WO2023183954A1 - An aqueous antimicrobial polymer dispersion - Google Patents
An aqueous antimicrobial polymer dispersion Download PDFInfo
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- WO2023183954A1 WO2023183954A1 PCT/ZA2023/050015 ZA2023050015W WO2023183954A1 WO 2023183954 A1 WO2023183954 A1 WO 2023183954A1 ZA 2023050015 W ZA2023050015 W ZA 2023050015W WO 2023183954 A1 WO2023183954 A1 WO 2023183954A1
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- Prior art keywords
- alkyl
- polymer
- formula
- styrene
- antimicrobial
- Prior art date
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- 229920002118 antimicrobial polymer Polymers 0.000 title claims abstract description 22
- 239000004815 dispersion polymer Substances 0.000 title description 3
- 229920000642 polymer Polymers 0.000 claims abstract description 56
- 239000000758 substrate Substances 0.000 claims abstract description 44
- 230000000845 anti-microbial effect Effects 0.000 claims abstract description 43
- 239000006185 dispersion Substances 0.000 claims abstract description 39
- 238000000576 coating method Methods 0.000 claims abstract description 38
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 32
- 239000011248 coating agent Substances 0.000 claims abstract description 32
- 238000000034 method Methods 0.000 claims abstract description 26
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims abstract description 15
- 239000004599 antimicrobial Substances 0.000 claims abstract description 15
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims abstract description 15
- -1 halide anion Chemical class 0.000 claims abstract description 13
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims abstract description 12
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 37
- 229920000147 Styrene maleic anhydride Polymers 0.000 claims description 25
- 238000006243 chemical reaction Methods 0.000 claims description 25
- FPYJFEHAWHCUMM-UHFFFAOYSA-N maleic anhydride Chemical group O=C1OC(=O)C=C1 FPYJFEHAWHCUMM-UHFFFAOYSA-N 0.000 claims description 14
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- 150000001347 alkyl bromides Chemical class 0.000 claims description 6
- 238000003756 stirring Methods 0.000 claims description 5
- MYMSJFSOOQERIO-UHFFFAOYSA-N 1-bromodecane Chemical compound CCCCCCCCCCBr MYMSJFSOOQERIO-UHFFFAOYSA-N 0.000 claims description 3
- 206010052428 Wound Diseases 0.000 description 24
- 208000027418 Wounds and injury Diseases 0.000 description 24
- 150000001350 alkyl halides Chemical class 0.000 description 19
- 239000004753 textile Substances 0.000 description 10
- 239000004816 latex Substances 0.000 description 8
- 229920000126 latex Polymers 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- KFYRJJBUHYILSO-YFKPBYRVSA-N (2s)-2-amino-3-dimethylarsanylsulfanyl-3-methylbutanoic acid Chemical compound C[As](C)SC(C)(C)[C@@H](N)C(O)=O KFYRJJBUHYILSO-YFKPBYRVSA-N 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 6
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 6
- 230000004048 modification Effects 0.000 description 6
- 238000012986 modification Methods 0.000 description 6
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 6
- 231100000331 toxic Toxicity 0.000 description 6
- 230000002588 toxic effect Effects 0.000 description 6
- 238000013019 agitation Methods 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 239000003960 organic solvent Substances 0.000 description 5
- 238000004483 ATR-FTIR spectroscopy Methods 0.000 description 4
- 238000002835 absorbance Methods 0.000 description 4
- 239000000178 monomer Substances 0.000 description 4
- 238000001228 spectrum Methods 0.000 description 4
- 150000003512 tertiary amines Chemical group 0.000 description 4
- 241000894006 Bacteria Species 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 238000004132 cross linking Methods 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 239000000835 fiber Substances 0.000 description 3
- 231100001261 hazardous Toxicity 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 125000001453 quaternary ammonium group Chemical group 0.000 description 3
- 239000000376 reactant Substances 0.000 description 3
- 241000588724 Escherichia coli Species 0.000 description 2
- 241000191967 Staphylococcus aureus Species 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000004035 construction material Substances 0.000 description 2
- 239000013068 control sample Substances 0.000 description 2
- 229920001577 copolymer Polymers 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 210000000416 exudates and transudate Anatomy 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 238000002386 leaching Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000006011 modification reaction Methods 0.000 description 2
- 239000002105 nanoparticle Substances 0.000 description 2
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 238000004806 packaging method and process Methods 0.000 description 2
- 229920000728 polyester Polymers 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000005956 quaternization reaction Methods 0.000 description 2
- 125000003011 styrenyl group Chemical group [H]\C(*)=C(/[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 230000029663 wound healing Effects 0.000 description 2
- 229940105325 3-dimethylaminopropylamine Drugs 0.000 description 1
- SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Chemical group CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 230000009435 amidation Effects 0.000 description 1
- 238000007112 amidation reaction Methods 0.000 description 1
- 150000008064 anhydrides Chemical group 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 150000001649 bromium compounds Chemical group 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- IUNMPGNGSSIWFP-UHFFFAOYSA-N dimethylaminopropylamine Chemical compound CN(C)CCCN IUNMPGNGSSIWFP-UHFFFAOYSA-N 0.000 description 1
- 238000007598 dipping method Methods 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000009931 harmful effect Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000003949 imides Chemical class 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000012035 limiting reagent Substances 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000005935 nucleophilic addition reaction Methods 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 238000010422 painting Methods 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 238000013341 scale-up Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 229920006301 statistical copolymer Polymers 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 229920002994 synthetic fiber Polymers 0.000 description 1
