US20100196306A1 - Bioactive aniline copolymers - Google Patents

Bioactive aniline copolymers Download PDF

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Publication number
US20100196306A1
US20100196306A1 US12/680,113 US68011308A US2010196306A1 US 20100196306 A1 US20100196306 A1 US 20100196306A1 US 68011308 A US68011308 A US 68011308A US 2010196306 A1 US2010196306 A1 US 2010196306A1
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Prior art keywords
aniline
copolymer
amino
industry
acid
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US12/680,113
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Marija Gizdavic-Nikolaidis
Allan James Easteal
Srdjan Stepanovic
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Auckland Uniservices Ltd
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Auckland Uniservices Ltd
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Assigned to AUCKLAND UNISERVICES LIMITED reassignment AUCKLAND UNISERVICES LIMITED ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: EASTEAL, ALLAN JAMES, GIZDAVIC-NIKOLAIDIS, MARIJA, STEPANOVIC, SRDJAN
Publication of US20100196306A1 publication Critical patent/US20100196306A1/en
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    • 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
    • A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/10—Aromatic or araliphatic carboxylic acids, or thio analogues thereof; Derivatives thereof
    • 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
    • A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
    • A01N25/34—Shaped forms, e.g. sheets, not provided for in any other sub-group of this main group
    • 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
    • A01N33/06—Nitrogen directly attached to an aromatic ring system
    • 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
    • A01N35/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having two bonds to hetero atoms with at the most one bond to halogen, e.g. aldehyde radical
    • A01N35/08—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having two bonds to hetero atoms with at the most one bond to halogen, e.g. aldehyde radical at least one of the bonds to hetero atoms is to nitrogen
    • A01N35/10—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having two bonds to hetero atoms with at the most one bond to halogen, e.g. aldehyde radical at least one of the bonds to hetero atoms is to nitrogen containing a carbon-to-nitrogen double bond
    • 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
    • A01N41/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a sulfur atom bound to a hetero atom
    • A01N41/02—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a sulfur atom bound to a hetero atom containing a sulfur-to-oxygen double bond
    • A01N41/04—Sulfonic acids; Derivatives thereof
    • 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
    • C08G73/026—Wholly aromatic polyamines
    • C08G73/0266—Polyanilines or derivatives thereof
    • 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
    • C08G75/00—Macromolecular compounds obtained by reactions forming a linkage containing sulfur with or without nitrogen, oxygen, or carbon in the main chain of the macromolecule
    • C08G75/24—Polysulfonates
    • 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
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09D—COATING COMPOSITIONS, e.g. PAINTS, VARNISHES OR LACQUERS; FILLING PASTES; CHEMICAL PAINT OR INK REMOVERS; INKS; CORRECTING FLUIDS; WOODSTAINS; PASTES OR SOLIDS FOR COLOURING OR PRINTING; USE OF MATERIALS THEREFOR
    • C09D179/00—Coating compositions based on 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 C09D161/00 - C09D177/00
    • C09D179/02—Polyamines
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09D—COATING COMPOSITIONS, e.g. PAINTS, VARNISHES OR LACQUERS; FILLING PASTES; CHEMICAL PAINT OR INK REMOVERS; INKS; CORRECTING FLUIDS; WOODSTAINS; PASTES OR SOLIDS FOR COLOURING OR PRINTING; USE OF MATERIALS THEREFOR
    • C09D5/00—Coating compositions, e.g. paints, varnishes or lacquers, characterised by their physical nature or the effects produced; Filling pastes
    • C09D5/14—Paints containing biocides, e.g. fungicides, insecticides or pesticides

Definitions

  • the present invention relates to polyaniline copolymers and the use of polyaniline copolymers as antimicrobial agents and more particularly as antibacterial, antifungal and antiviral agents.
  • the invention has been developed primarily for preventing bacterial and/or fungal and/or virus growth on a surface and will be described hereinafter with reference to this application. However, it will be appreciated that the invention is not limited to this particular field of use.
  • PANIs polyanilines
  • NMP N-methyl-2 pyrrolidone
  • HFP hexafluoro-2-propanol
  • PANI Films containing PANI have recently been found to act as antibacterial materials.
  • PANI either as a powder or in a composite film with polyvinyl alcohol or polyethylene, is disclosed as having antibacterial activity against the growth of Escherichia coli and staphylococcal organisms.
  • the films contained low quantities (1-10 wt %) of PANI relative to the amount of polyvinyl alcohol or polyethylene used, which is indicative of the processability problems that would prohibit higher amounts of PANI being used.
  • copolymers of aniline with substituted anilines have a fast inhibitory effect on microorganisms, including pathogenic bacteria, when present in small amounts, for instance from 0.03-1 wt % upwards.
  • the copolymers are surprisingly amenable to processing, and may for example be readily incorporated into films or gels, or electrospun as nanofibres.
  • microorganism microbial and the like as used herein is used in a broad sense and includes not only bacteria, but also fungi and viruses. Similarly, “antimicrobial” and the like is used to indicate a reduction or growth suppression in bacteria, fungi, viruses and so on.
  • the invention provides the use of an aniline copolymer as an antimicrobial material.
  • the use of the aniline copolymer is as an antibacterial and/or antifungal and/or antiviral material.
  • the invention provides the use of an aniline copolymer for the manufacture of an antimicrobial material.
  • the aniline copolymer is used for the manufacture of an antibacterial and/or antifungal and/or antiviral object.
  • said aniline polymer is an aniline conducting copolymer.
  • said aniline copolymer is an antioxidant.
  • aniline copolymer is soluble to at least 0.05 mg/mL in a solvent selected from the group consisting of N-methyl-2-pyrrolidone, pyridine, 2,6-dimethyl pyridine, 2,4,6-trimethylpyridine, dimethyl sulfoxide, N,N-dimethyl acetamide anhydrous, tetrahydrofuran, dimethylformamide, hexafluoro-2-propanol, chloroform and dichloromethane.
  • a solvent selected from the group consisting of N-methyl-2-pyrrolidone, pyridine, 2,6-dimethyl pyridine, 2,4,6-trimethylpyridine, dimethyl sulfoxide, N,N-dimethyl acetamide anhydrous, tetrahydrofuran, dimethylformamide, hexafluoro-2-propanol, chloroform and dichloromethane.
  • the copolymer has a leucoemeraldine, emeraldine, or pernigraniline structure. Most preferably the copolymer has an emeraldine structure. Preferably the copolymer is in a salt or free-base form. The emeraldine salt form is the most preferred.
