AU2020403448B2

AU2020403448B2 - Universal formulation

Info

Publication number: AU2020403448B2
Application number: AU2020403448A
Authority: AU
Inventors: Adrian Fellows; Dharmit MISTRY
Original assignee: Gama Healthcare Ltd
Current assignee: Gama Healthcare Ltd
Priority date: 2019-12-10
Filing date: 2020-12-08
Publication date: 2026-02-05
Anticipated expiration: 2040-12-08
Also published as: WO2021116092A1; GB2603446B; CN115103592A; GB2603446A; GB201918088D0; GB202208395D0; EP4072291A1; AU2020403448A1

Abstract

The present invention concerns a composition comprising at least one quaternary ammonium compound, at least one alcohol ethoxylate and at least one preservative, a wet wipe comprising a substrate that has been impregnated with said composition as well as the use of said composition or of said wet wipe for disinfection of a surface.

Description

WO wo 2021/116092 PCT/EP2020/085048

Universal Formulation

The present invention relates to a composition comprising at least one quaternary ammonium compound, at least one alcohol ethoxylate and at least one preservative/slower acting biocide, a wet wipe comprising a substrate that has

been impregnated with said composition as well as the use of said composition or of said wet wipe for disinfection of a surface.

In a healthcare environment there are a very wide range of surfaces, equipment,

and devices which must not only be kept clean, but which must appear clean and not harbour residues that detract aesthetically or functionally from their roles in

patient care or cross-infection control. Typically, such items are made of stainless

steel, other metals, glass and/or a wide range of plastics and rubbers. They may

include screens, keyboards, trays, wheelchairs, trolleys, walls, windows and many

diverse pieces of medical equipment and equipment stands, bed frames,

mattresses, commodes and furniture.

As the infection control market has evolved the requirement of broad-spectrum products, which would include efficacy against more resilient microorganisms

such as non-enveloped viruses and mycobacteria is evident. These organisms are highly infectious pathogens responsible for significant healthcare associated

infections.

Non-enveloped viruses are a challenge for disinfection due to the structural

differences of the capsid core, availability and number of targets, and

accessibility to the nucleic acid.

Mycobacteria have an outer layer which makes them resistant to commercially

available disinfectant products. Gama Healthcare sought to develop strong product formulations which will eliminate virucidal and tuberculocidal infections

from surfaces in healthcare settings.

Biofilms are becoming more widely recognised as a significant healthcare challenge. It is thought that biofilms may be responsible for continued survival

and transmission of organisms from one surface to another and thus a route to infection. Biofilms are particularly difficult to eradicate due the adhesive

properties and protective extracellular polymeric substances (EPS) that coat and protect the organism's matrix. It is difficult for biocides to penetrate the EPS and exert an effect on the organisms, in addition the organisms in a biofilm have a slower metabolism which decreases the intake of biocides. Therefore, the biofilm performance was also a key area that was focussed on throughout development (Maillard, JY and McBain, A. 2019; Ledwoch, K et al. 2019). 2020403448

Wet wipes comprising a substrate that has been impregnated with a disinfecting composition have been on the market for years and have provided the healthcare services and other areas with a simple, effective infection control solution.

Whilst said wipes possess broad antimicrobial capability, the performance in short contact times against adenovirus and mycobacterium terrae and activity against biofilms could be improved.

It is an object of the present invention to overcome or ameliorate at least one of the disadvantages of the prior art, or to provide a useful alternative.

The present invention provides a composition that is efficacious in short, appropriate and relevant contact times for healthcare settings, in particular that has improved activity against viruses and mycobacteria in relevant short contact times that are be required in hospital disinfection.

Provided is a composition comprising at least one quaternary ammonium compound, at least one alcohol ethoxylate, at least one polyoxypropylene-/polyoxyethylene block copolymer and at least one preservative, wherein the at least one preservative comprises 2-phenylphenol, wherein the at least one preservative is present in an amount of 0.02 to 3 % w/w wherein the at least one alcohol ethoxylate comprises at least one primary alcohol ethoxylate. Also provided is a wet wipe comprising a substrate that has been impregnated with such a composition. Also provided is the use of such a composition or such a wet wipe for disinfection of a surface.

Provided is a composition comprising at least one quaternary ammonium compound, at least one alcohol ethoxylate and at least one preservative and/or slower acting biocide with a mode of action different to the QAC (herein only referred to as a preservative).

2a 12 Jan 2026

This composition is based on the combination of a quaternary ammonium compound, a preservative and the surfactant alcohol ethoxylate. This composition successfully formulates both cationic and anionic ingredients together, which have previously been thought to be inactivated when combined, and thus prevented activity against microorganisms what, however, was not the case. Instead this particular combination is capable of having extended claims against viruses and mycobacteria in relevant short contact times that would be required in hospital disinfection. 2020403448

This composition provides a range of antimicrobial activity including viricidal, mycobacterial and biofilm activity which the current wet wipes comprising a

WO wo 2021/116092 PCT/EP2020/085048 PCT/EP2020/085048

3

substrate that has been impregnated with a disinfecting composition do not

possess. possess.

