WO2010043863A2

WO2010043863A2 - Anti-microbial composition

Info

Publication number: WO2010043863A2
Application number: PCT/GB2009/002461
Authority: WO
Inventors: Stephen Brian Falder; Thomas Trevor Francis; Andromachi Malandraki
Original assignee: Byotrol Plc
Priority date: 2008-10-15
Filing date: 2009-10-14
Publication date: 2010-04-22
Also published as: GB2464399A; GB0917918D0; GB0917980D0; WO2010043863A3; GB0818869D0

Abstract

Anti-microbial compositions comprising (i) an antimicrobial component; (ii) a non- ionic surfactant; and (iii) a polar solvent, wherein the antimicrobial component (i) comprises (I) (a) at least two quaternary ammonium compounds and optionally (b) one or more additional anti-microbial agents, or (II) at least one polymeric biguanide as the only antimicrobial agent and wherein the composition is substantially free of anionic surfactant. The anti-microbial compositions of the invention may provide a residual anti-microbial effect and/or an enhanced kill rate when they are applied to a surface and/or they are effective at significantly lower concentration of anti-microbial agent than previously known compositions.

Description

ANTl-MICROBIAL COMPOSITION

This invention relates to anti-microbial compositions and to formulations including the anti-microbial compositions.

Microorganisms are known to present health hazards due to infection or contamination. When microorganisms are present on the surface of a substrate they can replicate rapidly to form colonies. The microbial colonies form a coating on the substrate surface, which is known as a biofilm. Biofilms frequently consist of a number of different species of microorganisms which in turn can be more difficult to eradicate and thus more hazardous to health than individual microorganisms. Some microorganisms also produce polysaccharide coatings, which makes them more difficult to destroy.

Microorganisms attach themselves to substrates forming a biofilm comprising a "calyx" of polysaccharides and/or similar natural polymers as the affixing mechanism. Without this affixing point, the reproduction of the microorganism particularly bacteria cannot proceed, or is at least seriously impaired.

Biofilms form when microorganisms such as bacteria adhere to surfaces in aqueous environments and begin to excrete extra-cellular secretion, a slimy, glue-like substance that can anchor them to all kinds of materials such as metals, plastics, soil particles, medical implant materials and tissue. A biofilm can be formed by a single bacterial species but more often biofilms consist of several species of bacteria, as well as fungi, algae, protozoa, debris and corrosion products. Essentially, bacterial biofilms may form on any surface exposed to bacteria and some amount of water. Once anchored to a surface, biofilm microorganisms carry out a variety of detrimental or beneficial reactions (by human standards), depending on the surrounding environmental conditions.

Many anti-microbial agents that can destroy microorganisms which are present in a wide range of environments such as medical, industrial, commercial, domestic and marine environments are known. Many of the known anti-microbial agents have previously been included in compositions for use in various applications and environments. The known anti-microbial agents and the compositions that contain these antimicrobial agents destroy microorganisms by a number of different mechanisms.

For example, many anti-microbial agents are poisonous to microorganisms and, therefore, destroy microorganisms with which they are contacted. Examples of this type of anti-microbial agent include hypochlorites (bleaches), phenol and compounds thereof, and salts of copper, tin and arsenic. However, such agents typically can be highly toxic to humans and animals as well as to microorganisms. Consequently these anti-microbial agents are dangerous to handle, and specialist handling, treatment and equipment are therefore required in order to handle them safely. The manufacture and disposal of compositions comprising this type of anti-microbial agent can, therefore, be problematic. There can also be problems associated with the use of compositions containing this type of anti-microbial agent, particularly in consumer materials where it is difficult to ensure that they are used for designated purposes.

Herein, unless the context indicates otherwise, "toxicity" is intended to refer to toxicity to complex organisms such as mammals. References to "toxic" are to be construed accordingly.

Once the anti-microbial agents enter the environment they can affect the health of life forms that they were not intended to affect. Furthermore, the anti-microbial agents are often highly stable and can cause environmental problems for long periods of time.

Other known anti-microbial agents that are commonly used include organic and inorganic salts of heavy metals such as silver, copper or tin. These salts produce toxic rinsates, which can cause problems to the environment. For example, the rinsates of such salts are poisonous to aquatic life. Again, once the toxic compounds enter the environment they are not easily broken down and can cause persistent problems.

Other anti-microbial agents currently in use include antibiotic type compounds.

Antibiotics disrupt the biochemistry within microorganisms, for example by selectively inhibiting the growth of harmful microorganisms. Although antibiotics are effective, it is currently believed that they may selectively permit the development of resistant strains of the species that they are used against. These resistant strains are then able to reproduce unimpeded by the use of known antibiotics. Thus, there is a growing concern that wide and uncontrolled use of antibiotic materials in the wider environment, as opposed to their controlled use in medical contexts, could produce significant long-term risks.

Another method of microbial control is the use of oxidising agents in materials, such as household bleach, which can be based on hypochlorite or peroxides such as hydrogen peroxide. These materials are effective in a wet environment for sterilization and cleansing. However, the materials do not provide long-term passive anti-microbial control and sanitisation. By "passive control" we mean that the substrate counters microbial infection on its own by some property within it even in a dry environment, so that it does not require a cleaning regime to be effective at controlling microorganisms.