  • said copolymer is formed by reaction of aniline with a compound of formula (I)
  • R is hydrogen or a C 1 -C 6 alkyl
  • n 1, 2 or 3
  • R 1 is independently selected from the group consisting of C 1 -C 6 alkyl
  • R 2 is selected from hydrogen, C 1 -C 6 alkyl, an alkali metal, ammonium and a substituted ammonium salt;
  • R 4 is selected from hydrogen, C 1 -C 6 alkyl, phenyl; and salts thereof.
  • the benzene ring may optionally contain one or more hetero atoms in place of a carbon atom, preferably selected from N, O, S, and more preferably one, two or three nitrogen atoms.
  • R is hydrogen and R 1 is —CO 2 R 2 , more preferably R is hydrogen and R 1 is —CO 2 H, —CO 2 Me, or —CO 2 Et.
  • formula (I) is a compound selected from the group consisting of 3-aminobenzoic acid, 2-aminobenzoic acid and ethyl 3-aminobenzoate.
  • the independently variable R 1 groups are preferably, but not necessarily, meta to the NHR group.
  • the independently variable R 1 groups are preferably, but not necessarily, ortho and para to the NHR group.
  • the copolymer may be formed by the reaction of aniline with compounds in which the aromatic ring is not necessarily benzenoid, but is any suitable aromatic ring, ie a heterocyclic ring having any number of atoms, more usually 5 or 6. That is, preferably said copolymer is formed by reaction of aniline with a compound of formula Ia,
  • R, R 1 and n are as above, with Ar being a N-containing heterocycle such as pyridine, pyridazine, pyrimidine, pyrazine, pyrrole, pyrazole, an O-containing heterocycle such as pyran or furan, an S-containing heterocycle such as thiophen, mixed heterocyclic systems such as isoxazole or polycyclic systems such as naphthalene, quinoline or quinoxaline.
  • N-containing heterocycle such as pyridine, pyridazine, pyrimidine, pyrazine, pyrrole, pyrazole, an O-containing heterocycle such as pyran or furan, an S-containing heterocycle such as thiophen, mixed heterocyclic systems such as isoxazole or polycyclic systems such as naphthalene, quinoline or quinoxaline.
  • Other preferred comonomers include one or more compounds from the group consisting of: 3-acetylaniline; 2-aminobenzaldehyde; 2-aminobenzenesfonamide; 2-aminophenol; 3-aminophenol; 2-aminophenylacetic acid; 3-aminophenylacetic acid; 2-aminobenzonitrile; 3-aminobenzonitrile; 2-aminobenzophenone; 3-aminobenzophenone; 2-aminobenzyl alcohol; 3-aminobenzyl alcohol; 2-aminobenzylamine; 2-aminobenzyl cyanide; 2-amino-4-bromobenzoic acid; 2-amino-6-chlorobenzoic acid; 2-amino-4-chlorobenzoic acid; 2-amino-4-chlorophenol; 2-amino-4-methylphenol; 2-amino-4,6-dihydroxypyrimidine; 2-amino-1,3-diethylbenzene; 1-amino-3
  • said antimicrobial material is effective against bacteria selected from Gram-positive bacteria and Gram-negative bacteria.
  • said Gram-positive bacteria and said Gram-negative bacteria belong to genera selected from the group consisting of Bordetella, Neisseria, Legionella, Pseudomonas, Salmonella, Shigella, Erwinia, Enterobacter, Escherichia, Vibrio, Haemophilus, Actinobacillus, Klebsiella, Staphylococcus, Streptococcus, Enterococcus, Corynebacterium, Listeria, Bacillus, Mycobacterium, Enterococcus, Leptospira, Serpulina, Mycoplasma, Bacteroides, Yersinia, Chlamydia, Porphyromonas, Pasteurella, Peptostreptococcus, Propionibacterium, Dermatophilus, Campylobacter and Erysipelothrix.
  • said Gram-positive bacteria and said Gram-negative bacteria are selected from the group consisting of Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Salmonella enterica serotype Enteritidis, Enterococcus sp., Staphylococcus sciuri, Enterobacter sp., and Campylobacter jejuni.
  • said antimicrobial material is effective against fungal genera selected from the group consisting of Aspergillus, Blastomyces, Candida, Coccidioides, Cryptococcus, Epidermophyton, Histoplasma, Microsporum, Mucor, Rhizopus, Sporothrix, Trichophyton, Paracoccidioides, Absidia, Fusarium, Penicillium, Torulopsis, Trichosporon, Rhodotorula, Malassezia, Cladosporium, Fonsecea and Phialophora.
  • fungal genera selected from the group consisting of Aspergillus, Blastomyces, Candida, Coccidioides, Cryptococcus, Epidermophyton, Histoplasma, Microsporum, Mucor, Rhizopus, Sporothrix, Trichophyton, Paracoccidioides, Absidia, Fusarium, Penicillium, Torulopsis, Trichosporon, Rhodotorula, Malassezia, Cladosporium, Fon
  • the viruses may be DNA viruses or RNA viruses.
  • said DNA viruses and said RNA viruses belong to families selected from the group consisting of Parvoviridae, Papillomaviridae, Polyomaviridae, Adenoviridae, Hepadnaviridae, Herpesviridae, Poxviridae, Picornaviridae, Caliciviridae, Reoviridae, Togaviridae, Flaviviridae, Coronaviridae, Orthomyxoviridae, Paramyxoviridae, Rhabdoviridae, Filoviridae, Bunyaviridae, Arenaviridae and Retroviridae.
  • Preferably said object is employed in the health industry, food industry, packaging industry, textile industry, plastic industry, glass industry, paper industry, rubber industry, ceramic industry, water industry, paint industry, wood industry, poultry industry, seafood industry, sports industry and agricultural industry.
  • the materials of the present invention can be used to fabricate objects suitable for use in a wide range of applications requiring combating of microbes, provided the physical properties of the material are suitable.
  • Some preferred but non-limiting examples of antimicrobial objects include medical dressings, urine catheters, endoscopes, medical instruments, hospital furniture, pipettes, masks, gloves, floors, doors and walls, food utensils and food packets, food processing surfaces and apparatus, plastic film wraps and plastic containers, computer keyboards and mouses, cosmetics, handles, water tanks, membranes for water purification, toilets, door handles, drainage pipes, water pipes, ear pieces, shoe insoles, pools, bags for urine or feces or blood platelets, air-conditioning units, filtration equipment, pasteurization equipment and furniture.
  • the aniline copolymers of the present invention are incorporated into films or wraps or nanofibres which are useful in the food storage and food packaging industry or which may be useful as wound dressings or for bandages.
  • the aniline copolymers may be present in the film, gel, wrap or dressing either as a component which is dispersed, blended or alloyed with the other film, gel, wrap or dressing forming components, or the aniline copolymers may be present in a form covalently bonded with the other film, gel, wrap or dressing forming components.