The addition of alcohol ethoxylates and preservatives have altered the

performance of such a product to which it supersedes the known formulations.

The composition according to the invention has been developed to enable harder to kill viruses such as non-enveloped viruses and mycobacteria to be killed and to

eradicate biofilms.

The composition comprises at least one quaternary ammonium compound (QUAT). Quaternary ammonium compounds are the most commonly used biocides

within disinfectant products in both the healthcare environment and outside because they exhibit a broad range of antimicrobial efficacy. QUATs are cationic

and bind with anionic components of the cell membrane of Gram-negative organisms or cell wall of Gram-positive organisms which aggregates and solubilises the hydrophobic components. This causes generalised damage and leakage of cell contents to cause cell death (Sharma, N et al., 2017).

In addition, QUATs interfere with the intracellular processes, enzyme activity or

DNA/RNA replication cycle, therefore, products that contain QUATs are effective against Gram-positive and Gram-negative bacteria, enveloped viruses with limited fungi and mycobacteria activity.

The composition comprises at least one preservative. A preservative is a

substance or a chemical that is added to prevent decomposition by microbial growth or by undesirable chemical changes. The preservative is preferably an antimicrobial preservative, that prevent degradation by bacteria.

The composition comprises at least one alcohol ethoxylate. Alcohol ethoxylates are a group of nonionic surfactants that are obtained by alkoxylation, i.e. by

reacting ethylene oxide, propylene oxide or butylene oxide (preferably ethylene

oxide) with primary long-chain fatty- or oxo-alcohols in the presence of basic or

acidic catalysts at temperatures of 120-200°C and pressures of 1-10 bar.

In the usual application, alcohols are converted into compounds of the general

formula R(OC2H4)nOH where in ranges from 1 to 22.

WO wo 2021/116092 PCT/EP2020/085048

4

Preferably, the at least one alcohol ethoxylate is a compound of the general

formula R(OC2H4)nOH where in ranges from C6 to C22. primary, secondary or tertiary alcohol ethoxylates can be used. Preferred n ranges from C9 to C11.

Usually alcohol ethoxylates have multifunctional properties, which include

detergency, foaming, builders and lowering surface tension. The addition of the alcohol ethoxylate(s) improve the solubilization of fats and proteins, which may

aid microbiological activity.

The composition according to the invention is preferably characterized in that the

at least one alcohol ethoxylate comprises at least one primary alcohol ethoxylate.

A primary alcohol ethoxylate is an alcohol ethoxylate as described above, wherein

the alcohol moiety is a primary alcohol.

Particularly preferred alcohol ethoxylates include Neodol, Marlipal, Exxal,

Libranone from Monarch Chemicals, Rocara, among other manufactuers and

suppliers. Such other alcohol ethoxylates can be used for examples as secondry and teriary alcohol ethoxylates.

at least one preservative comprises 2-phenylphenol, phenoxyethanol, phenethyl alcohol, tocopherols, 2-bromo-2-nitro-1,3-propanediol, amidines including

diamidines, propamidines etc, iodohexamidines, para hydroxy benzoate esters, benzyl alcohol and its subsituted, isothiazolinones such as methylisothiazolinone

and methylchloroisothiazolinone, IBPC and/or others include parabens and phenolics.

at least one quaternary ammonium compound comprises benzalkonium chloride,

didecyldimethylammonium chloride, PHMB and/or CHG.

at least one quaternary ammonium compound is present in an amount of 0.2. to

1.0. % w/v, preferably in an amount of 0.3. to 0.7 %w/v.

WO wo 2021/116092 PCT/EP2020/085048

5

at least one alcohol ethoxylate is present in an amount of 0.1 to 10 % w/v,

preferably in an amount of 0.3 to 3.0 %w/v.

at least one preservative is present in an amount of 0.02 to 2.0 % w/v,

preferably in an amount of 0.02 to 1.0 %w/v.

composition further comprises at least one polyoxypropylene-/polyoxyethylene

block copolymer.

Preferably, the block co-polymers comprise varying units of polyoxypropylene (poly(propylene oxide)) and polyoxyethylene (poly(ethylene oxide)). Such block copolymers increase the solubility of hydrophobic substances.