Another method involves the use of materials such as quaternary ammonium compounds that act as lytic (bursting) agents for the microbial cells. This method has the disadvantage of not being effective against all strains of microorganism so that resilient colonies can develop that have a high degree of "survivability" to disinfection with quaternary ammonium compounds so that they need to be alternated in use. Additionally, these materials are highly water soluble so easily wash away or can easily contaminate moist materials in contact with them.

The present invention provides anti-microbial compositions which address one or more of the foregoing deficiencies.

The anti-microbial compositions of the invention may provide a residual antimicrobial effect and/or an enhanced kill rate when they are applied to a surface and/or they are effective at significantly lower concentrations of anti-microbial agent than previously known compositions.

The composition of the invention comprises (i) an anti-microbial component; (ii) a non-ionic surfactant; and (iii) a polar solvent, wherein the anti-microbial component (i) comprises (I) a) at least two quaternary ammonium compounds and optionally (b) one or more additional anti-microbial agents, or (II) at least one polymeric biguanide as the only anti-microbial agent and wherein the composition is substantially free of anionic surfactant.

When the compositions of the invention comprise (II) at least one polymeric biguamide as the only anti-microbial agent they may contain one or more polymeric biguanides but may not contain any antimicrobial agents in addition to polymeric biguanides.

As used herein, by the term "substantially free of we mean that the composition need not be totally free of a specified ingredient but if that ingredient is present it must be present in an amount that does not affect the properties of the compositions or formulations of the invention.

While it is envisaged that compositions of the invention can contain additional ingredients as described below and other ingredients that are standard in the art, the compositions of the invention may consist of or consist essentially of the components listed in the paragraph above.

As will be appreciated, the percentage by weight of the components (i) and (ii) in the compositions of the invention will depend to a large extent on the form in which a composition is provided and the intended use of a composition. It is envisaged that the compositions will be made in a concentrated form and then diluted to a suitable concentration for the intended use. More particularly, it is envisaged that commercially available solutions will include concentrated solutions which can be diluted by the user before use and ready diluted solutions that are ready to use.

The important thing for compositions of the invention to provide the required antimicrobial effect is not typically the concentration of the components in the final solution, rather it is the ratio of the number of molecules of the components. This ratio will remain the same whether the composition is in a concentrated form or whether it is in a dilute (ready-to-use) form.

Typically, the ratio of the number of molecules of the component (ii) to the number of monomer units of component (i) ranges from about 100:1 to about

0.1 :1 or 1 :1 or to about 5:1 or to about 10:1 , preferably from about 90:1 to about 5:1 or from 40:1 to 0.1 :1 , more preferably from about 80:1 to about 5:1 , still more preferably from about 70:1 to about 25:1 or about 10:1 , most preferably from about 30:1 to about 60:1 , for example from about 10:1 to about 50:1.

In this ratio we have referred to the number of monomer units rather than the number of molecules because some of the compounds used as component (i) are polymeric. For polymeric compounds it is the ratio of active units, i.e. the ratio of monomer units to the number of molecules of component (ii) that is important. Polymeric biguanides such as PHMB are polymeric. For example Vantocil IB (a commercial PHMB) has the formula (C₈Hi₈N₅CI)_n wherein n =12 to 16. In this case, the number of active units is 12 to 16 times the number of molecules. The quaternary ammonium compounds used in this invention are typically monomeric. The number of monomer units of these quaternary ammonium compounds is the same as the number of molecules.

Typically, but not essentially, the compositions of the invention have a concentration of component (i) of from about 10 to about 10,000 ppm, such as from about 250 to about 1000 ppm or from about 60 to about 100 ppm and a concentration of component (ii) of from about 10 to about 10,000 ppm, such as from 250 to about 1000 ppm or from about 60 to about 100 ppm (based on the number of molecules). Without wishing to be bound by theory it is believed that for many combinations of non-ionic surfactant and anti-microbial component these minimum concentrations are required to obtain the necessary dispersion properties in the compositions. However, it will be appreciated that for some applications lower concentrations of components (i) and (ii) may be suitable.

By the term "anti-microbial" we mean that a compound or composition that kills and/or inhibits the growth of microbes (microorganisms). The term "microbiocidal" is used to refer to compounds or compositions that kill microbes. The compositions of the invention are anti-microbial and/or microbiocidal.

A microorganism or microbe is an organism that is microscopic (too small to be seen by the human eye). Examples of microorganisms include bacteria, fungi, yeasts, moulds, mycobacteria, algae spores, archaea and protists. Microorganisms are generally single-celled, or unicellular organisms. However, as used herein, the term "microorganisms" also includes viruses. Preferably, the compositions of the invention comprise at least one anti-microbial agent selected from anti-bacterial, anti-fungal, anti-algal, anti-sporal, anti-viral, anti-yeastal and anti-moldal agents and mixtures thereof. More preferably, the compositions of the invention comprise at least one anti-bacterial, anti-viral, antifungal and/or anti-moldal agent.

As used herein, the terms anti-bacterial, anti-fungal, anti-algal, anti-viral, anti- yeastal and anti-moldal agents are intended to refer to agents, which inhibit the growth of the respective microorganisms but do not necessarily kill the microorganisms and agents which kill the respective microorganisms. Thus, for example, within the term anti-bacterial we include agents, which inhibit the growth of bacteria but may not necessarily kill bacteria and bactericidal agents which do kill bacteria.