  • the invention provides an aniline copolymer of the following formula:
  • R 3 H or R 1 as above, R is as above, x is an integer between 1 and 0 and m indicates the degree of polymerisation.
  • the compound is not polyaniline per se.
  • the benzene rings may optionally contain one or more hetero atoms in place of a carbon atom, preferably selected from N, O, S, and more preferably one, two or three nitrogen atoms.
  • the degree of polymerisation, m can be anywhere from 1 up to 10 8 .
  • the invention provides a process for preparing an aniline copolymer, said process comprising the step of reacting aniline with a compound of formula (I) in a mineral acid solution containing an oxidizing agent
  • the benzene ring may optionally contain one or more hetero atoms in place of a carbon atom, preferably selected from N, O, S, and more preferably one, two or three nitrogen atoms.
  • R is hydrogen and R 1 is —CO 2 R 2 , more preferably R is hydrogen and R 1 is —CO 2 H, —CO 2 Me, or —CO 2 Et.
  • formula (I) is a compound selected from the group consisting of 3-aminobenzoic acid, 2-aminobenzoic acid and ethyl 3-aminobenzoate.
  • the independently variable R 1 groups are preferably, but not necessarily, meta to the NHR group.
  • the independently variable R 1 groups are preferably, but not necessarily, ortho and para to the NHR group.
  • the copolymer may also be formed by the reaction of aniline with compounds in which the aromatic ring is not be benzenoid, but is any suitable aromatic ring, ie a heterocyclic ring having any number of atoms, more usually 5 or 6. That is, preferably said copolymer is formed by reaction of aniline with a compound of formula Ia,
  • R, R 1 and n are as above, with Ar being a N-containing heterocycle such as pyridine, pyridazine, pyrimidine, pyrazine, pyrrole, pyrazole, an O-containing heterocycle such as pyran or furan, an S-containing heterocycle such as thiophen, mixed heterocyclic systems such as isoxazole or polycyclic systems such as naphthalene, quinoline or quinoxaline.
  • N-containing heterocycle such as pyridine, pyridazine, pyrimidine, pyrazine, pyrrole, pyrazole, an O-containing heterocycle such as pyran or furan, an S-containing heterocycle such as thiophen, mixed heterocyclic systems such as isoxazole or polycyclic systems such as naphthalene, quinoline or quinoxaline.
  • the compounds will be further with reference to a benzene ring bearing a single R 1 but it will be appreciated that they will encompass compounds further substituted with having a mixture of R 1 groups, or a mixture of any or all of mono, di, tri or otherwise R 1 substituted rings.
  • Other preferred comonomers include one or more compounds from the group consisting of 3-acetylaniline; 2-aminobenzaldehyde; 2-aminobenzenesfonamide; 2-aminophenol; 3-aminophenol; 2-aminophenylacetic acid; 3-aminophenylacetic acid; 2-aminobenzonitrile; 3-aminobenzonitrile; 2-aminobenzophenone; 3-aminobenzophenone; 2-aminobenzyl alcohol; 3-aminobenzyl alcohol; 2-aminobenzylamine; 2-aminobenzyl cyanide; 2-amino-4-bromobenzoic acid; 2-amino-6-chlorobenzoic acid; 2-amino-4-chlorobenzoic acid; 2-amino-4-chlorophenol; 2-amino-4-methylphenol; 2-amino-4,6-dihydroxypyrimidine; 2-amino-1,3-diethylbenzene; 1-amino-3,
  • any suitable oxidising agent may be used.
  • the oxidising agent is selected from the group consisting of ammonium persulphate, potassium ferricyanide, an iodate salt and hydrogen peroxide.
  • the oxidising agent is potassium iodate.
  • suitable mineral acids are hydrochloric, sulphuric, nitric and perchloric acids.
  • the mineral acid is hydrochloric acid.
  • the iodate salt is potassium iodate and the mineral acid is hydrochloric acid.
  • the ratio of said aniline to said compound of formula (I) is 1:2 to 2:1, and more preferably said ratio is about 1:1.
  • the aniline copolymer is also preferably purified by treatment with a compound in which the aniline copolymer is largely insoluble, but which acts as a solvent for the removal of starting monomers, intermediate oligomers and the like.
  • Acetone is a preferred compound for this purpose.
  • the invention also provides an aniline copolymer when prepared by the process of the preceding aspect.
  • the invention provides an aniline copolymer wherein said copolymer is produced by reacting aniline and a compound of formula (I)
  • the benzene ring may optionally contain one or more hetero atoms in place of a carbon atom, preferably selected from N, O, S, and more preferably one, two or three nitrogen atoms.
  • R is hydrogen and R 1 is —CO 2 R 2 , more preferably R is hydrogen and R 1 is —CO 2 H, —CO 2 Me, or —CO 2 Et.
  • formula (I) is a compound selected from the group consisting of 3-aminobenzoic acid, 2-aminobenzoic acid and ethyl 3-aminobenzoate.
  • the independently variable R 1 groups are preferably, but not necessarily, meta to the NHR group.
  • the independently variable R 1 groups are preferably, but not necessarily, ortho and para to the NHR group.
  • the copolymer may also be formed by the reaction of aniline with compounds in which the aromatic ring is not be benzenoid, but is any suitable aromatic ring, ie a heterocyclic ring having any number of atoms, more usually 5 or 6. That is, preferably said copolymer is formed by reaction of aniline with a compound of formula Ia,
  • R, R 1 and n are as above, with Ar being a N-containing heterocycle such as pyridine, pyridazine, pyrimidine, pyrazine, pyrrole, pyrazole, an O-containing heterocycle such as pyran or furan, an S-containing heterocycle such as thiophen, mixed heterocyclic systems such as isoxazole or polycyclic systems such as naphthalene, quinoline or quinoxaline.
  • N-containing heterocycle such as pyridine, pyridazine, pyrimidine, pyrazine, pyrrole, pyrazole, an O-containing heterocycle such as pyran or furan, an S-containing heterocycle such as thiophen, mixed heterocyclic systems such as isoxazole or polycyclic systems such as naphthalene, quinoline or quinoxaline.
  • the compounds will be further with reference to a benzene ring bearing a single R 1 but it will be appreciated that they will encompass compounds further substituted with having a mixture of R 1 groups, or a mixture of any or all of mono, di, tri or otherwise R 1 substituted rings.