- 238000005809 transesterification reaction Methods 0.000 description 1
- 125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F222/00—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 carboxyl radical and containing at least one other carboxyl radical in the molecule; Salts, anhydrides, esters, amides, imides, or nitriles thereof
- C08F222/04—Anhydrides, e.g. cyclic anhydrides
- C08F222/06—Maleic anhydride
- C08F222/08—Maleic anhydride with vinyl aromatic monomers
-
- 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
- A01N25/08—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 containing solids as carriers or diluents
- A01N25/10—Macromolecular 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
- 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
- A01N25/02—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 containing liquids as carriers, diluents or solvents
- A01N25/04—Dispersions, emulsions, suspoemulsions, suspension concentrates or gels
-
- 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
- A01N43/02—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms
- A01N43/04—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom
- A01N43/06—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom five-membered rings
- A01N43/08—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom five-membered rings with oxygen as the ring hetero atom
-
- 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
- A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
- A01N43/36—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom five-membered rings
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F212/00—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 an aromatic carbocyclic ring
- C08F212/02—Monomers containing only one unsaturated aliphatic radical
- C08F212/04—Monomers containing only one unsaturated aliphatic radical containing one ring
- C08F212/06—Hydrocarbons
- C08F212/08—Styrene
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F8/00—Chemical modification by after-treatment
- C08F8/30—Introducing nitrogen atoms or nitrogen-containing groups
- C08F8/32—Introducing nitrogen atoms or nitrogen-containing groups by reaction with amines
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L25/00—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 an aromatic carbocyclic ring; Compositions of derivatives of such polymers
- C08L25/02—Homopolymers or copolymers of hydrocarbons
- C08L25/04—Homopolymers or copolymers of styrene
- C08L25/08—Copolymers of styrene
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L35/00—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 carboxyl radical, and containing at least one other carboxyl radical in the molecule, or of salts, anhydrides, esters, amides, imides or nitriles thereof; Compositions of derivatives of such polymers
- C08L35/06—Copolymers with vinyl aromatic monomers
Definitions
- X’ is a halide anion selected from the group consisting of bromide (Br), chloride (Cl ) and iodide (i ); f is a fraction ranging from about 0.2 to about 0.5; g is a fraction ranging from about 0.7 to about 0.95; n is an integer ranging from about 20 to about 6000; and water. g may range between about 0.8 and 0.9. f may range between about 0.25 and 0.4.
- Ri may be a C3 or C4 alkyl, preferably a linear C3 alkyl.
- R 2 may be a Cs- C10 alkyl, preferably a linear Cs or C10 alkyl.
- R 3 and R 4 may be methyl or ethyl groups, preferably methyl groups.
- X- may be a bromide (Br).
- a polymer concentration of between 0.1-1 wt% in the aqueous dispersion may be selected to provide a wound dressing with antimicrobial properties whilst not substantially affecting the absorbance of the dressing. It was found that a coating with a 2 wt% dispersion of the polymer of Formula (I) reduced the absorbance of a dressing by about 50%, whereas use of 0.1 wt% dispersion resulted in substantially no reduction in the absorbance of the dressing. Moreover, partial crosslinking may facilitate the retention of the absorbance of the wound dressing.
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- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Zoology (AREA)
- Plant Pathology (AREA)
- Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Pest Control & Pesticides (AREA)
- Environmental Sciences (AREA)
- Agronomy & Crop Science (AREA)
- Dentistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Toxicology (AREA)
- General Chemical & Material Sciences (AREA)
- Dispersion Chemistry (AREA)
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
- Compositions Of Macromolecular Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Abstract
An aqueous antimicrobial dispersion including an antimicrobial polymer having the structure of Formula (I) in which R1 is a C2-C7 alkyl; R2 is a C8-C15 alkyl; R3 and R4 are each independently a C1-C4 alkyl; X- is a halide anion selected from the group consisting of bromide (Br-), chloride (Cl-) and iodide (I-); f is a fraction ranging from about 0.2 to 0.5; g is a fraction ranging from about 0.7 to about 0.95; and n is an integer ranging from about 20 to about 6000 and a solvent-free method of producing the aqueous antimicrobial dispersion are provided. The polymer of Formula (I) has antimicrobial activity, and an antimicrobial substrate may be provided by coating the substrate with the aqueous dispersion and curing it to crosslink the polymer to the substrate in a solvent-free manner.
Description
AN AQUEOUS ANTIMICROBIAL POLYMER DISPERSION
CROSS-REFERENCE(S) TO RELATED APPLICATIONS
This application claims priority from United Kingdom patent application number 2204191.7 filed on 24 March 2022, which is incorporated by reference herein.
FIELD OF THE INVENTION
This invention relates to an aqueous antimicrobial polymer dispersion to be applied as a coating to a suitable substrate. In particular, it relates to a latex for use in providing a polymeric antimicrobial coating including quaternary ammonium moieties.
BACKGROUND TO THE INVENTION
Antimicrobial coatings are applied to substrates such as wound dressings, personal hygiene or sanitary products, clothing, packaging, furniture, construction materials, textiles and the like to make them sterile and prevent bacterial growth. Antimicrobial coatings find particular use in wound dressings as the exudate from the wound contained in an absorptive wound dressing typically encourages the growth of bacteria, resulting in infections that compromise wound healing.