As the skilled person will appreciate, the word ending "cidal" as used in for example "bactericidal" and "fungicidal" is used to describe agents which kill the microorganism to which it refers. Thus, in these examples, bactericidal refers to an agent that kills bacteria and fungicidal refers to an agent that kills fungus. Examples of bactericides include myobactericides and tuberculocides. Preferably, the compositions of the invention comprise at least one agent selected from bactericidal, fungicidal, algicidal, sporicidal, virucidal, yeasticidal and moldicidal agents and mixtures thereof. More preferably, the compositions of the invention comprise at least one bactericidal, virucidal, fungicidal and/or moldicidal agent.

The compositions of the invention are effective against a wide range of organisms, including Gram negative and Gram positive spore formers, yeasts, and viruses.

By way of example, the microorganisms which the compositions of the present invention can be effective against include:

Viruses such as HIV-1 (AIDS Virus), Hepatitis B Virus (HVB), Hepatitis C Virus (HCV), Adenovirus, Herpes Simplex, Influenza (including seasonal flu, H1 N1 and

H5N1), Respiratory Syncytial Virus (RSV), Vaccinia, Avian Influenza virus, Avian Bronchitis, Pseudorabies virus, Canine Distemper, Newcastle Disease, Rubella, Avian Polyomavirus, Feline leukemia, Feline picornavirus, Infectious Bovine rhinotracheitis, Infectious Bronchitis (Avian IBV)₁. Rabies, Transmissible gastroenteritis virus, Marek's Disease.

Funguses such as Trichophyton mentagrophytes, Aspergillus niger, Candida albicans, Aspergillus flavus, Aspergillus fumigatus, Trichophyton interdigitale, Alternaria tenius, Fusarium oxysporum, Geotrichum candidum, Penicillium digitatum, Phytophthora infestans, Rhizopus nigricans, Trichoderma harzianum, Trichophyton interdigitale.

Bacteria such as Pseudomonas aeruginosa, Staphylococcus aureus, Salmonella choleraesuis, Acinetobacter baumannii, Brevibacterium ammoniagenes, Campylobacter jejuni, Enterobacter aerogenes, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas cepacia, Salmonella schottmuelleri, Salmonella typhi, Salmonella typhimurium, Serratia marcescens, Shigella dysenteriae, Shigella flexneri, Shigella sonnei, Staphyloccus epidermidis, Streptoccus faecalis, Streptoccus faecalis (Vancomycin resistant), Streptococcus pyogenes, Vibrio chlorae, Xanthomonas axonopodis pv citri (Citrus canker), Acinetobacter calcoaceticus, Bordetella bronchiseptica, Chlamydia psittaci, Enterobacter cloacae, Enterococcus faecalis, Fusobacterium necrophorum, Legionella pneumophila, Listeria monocytogenes, Pasteurella multocida, Proteus vulgaris, Salmonella enteritidis, Mycoplasma gallisepticum, Yersinia enterocolitica, Aeromonas salmonicida, Pseudomonas putida, Vibrio anguillarum.

In particular, the compositions of the invention are effective against P. aeruginosa (ATCC 15442, PaFH72/a), E.coli (ATCC 10536, ECFH64/a, 0157:H7 (toxin producing strain), CCFRA/896, 0157:H7 (non-toxigenic strain), CCFAA/6896, ATCC 10538), S. aureus (including MRSA, (e.g. NCTC 12493 MRSA, ATCC 12493 MRSA), VISA, ATCC 6538, 5a FH73/a), Entercoccus hirea (ATCC 10541 , EhFH 65/a), Feline Coronavirus (SARS surrogate), Feline Calcivirus (Hum. Norovirus surrogate), Salmonella typhimurium (StFH 68/b), Yersinia enterocolitica (YE FH67/b), Listeria monocytogenes (Lm FH66/c), Saccharomyces cerevisiae, Bacillus Subtilis (ATCC 6633), Bacillus stearothermophilus (NCTC 10339), Clostridium dificile (NCTC 11209), Candida albicans (ATCC 1023), Aspergillus niger (ATCC 16404), Mycobacterium smegmatis (TB stimulant) and Influenza (including seasonal flu, H1 N1 and H5N1).

In one aspect, the compositions of the invention must contain at least two quaternary ammonium anti-microbial agents. They may additionally comprise any other suitable anti-microbial agent(s), such as those described in the EPA (United States Environmental Protection Agency) Listing and Annex I of the EC Biocides Directive.

Suitable anti-microbial agents (b) include polymeric biguanidines, amphoteric compounds, iodophores, phenolic compounds, hypochlorites and nitrogen based heterocyclic compounds.

The anti-microbial agent(s) used in the present invention are preferably water soluble at room temperature and pressure.

Preferred anti-microbial agents include anti-microbial agents with surfactant properties and polymeric biguanidines (e.g. polyhexamethylene biguanidine (PHMB)), isothiazalones, ortho phenyl phenol (OPP), and nitro bromopropanes (e.g. broηopol (INN), 2-bromo-2-nitropropane-1 ,3-diol) and polymerised quaternary ammonium compounds.

