EP4258876A1 - Lactam composition and use - Google Patents

Lactam composition and use

Info

Publication number
EP4258876A1
EP4258876A1 EP21802746.4A EP21802746A EP4258876A1 EP 4258876 A1 EP4258876 A1 EP 4258876A1 EP 21802746 A EP21802746 A EP 21802746A EP 4258876 A1 EP4258876 A1 EP 4258876A1
Authority
EP
European Patent Office
Prior art keywords
lactam
hydrogen
film
polymers
polyvinylalcohol
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
EP21802746.4A
Other languages
German (de)
French (fr)
Inventor
Nicholas BROWNBILL
Joanne Clare O'keeffe
Neil James Parry
Craig Warren Jones
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Unilever Global IP Ltd
Unilever IP Holdings BV
Original Assignee
Unilever Global IP Ltd
Unilever IP Holdings BV
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Unilever Global IP Ltd, Unilever IP Holdings BV filed Critical Unilever Global IP Ltd
Publication of EP4258876A1 publication Critical patent/EP4258876A1/en
Pending legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • 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
    • 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
    • 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
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P1/00—Disinfectants; Antimicrobial compounds or mixtures thereof

Definitions

  • the invention relates to an improvement in the field of hygiene, in particular to a composition comprising a lactam which displays improved displays improved inhibition of bacterial species.
  • Hygiene in particular inhibition of bacterial species, is important to consumers.
  • Lactams are known as inhibitors of bacterial species. They may be applied to surfaces to inhibit bacterial species.
  • the invention relates in a first aspect to a composition
  • a composition comprising:-
  • a film-forming polymer from 0.1 to 80 wt.%, preferably from 0.25 to 40 wt.%, more preferably from 0.5 to 35 wt.% of a film-forming polymer; wherein the film-forming polymer is selected from polysaccharides, quaternised polysaccharide derivatives, polyvinylpyrrolidone (PVP) and co-polymers thereof, and, polyvinylalcohol (PVA) and co-polymers of polyvinylalcohol, and/or mixtures thereof; and, wherein the lactam is of formula (I) or (II):
  • R1 and R2 are each independently selected from hydrogen, halogen, alkyl, cycloalkyl, alkoxy, oxoalkyl, alkenyl, heterocyclyl, heteroaryl, aryl and aralalkyl;
  • R4 and R5 are independently selected from hydrogen, aryl, heterocyclyl, heteroaryl, and arylalkyl;
  • Re is selected from hydrogen and methyl
  • R1, R4 and R5 are H;
  • R3 is H, or (CH2) n N + (CH3)3, where n is an integer from 1 to 16, preferably 2 to 8;
  • R2 is a phenyl group, or a monosubstituted phenyl group; preferably R2 is selected from phenyl, 4-fluorophenyl, 2- fluorophenyl, 4-chlorophenyl, 3-chlorophenyl, 4-bromophenyl and 4-methylphenyl.
  • the lactam is a lactam selected from:
  • lactam is selected from:
  • lactam is: -chlorophenyl)-5-methylene-pyrrol-2-one
  • the lactam is delivered from an aqueous based composition, preferably comprising from 0.1 to 99 wt.%, preferably from 0.5 to 98 wt.%, more preferably from 1 to 98 wt.% water.
  • the solvent is preferably selected from the group: alcohol; levulinate derivatives; lactate derivatives; and solvents with a dielectric constant of 15 of higher, preferably the solvent is selected from the group: alcohol, levulinate derivatives; and lactate derivatives; more preferably the solvent is selected from the group: levulinate derivatives and lactate derivatives.
  • solvents are: of alcohols, preferably a C1-C4 alcohol, more preferably ethanol; of lactate derivatives, preferably ethyl lactate and/or butyl lactate; of levulinate derivatives, preferably 2-methyltetrahydrofuran, ethyl levulinate, and/or ethyl levulinate glycerol ketal (LGK); and of solvents with a dielectric constant of 15 of higher, preferably dimethyl sulfoxide (DMSO).
  • alcohols preferably a C1-C4 alcohol, more preferably ethanol
  • lactate derivatives preferably ethyl lactate and/or butyl lactate
  • levulinate derivatives preferably 2-methyltetrahydrofuran, ethyl levulinate, and/or ethyl levulinate glycerol ketal (LGK)
  • LGK ethyl levulinate glycerol ketal
  • the solvent is selected from the group: ethanol; ethyl lactate, butyl lactate; 2- methyltetrahydrofuran, ethyl levulinate, and ethyl levulinate glycerol ketal (LGK), or mixtures thereof.
  • the solvent is selected from the group: levulinate derivatives; and lactate derivatives.
  • the solvent is selected from the group: ethyl lactate, butyl lactate; 2- methyltetrahydrofuran, ethyl levulinate, and ethyl levulinate glycerol ketal (LGK), or mixtures thereof.
  • the solvent is selected from the group: 2-methyltetrahydrofuran, ethyl levulinate and ethyl levulinate glycerol ketal (LGK), or mixtures thereof.
  • the solvent is present at a level of from 0.5 to 95 wt.%, preferably from 0.5 to 90 wt.%, more preferably from 0.5 to 80 wt.%.
  • the solvent may be present at a lowest level of from 0.5 wt.%, 0.75 wt.%, 1 wt.%, 1.5 wt.%, 2 wt.%, 2.5 wt.% or even 5 wt.%.
  • the solvent may be present at a highest level of from 95 wt.%, 90 wt.%, 85 wt.%, 80 wt.%, 70 wt.%, 60 wt.%, 50 wt.%, 40 wt.%, 30 wt.%, 25 wt.%, 20 wt.% or even 10 wt.%. Any higher level of solvent is meant to be combinable with any lower level of solvent.
  • Preferred natural polymers are polysaccharides, for example xanthan and hydroxypropyl methylcellulose (HPMC), and quaternised polysaccharide derivative polymers, for example Celquat.
  • Preferred synthetic polymers include polyvinylpyrrolidone (PVP) and co-polymers thereof, polyvinylalcohol (PVA) and co-polymers of polyvinylalcohol.
  • More preferred film-forming polymers are polysaccharides, quaternised polysaccharide derivates, polyvinylpyrrolidone (PVP) and co-polymers thereof, and, polyvinylalcohol (PVA) and co-polymers of polyvinylalcohol.
  • Most preferred film-forming polymers are quaternised polysaccharide derivates, polyvinylpyrrolidone (PVP) and co-polymers thereof, and, polyvinylalcohol (PVA) and copolymers of polyvinylalcohol.
  • the composition comprises one or more surfactants.
  • the surfactant may be present at a level of from 0.25 to 25 wt.%, preferably from 0.25 to 20 wt.%, more preferably from 0.25 to 15 wt.%, even more preferably from 0.25 to 10 wt.%, or even 0.5 to 10 wt.% or even 0.5 to 5 wt.%.
  • the surfactant may be present at a level of from 0.25 to 25 wt.%, preferably from 0.25 to 20 wt.%, more preferably from 0.25 to 15 wt.%, even more preferably from 0.25 to 10 wt.%, or even 0.5 to 10 wt.% or even 0.5 to 5 wt.%.
  • the surfactant is preferably selected from anionic, nonionic, cationic and/or amphoteric surfactants.
  • Preferred surfactants are nonionic surfactants.
  • the invention relates in a second aspect to a non-therapeutic method of treatment of a surface, to improve resistance of said surface to bacterial fouling, by treatment with a composition according to the first aspect of the invention.
  • the surface to be treated is selected from plastic, metal, wood, polymer, paper, textile, and/or wipes.
  • the lactam is selected from:
  • the invention further relates in a third aspect to the use of a combination of a lactam and a film forming polymer to improve inhibition of bacterial species, wherein the film-forming polymer is selected from polysaccharides, quaternised polysaccharide derivatives, polyvinylpyrrolidone (PVP) and co-polymers thereof, and, polyvinylalcohol (PVA) and co-polymers of polyvinylalcohol, and/or mixtures thereof; and, wherein the lactam is of formula (I) or (II): wherein:
  • R1 and R2 are each independently selected from hydrogen, halogen, alkyl, cycloalkyl, alkoxy, oxoalkyl, alkenyl, heterocyclyl, heteroaryl, aryl and aralalkyl;
  • R4 and R5 are independently selected from hydrogen, aryl, heterocyclyl, heteroaryl, and arylalkyl;
  • Re is selected from hydrogen and methyl
  • the lactam is selected from: Detailed Description of the Invention
  • indefinite article “a” or “an” and its corresponding definite article “the” as used herein means at least one, or one or more, unless specified otherwise.
