EP4258867A1

EP4258867A1 - Lactam composition and use

Info

Publication number: EP4258867A1
Application number: EP21798735.3A
Authority: EP
Inventors: Nicholas Joseph BROWNBILL; Joanne Clare O'keeffe; Neil James Parry
Original assignee: Unilever Global IP Ltd; Unilever IP Holdings BV
Current assignee: Unilever Global IP Ltd; Unilever IP Holdings BV
Priority date: 2020-12-09
Filing date: 2021-11-05
Publication date: 2023-10-18
Also published as: WO2022122264A1; CN116669553A

Abstract

The invention relates to a composition comprising: (a) from 0.0001 to 5 wt.% of a lactam; (b) 1 to 80 wt.%, of a solvent selected from: 2-methyltetrahydrofuran, ethyl levulinate, and ethyl levulinate glycerol ketal (LGK); or mixtures thereof; the invention also relates to a non- therapeutic method of treatment of a surface, to improve resistance of said surface to bacterial fouling; and also to the use of a solvent selected from: 2-methyltetrahydrofuran, ethyl levulinate, and ethyl levulinate glycerol ketal (LGK); or mixtures thereof; or mixtures thereof, to improve the solubility of a lactam.

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 solubility of the lactam.

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 improving solubility of the lactam.

Summary of the Invention

We have found that by formulating a composition comprising a lactam in combination with one or more specific solvents, the resulting formulation displays improving solubility of the lactam. With the improved availability of the lactam, the resulting compositions can provide improved bacterial inhibition to a surface that the lactam composition is applied to.

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 selected from: 2-methyltetrahydrofuran, ethyl levulinate, and ethyl levulinate glycerol ketal (LGK); or mixtures thereof; or mixtures thereof.

Preferably 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⁺(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;

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 most preferred solvents are: 2-methyltetrahydrofuran, ethyl levulinate, and ethyl levulinate glycerol ketal (LGK).

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.

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 solvent selected from: 2-methyltetrahydrofuran, ethyl levulinate, and/or ethyl levulinate glycerol ketal (LGK); and dimethyl sulfoxide; or mixtures thereof to improve the solubility of a lactam.

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.

Preferably 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

Re is selected from hydrogen and methyl; and

R? is selected from hydrogen and -C(O)CR6=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, Ri is hydrogen. Preferably, R3 is hydrogen, or (CH2)_nN⁺(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; 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 selected from: 2-methyltetrahydrofuran, ethyl levulinate, and ethyl levulinate glycerol ketal (LGK); or mixtures thereof.

The most preferred solvents are: 2-methyltetrahydrofuran, ethyl levulinate, and ethyl levulinate glycerol ketal (LGK).

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).

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.%.

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.

The composition may preferably comprise a buffer to keep any resulting composition within a specified pH range.

Further

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.

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. Preparation of 4-(4-chlorophenyl)-5-hydroxy-5-methyl-1 H-pyrrol-2(5H)-one

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, 1H), 5.01 (s, 1H), 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 investigated

EtOH - ethanol

MeOH - methanol

DMSO - dimethyl sufoxide

MPG - monopropylene glycol

MeCN - acetonitrile

CPME - cyclopentyl methylether

2MeTHF - 2-methyltetrahydrofuran

Ethyl levulinate

LGK - ethyl levulinate glycerol ketal (LGK)

Example 2

This example shows the effect of the different solvents on the solubility of the lactam. 250-350 mg of lactam 488 (Vasant 99%) was added to 10ml of the tabulated solvents, until visibly saturated and placed on bottle rollers for 72hrs. The resultant saturated solutions were filtered using a 1 pm syringe filter to remove any insoluble material remaining.

For quantification of lactam in solution, 10pl of the stock was added to 4990pl of ethanol to ensure less than 0.1 mg/ml (100 ppm) of lactam 488 in 0.2% chosen solvent and 99.6% ethanol. Lactam concentration in plate was calculated against a calibration of known EtOH/Lactam solutions, and then multiplied by the dilution factor (500) to determine the actual lactam level in saturated solution (Lactam max solubility mg/ml in table 1).

Table 1 - Shows the lactam solubility (mg/ml) in various solvents along with where known various theoretical solubility parameters *denotes comparative solvents

The solvents according to the invention provided good to excellent solubility of the lactam (greater than ~7.5mg/ml). Notably some comparative surfactants performed much worse than expected from their theoretical solubility parameters. Notably, the level of lactam solubility is markedly different from expected based on theoretical solubility parameters (Hansen or Hildebrand solubility parameters) for the most preferred solvents: 2-methyltetrahydrofuran, ethyl levulinate, and ethyl levulinate glycerol ketal (LGK).

Claims

1. A composition comprising:

(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 selected from: 2-methyltetrahydrofuran, ethyl levulinate, and ethyl levulinate glycerol ketal (LGK); or mixtures thereof.

2. A composition according to claim 1 , wherein the lactam is of formula (I) or (II): wherein:

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. A composition according to claim 1 or claim 2, 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. A composition according to claim 1 , wherein the lactam is a lactam selected from: A composition according to claim 1 , wherein the lactam is selected from: A composition according to any preceding claim, wherein the composition 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. A composition according to any preceding claim, additional comprising 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.% of one or more surfactants, preferably selected from anionic, nonionic, cationic and/or amphoteric surfactants, more preferably nonionic surfactants. 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 7. A method according to claim 8, wherein the surface to be treated is selected from plastic, metal, wood, polymer, paper, textile, and/or wipes. A method according to claim 8 or claim 9, wherein the lactam is selected from: Use of a solvent selected from: 2-methyltetrahydrofuran, ethyl levulinate, ethyl levulinate glycerol ketal (LGK), and dimethyl sulfoxide; or mixtures thereof, to improve the solubility of a lactam. Use according to claim 11 , wherein the lactam is selected from: