monomer, the acylated monomer 5260 with a -N-CH2-CH2- backbone is optionally deacylated to yield a second monomer with a -N-CH 2 -CH 2 - backbone that is deacylated and deprotonated 5270.
  • the second monomer is protonated to form a deacylated and protonated monomer 5280 with a -NH + - CH2-CH2- backbone, with the nitrogen being protonated.
  • the first copolymer 5290 has repeating units of: (1) the acylated monomer 5260 with a -N-CH2-CH2- backbone and (2) the deacylated and protonated monomer 5280 with the -NH + -CH 2 -CH 2 - backbone, albeit where any number of the deacylated and protonated monomers 5280 are optionally unprotonated to form the deacylated and deprotonated -N-CH2-CH2- backbone, such as at higher pH values.
  • the two monomer types are optionally arranged in any order and with any repeating lengths in the copolymer.
  • any ratio of the first monomer-to-the second monomer is used in an antipathogen formulation. 180030844.1 85 Attorney Docket no. EXNI0001
  • a preferred ratio of the deacylated and protonated monomer 5280 with the -NH + -CH 2 -CH 2 - backbone-to-the acylated monomer 5260 with a -N- CH2-CH2- backbone exceeds 0.1, 0.25, 0.5, 1, or 2-to-1.
  • the inventors recognize that the three monomers in the polymer are optionally referred to as a tripolymer; however, the inventors further recognize that one skilled in the art would recognize that the second monomer of the copolymer is simply in different equilibrium forms dependent upon pH. Thus, for clarity of presentation the copolymer terminology is used herein.
  • the acylated monomers 5260 are fully converted into deacylated monomers that are unprotonated 5270 and protonated 5280 in various ratios
  • the first copolymer 5290 is fully converted to polyethylenimine, in various states of protonation, as described herein.
  • oxazolines 5220 illustrative of many possible oxazolines 5220, are illustrated: a 2-methyl-2-oxazoline 5221 (MeOx), a 2-ethyl-2-oxazoline 5222 (EtOx), a 2-propyl-2-oxazoline 5223 (PropOx), a 2- isopropyl-2-oxazoline 5224 (i-propOx), and a 2-phenyl-2-oxazoline (PhOx).
  • a cationic ring-opening polymerization CROP
  • CROP cationic ring-opening polymerization
  • a CROP reaction proceeds through an SN1 or SN2 propagation / polymer chain growth process, such as where a terminus of a polymer chain attacks cyclic monomers to form a longer polymer.
  • a poly(2-ethyl-2-oxazoline) 5252 is formed.
  • the poly(2- ethyl-2-oxazoline) 5252 is further described in Figure 54.
  • an acyl group 5251 is illustrated, such as bound to a monomer of the poly(2-alkyl-2-oxazoline) 5250.
  • R group of the acyl group 5251 is optionally any hydrocarbon chain 5253, such as the illustrated ethyl group.
  • the hydrocarbon chain is any chain of carbons with at least some hydrogens attached to the chain of carbons, such as where an alkyl group or hydrocarbon chain is a methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, hexyl, heptyl, octyl, nonyl, phenyl, or benzyl group.
  • An acyl group with a ethyl hydrocarbon chain 5261 attached to a nitrogen of a monomer of the polymer is illustrated in Figure 53B.
  • the ethyl hydrocarbon chain 5261 is an example of an alkyl / alkyl group.
  • an alkyl group is a carbon chain missing one hydrogen, where in chemistry the alkyl term is intentionally unspecific to allow for many possible substitutions.
  • cleaving an acyl group in a deacylation process 5400 from a poly(2-alkyl-2-oxazoline) 5250 is illustrated.
  • an acyl group 5251 also referred to herein as a pendant, is bound to the nitrogen in the monomer.
  • An acyl group 5251 is a moiety derived by the removal of at least one hydroxyl group from an oxoacid.
  • one or more monomers of the poly(2-alkyl-2-oxazoline) are deacylated and/or deacylated and protonated and/or a polyalkylenimine is generated, such as in an at least partially protonated state.
  • the poly(2-alkyl-2-oxazoline) is optionally used to form a copolymer.
  • the poly(2-alkyl-2-oxazoline) contains a first monomer with an acylated monomers comprising a -COR1 group attached to a nitrogen of a -N-CH 2 -CH 2 - element, wherein R 1 comprises an alkyl group.
  • the poly(2-alkyl-2-oxazoline) When the poly(2-alkyl-2-oxazoline) is reacted with an acid, such as a strong acid or a concentrated hydrochloric acid, the poly(2-alkyl-2-oxazoline) forms at least some second monomers.
  • the second monomers are unprotonated and/or are protonated monomers comprising a -NH 2 + -CH 2 -CH 2 - group.
  • the acylated monomers and the protonated monomers comprising any order in the copolymer. If the reaction is run to completion, the poly(2-alkyl- 180030844.1 87 Attorney Docket no.
  • EXNI0001 2-oxazoline is fully deacylated and a polyalkylenimine is formed, such as in a protonated state, as further described infra.
  • a polyalkylenimine is formed, such as in a protonated state, as further described infra.
  • an acid, H+, and water are reacted with the poly(2- alkyl-2-oxazoline) 5250 to form a protonated polyalkylenimine 5410 and a carboxylic acid 5420.
  • hydrochloric acid 632 is used as the acid.
  • any acid, and optionally and preferably any strong acid is used in conjunction with or in place of the hydrochloric acid 632.
  • use of another acid will substitute another counterion for chloride.
  • the counterion ion is HSO4- instead of Cl-.
  • the conjugate base of any acid, and preferably any strong acid is the generated counterion to the protonated sites 310 of the protonated polyalkylenimine 5410 / polyalkylenimine / polyethylenimine 250.