  • a lactam is a cyclic amide.
  • Preferred lactams are y-lactams which have 5 ring atoms.
  • the lactam is of formula (I) or (II): wherein:
  • Ri and R2 are each independently selected from hydrogen, halogen, alkyl, cycloalkyl, alkoxy, oxoalkyl, alkenyl, heterocyclyl, heteroaryl, aryl and aralalkyl; and
  • R4 and R5 are independently selected from hydrogen, aryl, heterocyclyl, heteroaryl, and arylalkyl;
  • Re is selected from hydrogen and methyl
  • R4 and R5 are hydrogen. It will be appreciated that, where appropriate groups may be optionally substituted. Optional substituents may include halogens, Ci-4alkyl, Ci.4haloalkyl (for example, CF3) and Ci.4alkoxy.
  • Alkyls may, for example, be Ci. ⁇ alkyls, such as Ci-ealkyls.
  • Aryls may, for example, be Ce- aryls, for example, phenyls.
  • At least one of R1 and R2 is selected from heterocyclyl, heteroaryl, aryl and arylalkyl.
  • R1 is hydrogen.
  • R3 is hydrogen, or (CH2) n N + (R a )3, where n is an integer from 1 to 16, preferably 2 to 8, and where each R a is independently H or C1.4 alkyl, more preferably R a is CH3;
  • R4 is hydrogen.
  • R5 is hydrogen.
  • Re is hydrogen.
  • R? is hydrogen.
  • R2 is aryl or aralalkyl. More preferably, R2 is a phenyl group or a substituted phenyl group, for example, a monosubstituted phenyl group. Substitution may be ortho, meta, or para.
  • R2 may be selected from phenyl, 4-fluorophenyl, 2-fluorophenyl, 4-chlorophenyl, 3-chlorophenyl, 4-bromophenyl and 4-methylphenyl.
  • R1, R4 and R5 are H;
  • R3 is H, or (CH2) n N + (CH3)3, where n is an integer from 1 to 16, preferably 2 to 8;
  • R2 is a phenyl group, or a mono-substituted phenyl group; preferably R2 is selected from phenyl, 4- fluorophenyl, 2-fluorophenyl, 4-chlorophenyl, 3-chlorophenyl, 4-bromophenyl and 4- methylphenyl.
  • the lactam is of formula (I), R1, R4 and R5 are H; R3 is H, or (CH2) n N + (CH3)3, where n is an integer from 1 to 16, preferably 2 to 8; and R2 is a phenyl group, or a mono-substituted phenyl group; preferably R2 is selected from phenyl, 4- fluorophenyl, 2-fluorophenyl, 4-chlorophenyl, 3-chlorophenyl, 4-bromophenyl and 4- methylphenyl.
  • the lactam is cationic in nature, it can be used as such, or suitably with a counterion (e.g. iodide)
  • a counterion e.g. iodide
  • the lactam is a lactam selected from:
  • lactam is selected from:
  • lactam is: -chlorophenyl)-5-methylene-pyrrol-2-one.
  • the lactam is cationic in nature
  • the cation can be used or with a suitable counterion (e.g. iodide).
  • a suitable counterion e.g. iodide.
  • the lactam is present at a level of from 0.0001 to 2.5 wt.%, preferably from 0.0001 to 1 wt.%.
  • the lactam may be suitably present at levels of 0.001 to 1 wt.%, or even 0.01 to 1 wt.%, or even 0.01 to 0.5 wt.%.
  • the lactam is delivered from an aqueous based composition, preferably comprising from 0.1 to 99 wt.%, preferably from 0.5 to 98 wt.%, more preferably from 1 to 98 wt.% water.
  • the lactam is delivered from an aqueous based composition, preferably comprising from 0.1 to 98 wt.%, preferably from 0.5 to 80 wt.%, more preferably from 1 to 75 wt.% water.
  • the composition may comprise any amount of water ranging from lower amounts of 0.1 , 0.5, 1 , 1.5, 2 or even 5 wt.% water up to 30, 40, 50, 60, 70, 75, 80, 85, 90, 95, 96, 97, 98, or even 99 wt.% water.
  • preferred levels of water include from 60 to 98 wt.%, preferably from 70 to 98 wt.%, more preferably from 80 to 98 wt.%, even more preferably from 85 to 98 wt.% or even from 90 to 98 wt.%.
  • the composition comprises a solvent, said solvent preferably selected from the group: alcohol; levulinate derivatives; lactate derivatives; and, solvents with a dielectric constant of 15 of higher.
  • alcohol solvents examples include glycols, for example propylene glycols, and polyethylene glycols; methanol, ethanol, propanol, butanol, isopropanol, benzyl alcohol, lanolin alcohols, and fatty alcohols.
  • examples of other solvent include ethyl acetate, oleic acid, and isopropyl myristate.
  • solvents are: of alcohols, preferably a C1-C4 alcohol, more preferably ethanol; of lactate derivatives, preferably ethyl lactate and/or butyl lactate; of levulinate derivatives, preferably 2-methyltetrahydrofuran, ethyl levulinate, and/or ethyl levulinate glycerol ketal (LGK); and of solvents with a dielectric constant of 15 of higher, preferably dimethyl sulfoxide (DMSO).
  • alcohols preferably a C1-C4 alcohol, more preferably ethanol
  • lactate derivatives preferably ethyl lactate and/or butyl lactate
  • levulinate derivatives preferably 2-methyltetrahydrofuran, ethyl levulinate, and/or ethyl levulinate glycerol ketal (LGK)
  • LGK ethyl levulinate glycerol ketal
  • the solvent is selected from the group: ethanol; ethyl lactate, butyl lactate; 2- methyltetrahydrofuran (2Me-THF), ethyl levulinate, and ethyl levulinate glycerol ketal (LGK), or mixtures thereof.
  • the solvent is selected from the group: levulinate derivatives; and lactate derivatives.
  • the solvent is selected from the group: ethyl lactate, butyl lactate; 2- methyltetrahydrofuran, ethyl levulinate, and ethyl levulinate glycerol ketal (LGK), or mixtures thereof.
  • 2Me-THF, ethyl levulinate and LGK can be classed as levulinic acid derivatives (or levulinate derivatives).
  • Levulinic acid may be derived from lignocellulosic biomass (i.e. corn husks, sugar cane waste etc), and can be converted in to 2Me-THF in a cyclisation reaction, ethyl levulinate in one step esterification, and LGK in 2 steps (esterification and ketal synthesis).
  • Ethyl lactate and butyl lactate are lactic acid (lactate) derivatives. Lactic acid is a byproduct of fermentation which is then reacted with ethanol or butanol to generate ethyl and butyl lactate.
  • the solvent is selected from the group: 2-methyltetrahydrofuran, ethyl levulinate, and ethyl levulinate glycerol ketal (LGK), or mixtures thereof.
  • the solvent is present at a level of from 0.5 to 95 wt.%, preferably from 0.5 to 90 wt.%, more preferably from 0.5 to 80 wt.%.
  • the solvent may be present at a lowest level of from 0.5 wt.%, 0.75 wt.%, 1 wt.%, 1.5 wt.%, 2 wt.%, 2.5 wt.% or even 5 wt.%.
  • the solvent may be present at a highest level of from 95 wt.%, 90 wt.%, 85 wt.%, 80 wt.%, 70 wt.%, 60 wt.%, 50 wt.%, 40 wt.%, 30 wt.%, 25 wt.%, 20 wt.% or even 10 wt.%. Any higher level of solvent is meant to be combinable with any lower level of solvent.
  • the solvent may be present at a level of from 1 to 80 wt.%, preferably from 1 to 50 wt.%, more preferably from 1 to 40 wt.%.
  • the solvent level may also be from 1 to 30 wt.%, 1 to 20 wt.%, or even 1 to 15 wt.% or 1 to 10 wt.%.
  • the composition comprises a film-forming polymer.
  • a film-forming polymer is a substance capable of forming a film upon application to a solid surface.
