EP4072291A1 - Universal formulation - Google Patents

Universal formulation

Info

Publication number
EP4072291A1
EP4072291A1 EP20824904.5A EP20824904A EP4072291A1 EP 4072291 A1 EP4072291 A1 EP 4072291A1 EP 20824904 A EP20824904 A EP 20824904A EP 4072291 A1 EP4072291 A1 EP 4072291A1
Authority
EP
European Patent Office
Prior art keywords
composition according
composition
test
alcohol ethoxylate
wet wipe
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
EP20824904.5A
Other languages
German (de)
French (fr)
Inventor
Adrian Fellows
Dharmit MISTRY
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.)
Gama Healthcare Ltd
Original Assignee
Gama Healthcare Ltd
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 Gama Healthcare Ltd filed Critical Gama Healthcare Ltd
Publication of EP4072291A1 publication Critical patent/EP4072291A1/en
Pending legal-status Critical Current

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Classifications

    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N33/00Biocides, pest repellants or attractants, or plant growth regulators containing organic nitrogen compounds
    • A01N33/02Amines; Quaternary ammonium compounds
    • A01N33/12Quaternary ammonium compounds
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION 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
    • A01N31/00Biocides, pest repellants or attractants, or plant growth regulators containing organic oxygen or sulfur compounds
    • A01N31/08Oxygen or sulfur directly attached to an aromatic ring system
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION 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
    • A01N31/00Biocides, pest repellants or attractants, or plant growth regulators containing organic oxygen or sulfur compounds
    • A01N31/08Oxygen or sulfur directly attached to an aromatic ring system
    • A01N31/14Ethers