  • nitric acid HNO 3
  • the counterion is nitrate, NO 3 -
  • sulfuric acid, H 2 SO 4 is used as the acid, then hydrogen sulfate, HSO 4 - and/or sulfate, SO4 2- , is the resulting counterion
  • hydrogen sulfate, HSO4- is used as the acid, then sulfate, SO 4 2-
  • phosphoric acid, H3PO4 is used as the acid then dihydrogen phosphate, H 2 PO 4 -, and/or hydrogen phosphate HPO 4 2- , is/are the resulting counterion(s).
  • the acid is optionally supplied on an ion exchange material, ion exchange bead, and/or an ion exchange resin.
  • the ion exchange resin as described supra, contains a sulfonic acid group, R-SO3H, then the counterion is hydrogen sulfate, HSO 4 - and/or sulfate, SO 4 2- .
  • ion exchange resins with sulfonic acid groups, -SO3H function as a strong acid catalyst to facilitate hydrolysis of the acyl group 5251 in the poly(2- alkyl-2-oxazoline) 5250 by providing protons, H + .
  • the deacylation process results in: an at least partially deacylated poly(2-alkyl-2- oxazoline), an at least partially deacylated and an at least partially protonated/acidified poly(2-alkyl-2-oxazoline), and/or an at least partially 180030844.1 88 Attorney Docket no. EXNI0001 protonated polyalkylenimine in the solution and/or a formulation derived therefrom.
  • the deacylation process 5400 of the poly(2-alkyl-2- oxazoline) 5250 yields a carboxylic acid 5420 in addition to the protonated polyalkylenimine 5410.
  • the inventors have determined that the yield of the protonated polyalkylenimine 5410 depends on not only temperature, acid concentration, reaction time, and pressure, but also on the removal of the carboxylic acid group 5420 from the reactor, which effectively drives the deacylation process 5400 forward, such as according to LeChatelier’s Principle.
  • FIG. 54B an exemplary case of reacting poly(2-ethyl-2- oxazoline) 5252 with acid and water to form a protonated polyethylenimine 251 and propanoic acid 5422, a carboxylic acid 5420, is illustrated.
  • Removal of at least 0.01, 0.02.0.05, 0.1, 0.25.1, 2, or 5 percent and preferably greater than 50, 75, 80, 90, 95, 99, or 99.9 percent of the carboxylic acid group 5420 from the reactor and/or from a final formulation is preferred as the propanoic acid and propanoate formed therefrom at preferred formulation pH’s in the range of 2.5 to 8 and/or within 0.25 or 0.5 pH units from a pH of 4, 5, or 6 is preferred.
  • propanoate is used as a counterion to the protonated sites 310 of the polyethylenimine 250 at any concentration, such as greater than 0, 1, 2, 5, or 10 percent and/or less than 100, 99.9, 99, 98, 95, or 90 percent of all counterions in a final formulation.
  • the propanoic acid / propanoate exchange further functions as a buffer to pH change in this case. 180030844.1 89 Attorney Docket no. EXNI0001 Referring now to Figure 55, formula preparation 5500, such as with polyethylenimine 250, is described.
  • Polyethylenimine is formed 5110 chemically through the reaction of poly(2-ethyl-2-oxazoline) with an acid, such as hydrochloric acid 632, and water 5512, as described supra.
  • an acid such as hydrochloric acid 632
  • the inventors have determined that the yield of the resulting protonated polyethylenimine 251 is dependent upon reaction conditions, such as heat 3719.
  • a reaction chamber / reactor, containing the reactants is maintained at greater then 80, 90, 100, 110, 120, or 130 °C for greater than 1, 2, 4, 7, 8, 15, 16, 23, or 24 hours.
  • Maintaining the reactor at an increased pressure 3721 such as at greater than 1, 1.1, 2, 2.1, 2.2, 2.5, 3, 3.5, 3.9, or 4 bar is preferred, which results in effectively higher temperatures, such as greater than 131, 135, 140, or 145 °C.
  • the reaction removes the pendant 5120.
  • the reactor is optionally and preferably opened up to atmosphere, which reduces the pressure 3723.
  • Maintaining the reactor at an elevated temperature such as at greater than 50, 70, 80, 90, 100, 110, 120, or 130 °C for greater than 1, 2, 4, 7, 8, 15, 16, 23, or 24 hours drives off the propionic acid / propanoic acid 5422 / carboxylic acid 5420, which pulls the reaction forward and allows more of the poly(2-ethyl-2-oxazoline) to react with the acid to form more of the protonated polyethylenimine.
  • the poly(2-ethyl-2- oxazoline) is deacylated and the pendant is removed 5120 from the poly(2- ethyl-2-oxazoline), at greater then 90, 95, 98, 99, 99.5, 99.9, or 99.99 percent and/or the reaction is driven forward to greater than 95, 99, 99.9, or 99.99 percent yield.
  • Opening the reactor to atmospheric pressure and maintaining the reactor at elevated temperatures also functions to vent the hydrochloric acid 633, such as into a filter or acid trap, which reduces the amount of acid in the reactor by greater than 0, 0.1, 0.5, 1, 2, 3, 5, or 10 percent.
  • the removal of hydrochloric acid and/or the propanoic acid 5422 functions to purify the generated polyethylenimine 250.
  • Each of the elevated temperature, elevated pressure, and carboxylic acid removal processes are observed to alter inactivation properties of formulations using the polyethylenimine 250, which might be due to unfolding of the polyethylenimine 250 and/or effective activity 180030844.1 90 Attorney Docket no. EXNI0001 of protonated sites on the polyethylenimine 250.
  • Further purification of the polyethylenimine 5130 is described infra. Still referring to Figure 55, steps of purifying the polyethylenimine 5130 are further described.
  • reducing the pressure 3723 and maintaining the reactor at an elevated temperature drives off the pendant 5120 from the reactor.
  • the supernatant 5134 is separated from the precipitate 5132, such as the polyethylenimine precipitates.