A particularly preferred anti-microbial agent for use in the present invention is polyhexamethylene biguanidine (PHMB). PHMB is commercially available from Arch Biocides as Vantocil IB.

A preferred combination of anti-microbial agents is the combination of at least one polymeric biguanidine such as PHMB with two or more quaternary ammonium compounds.

In another aspect, the compositions of the invention comprise at least one polymeric biguanide as the only anti-microbial component. Compositions comprising PHMB as the only antimicrobial agent are preferred.

The quaternary ammonium compounds used in the present invention are examples of "anti-microbial agent with surfactant properties". By the term "antimicrobial agent with surfactant properties" we mean a material which can kill or inhibit the growth of microbes (microorganisms) and also has the effect of altering the interfacial tension of water and other liquids or solids and/or reduces the surface tension of a solvent in which it is used. More particularly, the antimicrobial agents with surfactant properties used in the present invention can kill or inhibit the growth of microbes and typically when introduced into water lower the surface tension of water.

A class of compounds that is particularly suitable for use as the anti-microbial agent with surfactant properties in the present invention is the class of compounds known as quaternary ammonium compounds, also know as "quats". These compounds typically comprise at least one quaternary ammonium cation with an appropriate anion. The quaternary ammonium cations are permanently charged, independent of the pH of their solution.

The structure of the cation can be represented as follows:

The groups R₁, R₂, R₃ and R₄ can vary within wide limits and examples of quaternary ammonium compounds that have anti-microbial properties will be well known to the person of ordinary skill in the art.

Each group R₁, R₂, R₃ and R₄ may, for example, independently be a substituted or unsubstituted and/or straight chain or branched and/or interrupted or uninterrupted alkyl, aryl, alkylaryl, arylalkyl, cycloalkyl, (aromatic or non-aromatic) heterocyclyl or alkenyl group. Alternatively, two or more of R₁, R₂, R₃ and R₄ may together with the nitrogen atom form a substituted or unsubstituted heterocyclic ring. The total number of carbon atoms in the groups R₁, R₂, R₃ and R₄ must be at least 4. Typically the sum of the carbon atoms in the groups R₁, R₂, R₃ and R₄ is 10 or more. In a preferred aspect of the invention at least one of the groups R₁, R₂, R₃ and R₄ contains from 8 to 18 carbon atoms. For example, 1 , 2, 3 or 4 of R₁, R₂, R₃ and R₄ can contain from 8 to 18 carbon atoms or 10 to 16 carbon atoms.

Suitable substituents for the groups R-i, R₂, R₃ and R₄ may be selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, heterocyclyl, substituted heterocyclyl, cycloalkyl, substituted cycloalkyi, aryl, substituted aryl, alkylaryl, substituted alkylaryl, arylalkyl, substituted arylalkyl, F, Cl, Br, I, -OR¹, -NR¹R", -CF₃, -CN, -NO₂, -C₂R¹, -SR', -N₃, -C(=O)NR'R", -NR¹C(O) R", -C(=O)R\ -C(=O)OR\ -OC(O)R¹, -O(CR'R^π)_rC(=O)R',

0(CR'R")_rNR"C(0)R', -O(CR'R")_rNR"SO₂R', -OC(O)NR¹R", -NR¹C(O)OR", - SO₂R', -SO₂NR¹R", and -NR¹SO₂R", wherein R¹ and R" are individually hydrogen, C₁-C₈ alkyl, cycloalkyl, heterocyclyi, aryl, or arylalkyl, and r is an integer from 1 to 6, or R' and R" together form a cyclic functionality, wherein the term "substituted" as applied to alkyl, alkenyl, heterocyclyl, cycloalkyl, aryl, alkylaryl and arylalkyl refers to the substituents described above, starting with F and ending with -NR¹SO₂R".

When one or more of R-i, R₂, R₃ and R₄ is interrupted, suitable interrupting groups include but are not limited to heteroatoms such as oxygen, nitrogen, sulphur, and phosphorus-containing moieties (e.g. phosphinate). A preferred interrupting group is oxygen.

Suitable anions for the quats include but are not limited to halide anions such as chloride, fluoride, bromide or iodide and the non halide sulphonate.

Preferred quats are those having the formula: (CH₃)_n(A)_mN⁺X- wherein A may be as defined above in relation to R₁, R₂, R₃ and R₄. X^" is selected from chloride, fluoride, bromide or iodide and sulphonate (preferably chloride or bromide), n is from 1 to 3 (preferably 2 or 3) and m is from 1 to 3 (preferably 1 or 2) provided that the sum of n and m is 4. Preferably, A is a C_6-20 (e.g. C_8-18, i.e. having 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17 or 18 carbon atoms or C_8--_I2 or C_12-18) substituted or unsubstituted and/or straight chain or branched and/or interrupted or uninterrupted alkyl, aryl, alkylaryl, arylalkyl or cycloalkyl group (wherein suitable substituents are as defined above in relation to R₁, R₂, R₃ and R₄). Each group A may be the same or different.