Definitions

  • the present invention relates to a composition
  • 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.
  • 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)
  • 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.
  • 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).
  • 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.
  • This composition provides a range of antimicrobial activity including viricidal, mycobacterial and biofilm activity which the current wet wipes comprising a substrate that has been impregnated with a disinfecting composition do not possess.
  • 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).
  • 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.
  • alcohols are converted into compounds of the general formula R(OC H ) n OH where n ranges from 1 to 22.
  • the at least one alcohol ethoxylate is a compound of the general formula R(OC2H 4 ) n OH where n ranges from C 6 to C22.
  • primary, secondary or tertiary alcohol ethoxylates can be used.
  • Preferred n ranges from C9 to Cn.
  • 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.
  • 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.
  • composition according to the invention is preferably characterized in that the at least one preservative comprises 2-phenylphenol, phenoxyethanol, phenethyl alcohol, tocopherols, 2-bromo-2-nitro-l, 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.
  • the at least one preservative comprises 2-phenylphenol, phenoxyethanol, phenethyl alcohol, tocopherols, 2-bromo-2-nitro-l, 3-propanediol, amidines including diamidines, propamidines etc, iodohexamidines, para hydroxy benzoate esters, benzyl
  • composition according to the invention is preferably characterized in that the at least one quaternary ammonium compound comprises benzalkonium chloride, didecyldimethylammonium chloride, PHMB and/or CHG.
  • composition according to the invention is preferably characterized in that the 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.
  • the composition according to the invention is preferably characterized in that the 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.
  • composition according to the invention is preferably characterized in that the 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 according to the invention is preferably characterized in that the composition further comprises at least one polyoxypropylene-/polyoxyethylene block copolymer.
  • the block co-polymers comprise varying units of polyoxypropylene (polypropylene oxide)) and polyoxyethylene (poly(ethylene oxide)).
  • 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 according to the invention is preferably characterized in that the 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.
  • 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 according to the invention is preferably characterized in that the 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.
  • 2-phenoxyethanol has the advantage that it would act as a slower acting biocide.
  • composition according to the invention is preferably characterized in that the composition further comprises 2-Hydroxypropane-l,2,3-tricarboxylic acid anhydrous, preferably in an amount of 0.001 to 10.0 % w/v, preferably in an amount of 0.001 to 5.0 %w/v.
  • composition according to the invention is preferably characterized in that the 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.
  • trisodium citrate dihydrate among other acids which are used as a buffering agent.
  • composition according to the invention is preferably characterized in that the 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 according to the invention is preferably characterized in that the 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-l-ol and/or 3- Butoxypropan-2-ol.
  • composition according to the invention is preferably characterized in that the 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.
  • the polyoxypropylene-/polyoxyethylene block copolymer comprises preferably poloxamer 184.
  • the alcohol ethoxylate preferably comprises of a primary alcohol ethoxylate with a n of Cg - Cn.
  • composition according to the invention is preferably characterized in that the 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 from 0.01 to 0.3 % perfume from 0.001 to 5.0 % 2-hydroxypropane-l,2,3-tricarboxylic acid anhydrous, from 0.001 to 5.0 % trisodium citrate dihydrate, with the solvent being water.
  • the polyoxypropylene-/polyoxyethylene block copolymer comprises preferably poloxamer 184.
  • the alcohol ethoxylate preferably comprises of a primary alcohol ethoxylate with a n of Cg - Cn.
  • composition according to the invention is preferably characterized in that the composition comprises 1 % w/v alcohol ethoxylate,
  • the polyoxypropylene-/polyoxyethylene block copolymer comprises preferably poloxamer 184.
  • the alcohol ethoxylate preferably comprises of a primary alcohol ethoxylate with a n of Cg - Cn.
  • 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.
  • binder free nonwoven materials include spun laced or hydro-entangled nonwoven materials.
  • 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.
  • impregnated wipes may be individually sealed in a wrapper made of a suitable packaging material, such as an impermeable foil, cellophane and the like.
  • 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.
  • 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.
  • 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 Cambridge University (K. Ledwoch et al 2019).
  • 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.
  • 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.
  • the product shall demonstrate at least a 5 decimal log (Ig) reduction.
  • test-surface is marked with 4 squares of 5 x 5 cm, the "test fields", in a row.
  • 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.
  • a water control is performed: a wipe is soaked with water instead of the product.
  • 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 (Ig) 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.
  • fungicidal or yeasticidal activity 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.
  • the product shall demonstrate at least a 4 decimal log (Ig) reduction.
  • test-surface is marked with 4 squares of 5 x 5 cm, the "test fields", in a row.
  • 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.
  • a water control is performed: a wipe is soaked with water instead of the product.
  • 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 (Ig) 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 equal or less than 50, the mean of the cfus of the water control shall be equal or more than 10.
  • 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 (Ig) reduction in counts of 4.
  • 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.
  • the titres of infectivity are calculated according to Spearman and Karber 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 (Ig) reduction of 4 in virus titre.
  • This test method is to determine if a test substance can inactivate viruses in suspension.
  • test and recovery suspensions 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.
  • the assay is scored using standard cell culture methods.
  • CPE cytopathic effects
  • the Spearman-Karber method is used to quantify the amount of infectious virus present in the assay.
  • the product shall demonstrate at least a decimal log (Ig) reduction of 4 in virus titre.
  • 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 (LoglO reduction in CFU per ml) gave the number of bacteria that were removed or and killed following wiping. LoglO 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.
  • a composition according to table 1 was prepared by mixing the listed ingredients in water.
  • 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 as described in the preceding.
  • BACTERIA EN 13727 A. bau manii 10 sec >6.52 EN 13727 E. faeca lis 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 Klebsiel la pneumoniae ESBL 10 sec >6.74 EN 13737 Klebsiel la 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.
  • 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.
  • this composition 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.
  • 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.
  • Table 2 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.
  • 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.
  • 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).
  • 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 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. 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.

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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