  • temperature control 5136 is used to evaporate water and/or the water concentration is reduced 5513 through a drying step. The drying step also further reduces the hydrochloric acid 635 by greater than 1, 2, 5, 10, 25, 50, 75, 90, 95, or 99 percent.
  • Controlling humidity 5138 such as to less than 90, 75, 50, 25, or 10 percent further aids the removal of water 5513 and also is optionally used to still further remove the hydrochloric acid 635, which is attracted to any remaining water.
  • a reduction in pressure, stirring, and/or rinsing the precipitate is used to still further reduce the hydrochloric acid content to less than 25, 10, 5, 2, 1, 0.1, or 0.01 percent by mass.
  • the reduction of the chloride counterion concentration and/or the chloride counterion concentration is observed to alter the antibacterial / antiviral efficacy of formulations generated using the purified polyethylenimine.
  • the polyethylenimine is purified 5120 and tuned 5130, as described supra.
  • a formulation 5140 is subsequently prepared.
  • the formulation 5140 is prepared by mixing any amount of the polyethylenimine 250 with any solvent 5142, such as ethanol, any amount of polyDADMAC 554, any amount of any quaternary amine 5150 / quaternary ammoniums, any acid(s) 5160, any buffer, and/or any amount of formate 324, acetate 326, citrate- and citrate 2- 327, chloride 322, iodide 325, bromide, nitrate, sulfate, nitrite, hydrogen carbonate, hydroxide ion, sulfide, and/or S 2- , any of which are optionally used as counterions and/or in a control of counterions 5162, such as type, to any positively charged species in the final formulation.
  • any anion is present at a mass concentration of greater than 0, 0.01, 0.03, 0.05, 0.1, 1, or 5 percent.
  • the ratio of a first ion to a second ion is greater than 1:1, 1:0.5, 1:0.1, or 1:0.01; the ratio of the first ion and/or the second ion to a third ion is greater than 1:1, 1:0.5, 1:0.1, or 1:0.01; the ratio of the third ion to a fourth ion is greater than 1:1, 1:0.5, 1:0.1, or 1:0.01; the ratio of the third ion and/or a fourth ion to a fifth ion is greater than 1:1, 1:0.5, 1:0.1, or 1:0.01.
  • the pH 3722 of the formulation is optionally and preferably set to a pH greater than 2, 3, 4, or 5; to a pH less than 14, 12, 10, 8, 7, or 6; in a pH range of 2-10, 3-9, 3-8, 3-7, and/or 4-6; and/or to a pH within any of ⁇ 0.25, 0.5, 0.75, 1.0, or 2 of any of 3, 4, 5, 6, or 7.
  • the salt content 5170 affects the ability of the charges on the polyethylenimine 250 to interact with surfaces of the bacteria and/or virus.
  • the salt content 5170 / salt concentration is optionally and preferably set to greater than 0, 1, 2, 5, 10, 50, or 100 ppm and/or to less than 3000, 2500, 2000, 1000, 750, 500, 250, 100, 50, 40, 30, or 20 ppm, which further tunes efficacy of the formulation antibacterial / antiviral effectiveness.
  • denaturant components of the ethanol such as methyl ethyl ketone, acetone, and/or methanol, are left in the formulation at concentrations of greater than 1, 2, 5, 10, 50, or 100 ppm.
  • the denaturants are optionally removed from the formulation.
  • a surfactant is optionally provided in the formulation.
  • a surfactant examples include Tween 20, a polyethylene glycol sorbitan monolaurate, and/or a non- ionic detergent.
  • the formulation 5140 is optionally used directly, such as in a 180030844.1 92 Attorney Docket no. EXNI0001 spray, and/or is used to form a film 4750.
  • the film 4750 is further described infra.
  • Film A film 4750 is optionally formed from the formulation, such as by drying.
  • the film 4750 of preferred formulations have properties, described infra.
  • the formulation / formulation of the solution prior to drying comprises: a polyethylenimine concentration of 0 ppm; greater than 10, 50, 100, 1000, 2000, 3000, 4000, 5000, 7500, or 10,000 ppm; and/or less than 15,000, 10,000, 7,500, 5500, 4500, or 3500 ppm; a polyDADMAC concentration and or a concentration of any one or more quaternary ammonium compounds of 0 ppm; greater than 10, 50, 100, 1000, 2000, 3000, 4000, 5000, 7500, or 10,000 ppm; and/or less than 15,000, 10,000, 7,500, 5500, 4500, or 3500 ppm; an acid / conjugate base pair with a concentration of 0 ppm; greater than 1, 5, 10, 50, 100, 200, 300, 400, 500, 750, or 1000 ppm; and/or less than 5,000, 2500, 1000, 500, 300, or 200 ppm, where the acid / conjugate base pair is optionally any
  • Film properties are tuned for safety, efficacy, durability, additive killing, and/or longevity of killing using particular formulations in the ranges set forth herein.
  • Film Properties Referring now to Figure 57, an optional and preferred film property is additive killing 5700.
  • additive killing refers to treating a surface and killing / inactivating a percent of an original dose of bacteria, virus, and/or fungus present on the surface or applied to the film 4750 at a single point in time.
  • a representative formulation of 4000 ppm polyethylenimine 250, 2000 ppm polyDADMAC 554, 3600 ppm formic acid in balance with formate at a pH of 4.0, and 500 ppm hydrochloric acid is used to kill / inactivate greater than 1, 5, 9, 10, 50, or 99 percent of the bacteria Staphylococcus aureus and/or 180030844.1 93
  • Attorney Docket no. EXNI0001 the germ Pseudomonas aeruginosa in 10 minutes or less and greater than 99.9999 percent of the Staphylococcus aureus and/or the Pseudomonas aeruginosa in 100 minutes or less.