A preferred group of the compounds of formula (CH₃)_n(A)_mN⁺X^' are those wherein n = 3 and m = 1. In such compounds A may be as defined above and is preferably a C_6-2o substituted or unsubstituted and/or straight chain or branched and/or interrupted or uninterrupted alkyl, aryl, or alkylaryl group. Examples of this type of quaternary ammonium compound include Cetrimide (which is predominately trimethyltetradecylammonium bromide), dodecyltrimethylammonium bromide, trimethyltetradecylammonium bromide, hexadecyltrimethylammonium bromide.

Another preferred group of the compounds of formula (CH₃)_n(A)_mN⁺X^' are those wherein n = 2 and m = 2. In such compounds A may be as defined above in relation to R₁, R₂, R₃ and R₄. Preferably A is a C_6-2o substituted or unsubstituted and/or straight chain or branched and/or interrupted or uninterrupted alkyl, aryl, or alkylaryl group. For example, A may represent a straight chain, unsubstituted and uninterrupted C_8--_I2 alkyl group or a benzyl group. In these compounds, the groups A may be the same or different. Examples of this type of compound include didecyl dimethyl ammonium chloride and dioctyl dimethyl ammonium chloride.

Examples of the preferred quaternary ammonium compounds described above include the group of compounds which are generally called benzalkonium halides and aryl ring substituted derivatives thereof. Examples of compounds of this type include benzalkonium chloride, which has the structural formula:

wherein R may be as defined above in relation to R_t, R₂, R₃ and R₄. Preferably, R is a C_8-18 alkyl group or the benzalkonium chloride is provided and/or used as a mixture of C_8-is alkyl groups, particularly a mixture of straight chain, unsusbtituted and uninterrupted alkyl groups n-C₈H₁₇ to n-C₁₈H₃7, e.g. n-Ci₂H₂5 to n C₁₈H₃₇ mainly n-C₁₂H₂s (dodecyl), n-C₁₄H₂₉ (tetradecyl), and n-C₁₆H₃₃ (hexadecyl).

Other preferred quaternary ammonium compounds include those in which the benezene ring is substituted, for example alkyldimethyl ethylbenzyl ammonium chloride. As an example, a mixture containing, for example, equal molar amounts of alkyl dimethyl benzyl ammonium chloride and alkyldimethyl ethylbenzyl ammonium chloride may be used. Mixtures of, for example, one or more alkyl dimethyl benzyl ammonium chlorides and one or more compounds of formula (CH₃MA)₂N⁺X^', such as didecyl dimethyl ammonium chloride may be used.

Typically, mixtures of quaternary ammonium compounds are used. In these mixtures, the quaternary ammonium compounds may be mixed with any suitable inert ingredients. Commercially available benzalkonium chloride often contains a mixture of compounds with different alkyl chain lengths. Examples of commercially available benzalkonium chlorides are shown in the following Table.

It will be appreciated that a single CAS number often refers to more than one blend or mixture. A CAS classification for commercial preparation typically covers blends comprising specified compounds in amounts within defined ranges. The compositions which have the CAS numbers quoted above are only examples of compositions having a given CAS number that may be used in the present invention.

Suitable quaternary ammonium compounds in which R¹, R², R³, R⁴ are interrupted by a heteroatom include domiphen bromide ((Dodecyldimethyl-2- phenoxyethyl)ammonium bromide) and benzethonium chloride (benzyidimethyl[2- [2-[4-(1 ,1 ,3,3-tetramethylbutyl)phenoxyJethoxy]ethyl] ammonium chloride).

Other quaternary ammonium compounds suitable for use in the invention include, but are not limited to, alkylpyridinium compounds, such as cetylpyridinium chloride, and bridged cyclic amino compounds such as the hexaminium compounds.

Other examples of quats which may be used in the present invention include Cetalkonium Chloride, Cetylpyridinium Chloride, Glycidyl Trimethyl Ammonium Chloride, Stearalkonium Chloride; Zephiran chloride (R); Hyamine 3500; Diisobutylphenoxyethoxyethyldimethylbenzylammonium chloride; Hyamine 1622(R); Cetalkonium Chloride; Cetyldimethylbenzyl-ammonium chloride; Triton K 12; Cetyltrimethylammonium bromide; Retarder LA; 1-Hexadecylpyridinium chloride; Glycidyltrimethyl-ammonium chloride; Benzethonium Chloride CAS 121- 54-0; Cetalkonium Chloride CAS 122-18-9; Cetrimide CAS 8044-71-1 ; Cetylpyridinium Chloride (anhydrous) CAS 123-03-5; Stearalkonium Chloride CAS 122-19-0; Cetrimonium Bromide CAS 57-09-0.

Particularly preferred quaternary ammonium compounds include benzyldimethyl- n-tetradecyl-ammonium chloride, benzyldimethyl-n-dodecyl-ammonium chloride, n-dodecyl-n-tetradecyldimethyl-ammonium chloride and benzyl-Ci₂-C₁₆-alkyl- dimethyl-ammonium chloride, benzyl-cocoalkyl-dimethyl-ammonium chloride, di- n-decyldimethylammonium chloride.