  • the materials most commonly used as film-forming materials include reactive (irreversible) oligomers such as alkyd, phenol-formaldehyde, epoxy, and polyester resins, as well as non- reactive (reversible) polymers of relatively low molecular weight, among them chlorinated polyvinyl chloride resins, polyacrylates, and cellulose nitrates.
  • reactive (irreversible) oligomers such as alkyd, phenol-formaldehyde, epoxy, and polyester resins
  • non- reactive (reversible) polymers of relatively low molecular weight among them chlorinated polyvinyl chloride resins, polyacrylates, and cellulose nitrates.
  • Natural film-forming materials include particularly vegetable oils and rosin derivatives.
  • Film-forming materials are most often used in the form of solutions and dispersions in organic solvents; they can also be aqueous solutions or dispersions and are applied by various methods known to those skilled in the art.
  • Nonreactive film-forming materials form films as a result of evaporation of the solvent; film formation by reactive materials is accompanied by chemical transformations.
  • the general properties of film-forming materials may include (1) good wetting of the surface to be protected; (2) firm binding of any particles in the film; (3) rapid drying in a thin layer (from a few minutes to 24 hrs at 15°-200°C), with formation of strong moisture- and gasresistant films that can withstand prolonged action of the external medium; and (4) good adhesion to the surface being protected. In many cases, these properties are obtained by combining two or more film-forming materials, as well as by the introduction of plasticizers.
  • a range of useful film forming polymers includes:
  • HPMC Hydroxy(propylmethyl) cellulose
  • Ethylcellulose which are commercially available under the tradenames of EthocelTM including the grades 100, 200, 300
  • Poly(vinyl pyrolidine (PVP) which are commercially available under the tradenames of Kolidon® 30; Kolidon® 64; PVP K-30
  • P A Poly(vinyl alcohol) which are commercially available under the tradenames of SelvolTM 205; 503; 805; 823; 840; MowiolTM 18-88; 5-88
  • Methacrylic acid co-polymers which are commercially available under the tradenames of Eudragit® L-30; D-55; E; RS 100, RL 100, NE, RS 30D, S 100
  • Poly(ethylene oxides) which are commercially available under the tradenames PolyoxTM WSR N10; N 750
  • Preferred molecular weight ranges of the film-forming polymers are from 3,000-800,000 Daltons.
  • Preferred film forming polymers are PVA, vinyl alcohol/vinyl acetate copolymers, PVP, polysaccharides, and mixtures of any of the foregoing.
  • the film forming polymer may be further modified with various reagents commonly employed in the art such as plasticizers, surfactants, antifoamers, defoamers, biocides, and the like.
  • plasticizers include glycerol, polyethylene glycol, trimethylolpropane, polyglycerols, alkane diols such as diethylene glycol, triethylene glycol, tetra(ethyleneglycol) and 1 ,3- butanediol; alkanolamines such as triethanolamine; alkanolamine acetates such as triethanolamine acetate; and alkanolacetamides such as ethanol acetamide.
  • the plasticizers may be used in amounts conventionally employed in the film forming art to provide sufficient plasticization, for example, about 20-40% on weight of film forming polymer.
  • Particularly preferred film-forming polymers include natural film-forming polymers and synthetic film-forming polymers.
  • Preferred natural polymers are polysaccharides, for example xanthan and hydroxypropyl methylcellulose (HPMC), and quaternised polysaccharide derivative polymers, for example Celquat.
  • Preferred synthetic polymers include polyvinylpyrrolidone (PVP) and co-polymers thereof, polyvinylalcohol (PVA) and copolymers of polyvinylalcohol.
  • the film-forming polymers are polysaccharides, quaternised polysaccharide derivates, polyvinylpyrrolidone (PVP) and co-polymers thereof, and, polyvinylalcohol (PVA) and copolymers of polyvinylalcohol.
  • Most preferred film-forming polymers are selected from: quaternised polysaccharide derivatives, polyvinylpyrrolidone (PVP) and co-polymers thereof, and, polyvinylalcohol (PVA) and co-polymers of polyvinylalcohol, and/or mixtures thereof; and,
  • the level of the film-forming polymer is from 0.1 to 80 wt.%, preferably from 0.25 to 40 wt.%, more preferably from 0.5 to 35 wt.%. Further preferable weight ranges of the film-forming polymer include 0.5 to 20 wt.%, 0.5 to 15 wt.% or even 0.5 to 10 wt.%.
  • the composition comprises one or more surfactants.
  • the surfactant may be present at a level of from 0.25 to 25 wt.%, preferably from 0.25 to 20 wt.%, more preferably from 0.25 to 15 wt.%, even more preferably from 0.25 to 10 wt.%, or even 0.5 to 10 wt.% or even 0.5 to 5 wt.%.
  • the surfactant is preferably selected from anionic, nonionic, cationic and/or amphoteric surfactants.
  • Preferred surfactants are nonionic surfactants.
  • the composition may preferably comprise a buffer to keep any resulting composition within a specified pH range.
  • Buffering systems may be any usual buffering system known in the art. These may for example include citrate, acetate, phosphate, and or carbonate buffers, or mixtures thereof.
  • composition may comprise further ingredients such as surfactants, chelating agents, thickeners, pH modifiers, and perfumes.
  • 1-(4-Chlorophenyl)propan-2-one (40.00 g, 34.75 mL, 237.2 mmol), glyoxylic acid monohydrate (32.75 g, 355.8 mmol) and phosphoric acid (69.74 g, 711.7 mmol) were combined at room temperature before heating to 85 °C overnight. After cooling to room temperature, the mixture was poured into a mixture of water (500 mL) and ethyl acetate (500 mL). The layers were separated and the aqueous phase extracted with ethyl acetate (500 mL).
  • aqueous layer was extracted with dichloromethane (100 mL), and the combined organic layers washed with a 1 :1 mixture of water and saturated aqueous sodium hydrogen carbonate solution (100 mL), dried (MgSC ) and filtered. Silica was added to the filtrate and the mixture stirred for 10 minutes before filtering through a plug of silica, washing through with dichloromethane followed by a 3:1 mixture of dichloromethane:diethyl ether. Fractions containing the desired product were combined and concentrated under reduced pressure.
  • lactam used was lactam 488.
  • Solvents used butyl lactate (BL) or ethyl levulinate glycerol ketal (LGK)
  • This example shows the effect of the combination of the film-forming polymer with the lactam.
  • the lactam 488 was solubilised using a solvent, either butyl lactate (BL) or ethyl levulinate glycerol ketal (LGK) to form a 5 mg/ml solution.
  • BL butyl lactate
  • LGK ethyl levulinate glycerol ketal
  • This material was added into an aqueous base formulation containing 2 wt.% nonionic surfactant, and 4 wt.% citric acid.
  • the total amount of lactam in the composition was 0.01 wt.%.
  • the amount of solvent was 2 wt.%; the amount of film-forming polymer (when present) was 0.5 wt.% and the remaining amount up to 100 wt.% was water.
  • the above base formulation included polymer, but no lactam.
  • the inhibition activity of the solubilised lactam was tested against various microorganisms (P. aeruginosa and P. mirabilis). Comparators of the base formulation with the film-forming polymer and chosen solvent were also tested for inhibition. These comparators were found to not inhibit bacterial re-growth. Samples were dried down neat in wells of a microplate, then a bacterial suspension added for 1 hr. Unattached cells were removed, and media added. Remaining cells then grew overnight. The inhibition effect was determined by the frequency of samples (from 18 replicates) where no further growth was detected.
  • lactam and film-forming polymer as made above were tested, these gave a statistically significant improvement for the combination of the lactam with the film- forming polymer over either the polymer alone or the lactam alone, or the additive effects of polymer alone + lactam alone.