  • various formulations, as described herein, using at least the polyethylenimine 250 as prepared using a methodology as described herein are used to reduce activity of the a bacteria contacting the film by: greater than 1, 5, 9, 10 or 20% and less than 99.99995% in less than one minute; greater than 99.999% in less than four days; and greater than 99.99995% in less than seven days.
  • the additive killing, longevity of killing, and/or the durability of killing of bacteria, viruses, and/or fungi is optionally and preferably performed in any order and/or simultaneously. For instance, a film is applied to a surface, the bacteria and virus are both treated simultaneously.
  • a film is applied to a surface and bacteria subsequently are applied to the surface and inactivated, then viruses co-placed with the bacteria on the film are treated at the same time as the bacteria.
  • viruses co-placed with the bacteria on the film are treated at the same time as the bacteria.
  • a virus/bacteria is placed on a film, subsequent placement of second or later batched of virus/bacteria are later treated by the film, such as when newly introduced virus/bacteria make contact with the film.
  • Formulations Referring now to Figure 58, preparation / use of a formulation 5800 is described.
  • a charged polymer is provided 5810, such as in a solvent and/or a solvent is added 5820 to the charged polymer and/or to the formulation 5140 in step(s) of generating a formulation 5830.
  • one or more buffers are added 5840 to the formulation 5840 at any concentration.
  • one or more salts are added 5850 to the formulation 5140 and/or are removed from the formulation 5140, such as to tune the conductivity and/or activity coefficient, which aids inactivation/killing properties of the formulation 5140 against pathogen(s).
  • one or more acids and/or bases are added 5860 to the formulation 5140.
  • one or more adhesion promoters 5870 are added to the formulation, which, in combination with the above steps, alters the critical load 180030844.1 94 Attorney Docket no. EXNI0001 of adhesion of the formulation 5140 in a dried film state to the substrate 5010.
  • the formulation is formulated to contain a desired total cationic charge and/or a total anionic charge per mL, per dose, or per volume, where the total cationic charge and/or the total anionic charge is offset by counterions in the formulation.
  • the types of charge sources affects inactivation of pathogens performance as described throughout.
  • the formulation 5140 is sprayed 5880 and/or wiped on a surface to form a film 5890, such as a liquid film and/or a semi-solid / solid film after drying as described herein.
  • Silanes and polyDADMAC are examples of adhesion promoters, where polyDADMAC has an additional advantage of being an antipathogen in the formulation.
  • adhesion 5900 is illustrated, such as between a dried film containing the polyethylenimine / charged polymer and the substrate 5010.
  • a 4000 ppm polyethylenimine in a solvent of 25% water and 75% ethanol with a 2000 ppm polyDADMAC adhesion promoter is illustrated, where the formulation also included 100 ppm citric acid, which provides an antipathogen counterion as well as a pH buffer.
  • the charged polyDADMAC additionally functions as an antipathogen.
  • the adhesion or critical load of adhesion to a glass substrate was 180, 120, and 80 ⁇ N at a pH of 4, 5, and 6, respectively.
  • the achieved, optional, and/or preferred adhesions of the dried formulation on a substrate are greater than 10, 20, 30, 50, 75, 100, or 125 and/or less than 1000, 600, 500, 400, 300, 250, 200, or 150 ⁇ N.
  • critical load of adhesion or simply adhesion refers to the minimum applied load at which a coating or thin film begins to detach or delaminate from its substrate, signifying the point where the adhesive forces between the two materials are overcome and failure occurs.
  • a critical load of adhesion is typically measured using a scratch test method, as was done to obtain the illustrative values in Figure 59 for the illustrative specified formulation, where 180030844.1 95 Attorney Docket no.
  • the critical load is considered a measure of the adhesion strength between the coating and substrate.
  • the critical load of adhesion is typically measured in units of force (Newtons, N) as it represents the maximum load that can be applied to an adhesive joint before it fails, and is usually expressed as force per unit area (Pascals, Pa) when considering the adhesion strength of a material.
  • Force, stress, scratch test results, coating thickness, substrate, scratch stylus form, and surface roughness are all optionally and preferably considered/included in determination of the adhesion strength.
  • Example I In a first example, additive killing / inactivation of less than 99.99% of bacteria/virus in 10 minutes and greater than 99.999% within 100 minutes uses a film incorporating at least one quaternary ammonium, such as polyDADMAC at a concentration of 500 ppm, and a total positive charge of at least 10, 50, 100, 500, 1000, 2000, 3000, 4000, 5000, 6000, 7000, 10000, and/or 15,000 C/in 3 , where the total positive charge is the charge of all of the positive sites in the formulation, which are offset by anionic counterions in the formulation.
  • quaternary ammonium such as polyDADMAC at a concentration of 500 ppm
  • the film is formed on one square inch of substrate with greater than 100, 200, 299, 300, 400, or 500 ⁇ L of polyethylenimine at a concentration of with 500 ppm or 3000, 4000, or 5000 ppm or of at least 500, 1000, or 2000 ppm.
  • the polyDADMAC aids bacterial / viral inactivation as the polyDADMAC with or without a surfactant helps the formulation adhere to a substrate, such as metal or glass.
  • Example II In a second example, the number/density of charged sites / protonated sites is set at a high enough level to inactivate the bacteria/virus. Without wishing to 180030844.1 96 Attorney Docket no.
  • EXNI0001 be held to any one theory, the charged sites of the film electrostatically bind to and/or block corresponding oppositely charged sites of the bacteria / virus. It is found that a film with greater than 1 x 10 5 and preferably greater than 5 x 10 10 or 5 x 10 15 protonated sites/in 2 functions to inactivate / block at least 99.999% of bacteria within 1 hour.
  • the protonated sites such as a protonated secondary amine of polyethylenimine and/or a protonated site of a quaternary amine, such as a quaternary ammonium and/or polyDADMAC each have corresponding negatively charged counterions.