  • Other preferred comonomers include one or more compounds from the group consisting of: 3-acetylaniline; 2-aminobenzaldehyde; 2-aminobenzenesfonamide; 2-aminophenol; 3-aminophenol; 2-aminophenylacetic acid; 3-aminophenylacetic acid; 2-aminobenzonitrile; 3-aminobenzonitrile; 2-aminobenzophenone; 3-aminobenzophenone; 2-aminobenzyl alcohol; 3-aminobenzyl alcohol; 2-aminobenzylamine; 2-aminobenzyl cyanide; 2-amino-4-bromobenzoic acid; 2-amino-6-chlorobenzoic acid; 2-amino-4-chlorobenzoic acid; 2-amino-4-chlorophenol; 2-amino-4-methylphenol; 2-amino-4,6-dihydroxypyrimidine; 2-amino-1,3-diethylbenzene; 1-amino-3
  • the aniline copolymer is also preferably purified by treatment with a compound in which the aniline copolymer is largely insoluble, but which acts as a solvent for the removal of starting monomers, intermediate oligomers and the like.
  • Acetone is a preferred compound for this purpose.
  • the invention provides an antimicrobial object including an aniline copolymer.
  • the invention provides a product incorporating an aniline copolymer.
  • the product may be, for preference, a film suitable for use in food packaging.
  • the product may be, for preference, a wound dressing.
  • the invention provides a composite material comprising an aniline copolymer, preferably those of the present invention, and at least one other substance.
  • the composite material may be in the form of a powder, a blend or as a coating on the at least one other substance.
  • the at least one other substance is selected from the group consisting of poly(vinyl alcohol), poly(vinyl acetate), poly(methyl methacrylate) or acrylic polymers, poly(ethylene terephthalate) or other polyesters, polyamides, polyethylene and polypropylene, polyvinylidene fluoride, ethylene vinyl acetate copolymers, methyl acrylate copolymers, butane copolymers, hexane copolymers, rubber, natural rubber latex, acrylic latexes, epoxy latexes, ethyl cellulose, cellulose, polysaccharides, and proteins.
  • the composite material is preferably synthesised by in situ polymerisation or surface coating.
  • the composite material has aniline copolymer present in a MIC such that the composite has suitable antimicrobial activity.
  • the invention also provides a method of preserving food comprising the step of contacting the food with an aniline copolymer.
  • FIG. 1 shows a TEM image of E. coli bacteria after interaction with 3ABAPANI (ES).
  • FIG. 2 shows a graph of Log 10 reduction of the viable count of Staphylococcus aureus ATCC 25923 in the presence of 2% 3ABAPANI (ES).
  • FIG. 3 shows a graph of Log 10 reduction of the viable count of Escherichia coli ATCC 25922 in the presence of 2% 3ABAPANI (ES).
  • FIG. 4 shows a graph of Log 10 reduction of the viable count of Pseudomonas aeruginosa ATCC 27853 in the presence of 2% 3ABA PANI (ES).
  • FIG. 5 shows a graph of Log 10 reduction of the viable count of Candida albicans in the presence of 2% 3ABAPANI (ES).
  • FIG. 6 shows a graph of Log 10 reduction of the viable count of Staphylococcus aureus ATCC 25923 in the presence of 2% 3ABAPANI (ES)—high initial inoculum.
  • FIG. 7 shows a graph of Log 10 reduction of the viable count of Staphylococcus aureus ATCC 25923 in the presence of 2% 3ABAPANI (ES) and 20% plasma.
  • FIG. 8 shows a graph of Log 10 reduction of the viable count of Escherichia coli ATCC 25922 in the presence of 2% 3ABAPANI (ES) and 20% plasma.
  • FIG. 9 shows a graph of Log 10 reduction of the viable count of Pseudomonas aeruginosa ATCC 27853 in the presence of 2% 3ABAPANI (ES) and 20% plasma.
  • FIG. 10 shows a graph of Log 10 reduction of the viable count of Candida albicans in the presence of 2% 3ABAPANI (ES) and 20% plasma.
  • FIG. 11 shows a graph of Log 10 reduction of the viable count of Candida albicans in the presence of 2% 3ABAPANI (ES) and 5% plasma.
  • FIG. 12 shows a graph of Log 10 reduction of the viable count of Candida albicans in the presence of 2% 3ABAPANI (ES) and 10% plasma.
  • FIG. 13 shows a graph of Log 10 reduction of the viable count of Staphylococcus aureus ATCC 25923 in the presence of 2% 3ABAPANI (ES) and 16 mmol NAC.
  • FIG. 14 shows Film ⁇ 4 (PVA and PANI) coated on PMMA after interaction with Staphylococcus aureus ATCC 25923.
  • FIG. 15 shows Film ⁇ 2 (PVA and Poly3ABA) coated on PMMA after interaction with Staphylococcus aureus ATCC 25923.
  • the present invention provides an aniline copolymer for inhibiting growth of microbes.
  • the invention is particularly useful in preventing or treating nosocomial infections, in particular wound infections and infections associated with medical implants and infections associated with the consumption of food and/or water, although the present invention may be used to target microorganisms in any environment or any type of surface, including but not limited to human and animal subjects or materials to be decontaminated.
  • Non pathogenic bacteria are also targeted by the present invention, especially where they can cause unwanted effects such as food tainting and spoilage.
  • copolymers of the present invention are aniline copolymers, which can be synthesised by reacting aniline with a compound of formula (I)
  • the benzene ring may optionally contain one or more hetero atoms in place of a carbon atom, preferably selected from N, O, S, and more preferably one, two or three nitrogen atoms.
  • R is hydrogen and R 1 is —CO 2 R 2 , more preferably R is hydrogen and R 1 is —CO 2 H, —CO 2 Me, or —CO 2 Et.
  • formula (I) is a compound selected from the group consisting of 3-aminobenzoic acid, 2-aminobenzoic acid and ethyl 3-aminobenzoate.
  • the independently variable R 1 groups are preferably, but not necessarily, meta to the NHR group.
  • the independently variable R 1 groups are preferably, but not necessarily, ortho and para to the NHR group.
  • the copolymer may also be formed by the reaction of aniline with compounds in which the aromatic ring is not be benzenoid, but is any suitable aromatic ring, ie a heterocyclic ring having any number of atoms, more usually 5 or 6. That is, preferably said copolymer is formed by reaction of aniline with a compound of formula Ia,
  • R, R 1 and n are as above, with Ar being a N-containing heterocycle such as pyridine, pyridazine, pyrimidine, pyrazine, pyrrole, pyrazole, an O-containing heterocycle such as pyran or furan, an S-containing heterocycle such as thiophen, mixed heterocyclic systems such as isoxazole or polycyclic systems such as naphthalene, quinoline or quinoxaline.