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)
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 provide 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.
This objective was solved by 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).
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.
This composition provides a range of antimicrobial activity including viricidal, mycobacterial and biofilm activity which the current wet wipes comprising a substrate that has been impregnated with a disinfecting composition do not 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(OC H )nOH where n ranges from 1 to 22. Preferably, the at least one alcohol ethoxylate is a compound of the general formula R(OC2H4)nOH where n ranges from C6 to C22. primary, secondary or tertiary alcohol ethoxylates can be used. Preferred n ranges from C9 to Cn.
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.
The composition according to the invention is preferably characterized in that the at least one preservative comprises 2-phenylphenol, phenoxyethanol, phenethyl alcohol, tocopherols, 2-bromo-2-nitro-l, 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.
The composition according to the invention is preferably characterized in that the at least one quaternary ammonium compound comprises benzalkonium chloride, didecyldimethylammonium chloride, PHMB and/or CHG.
The composition according to the invention is preferably characterized in that the 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. The composition according to the invention is preferably characterized in that the 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.
The composition according to the invention is preferably characterized in that the 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.
The composition according to the invention is preferably characterized in that the composition further comprises at least one polyoxypropylene-/polyoxyethylene block copolymer.
Preferably, the block co-polymers comprise varying units of polyoxypropylene (polypropylene 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.
The composition according to the invention is preferably characterized in that the 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.
The composition according to the invention is preferably characterized in that the 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.
The composition according to the invention is preferably characterized in that the composition further comprises 2-Hydroxypropane-l,2,3-tricarboxylic acid anhydrous, 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 2-Hydroxypropane-l,2,3- tricarboxylic acid anhydrous among other acid which are used as a buffering agent.
The composition according to the invention is preferably characterized in that the 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.
The composition according to the invention is preferably characterized in that the 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.
The composition according to the invention is preferably characterized in that the 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-l-ol and/or 3- Butoxypropan-2-ol.
The composition according to the invention is preferably characterized in that the 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 poloxamer 184. The alcohol ethoxylate preferably comprises of a primary alcohol ethoxylate with a n of Cg - Cn.
The composition according to the invention is preferably characterized in that the 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 from 0.01 to 0.3 % parfum from 0.001 to 5.0 % 2-hydroxypropane-l,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 poloxamer 184. The alcohol ethoxylate preferably comprises of a primary alcohol ethoxylate with a n of Cg - Cn.
The composition according to the invention is preferably characterized in that the 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-l,2,3-tricarboxylic acid anhydrous,
0.1 % trisodium citrate di hydrate, 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 n of Cg - Cn.
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. 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 (Ig) 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. 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 (Ig) 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 (Ig) 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. 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 (Ig) 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 equal or less than 50, the mean of the cfus of the water control shall be equal or 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 (Ig) 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 Karber 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 (Ig) 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 (Ig) 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 (LoglO reduction in CFU per ml) gave the number of bacteria that were removed or and killed following wiping. LoglO 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.
The invention is further illustrated in the following non-limiting examples.
Example:
A composition according to table 1 was prepared by mixing the listed ingredients in water.
Table 1:
Table 2:
Table 3:
Table 4:
Table 5:
Table 6:
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 as described in the preceding.
The results are summarized in table 7.
Table 7:
Contact
MICROORGANISM EN TEST Strain_ time Log reduction
BACTERIA EN 13727 A. bau manii 10 sec >6.52 EN 13727 E. faeca lis 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 Klebsiel la pneumoniae ESBL 10 sec >6.74 EN 13737 Klebsiel la 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. au reus 10 sec >6.78 EN 13727 E. hirae 10 sec >6.85 EN 16615 P. aeruginosa 2 min >5.45 EN 16615 S. au reus 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 S. au reus 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 vu lgaris 1 min >5.33
En 1656 Staph au reus 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. au reus 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. al bicans 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
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. 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. 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

Claims
1. Composition comprising at least one quaternary ammonium compound, at least one alcohol ethoxylate and at least one preservative.
2. Composition according to claim 1, wherein the at least one alcohol ethoxylate comprises at least one primary alcohol ethoxylate.
3. Composition according to any of claim 1 or 2, wherein the at least one preservative comprises 2-phenylphenol.
4. Composition according to any of claim 1 or 3, wherein the at least one quaternary ammonium compound comprises benzalkonium chloride and/or didecyldimethylammonium chloride.
5. Composition according to any of claim 1 or 4, wherein the at least one quaternary ammonium compound is present in an amount of 0.2 to 1 % w/v.
6. Composition according to any of claim 1 or 5, wherein the at least one primary alcohol ethoxylate is present in an amount of 0.1 to 10 % w/v.
7. Composition according to any of claim 1 or 6, wherein the at least one preservative is present in an amount of 0.02 to 2 % w/v.
8. Composition according to any of claim 1 or 7, wherein the composition further comprises at least one polyoxypropylene-/polyoxyethylene block copolymer.
9. Composition according to any of claim 1 or 8, 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.
10. Composition according to any of claim 1 or 9, in the form of an aqueous or aqueous alcohol solution or dispersion.
11. Composition according to any of claim 1 or 10, wherein the 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.
12. A wet wipe comprising a substrate that has been impregnated with a composition according to any of claims 1 to 11.
13. The wet wipe according to claim 12, 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.
14. The wet wipe according to any of claims 12 or 13, wherein the substrate being packaged ready to be dispensed from a tub, a bucket, a flow-wrap pack or an individually sealed wrapper.
15. Use of a composition according to any of claims 1 to 11 or of a wet wipe according to any of claims 12 to 14 for disinfection of a surface.
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