  • Example III In a third example, during the deacylation step of a starting material for polyethylenimine, such as poly(2-ethyl-2-oxazoline), efficacy of a final formulation is altered / improved by driving out of the formulation the released carboxylic acid, such as removal of greater than 1, 2, 5, 10, 25, 50, 60, 70, 80, 90, 95, 96, 97, 98, 99, or 99.9 percent and/or less than 100, 99, 98, 97, 95, or 90 percent of the carboxylic acid.
  • a starting material for polyethylenimine such as poly(2-ethyl-2-oxazoline
  • Example IV In a fourth example, longevity of inactivation of bacteria/virus is demonstrated with formulations as described herein, especially those with adherence properties of the film to a substrate with greater than 1, 5, 10, 25, or 50 ⁇ N. Adherence is aided through use of low concentrations of polyDADMAC, such as greater than 10, 20, or 50 ppm and less than 2000, 1000, 500, 250, or 100 ppm in combination with polyethylenimine at concentrations greater than 500 or 1000 ppm.
  • Presence of some of the non-chloride counterions also aids the longevity of inactivation, such as to bacteria / virus introduced to a film resulting 180030844.1 97 Attorney Docket no. EXNI0001 from the formulation at periods greater than 1, 2, 3, 4, 7, 14, 21, or 28 days after film formation.
  • Example V it is determined that coating a garment with greater than 1 and preferably greater than 2, 5, 10, 20, or 50 milligrams of the formulation, such as including at least polyethylenimine, such as with the adherence properties described supra, function to inactivate current and/or newly introduced bacteria, as described herein.
  • Example VI In a sixth example, formulations resulting in dried film thickness in a range of 0.2 to 20 ⁇ m range, for greater than 95% of the film coverage are preferable, especially when coupled with a charge density, from a calculation of only the protonated sites of the film/formulation, of greater than 200, 400, or 600 C/in 3 and/or less than 7000, 14000, or 25000 C/in 3 .
  • Example VII In a seventh example, formulations, as described herein, that show persistence of inactivation, such as greater than 99.9% inactivation, after rubbing or cleaning the surface are preferred, such as with the EPA 01-1A protocol.
  • Formulations particularly effective at persistence of inactivation include those with polyDADMAC at a pH of 4 or 4.5 ⁇ 0.25 or 0.5 pH units and/or those with a surfactant.
  • Example VIII In an eighth example, a method for treating a pathogen, comprising the steps of: (1) reacting, in a solution, poly(2-alkyl-2-oxazoline) with a strong acid to form a polyethylenimine and a carboxylic acid, the polyethylenimine comprising protonated sites; (2) increasing relative concentration of the 180030844.1 98 Attorney Docket no.
  • EXNI0001 polyethylenimine through removal of at least 95% of the carboxylic acid from the solution; (3) adjusting pH of the solution to greater than 2.5; (4) producing a film on a substrate from the solution; (5) contacting first bacteria with the film; and (6) reducing activity of the first bacteria contacting the film by: greater than 9% and less than 99.99995% in less than one minute; greater than 99.999% in less than four days; and greater than 99.99995% in less than seven days.
  • Example IX In a ninth example, a method for treating a pathogen, comprising the steps of: (1) removing, with an acid, less than 99% of -COR1 acyl groups from nitrogen sites of a poly(2-alkyl-2-oxazoline) in a solution to form a partially protonated and partially acylated poly(2-alkyl-2-oxazoline), where R1 comprises an alkyl group; (2) adjusting a pH of the solution to greater than 2.5; and (3) optionally forming a film from the solution with any of the properties described herein, such as charge density, additive killing properties, and longevity of killing properties, with or without any additives as described herein, such as a quaternary ammonium salt, a surfactant, and/or an organic acid.
  • Example X In a tenth example, a partially protonated and partially acylated poly(2-alkyl-2- oxazoline) polymer, such as a poly(2-etyhl-2-oxazoline) is used with or without a polyethylenimine or related polyalkylenimine. Further, any of the reactions / procedures described herein, such as counterion control, is optionally performed for individual stock solutions (stocks) for one or the other of the partially protonated and partially acylated poly(2-alkyl-2-oxazoline) polymer or the polyethylenimine / polyalkylenimine.
  • Example XI In an eleventh example, addition of a polyDADMAC salt to a partially protonated polyethylenimine is observed to increase a thickness of a resulting film.
  • adding 500, 1500, or 2000 ppm of the polyDADMAC salt to a solution used to form a film also using 5000 ppm polyethylenimine with a polyethylene glycol sorbitan monolaurate surfactant increased the film thickness, for a 200 ⁇ L sample on one square inch, to greater than 200 nm, such as with an average thickness of between 200 and 800 nm.
  • the polyDADMAC salt in combination with a surfactant also increased durability of the film, such as a resistance to losing film thickness and/or film charge when rubbed.
  • Example XII In a twelfth example, addition of a polyDADMAC salt and/or a surfactant to a partially protonated polyethylenimine is observed to a static coefficient of friction, ⁇ s , to greater than 0.8, 1, 1.2, 1.4, 1.6, 1.8, 2.0, or 2.2 depending on the concentrations of elements of the film.
  • Example XIII In a thirteenth example, increasing a tackiness of a film of the formulations described herein is observed to increase inactivation of the film properties against bacteria and viruses.
  • a solution of a polyDADMAC dried to yield a coefficient of friction, ⁇ s , of greater than 0.8, 1, 1.2, 1.4, or, 1.6 and/or to less than 4, 3.5, 3, 2.5, or 2.0 is observed to enhance antibacterial/antiviral properties in terms of longevity of action, additive killing of action, and/or effectiveness after extended periods, such as killing properties retained after greater than 1, 2, 4, 6, 12, 18, 24, 48, or 96 hours.
  • Example XIV In a fourteenth example, a combination a polyethylenimine, a quaternary ammonium, and/or a surfactant yields a film, when at least partially dried that resists scratching.