Suitable polyoxypropylene-/polyoxyethylene block copolymers include Poloxamer

184 Poloxamer 181, Poloxamer 182, Poloxamer 183, Poloxamer 185, Poloxamer

188, Poloxamer 101, Poloxamer 105, Poloxamer 108, Poloxamer 123, Poloxamer

212, Poloxamer 217, Poloxamer 234, Poloxamer 235, Poloxamer 333, Poloxamer

335, Poloxamer 401, Poloxamer 403 and/or Poloxamer 407.

composition further comprises propane-1,2-diol glycerol, panthenol and/or allantoin preferably in an amount of 0.01. to 1.0. % w/v, preferably in an amount

of 0.1 to 0.8 %w/v. The addition of propane-1,2-diol has the advantage that may be provided to aid use on skin. More complex emollients and skin conditioning agents can be used such as Aloe vera and/or vitamine E.

composition further comprises 2-phenoxyethanol, preferably in an amount of 0.05. to 1 % w/v, preferably in an amount of 0.2 to 0.8 %w/v. The addition of 2-

phenoxyethanol has the advantage that it would act as a slower acting biocide.

composition further comprises 2-Hydroxypropane-1,2,3-tricarboxylic acid

anhydrous, preferably in an amount of 0.001 to 10.0 % w/v, preferably in an

WO wo 2021/116092 PCT/EP2020/085048 PCT/EP2020/085048

6

amount of 0.001 to 5.0 %w/v. The addition of 2-Hydroxypropane-1,2,3- tricarboxylic acid anhydrous among other acid which are used as a buffering

agent.

composition further comprises trisodium citrate dihydrate, preferably in an

amount of 0.001 to 10.0 % w/v, preferably in an amount of 0.001 to 5.0 %w/v.

The addition of trisodium citrate dihydrate among other acids which are used as a buffering agent.

composition further comprises one or more additives selected from a group consisting of one or more disinfectants, stabilizers, preservatives, chelates,

metals, natural oils, dyes, fragrances, odor masking agents and/or mixtures

thereof.

Each of these additives is preferably present in an amount of 0.001 to 2.0 % w/v,

preferably in an amount of 0.001 to 1.50 %w/v.

composition is in the form of an aqueous or aqueous alcohol solution or dispersion.

The aqueous alcohol solution or dispersion preferably comprises a mixture of 80 % water and 20 % alcohol.

Preferred alcohols include ethanol, Propan-2-ol, propan-1-ol and/or 3-

Butoxypropan-2-ol.

composition comprises from 0.3 to 3.0 % w/v primary alcohol ethoxylate,

from 0.02 to 3.0 % w/v 2-phenylphenol, from 0.3 to 0.7 % w/v benzalkonium chloride,

from 0.3 to 0.7 % w/v didecyldimonium Chloride,

from 0.0001 to 0.5 % w/v of a polyoxypropylene-/polyoxyethylene block

copolymer, preferably poloxamer 184, from 0.1 to 0.8% w/v propane-1,2-diol and from 0.2 to 0.8% w/v 2-phenoxyethanol with the solvent being water.

Thereby, the polyoxypropylene-/polyoxyethylene block copolymer comprises preferably poloxamen 184. The alcohol ethoxylate preferably comprises of a primary alcohol ethoxylate with a n of C9 - C11.

composition comprises from 0.3 to 3.0 % w/v primary alcohol ethoxylate,

from 0.3 to 0.7 % w/v didecyldimonium Chloride,

from 0.0001 to 0.5 % w/v of a polyoxypropylene-/polyoxyethylene block copolymer, preferably poloxamer 184, from 0.1 to 0.8 % w/v propane-1,2-diol and

from 0.2 to 0.8 % w/v 2-phenoxyethanol

from 0.01 to 0.3 % parfum from 0.001 to 5.0 % 2-hydroxypropane-1,2,3-tricarboxylic acid anhydrous, from 0.001 to 5.0 % trisodium citrate dihydrate,

with the solvent being water.

Thereby, the polyoxypropylene-/polyoxyethylene block copolymer comprises

preferably poloxamen 184. The alcohol ethoxylate preferably comprises of a primary alcohol ethoxylate with a n of C9 - C11

composition comprises 1 % w/v alcohol ethoxylate,

0.1% w/v 2-phenylphenol, 0.54 % w/v benzalkonium chloride (50%),

0.54 % w/v didecyldimonium Chloride (80%),

0.12 % w/v of a polyoxypropylene-/polyoxyethylene block copolymer, 0.2 % w/v propane-1,2-diol and

0.6 % w/v 2-phenoxyethanol

0.05 % parfum

0.03 % 2-hydroxypropane-1,2,3-tricarboxylic acid anhydrous, 0.1 % trisodium citrate dihydrate,

with the solvent being water.

Thereby, the polyoxypropylene-/polyoxyethylene block copolymer comprises preferably poloxamer 184. The alcohol ethoxylate preferably comprises of a primary alcohol ethoxylate with a in of C9 - C11.

The present invention further concerns a wet wipe comprising a substrate that

has been impregnated with a composition as described in the preceding sections.