  • N-containing heterocycle such as pyridine, pyridazine, pyrimidine, pyrazine, pyrrole, pyrazole, an O-containing heterocycle such as pyran or furan, an S-containing heterocycle such as thiophen, mixed heterocyclic systems such as isoxazole or polycyclic systems such as naphthalene, quinoline or quinoxaline.
  • Some preferred comonomers include individually or in any combination: 3-acetylaniline; 2-aminobenzaldehyde; 2-aminobenzenesfonamide; 2-aminophenol; 3-aminophenol; 2-aminophenylacetic acid; 3-aminophenylacetic acid; 2-aminobenzonitrile; 3-aminobenzonitrile; 2-aminobenzophenone; 3-aminobenzophenone; 2-aminobenzyl alcohol; 3-aminobenzyl alcohol; 2-aminobenzylamine; 2-aminobenzyl cyanide; 2-amino-4-bromobenzoic acid; 2-amino-6-chlorobenzoic acid; 2-amino-4-chlorobenzoic acid; 2-amino-4-chlorophenol; 2-amino-4-methylphenol; 2-amino-4,6-dihydroxypyrimidine; 2-amino-1,3-diethylbenzene; 1-amino-3,5-di
  • the reaction of aniline with a compound of formula (I) is carried out in a mineral acid in the presence of an oxidising agent.
  • Any suitable oxidising agent may be used.
  • Suitable oxidising agents include, although are not limited to ammonium persulphate, potassium ferricyanide, potassium iodate, hydrogen peroxide, cerium (IV) sulphate, potassium dichromate and sodium vanadate.
  • Suitable mineral acids include, although are not limited to hydrochloric acid, sulphuric acid, nitric acid or perchloric acid.
  • the mineral acid is hydrochloric acid and the oxidising agent is potassium iodate KIO 3 .
  • the copolymers of the present invention were synthesized using a reaction mixture with a 1:1 mole ratio of aniline to functionalised aniline, which resulted in good yields and produced products with enhanced solubility, relative to PANI, in common organic solvents, which include but are not limited to N-methyl-2-pyrrolidone (NMP), pyridine, 2,6-dimethylpyridine, 2,4,6-trimethylpyridine, dimethyl sulfoxide, anhydrous N,N-dimethyl acetamide, tetrahydrofuran and dimethylformamide (DMF) and to a lesser extent by hexafluoro-2-propanol (HFP), chloroform and dichloromethane.
  • NMP N-methyl-2-pyrrolidone
  • pyridine 2,6-dimethylpyridine
  • 2,4,6-trimethylpyridine dimethyl sulfoxide
  • dimethyl sulfoxide anhydrous N,N-dimethyl acetamide, tetrahydrofur
  • the aniline copolymers of the present invention are substantially insoluble in water, and are stable to wet heat sterilization at 121° C.
  • a 2:1 mole ratio of aniline to functionalised aniline showed lower solubility in common organic solvents.
  • the comonomer reactivity ratios for aniline and either 2-aminobenzoic acid or 3-aminobenzoic acid indicate that the corresponding copolymer chains should have about 90% aniline units and 10% functionalised aniline units.
  • the ratio of the aniline and functionalised aniline units in the copolymers is governed by comonomer reactivity ratios and the relative proportions of the comonomers in the reaction mixtures.
  • the copolymer contains at least about 0.01% functionalised aniline units, more preferably at least about 1% functionalised aniline units, most preferably at least about 10% functionalised aniline units.
  • the copolymers Due to the relative values of the reactivity ratios (aniline>functionalised aniline), the copolymers have longer sequences of aniline units, on average, than of functionalised aniline units.
  • the functionalised anilines can be randomly distributed in the copolymer chains or they can form block copolymers. Typically the functionalised anilines are randomly distributed.
  • X indicates the degree of polymerisation
  • A is an anion
  • the emeraldine forms can be isolated as its salt (ES) or base (EB) form.
  • the EB form can be obtained from its salt (ES) by addition of a base.
  • the base is a 1-15% (typically 6%) ammonia solution.
  • suitable bases include, although are not limited to metal hydroxides, such as sodium hydroxide and lithium hydroxide.
  • the aniline copolymers of the present invention also demonstrate antioxidant activity. In combination with their antibacterial properties, this makes them particularly useful in the field of food packaging and preservation.
  • the workability of the polyanilines of the present invention means they can be incorporated into cling film wraps, bags and the like.
  • the presence of functional groups can further enable the aniline copolymers to be covalently linked into other film forming components if desired.
  • the conducting polymers therefore have potential application as antioxidants in the food and rubber industries. Oxidation is the main cause of deterioration of foodstuffs.
  • Conducting polymer antioxidants may also be employed to inhibit uncontrolled oxidation of lipids, proteins and DNA in biological systems, which are important in the progression of various diseases, cancer and aging.
  • Scavenging of free radicals is a property that is widely regarded as beneficial for compounds that are likely to be present, or to come into contact with, biological tissues.
  • the various vitamin and polyphenol free radical scavenging antioxidants present in beverages, fruits and vegetables are currently of great interest due to the protection they may afford against various diseases, such as cardio-vascular diseases and cancer.
  • Their mechanisms of action, while still to be fully confirmed, include the chelation of pro-oxidant metal ions, and the ability to scavenge, by their action as reducing agents, excessive levels of damaging free radicals, which otherwise contribute to the oxidation and degradation of lipid material and DNA.
  • Aniline copolymers in their emeraldine salt form typically show better radical scavenging than emeraldine base forms.
  • Oxidative aging of rubber is one of the most important problems in rubber technology because the absorption of a small amount of oxygen by rubber causes a considerable change in its physicomechanical properties. Such changes can be retarded but not completely avoided by the addition of antioxidants.
  • Polyanilines were shown to be efficient in slowing down the rate of oxidation, particularly when a methoxy-substituted polyaniline was used.
  • aniline copolymers of the present invention are useful against a wide variety of bacteria, including both pathogenic and non pathogenic varieties.
  • Aniline copolymers in their emeraldine salt forms show better antimicrobial activities than emeraldine base forms.
  • Bacteria which are target organisms of the present invention can be aerobic, anaerobic, facultatively anaerobic or microaerophilic.
  • Gram-negative aerobic and microaerophilic rods and cocci include the genera Bordetella, Neisseria , and Legionella .
  • Facultatively anaerobic Gram-negative rods include genera Pseudomonas, Salmonella, Shigella, Erwinia, Enterobacter, Escherichia, Vibrio, Haemophilus, Actinobacillus and Klebsiella .
  • Bacteria that are particularly targeted by the present invention include Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Salmonella enterica serotype Enteritidis, Enterococcus sp., Staphylococcus sciuri, Enterobacter sp. and Campylobacter jejuni.