Most antimicrobial coatings include antimicrobial agents that are not permanently bonded to the substrate and eventually leach from the coating or are released from it. Such coatings lose their efficacy over time and the microbes may develop resistance against the active agents. Moreover, the antimicrobial agents may in some instances have a toxic or harmful effect if concentrations are increased in an attempt to prolong efficacy.
Polymeric material with antimicrobial properties may be used as antimicrobial coatings for substrates such as wound dressings. However, their production requires the use of organic solvents and the coating solutions produced may therefore include hazardous and/or toxic solvents. Such solvents need to be removed prior to use, particularly when the coating is to be applied to a wound dressing or the like. This may prove difficult when the production and application of the coating involves a high-boiling organic solvent. Moreover, polymer production and coating methods involving organic solvents are less environmentally friendly and more costly.
Accordingly, there is a need for an antimicrobial coating that may be permanently bonded to a substrate and has the required antimicrobial activity to protect the substrate and surrounding environment from microbial infection for extended periods of time which can be produced and then applied to a substrate without using hazardous or toxic solvents.
The preceding discussion of the background to the invention is intended only to facilitate an understanding of the present invention. It should be appreciated that the discussion is not an acknowledgment or admission that any of the material referred to was part of the common general knowledge in the art as at the priority date of the application.
SUMMARY OF THE INVENTION
In accordance with an aspect of the invention there is provided an aqueous dispersion comprising an antimicrobial polymer having the structure of Formula (I):
Formula (I) wherein Ri is a C2-C7 alkyl;
R2 is a C8-C15 alkyl;
R3 and R4 are each independently a C1-C4 alkyl;
X’ is a halide anion selected from the group consisting of bromide (Br), chloride (Cl ) and iodide (i ); f is a fraction ranging from about 0.2 to about 0.5; g is a fraction ranging from about 0.7 to about 0.95; n is an integer ranging from about 20 to about 6000; and water.
g may range between about 0.8 and 0.9. f may range between about 0.25 and 0.4. Ri may be a C3 or C4 alkyl, preferably a linear C3 alkyl. R2 may be a Cs- C10 alkyl, preferably a linear Cs or C10 alkyl. R3 and R4 may be methyl or ethyl groups, preferably methyl groups. X- may be a bromide (Br).
In accordance with a second aspect of the invention there is provided a method of producing an aqueous dispersion comprising an antimicrobial polymer having the structure of Formula (I):
Formula (I) wherein R1 is a C2-C7 alkyl;
R2 is a C8-C15 alkyl;
Rs and R4 are each independently a Ci-C4 alkyl;
X’ is a halide anion selected from the group consisting of bromide (Br), chloride (Cl ) and iodide (i ); f is a fraction ranging from about 0.2 to about 0.5; g is a fraction ranging from about 0.7 to about 0.95; n is an integer ranging from about 20 to about 6000; and water; the method being carried out in water and comprising the steps of: reacting poly(styrene-co-maleic anhydride) copolymer with /V,/V-disubstituted amino(C2- C?)alkyl-1-amine to form poly(styrene-co-/V-(/\/’,/\/’-disubstituted amino-(C2-C7)alkyl)-maleimide); and reacting the poly(styrene-co-/V-(/\/’,/\/’-disubstituted amino(C2-C7)alkyl)-maleimide) with a Cs- C15 alkyl bromide, chloride or iodide to produce the polymer of Formula (I).
The two steps or reactions may be carried out consecutively in water. The second reaction of the poly(styrene-co-/V-(/\/’,/\/’-disubstituted-amino(C2-C7)alkyl)-maleimide) with a Cs-Cis alkyl bromide, chloride or iodide may be carried out with vigorous stirring and under heat.
About 80-90 mol% of the total maleic anhydride residues in the poly(styrene-co-maleic anhydride) copolymer may be converted into A/-(A/’,A/’-disubstituted amino(C2-C7)alkyl)-maleimide residues such that 10%-20% of the maleic anhydride residues remain unmodified.
More particularly, the poly(styrene-co-maleic anhydride) copolymer may be reacted with /V,/V- dimethyl-3-aminopropyl-1-amine to form poly(styrene-co-/V-(/V\/V’-dimethylaminopropyl)- maleimide and the poly(styrene-co-/V-(/V\/V’-dimethyl-3-aminopropyll)-maleimide) may be reacted with 1 -bromooctyl or 1 -bromodecane.
In accordance with a third aspect of the invention, there is provided a method of producing an antimicrobial substrate comprising the steps of: at least partially coating a substrate or a surface thereof with the aqueous dispersion comprising the polymer of Formula (I) and water described above; and curing the coating to crosslink the polymer of Formula (I) to the substrate.
In accordance with a fourth aspect of the invention, there is provided an antimicrobial substrate which includes a polymer of Formula (I)
Formula (I) wherein Ri is a C2-C7 alkyl;
R2 is a Cs-Cis alkyl;
Rs and R4 are each independently a C1-C4 alkyl;
X' is a halide anion selected from the group consisting of bromide (Br), chloride (Cl ) and iodide (i ); f is a fraction ranging from about 0.20 to 0.50; g is a fraction ranging from about 0.70 to about 0.95; and n is an integer ranging from about 20 to about 6000, crosslinked to the substrate.
The substrate may be a wound dressing, gauze, burn dressing, sponge, a medical or sanitary wipe, surgical gown, surgical glove, surgical scrubs, upholstery, floor mat, sheet, cover, liner, curtain or insole.