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Abstract

The invention relates to a composition comprising: (a) from 0.0001 to 5 wt.% of a lactam; (b) 0.5 to 95 wt.% of a solvent; and, (c) from 0.1 to 80 wt.%, of a film-forming polymer; wherein the film-forming polymer is selected from polysaccharides, quaternised polysaccharide derivatives, polyvinylpyrrolidone (PVP) and co-polymers thereof, and, polyvinylalcohol (PVA) and co-polymers of polyvinylalcohol, and/or mixtures thereof; and, wherein the lactam is of formula (I) or (II), wherein: R1 and R2 are each independently selected from hydrogen, halogen, alkyl, cycloalkyl, alkoxy, oxoalkyl, alkenyl, heterocyclyl, heteroaryl, aryl and aralalkyl; and R3 is selected from hydrogen, hydroxyl, alkyl, cycloalkyl, alkoxy, oxoalkyl, alkenyl, heterocyclyl, heteroaryl, cycloalkyl, aryl, aralalkyl, –C(O)CR6=CH2, and (CH2)nN +(Ra)3, where n is an integer from 1 to 16, and where each Ra is independently H or C1-4 alkyl; R4 and R5 are independently selected from hydrogen, aryl, heterocyclyl, heteroaryl, and arylalkyl; and R6 is selected from hydrogen and methyl; and R7 is selected from hydrogen and –C(O)CR6=CH2; the invention also relates to a method of treatment of a surface, to improve resistance of said surface to bacterial fouling; and also to the use of a combination of a lactam and a film forming polymer as defined earlier to improve inhibition of bacterial species.

Description

LACTAM COMPOSITION AND USE
Field of Invention
The invention relates to an improvement in the field of hygiene, in particular to a composition comprising a lactam which displays improved displays improved inhibition of bacterial species.
Background of the Invention
Hygiene, in particular inhibition of bacterial species, is important to consumers.
Lactams are known as inhibitors of bacterial species. They may be applied to surfaces to inhibit bacterial species.
There is a wish to improve lactam containing formulations in terms of their activity to inhibit bacterial species.
Summary of the Invention
We have found that by formulating a composition comprising a lactam in combination with a solvent and a film forming polymer, the resulting formulation displays improved inhibition of bacterial species.
The invention relates in a first aspect to a composition comprising:-
(a) from 0.0001 to 5 wt.%, preferably from 0.0001 to 2.5 wt.%, more preferably from 0.0001 to 1 wt.%, more preferably from 0.001 to 1 wt.% of a lactam; and,
(b) from 0.5 to 95 wt.%, preferably from 0.5 to 90 wt.%, more preferably from 0.5 to 80 wt.% of a solvent; and,
(c) from 0.1 to 80 wt.%, preferably from 0.25 to 40 wt.%, more preferably from 0.5 to 35 wt.% of a film-forming polymer; wherein the film-forming polymer is selected from polysaccharides, quaternised polysaccharide derivatives, polyvinylpyrrolidone (PVP) and co-polymers thereof, and, polyvinylalcohol (PVA) and co-polymers of polyvinylalcohol, and/or mixtures thereof; and, wherein the lactam is of formula (I) or (II):
wherein:
R1 and R2 are each independently selected from hydrogen, halogen, alkyl, cycloalkyl, alkoxy, oxoalkyl, alkenyl, heterocyclyl, heteroaryl, aryl and aralalkyl; and
R3 is selected from hydrogen, hydroxyl, alkyl, cycloalkyl, alkoxy, oxoalkyl, alkenyl, heterocyclyl, heteroaryl, cycloalkyl, aryl, aralalkyl, -C(O)CRe=CH2, and (CH2)nN+(Ra)3, where n is an integer from 1 to 16, preferably 2 to 8, and where each Ra is independently H or C1.4 alkyl;
R4 and R5 are independently selected from hydrogen, aryl, heterocyclyl, heteroaryl, and arylalkyl; and
Re is selected from hydrogen and methyl; and
R? is selected from hydrogen and -C(O)CRe=CH2; and preferably, at least one of R4 and R5 is hydrogen.
Preferably the lactam of formula (I) or (II), R1, R4 and R5 are H; R3 is H, or (CH2)nN+(CH3)3, where n is an integer from 1 to 16, preferably 2 to 8; and R2 is a phenyl group, or a monosubstituted phenyl group; preferably R2 is selected from phenyl, 4-fluorophenyl, 2- fluorophenyl, 4-chlorophenyl, 3-chlorophenyl, 4-bromophenyl and 4-methylphenyl.
Preferably the lactam is a lactam selected from:
More preferably the lactam is selected from:
Most preferably the lactam is: -chlorophenyl)-5-methylene-pyrrol-2-one
Preferably the lactam is delivered from an aqueous based composition, preferably comprising from 0.1 to 99 wt.%, preferably from 0.5 to 98 wt.%, more preferably from 1 to 98 wt.% water.
The solvent is preferably selected from the group: alcohol; levulinate derivatives; lactate derivatives; and solvents with a dielectric constant of 15 of higher, preferably the solvent is selected from the group: alcohol, levulinate derivatives; and lactate derivatives; more preferably the solvent is selected from the group: levulinate derivatives and lactate derivatives.
Preferred examples of solvents are: of alcohols, preferably a C1-C4 alcohol, more preferably ethanol; of lactate derivatives, preferably ethyl lactate and/or butyl lactate; of levulinate derivatives, preferably 2-methyltetrahydrofuran, ethyl levulinate, and/or ethyl levulinate glycerol ketal (LGK); and of solvents with a dielectric constant of 15 of higher, preferably dimethyl sulfoxide (DMSO).
Preferably the solvent is selected from the group: ethanol; ethyl lactate, butyl lactate; 2- methyltetrahydrofuran, ethyl levulinate, and ethyl levulinate glycerol ketal (LGK), or mixtures thereof.
Preferably the solvent is selected from the group: levulinate derivatives; and lactate derivatives.
Even more preferably the solvent is selected from the group: ethyl lactate, butyl lactate; 2- methyltetrahydrofuran, ethyl levulinate, and ethyl levulinate glycerol ketal (LGK), or mixtures thereof.
Most preferably the solvent is selected from the group: 2-methyltetrahydrofuran, ethyl levulinate and ethyl levulinate glycerol ketal (LGK), or mixtures thereof.
The solvent is present at a level of from 0.5 to 95 wt.%, preferably from 0.5 to 90 wt.%, more preferably from 0.5 to 80 wt.%. The solvent may be present at a lowest level of from 0.5 wt.%, 0.75 wt.%, 1 wt.%, 1.5 wt.%, 2 wt.%, 2.5 wt.% or even 5 wt.%. The solvent may be present at a highest level of from 95 wt.%, 90 wt.%, 85 wt.%, 80 wt.%, 70 wt.%, 60 wt.%, 50 wt.%, 40 wt.%, 30 wt.%, 25 wt.%, 20 wt.% or even 10 wt.%. Any higher level of solvent is meant to be combinable with any lower level of solvent.
Preferred natural polymers are polysaccharides, for example xanthan and hydroxypropyl methylcellulose (HPMC), and quaternised polysaccharide derivative polymers, for example Celquat. Preferred synthetic polymers include polyvinylpyrrolidone (PVP) and co-polymers thereof, polyvinylalcohol (PVA) and co-polymers of polyvinylalcohol.
More preferred film-forming polymers are polysaccharides, quaternised polysaccharide derivates, polyvinylpyrrolidone (PVP) and co-polymers thereof, and, polyvinylalcohol (PVA) and co-polymers of polyvinylalcohol. Most preferred film-forming polymers are quaternised polysaccharide derivates, polyvinylpyrrolidone (PVP) and co-polymers thereof, and, polyvinylalcohol (PVA) and copolymers of polyvinylalcohol.
Preferably the composition comprises one or more surfactants. The surfactant may be present at a level of from 0.25 to 25 wt.%, preferably from 0.25 to 20 wt.%, more preferably from 0.25 to 15 wt.%, even more preferably from 0.25 to 10 wt.%, or even 0.5 to 10 wt.% or even 0.5 to 5 wt.%.
The surfactant may be present at a level of from 0.25 to 25 wt.%, preferably from 0.25 to 20 wt.%, more preferably from 0.25 to 15 wt.%, even more preferably from 0.25 to 10 wt.%, or even 0.5 to 10 wt.% or even 0.5 to 5 wt.%.
The surfactant is preferably selected from anionic, nonionic, cationic and/or amphoteric surfactants. Preferred surfactants are nonionic surfactants.
The invention relates in a second aspect to a non-therapeutic method of treatment of a surface, to improve resistance of said surface to bacterial fouling, by treatment with a composition according to the first aspect of the invention.
Preferably the surface to be treated is selected from plastic, metal, wood, polymer, paper, textile, and/or wipes.