The substrate that is impregnated with the composition is preferably a nonwoven material. Suitable nonwoven materials include but are not limited to those types

which are binder free so that the binder is not deleteriously affected by the

composition nor itself contributes to smearing. Examples of binder free nonwoven materials include spun laced or hydro-entangled nonwoven materials. However other types such as wet laid, airlaid, thermobond or stitch bonded types may also

be used.

The wipes may comprise fibres made of any of or a mixture of polypropylene, polyester, polyethylene, viscose, cotton, regenerated wood pulp and cellulose.

They may also include micro-fibre and nano-fibre products

The substrate is preferably produced in the form of individual tissues or a

perforated roll of material from which individual tissues can be separated that are

impregnated with the composition and packaged ready to be dispensed from resealable tubs, buckets, flow-wrap packs or similar. Alternatively, impregnated

wipes may be individually sealed in a wrapper made of a suitable packaging material, such as an impermeable foil, cellophane and the like.

The ingredients of the inventive compositions are simply mixed together to form

an aqueous or aqueous alcohol solution or dispersion that can then be used to impregnate a substrate by soaking the substrate in the composition to thereby

produce a wet wipe in accordance with the invention.

WO wo 2021/116092 PCT/EP2020/085048

9

Such a wet wipe is suitable for cleaning a wide range of surfaces and materials

and removing various types and levels of soiling, both organic and inorganic in a

manner that leaves a clean and disinfected surface.

The present invention further concerns the use of a composition or of a wet wipe as described in the preceding for disinfection of a surface.

The inventive composition has been tested to measure the improvements of microbiological efficacy of the inventive composition and improvement of broad-

spectrum efficacy following standard methods.

The microbiologically efficacy was tested following the EN standards for bacteria

(EN 13727; EN 1656; EN 16615), yeast/fungi (EN 13624; EN 16615; EN 1657),

mycobacteria (EN 14348), viruses (EN 14476; ASTME1052) and Biofilm. There is

not a standard method approved for biofilm testing and therefore the model tested corresponded to the one developed and published at Cardiff University (K.

Ledwoch et al 2019).

For all microbiological testing, the formulation was tested as a liquid formula that

was extracted from the substrate. All tests were conducted representing in-use conditions of the product for healthcare settings regarding contact time,

temperature, test organisms and interfering substances.

Bactericidal tests

EN 13727 and EN 1656: Specify suspension tests for establishing bactericidal activity. The product is

added to a test suspension of bacteria in a solution of interfering substance and

maintained at specific temperature and contact time. At the end of this contact time, an aliquot is taken; the bactericidal action is

neutralized, and the numbers of surviving bacteria and reduction is calculated.

The product shall demonstrate at least a 5 decimal log (lg) reduction.

EN 16615 Specifies a carrier test for establishing bactericidal activity with wipes on

surfaces. A test-surface is marked with 4 squares of 5 X 5 cm, the "test fields", in

a row. row.

PCT/EP2020/085048

10

Test field 1 on the test surface is inoculated with a test suspension of bacteria in

a solution of interfering substances. The inoculum is dried. The test-surface is

wiped with the product starting in front of test field 1, turning immediately after

test field 4 and wiped back to the starting point. In parallel a water control is

performed: a wipe is soaked with water instead of the product. At the end of the contact time, the test organisms are recovered from each test

field with moistened cotton swabs. The swabs are brought into a tube containing

broth and neutralizer and the test organisms are to be severed from the swab by shaking. The numbers of surviving test organisms in each sample are determined, and the reduction is calculated.

The product shall demonstrate at least a decimal log (lg) reduction in counts of 5

for bacteria on test field 1. The mean of the cfus on the test fields 2 to 4 shall be

equal or less than 50, the mean of the cfus of the water control shall be equal or

more than 10.

Yeast/Fungi tests

EN 13624 and EN 1657 Specify suspension tests for establishing fungicidal or yeasticidal activity. The

product is added to a test suspension of fungi (yeast cells or mould spores) in a

solution of interfering substance and maintained at specific temperature and

contact time.

At the end of this contact time, an aliquot is taken; the fungicidal action is

neutralized, and the numbers of surviving fungi and reduction is calculated. The

product shall demonstrate at least a 4 decimal log (lg) reduction.

EN 16615 Specifies a carrier test for establishing yeasticidal activity with wipes on surfaces.

A test-surface is marked with 4 squares of 5 X 5 cm, the "test fields", in a row.

performed: a wipe is soaked with water instead of the product.

At the end of the contact time, the test organisms are recovered from each test

field with moistened cotton swabs. The swabs are brought into a tube containing broth and neutralizer and the test organisms are to be severed from the swab by shaking. The numbers of surviving test organisms in each sample are determined, and the reduction is calculated.