Embodiments of the invention will now be described, by way of example only, with reference to the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
In the drawings:
Figure 1 is an ATR-FTIR spectrum of starting poly(styrene-co-maleic anhydride) (SMA) copolymer and isolated poly(styrene-co-/V-(/V\/V’-dimethyl-3-aminopropyl)- maleimide) (SMI) product following imidization with /V,/V-dimethyl-3- aminopropyl-1-amine (DMAPA);
Figure 2 is an ATR-FTIR spectrum of the poly(styrene-co-/V-(/V\/V’-dimethyl-3- aminopropyl)-maleimide) SMI product and the isolated quaternized SMI-qn derivative formed via a reaction of the SMI product with an alkyl halide; and
Figure 3 is a graph showing the antimicrobial activity of various samples of wound dressings coated with the quaternized SMI-qn derivative against (A) Staphylococcus aureus and (B) Escherichia coli.
DETAILED DESCRIPTION WITH REFERENCE TO THE DRAWINGS
An aqueous dispersion comprising an antimicrobial polymer having the structure of Formula (I)
Formula (I) wherein Ri is a C2-C7 alkyl;
R2 is a C8-C15 alkyl;
R3 and R4 are each independently a C1-C4 alkyl;
X' is a halide anion selected from the group consisting of bromide (Br), chloride (Cl ) and iodide (I-); and n is an integer ranging from about 20 to about 6000, and water is provided.
The fractions f and g are indicative of the overall composition of the modified polymer, f is the fraction of maleic anhydride in the parent poly(styrene-co-maleic anhydride) and f may range from about 0.2 to about 0.5 (or about 0.20 to about 0.50), preferably from about 0.25 to about 0.4 (or about 0.25 to about 0.40). g is the fraction of maleic anhydride repeat units that is converted to the quaternary ammonium salt containing N-substituted maleimide and g may range from about 0.7 to about 0.95 (or about 0.70 to about 0.95), preferably from about 0.8 to 0.9 (or about 0.80 to 0.90).
The polymer of Formula (I) includes quaternary ammonium salt moieties on the modified maleic anhydride residues that provide the polymer with antimicrobial activity. The quaternary ammonium salt moieties include a Cs-Cis alkyl group (R2), which in preferred embodiments is a Cs or C10 alkyl group. The maleic anhydride residues (MAnh) in a poly(styrene-co-maleic anhydride) copolymer (SMA) may be modified to include antimicrobial quaternary ammonium salt groups by:
(i) nucleophilic addition to the MAnh residues of /V,/V-disubstituted amino(C2-C?)alkyl-1- amine (DSAAA) in which the alkyl group (R1) consists of 2 to 7 carbon atoms, preferably 3 to 4 carbon atoms, and more preferably, 3 carbon atoms, to form a tertiary amine group; and
(ii) subsequent alkylation of the tertiary amine group with an Cs-Cis alkyl halide.
Accordingly, Ri may be a C3 or C4 alkyl, preferably a linear C3 alkyl. R2 may be a Cs - C10 alkyl, preferably a linear Cs or C10 alkyl. R3 and R4 may be methyl or ethyl groups, preferably methyl groups. X’ may be a bromide (Br).
The ratio of styrene monomers to MAnh monomers in the precursor SMA and in the polymer of Formula (I) may be from about 1 : 1 (that is about 50% each) to about 4: 1 (that is about 80% styrene to 20% MAnh). In other words, f is a fraction ranging from about 0.2 to about 0.5.
The fraction g represents the degree of modification of the polymer. The larger the fraction of modified MAnh sub-units (g), the larger the antimicrobial effect. However, for covalent bonding or crosslinking to a substrate it is necessary for the polymer to include at least some unmodified MAnh sub-units. The proportion of modified sub-units (g) may be between 10% and 100%, i.e. 0.1 < g < 1.0. In some embodiments this can be between 50% and 95%, i.e. 0.50 < g < 0.95 or between 70% and 95%, i.e. 0.70 < g < 0.95. The fraction g in Formula (I) is preferably from about 0.8 to about 0.9, wherein 80-90 mol% of the MAnh residues are functionalised with the antimicrobial quaternary ammonium groups. This can be achieved by reacting only 80 to 90 mol% of MAnh residues in the bulk SMA copolymer with DSAAA and subsequently with alkyl halide such that 10-20% of the MAnh residues remain unsubstituted. The 10-20% MAnh residues may be modified in solution or functionalised with a second type of molecule to provide the polymer with a second functionality in addition to its antimicrobial properties.
The starting SMA copolymer is a statistical copolymer with a weight average molar mass of from about 2,000 - 600,000 g.mol’1, equivalent to approximately 20 - 6000 monomeric units of styrene and MAnh combined. The antimicrobial polymer of Formula (I) may also contain a corresponding 20 - 6000 monomeric units of styrene and MAnh. The integer n in Formula (I) has the usual meaning of indicating the repetition of monomer residues to the indicated total number of 20 - 6000.
A method of producing an aqueous dispersion comprising an antimicrobial polymer having the structure of Formula (I):
Formula (I) as defined above is also provided. The method is carried out in water and involves two steps or reactions which could surprisingly be carried out in water consecutively to yield a stable latex. At a first step poly(styrene-co-maleic anhydride) copolymer is reacted with /V,/V-disubstituted amino(C2-C?)alkyl-1 -amine (DSAAA) to form poly(styrene-co-/V-(/\/’,/\/’-disubstituted amino-(C2- C7)alkyl)-maleimide). Thereafter, the poly(styrene-co-/V-(/\/’,/\/’-disubstituted amino(C2-C?)alkyl)- maleimide) is reacted with a Cs-Cis alkyl bromide, chloride or iodide to produce the polymer of Formula (I). It is surprising that the last-mentioned reaction occurs in water given the poor solubility of the Cs-Cis alkyl halide in water.
The first reaction involves subjecting the copolymer to thermal imidization with a suitably substituted amine in water to form the corresponding imide. The thermal imidization reaction of the poly(styrene-co-maleic anhydride) copolymer may be carried out in a double walled oil heated autoclave equipped with a mechanical agitator to produce the corresponding poly(styrene-co- maleimide).
The mol fraction of DSAAA for the first reaction is selected such that about 80-90 mol% of the total maleic anhydride residues in the poly(styrene-co-maleic anhydride) copolymer may be converted into A/-(A/’, /’-disubstituted amino(C2-C7)alkyl)-maleimide residues. Consequently, IQ- 20 mol% of the maleic anhydride residues remain unmodified. The method therefore comprises a first step of reacting 80-90 mol% of the available MAnh residues in the bulk polymer with DSAAA to form poly(styrene-co-/V-(/\/’,/\/’-disubstituted amino(C2-C7)alkyl)-maleimide) in which 80-90% of the MAnh residues are modified with DSAAA. With the end-function or application of the polymer in an antimicrobial coating dispersion to be applied to a substrate in mind, the imidization is carried out with a sub-molar amount of the amine, DSAAA. The degree of imidization determines the remaining amount of maleic anhydride monomers in the polymer which are available to crosslink to the substrate to covalently bind the antimicrobial polymer to the substrate.
In one embodiment, 90 mol% of the MAnh units in the bulk polymer is reacted with the DSAAA such that about 90 mol% of the MAnh residues of the SMA copolymer are modified with DSAAA, and subsequently with an alkyl halide to produce the quaternary ammonium salt moieties. The subsequent reaction may also be carried out with 90 mol% of the DSAAA modified residues. By ensuring that DSAAA and then the alkyl halide are each the limiting reagent in the modification reactions, there should be no residual, unreacted DSAAA or alkyl halide in the produced antimicrobial aqueous coating dispersion, provided that both reactions proceed to completion. Residual reactants are undesirable as they may be toxic and leach from the coating once applied to a substrate. The remaining 10% of the MAnh residues that are not functionalized with DSAAA and the alkyl halide are free to be functionalized with any other molecule, if required.
In particular, the poly(styrene-co-maleic anhydride) copolymer may be reacted with /V,/V-dimethyl- 3-aminopropyl-1-amine in water to form poly(styrene-co-/V-(/V\/V’-dimethylaminopropyl)- maleimide. This imidization reaction typically yields white stable dispersions containing poly(styrene-co-maleimide) nanoparticles of 46 ± 4.9 nm, with the particle size depending on the agitation rate employed. Typical reaction conditions are 150° - 180 °C at a pressure of 4 - 7 bar for 6 hours. An agitation rate of about 200-1000 rpm, preferably 1000 rpm may be used.
The general reaction equation illustrating the amidation and cyclization during imidization is as follows:
Imidization of poly(styrene-co-maleic anhydride) with 3-dimethylamino-propylamine (1 :1) resulted in stable dispersions containing well dispersed, nano-sized poly(styrene-co-maleimide) particles of size ranging from about 150 nm at slow agitation rates of about 200 rpm to about 50 nm at higher agitation rates of about 1000 rpm.
After the first step of the method for synthesizing the polymer of Formula (I), the intermediate product is already a latex. The second step or reaction utilizes an alkyl halide, with moderate to low solubility in water. The limitations from the low water solubility of this reagent would present a challenge for successful reaction. Getting the alkyl halide through the aqueous phase to react with the polymer is surprising in view of the poor water solubility of the alkyl halide. It was
eventually discovered that with vigorous stirring under heat the alkylation reaction with the alkyl halide takes place. Therefore, the second reaction of the poly(styrene-co-/V-(/\/’,/\/’-disubstituted- amino(C2-C7)alkyl)-maleimide) with a Cs-Cis alkyl bromide, chloride or iodide may be carried out after the first reaction in water with vigorous stirring and under heat.
In the second step, an alkyl halide (CnH2nX, where X is Br, Cl or I) is added at a temperature around 80-90 °C while stirring at a rate of 500 - 1500 rpm, preferably 1500 rpm. The reaction is allowed to proceed for 6 hrs at 80-90 °C and then cooled down to room temperature. The product is a stable latex of the polymer in water. The molecular structure of an embodiment of the polymer of Formula (I) in which the unmodified maleic anhydride moieties are not shown is:
wherein n is the number average degree of polymerization, f is the mole fraction of maleic anhydride built in the starting polymer and Aik is an alkyl substituent selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl and dodecyl, preferably octyl or decyl.
Preferred quaternary ammonium salts may be formed on the SMA polymer backbone by reacting the SMA copolymer with /V,/V-dimethyl-3-aminopropyl-1-amine (DMAPA) to form poly(styrene-co- /V-(/V\/V’-dimethyl-3-aminopropyl)-maleimide) then reacting the poly(styrene-co-/V-(/\/’ ,/V’- dimethyl-3-aminopropyll)-maleimide) with 1-bromooctyl or 1 -bromodecane, i.e. a polymer of Formula (I) in which Ri = a C3 alkyl chain, R2 = a Cs or C10 alkyl chain, R3 and R4 are methyl groups and X' is a bromide.