  • an application of a force of greater than 10, 20, or 30 ⁇ N and less than 200, 100, or 75 ⁇ N and preferably 50 ⁇ N yields a mean scratch depth of more than 1, 5, 10, or 100 nm and less than 3000, 2000, 1000, or 750 nm.
  • the film is dried, such as through 180030844.1 100 Attorney Docket no. EXNI0001 removal of more than 10, 25, 50, 75, or 90 percent of a solvent and optionally less than 99.9, 99.5, 99, 98, 97, 96, or 95 percent of the solvent.
  • the film comprises a ratio of a polyethylenimine to an adhesion promoter, such as polyDADMAC, exceeding 1:1, 2:1, or 3:1 by mass and/or by parts per million.
  • the surfactant aids coverage of a substrate and the polyDADMAC aids adhesion to the substrate.
  • Example XV In a fifteenth example, a chloride concentration of a biocide formulation is maintained at a concentration greater than 0, 100, or 200 ppm and/or less than 2000, 1500, 1000, 800, 600, 500, 400, or 300 ppm, to aid in toxicity management of the formulation and/or to meet EPA guidelines/requirements.
  • Example XVI In a sixteenth example, a formulation comprising at least one of polyethylenimine, a quaternary ammonium, and/or a polydiallyldimethylammonium salt, such as with any one or more of the formulation additives described herein, is used to inactivate/kill greater than 5, 10, 25, 50, 75, 90, 95, 99, or 99.9 percent of a fungus, such as a Candida Auris within less than 1, 2, 5, 10, 30, 60, 360, or 2400 minutes of contact with the formulation.
  • a formulation comprising at least one of polyethylenimine, a quaternary ammonium, and/or a polydiallyldimethylammonium salt, such as with any one or more of the formulation additives described herein, is used to inactivate/kill greater than 5, 10, 25, 50, 75, 90, 95, 99, or 99.9 percent of a fungus, such as a Candida Auris within less than 1, 2, 5, 10, 30, 60, 360, or 2400
  • a method for treating a pathogen comprises the steps of: polymerizing a molecule to form a polymer, the molecule comprising an alkyl in a molecule comprising a 2-alkyl-2-oxalozine other than a 2-ethyl-2- oxazoline; preparing a formulation comprising a derivative of the polymer and an organic solvent, the derivative comprising protonization of greater than ten percent of monomers of the polymer; and inactivating at least ninety percent of the pathogen within ten minutes of contact of the pathogen with the formulation.
  • 180030844.1 101 Attorney Docket no.
  • a method for treating a pathogen comprising the steps of: acidifying, in a solution, a molecule, the molecule comprising an alkyl, the molecule comprising a poly(2-alkyl-2-oxazoline) other than poly(2-ethyl-2- oxazaline, the step of acidifying forming an at least partially deacylated poly(2- alkyl-2-oxazoline), the at least partially deacylated poly(2-alkyl-2-oxazoline) comprising an at least partially acidified state; adding at least one organic solvent to the solution to yield a formulation; tuning, for a protonated secondary amine of the at least partially deacylated poly(2-alkyl-2-oxazoline), the formulation to comprise an activity coefficient ( ⁇ ) in a range of 0.6 to 0.9991; and inactivating at least ninety percent of the pathogen within ten minutes of contact of the pathogen with the formulation.
  • ⁇ activity coefficient
  • an apparatus for treating a pathogen comprises a liquid formulation comprising: (1) a copolymer, the copolymer comprising: acylated monomers comprising a -COR 1 group attached to a nitrogen of a -N- CH2-CH2- element, wherein R1 comprises an alkyl group; and protonated monomers comprising a -NH2 + -CH2-CH2- group, the acylated monomers and the protonated monomers comprising any order in the copolymer; (2) a total cationic charge of the copolymer in a range of 0.4 to 15 C/cm 3 , the total cationic charge at least 98% offset by anionic counterions; and (3) an antipathogen property resultant in killing at least 99% of the pathogen within ten minutes of contact of the pathogen with the liquid formulation.
  • a method for treating a pathogen comprises the steps of: forming a polyethylenimine with hydrochloric acid in a solution, the polyethylenimine comprising secondary amines, the secondary amines being at least partially protonated; adding sodium hydroxide to the solution of the polyethylenimine to increase a pH of the solution by at least one pH unit, such as to above 9; removing at least five percent of non-amine cations, such as 180030844.1 102 Attorney Docket no.
  • EXNI0001 sodium ions in the solution from the solution; lowering the pH, subsequent to the step of removing, of the solution, such as to below 6, to yield a protonation level of the secondary amines in excess of fifty percent; and inactivating at least 50% of a bacteria within 10 minutes of contact of the bacteria with the solution.
  • a method for treating a fungus comprises the steps of: providing, in a formulation, a polyethylenimine at a pH of less than two, a majority of protonated sites on the polyethylenimine associated with chloride counterions; exchanging at least ten percent of the chloride counterions for hydroxide anions bound to an anion exchange material resultant in bound chloride ions on the anion exchange material; separating the anion exchange material from the solution, the step of separating resultant in at least a ten percent reduction of the chloride counterions associated with the polyethylenimine; and inactivating at least fifty percent of the fungus within ten hours through treatment of the fungus with the formulation.
  • a method for treating a pathogen comprises the steps of: (1) providing a polyethylenimine in a solution, the polyethylenimine comprising a total cationic charge of protonated secondary amines of the polyethylenimine, the solution comprising anionic counterions associated with the protonated secondary amines; (2) tuning a protonated site of the polyethylenimine, in a formulation of the solution containing ions, to an activity coefficient ( ⁇ ) in a range of 0.93 to 0.999; (3) forming from the formulation an antibacterial film, the antibacterial film comprising a mean thickness of less than 5 ⁇ m and the total cationic charge of the protonated secondary amines in a range of 0.1 to 1.8 C/in 2 ; and (4) inactivating greater than 99% of first bacteria within less than five minutes of contact with the antibacterial film.