The product shall demonstrate at least a decimal log (lg) reduction in counts of 4

for yeast on test field 1. The mean of the cfus on the test fields 2 to 4 shall be

more than 10.

Mycobacteria tests

EN 14348 Specifies a suspension test for establishing mycobactericidal activity. A test

suspension of mycobacteria in a solution of an interfering substance is added to a

sample of the product. The mixture is maintained at 20 °C + 1 °C for selected contact time. At the end of this contact time, an aliquot is taken; the

mycobactericidal and/or the mycobacteriostatic activity in this portion is

immediately neutralized or suppressed by a validated method. The numbers of surviving mycobacteria in each sample are determined and the reduction is calculated.

The mycobactericidal activity shall be evaluated using the following two test-

organisms. Mycobacterium avium ATCC 15769 and Mycobacterium terrae ATCC 15755. The tuberculocidal activity shall be evaluated using only Mycobacterium terrae. The product shall demonstrate at least a decimal log (lg) reduction in

counts of 4.

Virucidal tests

EN 14476 Specifies a suspension test for establishing virucidal activity. A sample of the

product is added to a test suspension of viruses in a solution of an interfering

substance. The mixture is maintained at one of the temperatures and the contact times specified. At the end of this contact time, an aliquot is taken; the virucidal

action in this portion is immediately suppressed by a validated method (dilution

of the sample in ice-cold cell maintenance medium). The dilutions are transferred into cell culture units (petri dishes, tubes or wells of microtitre plates) either using monolayer or cell suspension. Infectivity tests are done either by plaque test or quantal tests.

After incubation, the titres of infectivity are calculated according to Spearman

and Kärber or by plaque counting. Reduction of virus infectivity is calculated from

differences of Ig virus titres before (virus control) and after treatment with the

product. The product shall demonstrate at least a decimal log (lg) reduction of 4

in virus titre.

ASTME1052 This test method is to determine if a test substance can inactivate viruses in

suspension. 1 part of virus is added to 9 parts of test product, upon closure of the study

contact time, the test and recovery suspensions are neutralized. The neutralized

test, recovery, cytotoxicity control, and neutralization control suspensions are

serially diluted in the appropriate media. Each dilution is plated in quadruplicate

to host cell monolayers in a 24-well tray. Media is added to each well and the

host cell-virus system is allowed to incubate for the appropriate time.

At the close of the incubation time, the assay is scored using standard cell culture

methods. Each well in the tray is examined under microscope for the presence of cytopathic effects (CPE) of infection. Cytotoxicity control wells are examined for damage

caused by the test product.

The Spearman-Karber method, or another appropriate statistical method, is used to quantify the amount of infectious virus present in the assay. The product shall

demonstrate at least a decimal log (lg) reduction of 4 in virus titre.

Biofilm tests

Dry biofilm model Bacteria were initially cultured in normal hydrated conditions to allow initial

adherence and biofilm formation. This was followed by cycles of dry and hydrated phases for a total duration of 12 days. Reduction in bacterial viability (Log10

reduction in CFU per ml) gave the number of bacteria that were removed or and killed following wiping. Log10 reduction was calculated as the difference between

the number of bacteria recovered from untreated (control) and treated samples.

Transfer test was conducted to investigate the transferability of surviving bacteria from the dry surface biofilm following wiping. Positive growth/adpression was recorded and transferability calculated as the number of positive contact/numbers of adpressions.

Regrowth measures the time needed for the DSB to recover following treatment. The number of days for the DE broth colour to change from purple to yellow indicative of bacterial growth was recorded. 2020403448

The reference to any prior art in this specification is not, and should not be taken as, an acknowledgement or any form of suggestion that the prior art forms part of the common general knowledge.

As used herein, and except where the context requires otherwise, the terms “comprise”, “comprises”, “comprising” or similar terms are intended to mean a non-exclusive inclusion, such that a composition, method, or process that recites a list of elements does not include those elements solely, but may well include other elements not listed.

The invention is further illustrated in the following non-limiting examples.

wo 2021/116092 WO PCT/EP2020/085048

14

Example:

A composition according to table 1 was prepared by mixing the listed ingredients in water.