The synthesis of the polymer of Formula (I) may be via a one-pot or batch modification process with both reactions carried out consecutively in water, which is easy to scale up. The method does not require the polymer to be isolated between consecutive steps, which simplifies the synthesis and makes it less costly. The antimicrobial coating dispersion may be synthesized on large scale in commercially available reaction vessels (60-250 L) for example.
The quantities of the reactants and water may be selected to produce a latex that is suitable for direct application to a selected type of substrate so that it has the desired antimicrobial activity for a specific purpose or use. Accordingly, a method of producing an antimicrobial substrate is provided comprising the steps of at least partially coating a substrate or a surface thereof with the aqueous dispersion comprising the polymer of Formula (I) and water described above; and curing the coating to crosslink the polymer of Formula (I) to the substrate. The curing step may be carried out at about 100 °C to 110 °C under vacuum for about 1 hour. Advantageously, any potential residual water present after the curing step simply evaporates. Residual water can be removed more rapidly with heating under vacuum, if required. The method does not require any washing or more complex solvent removal steps since it is solvent-free.
Alternatively, the aqueous dispersion comprising the antimicrobial polymer of Formula (I) may be freeze-dried or lyophilised to remove water prior to the coating step. Reconstitution of a freeze- dried or lyophilised preparation of the antimicrobial polymer of formula (I) can be carried out with water or with a solvent for the polymer such as methanol. The antimicrobial solution may then be coated onto the substrate and cured according to the same method described above with reference to the aqueous dispersion.
A polymer concentration of 0.1 to 20 wt% in methanol may be used during the coating and curing process to produce a substrate with the polymer crosslinked thereto having the desired antimicrobial activity. Alternatively, the latex may be directly used in coating and curing (i.e., undiluted), or diluted with water to a concentration of 12.5 - 50 % of the original 10 wt% solids content. It has previously been found that the antimicrobial polymer is effective in inhibiting bacterial growth of both gram-positive and gram-negative bacteria.
An antimicrobial substrate is further provided which includes a polymer of Formula (I)
Formula (I) wherein Ri is a C2-C7 alkyl;
R2 is a C8-C15 alkyl;
R3 and R4 are each independently a C1-C4 alkyl;
X' is a halide anion selected from the group consisting of bromide (Br), chloride (Cl ) and iodide (i ); f is a fraction ranging from about 0.2 to about 0.5; g is a fraction ranging from about 0.7 to about 0.95; and n is an integer ranging from about 20 to about 6000, crosslinked to the substrate.
The antimicrobial polymer may be crosslinked to at least a portion of surface of the substrate. The substrate should ideally have available hydroxyl groups to enable the polymer of Formula (I) to be covalently bonded to the substrate. The anhydride moiety of the antimicrobial polymer react with hydroxyl groups on the substrate to form covalent bonds that are strong enough to substantially avoid leaching of the antimicrobial polymer coating from the substrate. Any type of substrate made of natural or synthetic material may be coated with the antimicrobial polymer of Formula (I), provided it has the requisite functional groups for covalent bonds to be formed on its surface. The substrate may be a wound dressing, gauze, burn dressing, sponge, a medical or sanitary wipe, surgical gown, surgical glove, surgical scrubs, upholstery, floor mat, sheet, cover, liner, curtain or insole. The substrate may also be personal hygiene or sanitary products, clothing, packaging, furniture, construction materials, textiles and the like.
In particular the antimicrobial dispersion may be applied to a textile made of polyester or cellulosic fibers, such as those used in biocompatible and absorptive wound dressings. Wound dressings are commonly used as part of the standard of care for wound bed preparation. They are usually extremely absorptive and effective at drawing exudate away from the wound surface and removing toxic components such as slough, wound debris and bacteria that compromise wound healing.
The coating step may include dipping the textile or a part thereof in the aqueous dispersion of the polymer of Formula (I) or spraying or painting the aqueous dispersion of the polymer of Formula (I) onto the textile or a part thereof prior to curing it to covalently bond the polymer coating to the dressing. A coating and curing process may be devised for high throughput coating and curing of a textile, for example, in an assembly line. For example, the textile may be dipped into a bath of the dispersion, passed through squeeze rollers to remove excess antimicrobial coating dispersion and control the coating thickness and then carried through a series of ovens (either horizontally or vertically) for drying and curing. During the curing step, the water from the dispersion is
substantially removed. If required, the assembly line may also include nozzles that spray a selected washing fluid onto the textile to remove any polymer that is not covalently bonded to the textile. In this manner an antimicrobial textile may be produced for use in wound dressings. The antimicrobial polymer of Formula (I) is crosslinked to the dressing and unable to leach from dressing into a wound bed.
To prepare an antimicrobial wound dressing, the whole or part of the dressing may be dipped or otherwise coated with the antimicrobial dispersion including particles of the polymer of Formula (I) at a concentration of about 0.1-20 % (w/w). The wound dressing is then cured, allowing the polymer to crosslink to the polymeric fibers, typically polyester and/or cellulose, of the dressing. If required, a drying step may form part of the process to remove any residual water after the curing step. It is believed that the crosslinking of the polymer to the wound dressing fibers proceeds via an intermolecular transesterification reaction. The water which evaporates during the curing step may be recovered and recycled. Next, the wound dressing is soaked and washed with water to get rid of any physically adsorbed polymer.