An example of a suitable mixture is a composition comprising octyl decyldimethyl ammonium chloride, didecyl dimethyl ammonium chloride, dioctyl dimethyl ammonium chloride, and alkyl (C₁₄, 50%; C₁₂, 40%, C₁₆, 10%) dimethyl benzyl ammonium chloride (in a ratio of about 2:1 :1:2.67). Another suitable mixture is a mixture of octyldecyl dimethyl ammonium chloride, didecyl dimethyl ammonium chloride, dioctyl dimethyl ammonium chloride, and alkyl (Ci₄, 50%, C₁₂, 40%, C₁₆, 10%) dimethyl benzyl chloride (in a ratio of about 2:1 :1 :2.67).

Another suitable mixture is octyldecyl dimethyl ammonium chloride, dioctyl dimethyl ammonium chloride, didecyl dimethyl ammonium chloride, and alkyl (C₁₄, 50%; C₁₂, 40%; C₁₆, 10%) dimethyl benzyl ammonium chloride (in a ratio of about 2:1 :1 :2.67).

Examples of other commercially available quaternary ammonium compounds include BAC 50 (from Thor biocides), and Nobac (Benzalkonium chloride, from Mason Quats).

The quaternary ammonium compounds may be used in combination with other anti-microbial agents with surfactant properties. Other suitable anti-microbial agents with surfactant properties include anionic and cationic surfactant materials as well as amphoteric materials. Examples include quaternary bisammonium surfactants, alkyl betaines, sulfobetaines, alkyl amine oxides, arginine-based cationic surfactants, anionic amino acid based surfactants and mixtures thereof, for example a mixture of alkyl betaine(s) or sulfobetaine(s) and alkyl amine oxides.

An example of a Betaine which is suitable for use in the present invention is Macat^® Ultra (available from Mason Chemical Company). Macat^® Ultra CG comprises 30% coco (Ci₂) amidopropyl dimethyl glycine (betaine) in water.

An example of an alkyl amine oxide which is suitable for use in the present invention is Macat^® Ultra CDO (available from Mason Chemical Company), a 30% solution of coco (C₁₂) amidopropyl dimethyl amine oxide in water.

One or more of any of the anti-microbial agents with surfactant properties described above can be used in the compositions of the invention.

In one aspect, the compositions of the invention comprise another anti-microbial agent (b) in addition to the component (a). The ratio of molecules of component (a) to molecules of another anti-microbial agent (b), is preferably from about 1 :2 or about 1:1 to about 50:1 , preferably about 2:1 to about 30:1 , more preferably from about 4:1 to about 20:1 , most preferably from about 8:1 to about 15:1 , for example about 10:1.

The amount of component (a) will vary depending on a number of factors, such as the intended use of the composition and the particular compound(s) used as component (a).

Typically, the compositions of the invention do not comprise 1 ,3-bis-(β- ethylhexyl)-5-aminohexahydropyrimidine (hexetidine). In particular, it is preferred not to use hexetidine in combination with PHMB.

Suitable non-ionic surfactants for use as component (ii) include but are not limited to ethylene oxide/propylene oxide block polymers, fatty esters and amides, alkylpolyglycosides and polyalkoxylated derivatives of general structure R(OCHXCH₂)_nOH, where R is derived from an alcohol, phenol, carboxylic acid, ester, amine or amide, X is independently H or CH₃ and n is from 1 to 50, preferably from 2 to 20. Examples of these include; polyethoxylated sorbitan esters, fatty esters of sorbitan, ethoxylated fatty esters (containing from 1 to 25 units of ethylene oxide), polyethoxylated C₈-C₂₂ alcohols (containing from 1 to 25 units of ethylene oxide), polyethyoxylated C₆-C₂₂ alkylphenols (containing from 5 to 25 units of ethylene oxide). Further polyalkoxylated derivatives include but are not limited to nonyl phenol ethoxylate (9EO), Nonyl phenol ethoxylate (2EO), octyl phenol ethoxylate (10EO), C₁₂/C₁₄ synthetic ethoxylate (8EO), stearyl alcohol ethoxylate (7EO), cetostearyl alcohol ethoxylate (20EO), coconut fatty amine ethoxylate (10EO), sorbitan monolaurate ethoxylate, 80%PO/20%EO and sorbitan monolaurate 4EO. Polypropoxylated compounds can also be used, as can the combination of polyethoxylated compounds and polypropoxylated compounds. Examples of fatty esters and amides include, but are not limited to coconut diethanolamide (shampoo foam booster), sorbitan monolaurate, di- isopropyl adipate and cetostearyl stearate. Alkyl poly glycosides (APGs), of typical structure R-O(SaC)_n where R is an alkyl group and Sac is a saccharide derivative. Examples of APGs include, but are not limited to, alkylpolyglucosides with n = 1 to 10 such as C_6-20, preferably C_8--_I0 alkyl glucosides, eg Surfac APG (D-Glucopyranose oligomers C₈-i₀ alkyl glucosides, CAS 161074-97-1 , available from Seppic, UK). Other commercial examples of suitable non-ionic surfactants include Neodol 25-7 (C12/15 alcohol 7 ethoxylate (EO), CAS 68131-39-5), Surfac LM90/85 (C12/15 alcohol 9 ethoxylate (EO), CAS 68131-39-5), Surfac 65/95 (C9/11 alcohol 6.5 ethoxylate (EO)₁ CAS 68439-45-2), Tomadol PF9 (C9/11 alcohol 6.0 ethoxylate (EO), CAS 68439-46-3), Surfac T80 Veg (Polysorbate 80, Polyoxyethylene sorbate mono oleate, CAS 9005-65-6), Tween 60 (Polysorbate 60, Polyoxyethylene sorbate mono stearate, CAS 9005-67-8), Tween 40 (Polysorbate 40, Polyoxyethylene sorbate mono palmitate, CAS 9005-66-7), Surfac T-20 (Polysorbate 20, Polyoxyethylene sorbate mono laurate, CAS 9005- 64-5), Surfac PGHC (Hydrogenated Castor oil 40EO, CAS 61788-85-0), Ninol 49- CE (Coconut diethanolamide, CAS 68603-42-9).

A preferred class of non-ionic surfactants for use in the present invention is alcohol ethoxylates, particularly alcohol ethoxylates having from 2 to 15 ethoxylated units. Examples of suitable alcohol ethoxylates include linear alcohol ethoxylates such as those sold under the Tomadol and Neodol trade names.

The compositions of the invention may contain more than one surfactant. For example, they may contain more than one non-ionic surfactant, eg 2, 3 or 4 non- ionic surfactants. Alternatively, in addition to the non-ionic surfactant the compositions may comprise one or more anionic, cationic and/or amphoteric surfactants or mixtures thereof. In a particular aspect of the invention the formulation comprises at least one non-ionic and at least one amphoteric surfactant.

Preferably, the compositions of the invention are substantially free of or do not comprise an anionic surfactant. In another aspect, the compositions of the invention do not comprise an amphoteric surfactant.

The compositions of the invention may optionally contain a hydrophobic material. Compounds suitable for use as the hydrophobic material include silanes, siloxanes, silicones, polysiloxanes, fluorine-containing aliphatic compounds and mixtures thereof. These hydrophobic materials can be used in combination with other materials such as polyalkylene glycols. In should be noted that in a particular aspect of the invention the compositions and formulations of the invention do not comprise a hydrophobic material, for example they do not comprise one or more of siloxanes, silicones, polysiloxanes (such as polydimethylsiloxanes), fluorine-containing aliphatic compounds and mixtures thereof.

If the compositions of the invention do comprise one or more hydrophobic materials, the hydrophobic material is typically chemically inert. The hydrophobic material is typically capable of associating with other components of the fluid by non-covalent bonds.

As used herein, the term "fluorine-containing aliphatic compounds" refers to C₈ to C₂₀ linear or branched alkanes or alkenes which contain at least 0.1 fluorine atoms per carbon atom and as a maximum are fully fluorinated. Typically, the fluorine-containing aliphatic compound will contain an average of from 1 to 2 fluorine atoms per carbon atom.

The hydrophobic material may for example comprise at least one polysiloxane, preferably at least one polydimethylsiloxane. For example, a mixture of two or more polysiloxanes having different molecular weights and/or viscosities may be used. When a mixture of polysiloxanes is used, the mixture preferably comprises at least one polysiloxane containing up to about 500, more preferably 50 to 200 (e.g. about 100) monomer units and at least one polysiloxane containing more than 500, more preferably 750 to 1000 monomer units. These polysiloxanes typically have a viscosity of from 35 to 750 centistokes, preferably 35 to 400 centistokes, more preferably 35 to 150 centistokes, for example about 100 centistokes.

These polysiloxanes typically have a surface tension of less than 20 mN/m at 20 ⁰C, for example from 5 to 19 mN/m, more preferably from 7 to 14 mN/m and most preferably from 8 to 12 mN/m at 20 ⁰C (eg about 10 mN/m at 20 ⁰C).

Other hydrophobic materials that may be included in the compositions of the present invention include shorter chain siloxanes selected from these having the formulae (H₃C)[Si0(CH3)2]nSi(CH₃)3, and (H₃C)[SiO(CH₃)H]_nSi(CH₃)S where n is an integer, of from 1 to 24, more preferably from 1 to 12 and most preferably from 1 to 8, for example n may be 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12, especially 1 , 2, 3 or 4. These materials are often referred to as (poly)dimethylsiloxanes (CAS # 9016-00-6) and (poly)methylhydrosiloxanes respectively. These materials are linear siloxanes. Cyclic siloxanes are typically not used in this invention. These materials are typically liquid at ambient temperature and pressure (e.g. about 20⁰C at atmospheric pressure).

Preferred siloxanes suitable for use in the compositions of the present invention typically have a molecular weight of from about 100 to about 2000 g/mol, preferably from about 148 to about 1864 (such as from about 162 to about 1864 or about 148 to about 1528), more preferably from about 148 to about 1000 or about 976 (e.g. from about 162 to about 976 or about 148 to about 808), such as from about 148 to about 680 (e.g. from about 162 to about 680 or about 148 to about 568), particularly from about 148 to about 384 (e.g. from about 162 to about 384 or about 148 to about 328).

Examples of preferred (poly)dimethylsiloxanes are hexamethyldisiloxane (CAS # 107-46-0), octamethyltrisiloxane (CAS # 107-51-7), decamethyltetrasiloxane (CAS # 141-62-8), dodecamethylpentasiloxane (CAS # 141-63-9). These (poly)dimethylsiloxanes correspond to the compounds of formula (H₃C)[Si0(CH₃)2]nSi(CH3)3, wherein n = 1 , 2, 3 and 4 respectively.