Table 1:

Ingredient Active %w/w ingredient concentration %w/w Primary Alcohol ethoxylate 0.3 - 3.0

2-Phenylphenol 0.02 - 3.0

Benzalkonium chloride (50%) 0.3 - 0.70 0.6 - 1.40

Didecyldimonium Chloride 0.3 - 0.70 0.37 - 0.88 (80%) Poloxamer 184 0.0001 - 0.5 Propane-1,2-diol 0.1 - 0.8

2-Phenoxyethanol 0.2 - 0.8 0.2 - 0.8

Parfum 0.01 - 0.3

2-Hydroxypropane-1,2,3 qs tricarboxylic acid anhydrous Trisodium citrate dihydrate qs qs Aqua to 100.00

Table 2:

Ingredient Active %w/w ingredient concentration %w/w Ethanol 10.0-20.0 2-Phenylphenol 0.02-0.30 Benzalkonium chloride (50%) 0.30 - 0.70 0.60 - 1.40 Didecyldimonium Chloride 0.30 - 0.70 0.37 - 0.88 (80%) Poloxamer 184 0.0001 - 0.50 Propane-1,2-diol 0.10 - 0.80 2-Phenoxyethanol 0.20 - 0.80 0.20 - 0.80 Propan-2-ol, propan-1-ol, 3- 5.0 -15.0 Butoxypropan-2- wo 2021/116092 WO PCT/EP2020/085048

15

Eucalyptus oil 0.01 - 0.1

Lavender oil 0.01 - 0.1

Aqua to 100.00

Table 3:

Ingredient Active %w/w ingredient concentration %w/w SA-9 0.20 - 0.80 2-Phenylphenol 0.02-0.30 Benzalkonium chloride (50%) 0.30 - 0.70 0.60 - 1.40 Didecyldimonium Chloride 0.30 - 0.70 0.37 - 0.88 (80%) Poloxamer 184 0.0001 - 0.50 Propane-1,2-diol 0.10 - 0.80 2-Phenoxyethanol 0.20 - 0.80 0.20 - 0.80 Propan-2-ol, propan-1-ol, 3- 5.0 -15.0 Butoxypropan-2- Eucalyptus oil 0.01 - 0.1 Lavender oil 0.01 - 0.1 Clove oil 0.01 - 0.1

Lactic acid qs Aqua to 100.00

Table 4:

Ingredient Active %w/w ingredient concentration %w/w Ethanol 10.0 - 30.0 2-Phenylphenol 0.20 -1.0

Benzalkonium chloride (50%) 0.30 - 0.70 0.60 - 1.40 Didecyldimonium Chloride 0.30 - 0.70 0.37 - 0.88 (80%) Poloxamer 184 0.0001 - 0.50 Propane-1,2-diol 0.10 - 0.80 2-Phenoxyethanol 0.20 - 0.80 0.20 - 0.80 wo 2021/116092 WO PCT/EP2020/085048

16

Propan-2-ol, propan-1-ol, 3- 5.0 -15.0 Butoxypropan-2- Salicylic acid 0.10 - 1.00 Sodium hydroxide qs Aqua to 100.00

Table 5:

Ingredient Active %w/w ingredient

concentration %w/w Propan-2-ol 10.0 - 30.0

2-Phenylphenol 0.20 -1.0

Benzalkonium chloride (50%) 0.30 - 0.70 0.60 - 1.40 Didecyldimonium Chloride 0.30 - 0.70 0.37 - 0.88 (80%) Poloxamer 184 0.0001 - 0.50 Propane-1,2-diol 0.10 - 0.80 2-Phenoxyethanol 0.20 - 0.80 0.20 - 0.80 Propan-2-ol, propan-1-ol, 3- 5.0 -15.0 Butoxypropan-2- Salicylic acid 0.10 - 1.00 Sodium hydroxide qs Aqua to 100.00

Table 6:

Ingredient Active %w/w ingredient concentration %w/w Propan-2-ol 10.0 - 30.0

2-Phenylphenol 0.20 -1.0

Benzalkonium chloride (50%) 0.10 - 0.50 0.20 - 1.00 Didecyldimonium Chloride 0.10 - 0.50 0.13 - 0.63 (80%) Silver 1.0 2.0 1.0 - 2.0

PEG 40 0.01 0.5 2-Phenoxyethanol 0.02 0.1 0.02 0.1

WO wo 2021/116092 PCT/EP2020/085048

17

Parfum 0.01- 0.5 Phenethyl alcohol 0.01 - 0.1 Salicylic acid 0.10 - 1.00 Disodium EDTA 0.01 - 0.1

Decylamine oxide 0.02 - 0.1

Poloxamer Poloxamer184 184 0.0001 - 0.50 Sodium hydroxide qs Aqua to 100.00

(EN 13727; EN 1656; EN 16615), yeast/fungi (EN 13624; EN 16615; EN 1657), mycobacteria (EN 14348), viruses (EN 14476; ASTME1052) and Biofilm as described in the preceding.

The results are summarized in table 7.