Preferably in the method, the lactam is selected from:
The invention further relates in a third aspect to the use of a combination of a lactam and a film forming polymer to improve inhibition of bacterial species, wherein the film-forming polymer is selected from polysaccharides, quaternised polysaccharide derivatives, polyvinylpyrrolidone (PVP) and co-polymers thereof, and, polyvinylalcohol (PVA) and co-polymers of polyvinylalcohol, and/or mixtures thereof; and, wherein the lactam is of formula (I) or (II): wherein:
R1 and R2 are each independently selected from hydrogen, halogen, alkyl, cycloalkyl, alkoxy, oxoalkyl, alkenyl, heterocyclyl, heteroaryl, aryl and aralalkyl; and
R3 is selected from hydrogen, hydroxyl, alkyl, cycloalkyl, alkoxy, oxoalkyl, alkenyl, heterocyclyl, heteroaryl, cycloalkyl, aryl, aralalkyl, -C(O)CRe=CH2, and (CH2)nN+(Ra)3, where n is an integer from 1 to 16, preferably 2 to 8, and where each Ra is independently H or C1.4 alkyl;
R4 and R5 are independently selected from hydrogen, aryl, heterocyclyl, heteroaryl, and arylalkyl; and
Re is selected from hydrogen and methyl; and
R? is selected from hydrogen and -C(O)CRe=CH2; and preferably, at least one of R4 and R5 is hydrogen.
Preferably in the use, the lactam is selected from: Detailed Description of the Invention
The indefinite article "a" or "an" and its corresponding definite article "the" as used herein means at least one, or one or more, unless specified otherwise.
It will be appreciated that, except where expressly provided otherwise, all preferences are combinable.
Lactam
A lactam is a cyclic amide. Preferred lactams are y-lactams which have 5 ring atoms.
The lactam is of formula (I) or (II): wherein:
Ri and R2 are each independently selected from hydrogen, halogen, alkyl, cycloalkyl, alkoxy, oxoalkyl, alkenyl, heterocyclyl, heteroaryl, aryl and aralalkyl; and
R3 is selected from hydrogen, hydroxyl, alkyl, cycloalkyl, alkoxy, oxoalkyl, alkenyl, heterocyclyl, heteroaryl, cycloalkyl, aryl, aralalkyl, -C(O)CRe=CH2, and (CH2)nN+(Ra)3, where n is an integer from 1 to 16, preferably 2 to 8, and where each Ra is independently H or C1.4 alkyl;
R4 and R5 are independently selected from hydrogen, aryl, heterocyclyl, heteroaryl, and arylalkyl; and
Re is selected from hydrogen and methyl; and
R? is selected from hydrogen and -C(O)CRe=CH2; and
Preferably, at least one of R4 and R5 is hydrogen. It will be appreciated that, where appropriate groups may be optionally substituted. Optional substituents may include halogens, Ci-4alkyl, Ci.4haloalkyl (for example, CF3) and Ci.4alkoxy.
Alkyls may, for example, be Ci. ^alkyls, such as Ci-ealkyls. Aryls may, for example, be Ce- aryls, for example, phenyls.
Preferably, at least one of R1 and R2 is selected from heterocyclyl, heteroaryl, aryl and arylalkyl.
Preferably, R1 is hydrogen. Preferably, R3 is hydrogen, or (CH2)nN+(Ra)3, where n is an integer from 1 to 16, preferably 2 to 8, and where each Ra is independently H or C1.4 alkyl, more preferably Ra is CH3; Preferably, R4 is hydrogen. Preferably, R5 is hydrogen. Preferably, Re is hydrogen. Preferably, R? is hydrogen. Preferably, R2 is aryl or aralalkyl. More preferably, R2 is a phenyl group or a substituted phenyl group, for example, a monosubstituted phenyl group. Substitution may be ortho, meta, or para. Preferred substituents include halogen and methyl. For example, and without limitation, R2 may be selected from phenyl, 4-fluorophenyl, 2-fluorophenyl, 4-chlorophenyl, 3-chlorophenyl, 4-bromophenyl and 4-methylphenyl.
More preferably in the lactam of formula (I) or (II), R1, R4 and R5 are H; R3 is H, or (CH2)nN+(CH3)3, where n is an integer from 1 to 16, preferably 2 to 8; and R2 is a phenyl group, or a mono-substituted phenyl group; preferably R2 is selected from phenyl, 4- fluorophenyl, 2-fluorophenyl, 4-chlorophenyl, 3-chlorophenyl, 4-bromophenyl and 4- methylphenyl.
Even more preferably the lactam is of formula (I), R1, R4 and R5 are H; R3 is H, or (CH2)nN+(CH3)3, where n is an integer from 1 to 16, preferably 2 to 8; and R2 is a phenyl group, or a mono-substituted phenyl group; preferably R2 is selected from phenyl, 4- fluorophenyl, 2-fluorophenyl, 4-chlorophenyl, 3-chlorophenyl, 4-bromophenyl and 4- methylphenyl.
Where the lactam is cationic in nature, it can be used as such, or suitably with a counterion (e.g. iodide) Preferably the lactam is a lactam selected from:
More preferably the lactam is selected from:
Most preferably the lactam is: -chlorophenyl)-5-methylene-pyrrol-2-one.
Where the lactam is cationic in nature, the cation can be used or with a suitable counterion (e.g. iodide). Levels of lactam Preferably the lactam is present at a level of from 0.0001 to 2.5 wt.%, preferably from 0.0001 to 1 wt.%. For example, the lactam may be suitably present at levels of 0.001 to 1 wt.%, or even 0.01 to 1 wt.%, or even 0.01 to 0.5 wt.%.
Compositions
Preferably the lactam is delivered from an aqueous based composition, preferably comprising from 0.1 to 99 wt.%, preferably from 0.5 to 98 wt.%, more preferably from 1 to 98 wt.% water.
Alternatively, preferably the lactam is delivered from an aqueous based composition, preferably comprising from 0.1 to 98 wt.%, preferably from 0.5 to 80 wt.%, more preferably from 1 to 75 wt.% water. The composition may comprise any amount of water ranging from lower amounts of 0.1 , 0.5, 1 , 1.5, 2 or even 5 wt.% water up to 30, 40, 50, 60, 70, 75, 80, 85, 90, 95, 96, 97, 98, or even 99 wt.% water. In one preferred embodiment, preferred levels of water include from 60 to 98 wt.%, preferably from 70 to 98 wt.%, more preferably from 80 to 98 wt.%, even more preferably from 85 to 98 wt.% or even from 90 to 98 wt.%.
Solvents
The composition comprises a solvent, said solvent preferably selected from the group: alcohol; levulinate derivatives; lactate derivatives; and, solvents with a dielectric constant of 15 of higher.
Examples of alcohol solvents include glycols, for example propylene glycols, and polyethylene glycols; methanol, ethanol, propanol, butanol, isopropanol, benzyl alcohol, lanolin alcohols, and fatty alcohols. Examples of other solvent include ethyl acetate, oleic acid, and isopropyl myristate.
Preferred examples of solvents are: of alcohols, preferably a C1-C4 alcohol, more preferably ethanol; of lactate derivatives, preferably ethyl lactate and/or butyl lactate; of levulinate derivatives, preferably 2-methyltetrahydrofuran, ethyl levulinate, and/or ethyl levulinate glycerol ketal (LGK); and of solvents with a dielectric constant of 15 of higher, preferably dimethyl sulfoxide (DMSO). Preferably the solvent is selected from the group: ethanol; ethyl lactate, butyl lactate; 2- methyltetrahydrofuran (2Me-THF), ethyl levulinate, and ethyl levulinate glycerol ketal (LGK), or mixtures thereof.
Preferably the solvent is selected from the group: levulinate derivatives; and lactate derivatives.
Most preferably the solvent is selected from the group: ethyl lactate, butyl lactate; 2- methyltetrahydrofuran, ethyl levulinate, and ethyl levulinate glycerol ketal (LGK), or mixtures thereof.
2Me-THF, ethyl levulinate and LGK can be classed as levulinic acid derivatives (or levulinate derivatives). Levulinic acid may be derived from lignocellulosic biomass (i.e. corn husks, sugar cane waste etc), and can be converted in to 2Me-THF in a cyclisation reaction, ethyl levulinate in one step esterification, and LGK in 2 steps (esterification and ketal synthesis). Ethyl lactate and butyl lactate are lactic acid (lactate) derivatives. Lactic acid is a byproduct of fermentation which is then reacted with ethanol or butanol to generate ethyl and butyl lactate.