  • a method for treating pathogens on a substrate comprises the steps of: providing a solid polyethylenimine in a basic pH form comprising protonated and unprotonated nitrogens, a ratio of the protonated nitrogens-to-the unprotonated nitrogens less than 5:95; solubilizing the solid polyethylenimine in a strong acid to form a solution of a polyethylenimine, the polyethylenimine comprising protonated nitrogen sites and counterions to the protonated nitrogen sites; removing at least ten percent of the strong acid from the solution; forming a formulation from the solution, the formulation further comprising at least one of ethanol and isopropyl alcohol; spraying the formulation onto the substrate to form a film, the film reducing activity of the first bacteria contacting the film by: greater than 9% and less than 99.99995% in less than three minutes; and greater than 99.99
  • a method for treating a substrate with a biocide comprises the steps of: combining in a formulation: a salt of a polydiallyldimethylammonium, an organic solvent, and water; controlling a concentration of the polydiallyldimethyl-ammonium to greater than 50 mg per liter in the formulation to yield a self-spreading surface tension, of the formulation, of less than 50 mN/m; limiting, in the formulation, the concentration of the polydiallyldimethylammonium to less than 1500 mg per liter to yield a sprayable liquid comprising a viscosity of less than 250 centipoise; spraying the substrate with the formulation to yield an antibacterial film, the antibacterial film comprising: (1) 15 to 500 ⁇ g per square inch of the polydiallyldimethylammonium; and inactivating, according to a test protocol of JIS X 2801 (2006), at least 90 percent of first bacteria with the antibacterial film.
  • an apparatus for coating a substrate comprises: an antimicrobial film, comprising: a partially protonated polyethylenimine in a range of 0.1 to 5 mg per square inch; a polydiallyldimethylammonium salt; chloride counterions; first conjugate base counterions of a first organic acid, the 180030844.1 104 Attorney Docket no.
  • EXNI0001 first conjugate base counterions comprising a first mass of 0.001 to 0.1 mg per square inch; second conjugate base counterions of a second organic acid, the second conjugate base counterions comprising a second mass of 0.05 to 1 mg per square inch; and a total cationic charge of the antimicrobial film in a range of 200 to 3000 C/m 2 , the total cationic charge countered by anions in the antimicrobial film, the antimicrobial film comprising an antimicrobial efficacy of greater than ninety percent according to PAS 2424:1024.
  • a method for forming a biocidal film comprises the steps of: forming a solution comprising a protonated polyalkylenimine, free chloride ions, and chloride counterions; removing at least fifty percent of the free chloride ions from the solution via density separation to yield a residual chloride concentration; reducing the residual chloride concentration by at least fifty percent with an anion exchange material; decreasing a percentage of protonated sites of the polyalkylenimine associated with the chloride counterions through addition of an organic acid to the solution; and forming, from the solution, the film with properties of: inactivating at least 99 percent of a first bacteria making contact with the film within one hour; and deactivating at least 99 percent of second bacteria within one hour, the second bacteria contacting the film at least one day later.
  • a method for treating a pathogen comprises the steps of: removing, with an acid, less than 99% of -COR 1 acyl groups from nitrogen sites of a poly(2-alkyl-2-oxazoline) in a solution to form a partially protonated and partially acylated poly(2-alkyl-2-oxazoline), where R 1 comprises an alkyl group; adjusting a pH of the solution to greater than 2.5; forming a film from the solution, the film comprising a total cationic charge in a range of 0.001 to 10.0 coulombs per square inch, the total cationic charge countered with counteranions; and reducing activity of the pathogen contacting the film by: greater than 9% and less than 99.99995% in less than one minute, greater than 180030844.1 105 Attorney Docket no.
  • a method for treating a pathogen comprises the steps of: (1) polymerizing a 2-ethyl-2-oxazoline to form a poly(2-ethyl-2- oxazoline); (2) acidifying at least five percent of the poly(2-ethyl-2-oxazoline) to form a first copolymer, the first copolymer comprising: a first monomer, the first monomer comprising an acyl group attached to a -N-CH2-CH2- group; and a second monomer, the second monomer comprising a -NH + -CH 2 -CH 2 - group; (3) forming a formulation comprising the first copolymer in a solvent, the formulation comprising a charge density of 0.2 to 10 C/mL; and (4) inactivating at least fifty percent of the pathogen within a ten minute
  • Example XXIX In a twenty-ninth example, any of the formulations described herein are optionally added to a washing machine rinse additive.
  • Example XXX In a thirtieth example, a method for inactivating pathogens is described, comprising the steps of: (1) partially deacylating a poly(2-ethyl-2-oxazoline) to yield a copolymer, the copolymer comprising: first monomers comprising a - NH + CH2CH2- group and second monomers comprising a -COCH2CH3 group attached to a nitrogen in a polymer backbone group comprising -NCH 2 CH 2 -, the first monomers and the second monomers arranged in any order in the copolymer; (2) preparing a formulation comprising the copolymer and a total cationic charge in a range of 0.2 to 10 C/cm 3 , the total cationic charge at least 95% offset by counteranions in the formulation; (3) contacting the pathogens with the
  • the method optionally and preferably controls salts/anions of the solution, to enhance the inactivating step, such as measured by conductivity, activity, sodium concentration, organic acid/base types, and/or counterion concentrations/types.
  • the formulation optionally sprayed to form a film, has antivirion, antiviral, antibacterial, and/or antifungal properties that persist through time.
  • the copolymer has monomers in equilibrium with other chemical forms, where the equilibrium is a function of pH of the formulation/process of making the formulation. Any additive to the formulation is optionally used, such as an addition of a quaternary ammonium, a polydiallyldimethylammonium salt, and/or a partially protonated polyethylenimine.