WO wo 2021/116092 PCT/EP2020/085048

18

Table 7:

Contact Strain Strain time Log reduction MICROORGANISM EN TEST BACTERIA EN 13727 A. baumanii 10 sec >6.52

EN 13727 E. faecalis 10 sec >6.70

EN 13727 E. coli 10 sec >6.96

EN 13727 V. cholerae** 5 min >5.23 EN 13727 Enterococcus faecium VRE 10 sec >5.79

EN 13727 MRSA 10 sec >6.57

EN 13727 Klebsiella pneumoniae ESBL 10 sec >6.74

EN 13737 Klebsiella pneumoniae CPE 10 sec >5.28

EN 13727 Carbapenem resistant enterobacteriacae CRE 10 sec >6.65

EN 13727 P. aeruginosa 10 sec >6.83

EN 13727 S. aureus 10 sec >6.78

EN 13727 E. hirae 10 sec >6.85

EN 16615 P. aeruginosa 2 min >5.45

EN 16615 S. aureus 2 min >5.56

EN 16615 E. hirae 2 min >5.90

EN 1276 P. aeruginosa 10 sec >5.22

EN 1276 E. hirae 10 sec >5.29 EN 1276 EN 1276 S. aureus 10 sec >5.13

EN 1276 E. coli K12 10 sec >4.43

EN 1276 E. coli Strain ATCC 10536 for PT4 10 sec >5.13

En 1656 Leptospira interrogans** 1 min >5.07 En 1656 Bordetella bronchiseptica 1 min >5.08 En 1656 Proteus vulgaris 1 min >5.33 En 1656 Staph aureus 1 min >5.51 En 1656 E. hirae 1 min >5.34

EN 13697 P. aeruginosa 2 min >4.17 EN 13697 E. coli K12 2 min >5.17

EN 13697 E. coli Strain ATCC 10536 for PT4 2 min >4.29

EN 13697 S. aureus 2 min 4.34

EN 13697 E. hirae 2 min >4.83

YEAST/FUNGI EN 13624 C. albicans 10 sec >5.63

EN 13624 C. auris 10 sec >5.67

EN 16615 C. albicans 2 min >4.96

EN 16615 A. brasiliensis 2 min 4.67

EN 1650 C. albicans 10 sec >4.15

MYCOBACTERIA EN 14348 M. smegmatis 10 sec 4.79 EN 14348 M. terrae 10 sec >4.93

WO wo 2021/116092 PCT/EP2020/085048

19

VIRUSES EN 14476 Norovirus-wipe 30 sec >5.33

EN 14476 Adenovirus 30 sec >4.70 Heptatitis C**: Bovine Viral Diarrhea Virus EN 14476 1 min 4.17 (BVD) VR-1422

EN 14476 Influenza H1N1 ATCC VR-1469 2 min 4.17 Human coronavirus: Feline Coronavirus VR- EN 14476 2 min 4.17 989-Surrogate

EN 14476 Respiratory Syncytial Virus ATCC VR-26 (RSV) 2 min 4.17

EN 14476 Human Rotavirus VR-2018 2 min 4.17

EN 14476 HIV: Feline Immunodeficiency virus VR-1312 30sec 4.5 Hepatitis B- Duck Hepatatis B virus, Strain ASTM E1052 1 min >3.50 9/1/15

EN 16777 Adenovirus 2 min 4.83

EN 14476 Herpes simplex virus (HSV-1) 2 min >5.24

> 7.50 Log Reduction 19% Transfer Cardiff model S. aureus 2 min >14 days regrowth BIOFILM > 6.29 Log Reduction 0% Transfer Cardiff model C. auris 2 min >10 days regrowth

The composition comprising QUATs combined with primary alcohol ethoxylate and 2-Phenylphenol has clearly shown a marked improvement in virucidal and mycobactericidal antimicrobial efficacy and possesses biofilm activity.

Microbiology efficacy data clearly demonstrates that the composition exhibits

short and relevant contact times under real in-use healthcare conditions with all

tests conducted under clinical dirty conditions.

Compared with known formulations, this composition has a wider broad-spectrum efficacy that was previously not possible until this composition was discovered. It

has demonstrated an improvement on the activity against non-enveloped viruses related with healthcare settings such adenovirus and norovirus in a contact time

of 30 sec. This is significant as drying times of surfaces in hospitals are usually 2-

5 minutes.

In addition, the composition is also capable of killing mycobacteria, in particular

M. terrae demonstrating tuberculocidal efficacy. This level of activity is also

considered as challenging to obtain due to the waxy outer coating being difficult

to break down quickly and exert a killing effect. The composition achieves this in

a relevant and short contact time of 10 seconds.

WO wo 2021/116092 PCT/EP2020/085048

20

Furthermore, it is clear to see from Table 2 that the formula demonstrates

excellent biofilm activity. It eradicates greater than 7 log and 6 log against

Staphylococcus aureus and Candia auris respectively. Furthermore, it demonstrates low transfer rates to surfaces and exhibits long regrowth times.

These results are significantly better known formulations.

Overall, it is clear to see that the composition has shown significant

improvements in efficacy. The composition is able to achieve extended and improved efficacy against non-enveloped viruses, adenovirus, and mycobacteria in addition to remarkable biofilm activity.