  • Additional bacterial genera include: Mycobacterium, Leptospira, Serpulina, Mycoplasma, Bacteroides, Yersinia, Chlamydia, Porphyromonas, Hemophilus, Pasteurella, Peptostreptococcus, Propionibacterium, Dermatophilus . These and other bacterial groups and genera not listed here will be recognized by the skilled artisan as suitable target bacteria for the present invention.
  • compositions of the present invention are particularly useful in treating skin infections, in particular superficial skin infections caused by various bacteria.
  • Fungal genera which are targeted by the aniline copolymers of the present inventions include, but are not limited to those genera selected from the group consisting of Aspergillus, Blastomyces, Candida, Coccidioides, Cryptococcus, Epidermophyton, Histoplasma, Microsporum, Mucor, Rhizopus, Sporothrix, Trichophyton, Paracoccidioides, Absidia, Fusarium, Penicillium, Torulopsis, Trichosporon, Rhodotorula, Malassezia, Cladosporium, Fonsecea and Phialophora.
  • DNA viruses and said RNA viruses include families selected from the group consisting of Parvoviridae, Papillomaviridae, Polyomaviridae, Adenoviridae, Hepadnaviridae, Herpesviridae, Poxviridae, Picornaviridae, Caliciviridae, Reoviridae, Togaviridae, Flaviviridae, Coronaviridae, Orthomyxoviridae, Paramyxoviridae, Rhabdoviridae, Filoviridae, Bunyaviridae, Arenaviridae and Retroviridae.
  • bacteria, fungi and viruses are illustrative suitable target organisms, but the invention is not to be considered limited to the species, genera, families, orders or classes listed.
  • 3ABAPANI the 1:1 copolymer of 3-amino benzoic acid with aniline
  • OABAPANI the 1:1 copolymer of anthranilic acid with aniline
  • 3EABPANI the 1:1 copolymer of ethyl 3-aminobenzoate with aniline
  • the ES forms of copolymers appear to be more effective than EB forms of the same copolymer.
  • 3ABAPANI and OABAPANI copolymers showed better inhibitory effect against microorganisms than 3EABPANI.
  • an acidic functional group ie. —COOH
  • the acidic dopants on the molecular chains of copolymers may react with the bacteria (or other relevant microbial organism) which result in their death.
  • the walls of bacteria may break and the contents of bacteria become exposed or leak out, which cause the bacteria to die.
  • Aniline copolymers can be applied to a surface as a solid, or in liquid form.
  • Aniline copolymers can be incorporated into conventional polymer films, which can be applied to a surface.
  • Conventional polymer films include, although are not limited to poly(vinyl alcohol), polyethylene, polypropylene, poly(ethylene terephthalate), poly(vinylidene fluoride), butene copolymers, hexene copolymers, methyl acrylate copolymers and ethylene vinyl acetate copolymers.
  • Aniline copolymers can be used in the manufacture of antibacterial and/or antifungal and/or antiviral objects.
  • objects include, although are not limited to medical dressings, urine catheters, endoscopes, medical instruments, hospital furniture, masks, floors, food packets, plastic film wraps, food processing surfaces and apparatus, pipettes, computer keyboards and mouses, cosmetics, handles, water tanks, membranes for water purification, toilets, door handles, drainage pipes, water pipes, ear pieces, shoe insoles, pools, bags for urine or feces or blood platelets, air-conditioning units, filtration equipment, pasteurization equipment and furniture.
  • Aniline polymers can be used in a variety of industries known to the skilled artisan. Such industries include although are not limited to the health industry, food industry, packaging industry, water industry, paint industry, textile industry, plastic industry, glass industry, paper industry, rubber industry, ceramic industry, wood industry, poultry industry, seafood industry, sports industry and agricultural industry.
  • aniline with 3-amino benzoic acid (3ABAPANI) or aniline with anthranilic acid (OABAPANI) was performed using 3.88 mL aniline, 5.85 g 3-amino benzoic acid or anthranilic acid respectively, 8.64 g of potassium iodate (KIO 3 ) and 240 mL of 1.25 M hydrochloric acid.
  • acetone serves to wash out unreacted or incompletely reacted starting materials (e.g. monomers) or intermediates (e.g. oligomers) which may have undesirable toxic side effects.
  • Acetone is a preferred compound for this purpose, but some other suitable solvent could be used.
  • the antimicrobial activity of the polyaniline was not observed to diminish following this treatment.
  • EB form of PANI has strong absorption peaks at 1586, 1493, 1305, 1162 and 828 cm ⁇ 1 .
  • the shifting of bands due to quinoid units from 1586 cm ⁇ 1 and 1162 cm ⁇ 1 to 1574 cm ⁇ 1 and 1135 cm ⁇ 1 , respectively were observed in protonated salt form (ES) of PANI.
  • the Raman spectra showed similar bands to those for PANI ES and EB forms.
  • the appearance of the band at 1336 cm ⁇ 1 in ES form of copolymers is assigned to C—N stretching of the cation radical species Amine deformation band for ES, N—H bending at 1414 cm ⁇ 1 was also observed.
  • Copolymers with an acidic functional group show better radical scavenging ability than copolymers without an acidic functional group.
  • the extent of DPPH scavenging by 3ABAPANI/OABAPANI copolymer and 3EABAPANI is 3.1 and 1.7 ⁇ mol, respectively.
  • the DPPH scavenging activity is approximately two times higher for 3ABAPANI/OABAPANI than for 3EABPANI samples.
  • the copolymers with a strongly acidic group (—SO 3 H) present in the polymer chain show the same DPPH activity as the copolymers with the more weakly acidic —COOH group.
  • Escherichia coli ATCC 25922 Gram-negative bacterium
  • Pseudomonas aeruginosa ATCC 27853 Gram-negative bacterium
  • Salmonella enterica serotype Enteritidis strain resistant to two antibiotics; Gram-negative bacterium
  • Enterococcus faecalis vancomycin resistant strain; Gram-positive bacterium), Staphylococcus sciuri (oxacillin resistant strain and multi drug resistant; Gram-positive bacterium), Enterobacter sp.
  • the antibacterial activity of copolymers was tested as a) copolymer dispersed in polyvinyl alcohol (PVA) films, and b) pure powders.
  • the copolymer/PVA film was mixed, sterilized in autoclave at 121° C. for 15 minutes, and poured in Petri-plates. Incubation at 35° C. for 48 h was used to evaporate water from the copolymer/PVA film.
  • 3ABAPANI 0.2 wt %) in PVA was tested with different amounts (10 6 , 10 5 , 10 4 and 10 3 cfu/mL) of Gram-negative Escherichia coli ATCC 25922 and Gram-positive Staphylococcus aureus ATCC 25923 bacteria.