  • the formulation is 180030844.1 107 Attorney Docket no. EXNI0001 generally an antipathogen, such as finding applications in a washing machine additive, a hand sanitizer, and/or in at least partial coating of a fabric/garment.
  • a formulation property and/or a film property results from specific properties of the formulation and/or of a film derived from the formulation.
  • parameters affecting the formulation/film properties include: concentrations of formulation elements, a pH of the formulation, an amount of the formulation applied to an area, a temperature of preparation of a formulation element, a reaction time of preparation of a formulation element, separation of reaction products, and/or interaction of formulation elements, such as counterions with charged polymer sites.
  • a polyethylenimine at 1000 ppm in a first solvent will have different formulation properties than a polyethylenimine at a second concentration, such as 6000 ppm at a different pH and/or with another antipathogen, such as a counterion, a ratio of counterions, a quaternary ammonium, and/or a copolymer.
  • any antipathogen formulation component is optionally in a concentration range exceeding 1, 2, 10, 100, 500, or 1000 ppm and/or is optionally in a concentration 180030844.1 108 Attorney Docket no. EXNI0001 range of less than 15,000, 10,000, 7000, 5000, 3000, 1000, 500, or 200 ppm.
  • the formulation elements are described, supra.
  • Example XXXIII In a thirty-third example, Aloe vera is incorporated into any of the formulations described herein, such as in a hand sanitizer functioning as an antipathogen.
  • An optional and preferred concentration of Aloe vera in a formulation is greater than 10, 20, 50, 100, 500, or 1000 ppm.
  • Example XXXIV In a thirty-fourth example, a method for treating a pathogen is described, comprising the steps of: (1) spraying a formulation onto a substrate, the formulation comprising: a charged polymer comprising charged monomers, counterions to the charged monomers; and, an adhesion promoter; (2) drying the formulation to yield a film comprising a critical load of adhesion in a range of 10 to 600 ⁇ N; (3) contacting the pathogen with the film; and (4) inactivating, with the film, at least fifty percent of the pathogen within thirty minutes of the step of contacting, where the adhesion promoter is optionally an antipathogen, such as a polydiallyldimethylammonium salt.
  • an antipathogen such as a polydiallyldimethylammonium salt.
  • Still yet another embodiment includes any combination and/or permutation of any polymer and/or copolymer described herein and/or any part of a polymer and/or any counterion and/or any formulation element described herein. Still yet another embodiment includes any combination and/or permutation of any of the elements described herein.
  • any number such as 1, 2, 3, 4, 5, is optionally more than the number, less than the number, or within 1, 2, 5, 10, 20, or 50 percent of the number. 180030844.1 109 Attorney Docket no. EXNI0001
  • the particular implementations shown and described are illustrative of the invention and its best mode and are not intended to otherwise limit the scope of the present invention in any way.

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Abstract

Est décrit un procédé d'inactivation de pathogènes, comprenant les étapes consistant à : désacyler partiellement une poly(2-alkyle-2-oxazoline) pour produire un copolymère, un alkyle dans la poly(2-alkyle-2-oxazoline) comprenant une chaîne hydrocarbonée, le copolymère comprenant : des premiers monomères, les premiers monomères comprenant un groupe -NH2 +CH2CH2- ; et des seconds monomères, les seconds monomères comprenant un groupe acyle, -C(=O)-R', fixé à un azote dans un groupe de squelette polymère comprenant -NCH2CH2-, R' comprenant la chaîne hydrocarbonée, les premiers monomères et les seconds monomères étant agencés dans n'importe quel ordre dans le copolymère ; préparer une formulation, la formulation comprenant le copolymère et une charge cationique totale dans une plage de 0,2 à 10 C/cm3, la charge cationique totale étant décalée d'au moins 95 % par des contre-anions dans la formulation ; mettre en contact des pathogènes avec la formulation ; et inactiver au moins quatre-vingt-dix pour cent des pathogènes dans les quatre-vingt-dix minutes suivant l'étape de mise en contact.
PCT/US2025/015785 2024-03-20 2025-02-13 Appareil antipathogène à base de poly(2-alkyle-2-oxazoline) et procédé d'utilisation associé Pending WO2025198753A1 (fr)

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US202418908004A 2024-10-07 2024-10-07
US18/908,004 2024-10-07
US202418913127A 2024-10-11 2024-10-11
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US18/937,301 2024-11-05
US18/940,362 2024-11-07
US18/940,362 US20250351822A1 (en) 2024-03-20 2024-11-07 Partially deacylated poly(2-ethyl-2-oxazoline) antipathogen apparatus and method of use thereof
US18/950,493 US20250073153A1 (en) 2016-07-28 2024-11-18 Partially deacylated poly(2-alkyl-2-oxazoline) antipathogen apparatus and method of use thereof
US18/950,493 2024-11-18
US18/953,361 2024-11-20
US18/953,361 US20250082562A1 (en) 2016-07-28 2024-11-20 Protonated and deprotonated polyethylenimine apparatus and method of use thereof
US18/964,384 2024-11-30
US18/964,384 US20250090446A1 (en) 2016-07-28 2024-11-30 Antipathogen copolymer formulation apparatus and method of use thereof
US18/973,785 US20250099362A1 (en) 2016-07-28 2024-12-09 Salt controlled antipathogen apparatus and method of use thereof
US18/973,785 2024-12-09
US18/980,530 US20250114291A1 (en) 2016-07-28 2024-12-13 Adhesion controlled antipathogen apparatus and method of use thereof
US18/980,530 2024-12-13

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PCT/US2025/016068 Pending WO2025198761A1 (fr) 2024-03-20 2025-02-14 Appareil à biocide à charge contrôlée et son procédé d'utilisation
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PCT/US2025/016370 Pending WO2025198772A1 (fr) 2024-03-20 2025-02-18 Appareil à film anti-pathogène de polyéthylènimine à teneur réduite en chlorure et procédé d'utilisation associé
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