A polymer concentration of between 0.1-1 wt% in the aqueous dispersion may be selected to provide a wound dressing with antimicrobial properties whilst not substantially affecting the absorbance of the dressing. It was found that a coating with a 2 wt% dispersion of the polymer of Formula (I) reduced the absorbance of a dressing by about 50%, whereas use of 0.1 wt% dispersion resulted in substantially no reduction in the absorbance of the dressing. Moreover, partial crosslinking may facilitate the retention of the absorbance of the wound dressing.
EXAMPLES
Modification of commercially available SMA to produce an antimicrobial polymer dispersed in water
Scheme 1 shows an exemplary synthetic route for producing quaternized poly(styrene-co- maleimide) (SMI) derivatives. Steps one and two are performed in water, yielding a stable polymer latex. The reactions were performed in varying mole ratios of maleic anhydride relative to DMAPA and the alkyl halide, indicated in Table 1.
Scheme 1. Exemplary modification of SMA with DMAPA and an alkyl halide to produce an antimicrobial polymer dispersed in water.
Table 1. Mole ratio of MAnh : DMAPA : alkyl halide investigated
Figure 1 is an ATR-FTIR spectrum of the starting SMA polymer and isolated poly(styrene-co- maleimide) (SMI) product following imidization with DMAPA according to step one of Scheme 1. The successful modification reaction in step one of Scheme 1 is indicated by a clear shift of the anhydride carbonyl signals (C=O stretching) at 1855 and 1774, to 1769 and 1695 cm-1. The appearance of a signal at 2766 cm-1 indicates the presence of the tertiary amine.
Figure 2 is an ATR-FTIR spectrum of the SMI polymer and isolated quaternized SMI derivative. The successful quaternization reaction in step two of Scheme 1 is indicated by the disappearance of the terminal tertiary amine signal (2766 cm-1) and the appearance of a broad band signal at 3393 cm-1 indicating a quaternary ammonium cation. Furthermore, the peaks at 2993 and 2853 cm-1 indicate the anti-symmetric and symmetric stretching of -CHs and -CH2 groups pertaining to the alkyl chain.
Figure 3 is a percentage inhibition graph showing the antimicrobial activity of wound dressings coated with the quaternized SMI-qn derivative against (A) Staphylococcus aureus and (B) Escherichia coli. The wound dressing samples are coated with quaternized SMI-qn derivatives having different percentage DMAPA modification relative to MAnh as listed in Table 2. A summary of the samples tested is given in Table 3.
Table 2. Sample coding
Table 3. The samples tested.
The control sample is plotted first on graphs A and B of Figure 3. The samples encoded CS003 H2O on graphs A and B of Figure 3 absorbed culture media. All data shown in Figure 3 represent the mean and standard error of three technical and three biological repeats (nine data points in total). Samples above the horizontal dotted line shown on Figure 3 are considered an improvement (for example samples CSOO3 H2O 25%, 50% & 100% amongst others on graph B of Figure 3), relative to the uncoated control sample.
The polymer of Formula (I) is antimicrobial and non-toxic to mammalian cells. The antimicrobial aqueous dispersion of the polymer of Formula (I) creates a permanent, non-leaching antimicrobial coating that can be produced and applied in a solvent-free and therefore “green” process. As a result, the antimicrobial coating is environmentally benign and solves the problem of using hazardous and/or toxic solvents in the production and application of an antimicrobial coating. Moreover, there is a cost-saving in the omission of solvents in the production and application process.
It was surprisingly found that a uniform dispersion or latex of the polymer of Formula (I) in water is obtainable. Attempts to synthesize the polymer in low-boiling organic solvents rather than high- boiling organic solvents resulted in an undesirable gel-like product.
It is desirable to obtain a full conversion of the alkyl halide in the quaternization reaction so that there is no residual alkyl halide present in the dispersion. It will be appreciated by those skilled in the art that the conditions (agitation rate and reaction temperature) and reactant ratios used in a method of producing the aqueous dispersion of the polymer of Formula (I) may be optimised to further minimize residual alkyl halide.
The foregoing description has been presented for the purpose of illustration; it is not intended to be exhaustive or to limit the invention to the precise forms disclosed. Persons skilled in the relevant art can appreciate that many modifications and variations are possible in light of the above disclosure.
The language used in the specification has been principally selected for readability and instructional purposes, and it may not have been selected to delineate or circumscribe the inventive subject matter. It is therefore intended that the scope of the invention be limited not by this detailed description, but rather by any claims that issue on an application based hereon. Accordingly, the disclosure of the embodiments of the invention is intended to be illustrative, but not limiting, of the scope of the invention, which is set forth in the following claims.
Finally, throughout the specification and accompanying claims, unless the context requires otherwise, the word ‘comprise’ or variations such as ‘comprises’ or ‘comprising’ will be understood to imply the inclusion of a stated integer or group of integers but not the exclusion of any other integer or group of integers.
Claims
1. An aqueous dispersion comprising an antimicrobial polymer having the structure of Formula (I):
Formula (I) wherein Ri is a C2-C7 alkyl;
R2 is a C8-C15 alkyl;
R3 and R4 are each independently a C1-C4 alkyl;
X’ is a halide anion selected from the group consisting of bromide (Br ), chloride (Cl ) and iodide (I ); f is a fraction ranging from about 0.2 to about 0.5; g is a fraction ranging from about 0.5 to about 0.95; n is an integer ranging from about 20 to about 6000; and water.