Most preferably the solvent is selected from the group: 2-methyltetrahydrofuran, ethyl levulinate, and ethyl levulinate glycerol ketal (LGK), or mixtures thereof.
The solvent is present at a level of from 0.5 to 95 wt.%, preferably from 0.5 to 90 wt.%, more preferably from 0.5 to 80 wt.%. The solvent may be present at a lowest level of from 0.5 wt.%, 0.75 wt.%, 1 wt.%, 1.5 wt.%, 2 wt.%, 2.5 wt.% or even 5 wt.%. The solvent may be present at a highest level of from 95 wt.%, 90 wt.%, 85 wt.%, 80 wt.%, 70 wt.%, 60 wt.%, 50 wt.%, 40 wt.%, 30 wt.%, 25 wt.%, 20 wt.% or even 10 wt.%. Any higher level of solvent is meant to be combinable with any lower level of solvent.
The solvent may be present at a level of from 1 to 80 wt.%, preferably from 1 to 50 wt.%, more preferably from 1 to 40 wt.%. The solvent level may also be from 1 to 30 wt.%, 1 to 20 wt.%, or even 1 to 15 wt.% or 1 to 10 wt.%.
Film-forming polymers
The composition comprises a film-forming polymer. A film-forming polymer is a substance capable of forming a film upon application to a solid surface.
The materials most commonly used as film-forming materials include reactive (irreversible) oligomers such as alkyd, phenol-formaldehyde, epoxy, and polyester resins, as well as non- reactive (reversible) polymers of relatively low molecular weight, among them chlorinated polyvinyl chloride resins, polyacrylates, and cellulose nitrates. Natural film-forming materials include particularly vegetable oils and rosin derivatives.
Film-forming materials are most often used in the form of solutions and dispersions in organic solvents; they can also be aqueous solutions or dispersions and are applied by various methods known to those skilled in the art. Nonreactive film-forming materials form films as a result of evaporation of the solvent; film formation by reactive materials is accompanied by chemical transformations.
The general properties of film-forming materials may include (1) good wetting of the surface to be protected; (2) firm binding of any particles in the film; (3) rapid drying in a thin layer (from a few minutes to 24 hrs at 15°-200°C), with formation of strong moisture- and gasresistant films that can withstand prolonged action of the external medium; and (4) good adhesion to the surface being protected. In many cases, these properties are obtained by combining two or more film-forming materials, as well as by the introduction of plasticizers.
A range of useful film forming polymers includes:
Hydroxy(propylmethyl) cellulose (HPMC) which are commercially available under the tradenames of Methocel™ including the grades E4M; E15; E50M; K4M)
Ethylcellulose (EC) which are commercially available under the tradenames of Ethocel™ including the grades 100, 200, 300
Poly(vinyl pyrolidine (PVP) which are commercially available under the tradenames of Kolidon® 30; Kolidon® 64; PVP K-30
Poly(vinyl alcohol) (P A) which are commercially available under the tradenames of Selvol™ 205; 503; 805; 823; 840; Mowiol™ 18-88; 5-88
Methacrylic acid co-polymers which are commercially available under the tradenames of Eudragit® L-30; D-55; E; RS 100, RL 100, NE, RS 30D, S 100
Chitosan polysaccharides which are commercially available from KitoZyme Acrylate polymers which are commercially available under the tradenames Avalure™ 120 PF; AC 118; UR 424 Polydimethylsiloxanes which are commercially available under the tradenames Dowsil™ 200; 1418; 1515;
Poly(ethylene oxides) which are commercially available under the tradenames Polyox™ WSR N10; N 750
Preferred molecular weight ranges of the film-forming polymers are from 3,000-800,000 Daltons.
Preferred film forming polymers are PVA, vinyl alcohol/vinyl acetate copolymers, PVP, polysaccharides, and mixtures of any of the foregoing.
The film forming polymer may be further modified with various reagents commonly employed in the art such as plasticizers, surfactants, antifoamers, defoamers, biocides, and the like. Suitable plasticizers include glycerol, polyethylene glycol, trimethylolpropane, polyglycerols, alkane diols such as diethylene glycol, triethylene glycol, tetra(ethyleneglycol) and 1 ,3- butanediol; alkanolamines such as triethanolamine; alkanolamine acetates such as triethanolamine acetate; and alkanolacetamides such as ethanol acetamide. The plasticizers may be used in amounts conventionally employed in the film forming art to provide sufficient plasticization, for example, about 20-40% on weight of film forming polymer.
Particularly preferred film-forming polymers include natural film-forming polymers and synthetic film-forming polymers. Preferred natural polymers are polysaccharides, for example xanthan and hydroxypropyl methylcellulose (HPMC), and quaternised polysaccharide derivative polymers, for example Celquat. Preferred synthetic polymers include polyvinylpyrrolidone (PVP) and co-polymers thereof, polyvinylalcohol (PVA) and copolymers of polyvinylalcohol.
The film-forming polymers are polysaccharides, quaternised polysaccharide derivates, polyvinylpyrrolidone (PVP) and co-polymers thereof, and, polyvinylalcohol (PVA) and copolymers of polyvinylalcohol. Most preferred film-forming polymers are selected from: quaternised polysaccharide derivatives, polyvinylpyrrolidone (PVP) and co-polymers thereof, and, polyvinylalcohol (PVA) and co-polymers of polyvinylalcohol, and/or mixtures thereof; and,
The level of the film-forming polymer is from 0.1 to 80 wt.%, preferably from 0.25 to 40 wt.%, more preferably from 0.5 to 35 wt.%. Further preferable weight ranges of the film-forming polymer include 0.5 to 20 wt.%, 0.5 to 15 wt.% or even 0.5 to 10 wt.%.
Surfactant
Preferably the composition comprises one or more surfactants. The surfactant may be present at a level of from 0.25 to 25 wt.%, preferably from 0.25 to 20 wt.%, more preferably from 0.25 to 15 wt.%, even more preferably from 0.25 to 10 wt.%, or even 0.5 to 10 wt.% or even 0.5 to 5 wt.%.
The surfactant is preferably selected from anionic, nonionic, cationic and/or amphoteric surfactants. Preferred surfactants are nonionic surfactants.
Buffer
The composition may preferably comprise a buffer to keep any resulting composition within a specified pH range. Buffering systems may be any usual buffering system known in the art. These may for example include citrate, acetate, phosphate, and or carbonate buffers, or mixtures thereof.
Further Ingredients
The composition may comprise further ingredients such as surfactants, chelating agents, thickeners, pH modifiers, and perfumes.
The invention will be further described with the following non-limiting examples.
Example 1 - Preparation of examples of preferred lactams Preparation of 4-(4-chlorophenyl)-5-hydroxy-5-methylfuran-2(5H)-one
1-(4-Chlorophenyl)propan-2-one (40.00 g, 34.75 mL, 237.2 mmol), glyoxylic acid monohydrate (32.75 g, 355.8 mmol) and phosphoric acid (69.74 g, 711.7 mmol) were combined at room temperature before heating to 85 °C overnight. After cooling to room temperature, the mixture was poured into a mixture of water (500 mL) and ethyl acetate (500 mL). The layers were separated and the aqueous phase extracted with ethyl acetate (500 mL). The combined organic layers were washed with a 1 :1 mixture of water and brine (2 x 500 mL), dried (MgSC ) and concentrated under reduced pressure to yield 4-(4- chlorophenyl)-5-hydroxy-5-methylfuran-2(5H)-one (66.00 g, >100% yield) as a brown oil. The material was used in the next step without further purification.