  • the suspension of bacteria 100 ⁇ L was poured above the dried copolymer/PVA film, and thereafter overlaid with Brain-Heart Infusion agar. The plates were incubated at 35° C. for 48 h before the reading of the results.
  • Candida albicans Candida albicans, Cryptococcus neoformans, Candida guilliermondii, Candida parapsilosis, Candida kefyr, Candida glabrata, Aspergillus flavus , and Aspergillus niger.
  • the yeast strains were transferred from the stock culture onto Saboraud dextrose agar (SDA) agar (bioMèrieux, France), and incubated overnight at 35° C., in an air atmosphere.
  • the moulds were transferred from the stock culture onto Saboraud dextrose agar (SDA) (bioMèrieux, France), and incubated 5 days at 35° C., in an air atmosphere. Moulds were subcultured once again under the same conditions, and the cultures were used for preparation of inoculum suspensions by covering the surface of Aspergillus colonies with 5 mL of BHI broth containing Tween-20 0.1% v/v and probing with a sterile loop. The conidia suspensions were transferred to a sterile tube, shaken vigorously by vortexing, and then adjusted by microscopic enumeration with a Neubauer cell-counting haemacytometer to provide a suspension of 1-5 ⁇ 10 6 conidia/mL. The suspensions were diluted as required.
  • SDA Saboraud dextrose agar
  • MIC Minimum Inhibitory Concentration
  • the MIC for copolymer powders was determined using the microdilution assay, which was performed in sterile flat-bottomed 96-well polystyrene non-tissue culture treated microtiterplate (microplate) with a lid in a final volume of 100 ⁇ L as follows.
  • copolymer or pure chemically synthesised polyaniline used as a reference material (PANI) was weighed on an analytical balance in a glass tube, and 2 mL of BHI broth (bioMèrieux, France) was added to obtain 2% suspension of copolymers or PANI. Thereafter copolymer or PANI suspension was sterilized at 121° C. for 15 min in an autoclave (using water-saturated steam under pressure).
  • the bacterial suspension equal to 0.5 McFarland ( ⁇ 10 8 cfu/mL) was two times 10-fold diluted in BHI broth to obtain ⁇ 10 6 cfu/mL, while yeast and mold suspensions were once 10-fold diluted in BHI broth.
  • Microtiterplates were covered with their lids and incubated for 2 days at 35° C., in air atmosphere, before reading the results. Microtiterplates with Campylobacter jejuni strains were incubated in a jar under the microaerophilic conditions obtained with GENbox microaer system (bioMèrieux, France).
  • the minimal inhibitory concentration was defined as the lowest concentration of an aniline copolymer or polyaniline preventing visible turbidity, as determined by naked eye.
  • Table 4 shows the inhibitory effect (wt %) on specific bacteria types by certain substituted polyanilines.
  • copolymers were most effective on Campylobacter jejuni bacteria. All three copolymers, 3ABAPANI, OABAPANI and 3EABPANI in both ES or EB forms showed greater effectiveness as antibacterial agents than pure chemically synthesised PANI and the copolymers OCH 3 PANI, CH 3 PANI and ClPANI. ES forms of copolymers were in all cases more effective than EB forms of the same copolymer.
  • Table 5 shows the results (wt %) for each sample for inhibitory effect on each type of tested yeast and mould.
  • aniline copolymers are soluble in common organic solvents and have antibacterial and antifungal activity.
  • Tablets 1.5 cm in diameter with average weight 100 ⁇ 5 mg were made from the copolymers listed in Table 6 below.
  • the antimicrobial activity was tested on Staphylococcus aureus ATCC 25923.
  • BHI agar 20 mL, was poured into a 90 mm Petri plate.
  • a suspension of Staphylococcus aureus ATCC 25923 equal to 0.5 McFarland was inoculated by cotton swabs onto BHI agar. Thereafter tablets were placed on the inoculated surface of BHI agar. The plates were incubated overnight at 35° C., in air. The size of the inhibition zone, in mm, was measured around each tablet.
  • copolymers of the present invention as antibacterial agents over pure chemically synthesised PANI was noted for all copolymer samples.
  • Copolymers with strongly acidic groups, such as 3ABAPANI, OABAPANI and SO 3 HPANI (ES) showed a strong inhibition zone.
  • a “static” or “inhibitory” effect means that agent/substance inhibits the growth of microorganisms, while bactericidal/fungicidal/viricidal means that agent/substance kills microorganisms.
  • the mechanism of action was determined for 3ABAPANI (ES) and PANI (ES) against the bacteria Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853 and the yeast Candida albicans.
  • Suspensions containing 2%, 1%, 0.5%, 0.25% and 0.125% of 3ABAPANI (ES) and PANI (ES) were made in 2 mL of BHI broth, in glass tubes, and sterilized at 121° C. in an autoclave. Thereafter suspensions were inoculated with microorganisms, to obtain 5 ⁇ 10 5 cfu/mL of bacteria, and 0.5-2.5 ⁇ 10 5 cfu/mL of yeast. After 24 h incubation 100 ⁇ L from all tubes was transferred to BHI agar plate, and spread over the BHI agar surface with a glass rod. After incubation of the BHI agar plates for 48 h at 35° C., the microorganism colonies were counted. If no more than 0.1% of microorganisms of the initial microorganism inoculum (99.9% killing) survived, the sample was considered to be bactericidal (or fungicidal, in the case of Candida albicans ).
  • This experiment confirmed bactericidal efficacy of aniline copolymer for 0.5 wt %, and fungicidal efficacy for slightly higher concentration 2 wt %.
  • 3ABAPANI 3ABAPANI
  • ES 3ABAPANI
  • the initial inoculum of microorganisms was calculated after CFU titration at time zero, and it was 3.4 ⁇ 10 5 cfu/ml for Staphylococcus aureus ATCC 25923, 3.8 ⁇ 10 5 cfu/ml for Escherichia coli ATCC 25922, 3.8 ⁇ 10 5 cfu/ml for Pseudomonas aeruginosa ATCC 27853, and 1.4 ⁇ 10 5 cfu/ml for Candida albicans .
  • Samples of 100 ⁇ L were taken at time intervals, ten-fold serially diluted in BHI broth, and from each dilution 100 ⁇ L was spread over the entire BHI agar surface plate with a glass rod. After incubation of the BHI agar plates for 48 h at 35° C., the colonies were counted. The minimum detection level was 100 colonies.
  • Results are expressed as the Log 10 reduction of the growth. Data points marked with an X signify the moment when the viable bacteria could no longer be detected.