REFERENCES

ASTM E1052-11, Standard Test Method to Assess the Activity of Microbicides

against Viruses in Suspension, ASTM International, West Conshohocken, PA,

2011, www.astm.org.

BS EN 13727:3012+A2:2015. Chemical disinfectants and antiseptics- Quantitative suspension test for the evaluation of bactericidal activity in the medical area-

Test method and requirements (phase 2, step 1). BSI Standards Publication.

BS EN 1656:2009. Chemical disinfectants and antiseptics Quantitative suspension test for the evaluation of bactericidal activity of chemical disinfectants and

antiseptics use in the veterinary area-Test method and requirements (phase 2, step 1). BSI Standards Publication.

BS EN 16615:2015. Chemical disinfectants and antiseptics - Quantitative test method for the evaluation of bactericidal and yeasticidal activity on non-porous

surfaces with mechanical action employing wipes in the medical area (4- field

test)- Test method and requirements (phase 2, step 2). BSI Standards Publication.

BS EN 13624:2013. Chemical disinfectants and antiseptics - Quantitative suspension test for the evaluation of fungicidal or yeasticidal activity in the

medical area - Test method and requirements (phase 2, step 1). BSI Standards Publication.

BS EN 1657:2016. Chemical disinfectants and antiseptics - Quantitative suspension test for the evaluation of fungicidal or yeasticidal activity of chemical

disinfectants and antiseptics used in the veterinary area -Test method and requirements (phase 2, step 1). BSI Standards Publication.

BS EN 14348:2005. Chemical disinfectants and antiseptics - Quantitative suspension test for the evaluation of mycobactericidal activity of chemical

disinfectants in the medical area including instrument disinfectants -Test

methods and requirements (phase 2, step 1). BSI Standards Publication.

WO wo 2021/116092 PCT/EP2020/085048

22

BS EN 14476:2013+A1:2015 Chemical disinfectants and antiseptics - Quantitative suspension test for the evaluation of virucidal activity in the medical

area - Test method and requirements (Phase 2/Step 1). BSI Standards Publication.

Ledwoch. K., Said, J., Norville, P and Maillard, J.-Y. 2019. Artificial dry surface

biofilm models for testing the efficacy of cleaning and disinfection. Letters in

Applied Microbiology. 68, 329-336.

Maillard JY and McBain A. 2019. Biofilm in healthcare settings and their control.

Lett Appl Microbiol. 2019 Apr;68(4):268.

Sharma, N., Aron, N. and Kumar, A. 2017. "Ocular Infections: Prophylaxis and

Management", Jaypee.

Claims

1. Composition comprising at least one quaternary ammonium compound, at least one alcohol ethoxylate, at least one polyoxypropylene-/polyoxyethylene block copolymer and at least one preservative, wherein the at least one preservative comprises 2-phenylphenol, wherein the at least one preservative is present in an amount of 0.02 to 3 % w/w wherein the at least one alcohol 2020403448

ethoxylate comprises at least one primary alcohol ethoxylate.

2. Composition according to claim 1, wherein the at least one quaternary ammonium compound comprises benzalkonium chloride and/or didecyldimethylammonium chloride.

3. Composition according to claim 1 or claim 2, wherein the composition further comprises one or more additives selected from a group consisting of one or more disinfectants, stabilizers, preservatives, dyes, fragrances, odor masking agents and/or mixtures thereof.

4. Composition according to any of one of claims 1 to 3, in the form of an aqueous or aqueous alcohol solution or dispersion.

5. Composition according to any one of claims 1 to 4, wherein the composition comprises from 0.3 to 3.0 % w/w primary alcohol ethoxylate, from 0.02 to 3.0 % w/w 2-phenylphenol, from 0.3 to 0.7 % w/w benzalkonium chloride, from 0.3 to 0.7 % w/w didecyldimonium Chloride, from 0.0001 to 0.5 % w/w of a polyoxypropylene-/polyoxyethylene block copolymer, preferably poloxamer 184, from 0.1 to 0.8 % w/w propane-1,2-diol and from 0.2 to 0.8 % w/w 2-phenoxyethanol with the solvent being water.

6. A wet wipe comprising a substrate that has been impregnated with a composition according to any one of claims 1 to 5.

7. The wet wipe according to claim 6, wherein the substrate comprises fibres made of any of or a mixture of polypropylene, polyester, polyethylene, viscose, cotton, regenerated wood pulp, cellulose, micro-fibres and nano-fibres.

8. The wet wipe according to claim 6 or claim 7, wherein the substrate being packaged ready to be dispensed from a tub, a bucket, a flow-wrap pack or an individually sealed wrapper.

9. Use of a composition according to any one of claims 1 to 5 or of a wet wipe according to any one of claims 6 to 8 for disinfection of a surface.