4-(4-Chlorophenyl)-5-hydroxy-5-methylfuran-2(5H)-one (66.00 g, 293.8 mmol) was dissolved in thionyl chloride (196.8 g, 120.0 mL, 1654 mmol) and heated at 40 °C for 1 hour, then 80 °C for 2 hours. The mixture was concentrated under reduced pressure and azeotroped with 2-methyltetrahydrofuran (200 mL). The residue was diluted with 2-methyltetrahydrofuran (160 mL) and this solution added to a cooled stirring mixture of 28% ammonia in water (180 mL) in 2-methyltetrahydrofuran (20 mL) at 0 °C. The mixture was warmed to room temperature and stirred overnight. Water (100 mL) and ethyl acetate (200 mL) were added and the layers separated. The aqueous phase was extracted with ethyl acetate (200 mL), and the combined organic extracts dried (MgSC ) and concentrated under reduced pressure. Purification by dry flash column chromatography (5-60% ethyl acetate in heptane) yielded 4-(4-chlorophenyl)-5-hydroxy-5-methyl-1 H-pyrrol-2(5H)-one (23.18 g, 35% yield) as a cream coloured solid. 1H NMR (400 MHz, d6-DMSO) 8.55 (brs, 1 H), 7.88-7.83 (m, 2H), 7.51-7.46 (m, 2H), 6.37 (d,
1 H), 6.32 (s, 1 H), 1.45 (s, 3H)
UPLC (Basic) 1.51/5.00 min, 100% purity, M+H+ 224
MP 177 °C
Preparation of 4-(4-chlorophenyl)-5-methylene-1 H-pyrrol-2(5H)-one
To a cooled solution of 4-(4-chlorophenyl)-5-hydroxy-5-methyl-1 H-pyrrol-2(5H)-one (10.00 g, 44.51 mmol) in dry dichloromethane (100 mL) at 0 °C was added a solution of boron trifluoride diethyl etherate (8.213 g, 7.142 mL, 57.87 mmol) in dry dichloromethane (45 mL) over 15 minutes. The mixture was stirred at 0 °C, before slowly warming to room temperature and stirring for 2 hours. The reaction was quenched with ice-water (100 mL) and the layers separated. The aqueous layer was extracted with dichloromethane (100 mL), and the combined organic layers washed with a 1 :1 mixture of water and saturated aqueous sodium hydrogen carbonate solution (100 mL), dried (MgSC ) and filtered. Silica was added to the filtrate and the mixture stirred for 10 minutes before filtering through a plug of silica, washing through with dichloromethane followed by a 3:1 mixture of dichloromethane:diethyl ether. Fractions containing the desired product were combined and concentrated under reduced pressure. Upon concentration a precipitate formed, which was collected by filtration, washing with diethyl ether, to yield 4-(4-chlorophenyl)-5-methylene-1 H-pyrrol-2(5H)-one (5.25 g, 57% yield) as a cream coloured solid.
1H NMR (400 MHz, d6-DMSO) 10.10 (s, 1 H), 7.54-7.47 (m, 4H), 6.36 (s, 1 H), 5.04 (t, 1 H), 4.85 (s, 1 H)
UPLC (Basic) 1.87/5.00 min, 100% purity, M+H+ 206 MP 182 °C Preparation of 5-hydroxy-5-methyl-4-(p-tolyl)furan-2(5H)-one
1-(p-Tolyl)propan-2-one (25.00 g, 24.00 mL, 168.7 mmol), glyoxylic acid monohydrate (23.29 g, 253.0 mmol) and phosphoric acid (49.60 g, 506.1 mmol) were combined at room temperature before heating at 90 °C overnight. After cooling to room temperature, the mixture was poured into a stirring mixture of ice-water (400 mL) and ethyl acetate (400 mL). The layers were separated and the organic phase washed with water (100 mL), dried (MgSC ) and concentrated under reduced pressure. The mixture was azeotroped with 2- methyltetrahydrofuran (50 mL) to yield 5-hydroxy-5-methyl-4-(p-tolyl)furan-2(5H)-one (16.50 g, 48% yield) as a brown solid.
1H NMR (400 MHz, d6-DMSO) 7.86 (s, 1 H), 7.75 (d, 2H), 7.28 (d, 2H), 6.59 (s, 1 H), 2.32 (s, 3H), 1.61 (s, 3H)
Preparation of 5-hydroxy-5-methyl-4-(p-tolyl)-1 H-pyrrol-2(5H)-one
5-Hydroxy-5-methyl-4-(p-tolyl)furan-2(5H)-one (16.50 g, 80.80 mmol) was dissolved in thionyl chloride (48.06 g, 29.47 mL, 404.0 mmol) and heated at 50 °C for 1 hour, before heating at reflux for 1 hour. After cooling to room temperature, the mixture was concentrated under reduced pressure and azeotroped with 2-methyltetra-hydrofuran (2 x 50 mL). The residue was diluted with 2-methyltetrahydrofuran (60 mL) and this solution added to a cooled stirring mixture of 28% ammonia in water (55 mL, 808.0 mol) in 2-methyltetrahydrofuran (10 mL) at 0 °C. The mixture was warmed to room temperature and stirred overnight. 2- Methyltetrahydrofuran was removed under reduced pressure, and the residue diluted with water (200 mL) and diethyl ether (100 mL) and the mixture stirred for 20 minutes at room temperature. The solids were collected by filtration and stirred in water (100 mL) and diethyl ether (50 mL) at room temperature for 10 minutes. The solids were collected by filtration and washed with water, diethyl ether and dried under vacuum at 50 °C to yield 5-hydroxy-5- methyl-4-(p-tolyl)-1 H-pyrrol-2(5H)-one (10.49 g, 31% yield) as a light beige solid.
1H NMR (400 MHz, d6-DMSO) 8.44 (brs, 1 H), 7.73 (d, 2H), 7.21 (d, 2H), 6.24 (s, 2H), 2.29 (s, 3H), 1.45 (s, 3H)
13C NMR (400 MHz, d6-DMSO) 170.4 (s, 1C), 161.1 (s, 1C), 139.8 (s, 1C), 129.7 (s, 2C), 128.9 (s, 1C), 128.2 (s, 2C), 119.1 (s, 1C), 87.8 (s, 1C), 26.7 (s, 1C), 21.5 (s, 1C) UPLC (Basic) 1.41/5.00 min, 100% purity, M+H+ 204
MP 178 °C Decomposition
Preparation of 5-methylene-4-(p-tolyl)-1 H-pyrrol-2(5H)-one
To a cooled solution of 5-hydroxy-5-methyl-4-(p-tolyl)-1 H-pyrrol-2(5H)-one (8.68 g, 42.7 mmol) in dry dichloromethane (87 mL) at 0 °C was added a solution of boron trifluoride diethyl etherate (6.85 g, 5.96 mL, 55.5 mmol) in dry dichloromethane (40 mL) over 15 minutes. After 1 hour the mixture was allowed to slowly warm to room temperature. After a further 3 hours, the reaction was diluted with dichloromethane (50 mL) and ice-water (100 mL) and stirred for 10 minutes. The layers were separated and the organic layer washed with water (100 mL), a 1 :1 mixture of water and saturated aqueous sodium hydrogen carbonate solution (100 mL) and brine (100 mL) and the organic layer filtered through Celite, washing with dichloromethane. Any excess water was removed by pipette before drying the filtrate (MgSC ) and concentrating under reduced pressure to a brown solid. The solids were stirred in hot dichloromethane (120 mL) for 15 minutes before slowly cooling to room temperature and then 0 °C. The solids were collected by filtration to yield 5-methylene-4-(p- tolyl)- 1 H-pyrrol-2(5H)-one (3.87 g, 49% yield) as a yellow solid. Silica was added to the filtrate and the mixture stirred for 10 minutes before filtering through a plug of silica, washing through with dichloromethane and then a 4:1 mixture of dichloromethane:diethyl ether. The filtrate was concentrated under reduced pressure to yield 5-methylene-4-(p-tolyl)-1 H-pyrrol- 2(5H)-one (0.58 g, 7%) as a yellow solid. Total yield of 5-methylene-4-(p-tolyl)-1 H-pyrrol- 2(5H)-one (4.45 g, 56% yield).
1H NMR (400 MHz, d6-DMSO) 10.11 (brs, 1 H), 7.35 (d, 2H), 7.25 (d, 2H), 6.25 (s, 1 H), 5.01 (s, 1 H), 4.85 (s, 1 H), 2.31 (s, 3H)
UPLC (Basic) 1.83/5.00 min, 100% purity, M+H+ 186 MP 200 °C Decomposition
Materials Used
In the following examples, the lactam used was lactam 488.
This is 4-(4-chlorophenyl)-5-methylene-pyrrol-2-one and the structure is shown below:-
Solvents used: butyl lactate (BL) or ethyl levulinate glycerol ketal (LGK) Film-forming polymers used: Celquat (quaternised polysaccharide derivative polymer), HPMC hydroxypropyl methylcellulose (a substituted natural polysaccharide film-forming polymer), Xanthan (a natural polysaccharide filmforming polymer)
Example 2
This example shows the effect of the combination of the film-forming polymer with the lactam.