2. The aqueous dispersion as claimed in claim 1 wherein the fraction of g ranges from about 0.8 to 0.9.
3. The aqueous dispersion as claimed in claim 1 or claim 2, wherein fraction f ranges from about 0.25 to about 0.4.
4. The aqueous dispersion as claimed in any one of the preceding claims, wherein R1 is a C3 alkyl.
5. The aqueous dispersion as claimed in any one of the preceding claims, wherein R2 is a Cs- C10 alkyl.
The aqueous dispersion as claimed in any one of the preceding claims, wherein R3 and R4 are methyl groups. The aqueous dispersion as claimed in any one of the preceding claims, wherein X- is bromide (Br). A method of producing an aqueous dispersion comprising an antimicrobial polymer having the structure of Formula (I):
Formula (I) wherein Ri is a C2-C7 alkyl;
R2 is a C8-C15 alkyl;
R3 and R4 are each independently a Ci-C4 alkyl;
X’ is a halide anion selected from the group consisting of bromide (Br), chloride (Cl ) and iodide (I ); f is a fraction ranging from about 0.2 to about 0.5; g is a fraction ranging from about 0.7 to about 0.95; n is an integer ranging from about 20 to about 6000; and water; the method being carried out in water and comprising the steps of: reacting poly(styrene-co-maleic anhydride) copolymer with /V,/V-disubstituted amino(C2-C7)alkyl-1-amine to form poly(styrene-co-/V-(/\/’,/\/’-disubstituted amino-(C2- C7)alkyl)-maleimide); and reacting the poly(styrene-co-/V-(/\/’,/\/’-disubstituted amino(C2-C7)alkyl)-maleimide) with a C8-C15 alkyl bromide, chloride or iodide to produce the polymer of Formula (I).
The method as claimed in claim 8, wherein the reactions are carried out consecutively in water. The method as claimed in claim 8 or claim 9, wherein the reaction of the poly(styrene- co-A/-(A/’,A/’-disubstituted amino(C2-C7)alkyl)-maleimide) with a Cs-Cis alkyl bromide, chloride or iodide is carried out with vigorous stirring under heat. The method as claimed in any one of claims 8 to 10, wherein about 80-90 mol% of the total maleic anhydride residues in the poly(styrene-co-maleic anhydride) copolymer are converted into /V-(/V’, /V’-disubstituted amino(C2-C7)alkyl)-maleimide residues and 10-20 mol% of the maleic anhydride residues remain unmodified. The method as claimed in any one of claims 8 to 11 , wherein the poly(styrene-co- maleic anhydride) copolymer is reacted with /V,/V-dimethyl-3-aminopropyl-1-amine to form poly(styrene-co-/V-(/V\/V’-dimethylaminopropyl)-maleimide and the poly(styrene- co-/V-(/V\/V’-dimethyl-3-aminopropyll)-maleimide) is reacted with 1-bromooctyl or 1- bromodecane. A method of producing an antimicrobial substrate comprising the steps of: at least partially coating a substrate or a surface thereof with the aqueous dispersion of any one of claims 1 to 7; and curing the coating to crosslink the polymer of Formula (I) to the substrate. An antimicrobial substrate which includes a polymer of Formula (I)
Formula (I) wherein Ri is a C2-C7 alkyl;
R2 is a C8-C15 alkyl;
R3 and R4 are each independently a C1-C4 alkyl;
X' is a halide anion selected from the group consisting of bromide (Br ), chloride (Cl ) and iodide (I ); f is a fraction ranging from about 0.2 to 0.5; g is a fraction ranging from about 0.7 to about 0.95; and n is an integer ranging from about 20 to about 6000, crosslinked to the substrate. An antimicrobial substrate as claimed in 14 in which the substrate is a wound dressing, gauze, burn dressing, sponge, a medical or sanitary wipe, surgical gown, surgical glove, surgical scrubs, upholstery, floor mat, sheet, cover, liner, curtain or insole.
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- 2022-03-24 GB GB2204191.7A patent/GB2616896A/en active Pending
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| WO2018062529A1 (en) * | 2016-09-29 | 2018-04-05 | 株式会社日本触媒 | Antimicrobial agent containing polymer having maleimide structure unit |
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| CLOETE WILLIAM J ET AL: "Permanently antimicrobial waterborne coatings based on the dual role of modified poly(styrene-co-maleic anhydride)", EUROPEAN POLYMER JOURNAL, PERGAMON PRESS LTD OXFORD, GB, vol. 49, no. 5, 6 February 2013 (2013-02-06), pages 1080 - 1088, XP028525392, ISSN: 0014-3057, DOI: 10.1016/J.EURPOLYMJ.2013.01.012 * |
| OVERDUIN MICHAEL ET AL: "Advancing membrane biology with poly(styrene-co-maleic acid)-based native nanodiscs", EUROPEAN POLYMER JOURNAL, vol. 110, 10 November 2018 (2018-11-10), pages 63 - 68, XP085572023, ISSN: 0014-3057, DOI: 10.1016/J.EURPOLYMJ.2018.11.015 * |
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| Publication number | Publication date |
|---|---|
| GB2616896A (en) | 2023-09-27 |
| GB202204191D0 (en) | 2022-05-11 |
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