  • FIGS. 2 to 5 show bactericidal as well as fungicidal properties of 3ABAPANI (ES) for 2% concentration.
  • the 3ABAPANI (ES) showed bactericidal effect for 1% but with 4-6 times longer killing time.
  • inoculum size was determined in exactly the same way as the kinetics (the speed of killing or killing rate), with the only difference being the inoculum size.
  • Suspensions containing 2% 3ABAPANI (ES) were made in 5 mL of BHI broth, in glass tubes, and sterilized at 121° C. in an autoclave. Thereafter suspensions were inoculated with microorganisms. The initial inoculum of microorganisms was calculated after CFU titration at time zero, and it was 1.2 ⁇ 10 10 cfu/ml for Staphylococcus aureus ATCC 25923.
  • Results are expressed as the Log 10 reduction of the growth, and are shown in FIG. 6 .
  • Data points marked with an X represent time when viable bacteria could not be detected.
  • This part of the experiment revealed that inoculum size did not have a significant influence on the antimicrobial activity of copolymers against Staphylococcus aureus ATCC 25923. Irrespective of the inoculum size 3ABAPANI (ES) retained its bactericidal effect.
  • the final volume was 5 mL, and it contained BHI broth, 3ABAPANI (ES) in the final concentration of 2% and human plasma in the final concentration of 20%, 10% or 5%, while the initial inoculum of microorganisms was calculated after CFU titration at time zero, and it was 1.2 ⁇ 10 10 cfu/ml for Staphylococcus aureus ATCC 25923, 5.7 ⁇ 10 11 cfu/ml for Escherichia coli ATCC 25922, 3.84 ⁇ 10 11 cfu/ml for Pseudomonas aeruginosa ATCC 27853, and 8.1 ⁇ 10 7 cfu/ml Candida albicans .
  • Results are expressed as the Log 10 reduction of the growth, and are shown in FIGS. 7 to 11 .
  • Data points marked with an X represent time when viable bacteria could not be detected.
  • aniline copolymers This is the worse possible scenario for antimicrobial activity of aniline copolymers: extremely high microbial inoculum, very high (20%) organic load (for this type of experiment 10% is often used, and even less), and finally, plasma instead of serum. These conditions slowed but did not stop the antimicrobial activity of aniline copolymers, against tested bacteria (bactericidal action remains for 20% organic load) and fungi (fungicidal action remains for 5% and fungistatic for 20% organic load).
  • the MBC minimum bactericidal concentration, and the same for minimum fungicidal concentration—MFC
  • MFC minimum fungicidal concentration
  • N-acetyl-L-cysteine N-acetyl-L-cysteine
  • Samples of 100 ⁇ L were taken at time intervals, ten-fold serially diluted in 0.9 mL of BHI, and from each dilution 100 ⁇ L were spread over the entire BHI agar surface plate with a glass rod. After incubation of the BHI agar plates for 48 h at 35° C., the microorganism colonies were counted. In order to avoid carryover effect, no sample was taken directly from the 3ABAPANI (ES) and BHI mixture, and therefore the minimum detection level was 100 colonies.
  • ES 3ABAPANI
  • NAC significantly increased the antimicrobial activity of 3ABAPANI (ES) as presented in FIG. 13 .
  • the system (3ABAPANI+NAC) also shows very strong antioxidant ability.
  • Films of ⁇ 4 (polyvinyl alcohol-PVA and 0.7 wt % PANI) coated on polymethyl methacrylate (PMMA) and ⁇ 2 (PVA and 0.2 wt % Poly3ABA) coated on PMMA were cut into pieces, approximately 1 ⁇ 1 cm. Films were placed at the bottom of a sterile plastic Petri dish, taking care to keep uppermost the film side covered with aniline copolymer or polyaniline.
  • Bacterial suspensions were placed in the middle of the films and spread over the entire surface of the films with a pipette tip. Thereafter each piece of film was covered with a piece of BHI agar (which was cut from the medium previously poured into separate Petri dishes, and solidified). The plastic Petri dishes, in which the pieces of films were placed, were covered with their lids, and incubated overnight at 35° C.
  • Staphylococcus aureus ATCC 25923 was completely inhibited on the surface of ⁇ 4 (PVA and 0.7 wt % PANI) coated on polymethyl methacrylate (PMMA) and ⁇ 2 (PVA and 0.2 wt % Poly3ABA) coated on PMMA. See FIGS. 14 and 15 as examples.
  • the efficacy of PANI and Poly3ABA was not reduced by incorporating them into PVA coatings.
  • aniline copolymers have antimicrobial activity, with the same MIC as in aniline copolymer powders, in blends or composites with other materials.
  • materials with which they may be blended or formed into a composite include: polymers including poly(vinyl alcohol), poly(vinyl acetate), poly(methyl methacrylate) and other acrylics, poly(ethylene terephthalate) and other polyesters, polyamides, polyethylene and polypropylene, polyvinylidene fluoride), ethylene vinyl acetate copolymers, methyl acrylate copolymers, butane copolymers, hexane copolymers, rubber, natural rubber latex, acrylic latexes and epoxy latexes, ethyl cellulose, cellulose and other polysaccharides, and proteins, either synthesised by in situ polymerisation or coated on the surface.
  • Suspensions of the autoclaved polymers 3ABAPANI (ES) and PANI (ES) were prepared in cell culture growth medium (DMEM) at concentrations 2, 1 and 0.4% (w/v).
  • Vaccinia virus (Strain WR) was serially diluted in DMEM to a final concentration between 10 3 -10 5 infectious particles per mL. Aliquots of virus were mixed with an equal volume of polymer suspension (and a control volume of DMEM without polymer) and incubated at room temperature with gentle agitation for 1 hour after which an equal volume of each suspension was added directly to duplicate monolayer cultures of CV-1 cells. The inoculum was removed after 1 hour and the cells overlayed with DMEM containing 5% fetal bovine serum. After two days, the medium was removed and the cells stained with 0.5% crystal violet. Infectivity of virus suspensions was determined by counting plaque number and the reduction in infectivity (relative to polymer-free control) determined for each starting concentration of polymer.
  • Percent of Vaccinia virus that survived after 1 h contact with 3ABAPANI (ES) and PANI (ES) is presented in Table 8. The results are expressed as a percentage of the number of viruses which survived (retained infectivity) after 1 h of contact with the polymers.
  • 3ABAPANI (ES) has resulted in a marked inhibition of viral infectivity, in contrast to PANI (ES).
  • a similar pattern of reduced infectivity was observed with 10 ⁇ and 100 ⁇ greater concentrations of viruses for 0.5 wt % and 1 wt % of 3ABAPANI (ES).

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