Method explanation
The lactam 488 was solubilised using a solvent, either butyl lactate (BL) or ethyl levulinate glycerol ketal (LGK) to form a 5 mg/ml solution. This material was added into an aqueous base formulation containing 2 wt.% nonionic surfactant, and 4 wt.% citric acid. The total amount of lactam in the composition was 0.01 wt.%. The amount of solvent was 2 wt.%; the amount of film-forming polymer (when present) was 0.5 wt.% and the remaining amount up to 100 wt.% was water. For the comparative examples of film-forming polymer alone, the above base formulation included polymer, but no lactam.
The inhibition activity of the solubilised lactam was tested against various microorganisms (P. aeruginosa and P. mirabilis). Comparators of the base formulation with the film-forming polymer and chosen solvent were also tested for inhibition. These comparators were found to not inhibit bacterial re-growth. Samples were dried down neat in wells of a microplate, then a bacterial suspension added for 1 hr. Unattached cells were removed, and media added. Remaining cells then grew overnight. The inhibition effect was determined by the frequency of samples (from 18 replicates) where no further growth was detected.
P. aeruginosa - Film-forming polymer alone
P. aeruginosa - Lactam alone
P. mirabilis - Film-forming polymer alone
P. mirabilis - Lactam alone
Certain combinations of lactam and film-forming polymer as made above were tested, these gave a statistically significant improvement for the combination of the lactam with the film- forming polymer over either the polymer alone or the lactam alone, or the additive effects of polymer alone + lactam alone.
P. aeruginosa
P. mirabilis
The results clearly demonstrate that the inhibition effect of the lactam in terms of inhibiting bacterial regrowth is improved by addition of a film-forming polymer. This is demonstrated across various film-forming polymers and in different solvents.
These results are especially surprising as the inhibition effects were seen even without rinsing of the surface prior to microbial challenge.

Claims

22
1. A composition comprising:
(a) from 0.0001 to 5 wt.%, preferably from 0.0001 to 2.5 wt.%, more preferably from 0.0001 to 1 wt.%, more preferably from 0.001 to 1 wt.% of a lactam; and,
(b) from 0.5 to 95 wt.%, preferably from 0.5 to 90 wt.%, more preferably from 0.5 to 80 wt.% of a solvent;
(c) from 0.1 to 80 wt.%, preferably from 0.25 to 40 wt.%, more preferably from 0.5 to 35 wt.% of a film-forming polymer; wherein the film-forming polymer is selected from polysaccharides, quaternised polysaccharide derivatives, polyvinylpyrrolidone (PVP) and co-polymers thereof, and, polyvinylalcohol (PVA) and co-polymers of polyvinylalcohol, and/or mixtures thereof; and, wherein the lactam is of formula (I) or (II): wherein:
Ri and R2 are each independently selected from hydrogen, halogen, alkyl, cycloalkyl, alkoxy, oxoalkyl, alkenyl, heterocyclyl, heteroaryl, aryl and aralalkyl; and
R3 is selected from hydrogen, hydroxyl, alkyl, cycloalkyl, alkoxy, oxoalkyl, alkenyl, heterocyclyl, heteroaryl, cycloalkyl, aryl, aralalkyl, -C(O)CRe=CH2, and (CH2)nN+(Ra)3, where n is an integer from 1 to 16, preferably 2 to 8, and where each Ra is independently H or C1.4 alkyl;
R4 and R5 are independently selected from hydrogen, aryl, heterocyclyl, heteroaryl, and arylalkyl; and
Re is selected from hydrogen and methyl; and
R? is selected from hydrogen and -C(O)CRe=CH2; and preferably, at least one of R4 and R5 is hydrogen.
2. A composition according to claim 1 , wherein in the lactam of formula (I) or (II), Ri, R4 and R5 are H; R3 is H, or (CH2)nN+(CHs)3, where n is an integer from 1 to 16, preferably 2 to 8; and R2 is a phenyl group, or a mono-substituted phenyl group; preferably R2 is selected from phenyl, 4-fluorophenyl, 2-fluorophenyl, 4-chlorophenyl, 3-chlorophenyl, 4-bromophenyl and 4-methylphenyl.
3. A composition according to claim 1 or claim 2, wherein the lactam is a lactam selected from:
4. A composition according to claim 1 , wherein the lactam is selected from:
5. A composition according to any preceding claim, wherein the lactam is an aqueous based composition, preferably comprising from 0.1 to 99 wt.%, preferably from 0.5 to 98 wt.%, more preferably from 1 to 98 wt.% water.
6. A composition according to any preceding claim, wherein the solvent is selected from the group: alcohol, levulinate derivatives; lactate derivatives; and, solvents with a dielectric constant of 15 of higher, preferably the solvents are: alcohols, preferably a C1-C4 alcohol, more preferably ethanol; lactate derivatives, preferably ethyl lactate and/or butyl lactate; levulinate derivatives, preferably 2-methyltetrahydrofuran, ethyl levulinate, ethyl levulinate glycerol ketal (LGK); and/or dimethyl sulfoxide. A composition according to any preceding claim, wherein the solvent is selected from the group: ethanol; ethyl lactate, butyl lactate; 2-methyltetrahydrofuran, ethyl levulinate, and ethyl levulinate glycerol ketal (LGK), or mixtures thereof; preferably the solvent is selected from the group: ethyl lactate, butyl lactate; 2- methyltetrahydrofuran, ethyl levulinate, and ethyl levulinate glycerol ketal (LGK), or mixtures thereof. A composition according to any preceding claim, wherein the solvent is selected from the group: 2-methyltetrahydrofuran, ethyl levulinate, and ethyl levulinate glycerol ketal (LGK), or mixtures thereof. A composition according to any preceding claim, wherein the film-forming polymer is selected from quaternised polysaccharide derivatives, polyvinylpyrrolidone (PVP) and co-polymers thereof, and, polyvinylalcohol (PVA) and co-polymers of polyvinylalcohol, and/or mixtures thereof. A non-therapeutic method of treatment of a surface, to improve resistance of said surface to bacterial fouling, by treatment with a composition according to any one of claims 1 to 9. A method according to claim 10, wherein the surface to be treated is selected from plastic, metal, wood, polymer, paper, textile, and/or wipes. A method according to claim 10 or claim 11, wherein the lactam is selected from: Use of a combination of a lactam and a film forming polymer to improve inhibition of bacterial species, wherein the film-forming polymer is selected from polysaccharides, quaternised polysaccharide derivatives, polyvinylpyrrolidone (PVP) and co-polymers thereof, and, polyvinylalcohol (PVA) and co-polymers of polyvinylalcohol, and/or mixtures thereof; and, wherein the lactam is of formula (I) or (II): wherein:
R1 and R2 are each independently selected from hydrogen, halogen, alkyl, cycloalkyl, alkoxy, oxoalkyl, alkenyl, heterocyclyl, heteroaryl, aryl and aralalkyl; and
R3 is selected from hydrogen, hydroxyl, alkyl, cycloalkyl, alkoxy, oxoalkyl, alkenyl, heterocyclyl, heteroaryl, cycloalkyl, aryl, aralalkyl, -C(O)CRe=CH2, and (CH2)nN+(Ra)3, where n is an integer from 1 to 16, preferably 2 to 8, and where each Ra is independently H or C1.4 alkyl;
R4 and R5 are independently selected from hydrogen, aryl, heterocyclyl, heteroaryl, and arylalkyl; and
Re is selected from hydrogen and methyl; and
R? is selected from hydrogen and -C(O)CRe=CH2; and preferably, at least one of R4 and R5 is hydrogen.
14. Use according to claim 14, wherein the lactam is selected from:
10
EP21802746.4A 2020-12-09 2021-11-05 Lactam composition and use Pending EP4258876A1 (en)

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BR112018003209B1 (en) * 2015-08-20 2021-07-13 Unilever Ip Holdings B.V. COMPOSITION INCLUDING A LACTAM AND AN ALKYL OR ALKENYL LACTATE
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WO2020053106A1 (en) * 2018-09-14 2020-03-19 Unilever Plc Wipe
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