These materials are generally also strongly hydrophobic. By this we include the meaning that it is repelled from a mass of water and by itself is substantially insoluble in water. By the term "substantially insoluble in water", we mean that the material typically has a solubility of less than 2g/100g water at 2O⁰C and atmospheric pressure, such as less than 1g/100g water, preferably, less than 0.5g/100g water, for example less than 0.1g/100g water, e.g. less than 0.01 g/10Og water.

The siloxanes which may be used in the compositions of the invention typically have a viscosity of from about 0.1 to about 100 centistokes at atmospheric pressure and at about 20 ⁰C, preferably from about 0.2 to about 20 centistokes. Preferred siloxanes have a viscosity of from about 0.5 to about 5 centistokes, e.g. 0.65, 1 , 1.5, 2, 3, 4, 5, 6, 7, 8, 9, or 10 centistokes or from 3 to 5 centistokes. The siloxanes preferably used in the present invention, due to their relatively low molecular weight, are relatively volatile. For example, they typically have a boiling point of less than about 120⁰C at atmospheric pressure, for example from about 100 to 120°C. Hexamethydisiloxane, for example, has a boiling point of about 101⁰C at atmospheric pressure.

The siloxanes described above may be used alone or in combination. Many commercially available siloxanes are provided as mixtures and these can be used in the present invention without the need to separate the components of the mixture. Details of commercially available siloxanes which are suitable for use in the compositions of the invention are set out, for example, at http://www.clearcoproducts.com/standard pure silicones.html.

For example a mixture of two, three, four, five or more siloxanes may be used. If a combination of siloxanes is used the materials may be used in equal or differing amounts. For example each siloxane may be used in equimolar amounts or the amount by weight of each siloxane may be the same. Other suitable ratios (in terms of molar amounts or by weight of the total amount of siloxanes) when a mixture of two siloxanes are used range from 0.1 :99.9 to 99.9:0.1 , preferably from 1 :99 to 99:1 , more preferably from 95:5 to 5:95, for example from 10:90 to 90:10 or from 25:75 to 75:25. For example, if a combination of hexamethyldisiloxane and octamethyltrisiloxane is used any ratio described above may be used. One particular combination comprises hexamethyldisiloxane: octamethyltrisiloxane in a ratio of 95:5.

It is a preferred aspect of the invention to use a mixture of two or more siloxanes. The use of the combination of hexamethyldisiloxane and octamethyltrisiloxane is particularly preferred.

If the composition comprises three silicone materials, the total siloxanes typically comprises from 0.1 to 99.8 % by weight of the total amount of siloxanes of each of the first, second, and third silicone material, preferably from 1 to 98 % weight of the total amount of siloxanes of each of the first, second, and third siloxanes, more preferably from 5 to 90 % weight of the total amount of siloxanes of each of the first, second, and third siloxanes, for example from 10 to 80 % weight of the total amount of silicone material of each of the first, second, and third siloxanes, such as from 25 to 50 % weight of the total amount of siloxanes of each of the first, second, and third siloxanes.

If the composition comprises four siloxanes, the total siloxanes typically comprises from 0.1 to 99.7% by weight of the total amount of siloxanes of each of the first, second, third and fourth siloxanes, preferably from 1 to 97% by weight of the total amount of siloxanes of each of the first, second, third and fourth siloxanes, more preferably from 5 to 85 % by weight of the total amount of siloxanes of each of the first, second, third and fourth siloxanes, for example from 10 to 70 % by weight of the total amount of siloxanes of each of the first, second, third and fourth siloxanes, such as from 20 to 40% by weight of the total amount of siloxanes of each of the first, second, third and fourth siloxanes.

If the composition comprises five siloxanes, the total siloxanes typically comprises from 0.1 to 99.6% by weight of the total amount of siloxanes of each of the first, second, third, fourth and fifth siloxanes, preferably from 1 to 96% by weight of the total amount of siloxanes of each of the first, second, third, fourth and fifth siloxanes, more preferably from 5 to 80 % by weight of the total amount of siloxanes of each of the first, second, third, fourth and fifth siloxanes, for example from 10 to 60% by weight of the total amount of siloxanes of each of the first, second, third, fourth and fifth siloxanes, such as 15 to 40% by weight of the total amount of siloxanes of each of the first, second, third, fourth and fifth siloxanes.

The compositions of the invention comprise a polar solvent, component (iii). Suitable polar solvents include, but are not limited to, water, alcohols, esters, hydroxy and glycol esters, polyols and ketones, and mixtures thereof.

Suitable alcohols include, but are not limited to, straight or branched chain C₁ to C₅ alcohols, such as methanol, ethanol, n-propanol, iso-propanol, mixtures of propanol isomers, n-butanol, sec-butanol, tert-butanol, iso-butanol, mixtures of butanol isomers, 2-methyl-1-butanol, n-pentanol, mixtures of pentanol isomers and amyl alcohol (mixture of isomers), and mixtures thereof.

Suitable esters include, but are not limited to, methyl acetate, ethyl acetate, n- propyl acetate, iso-propyl acetate, n-butyl acetate, iso-butyl acetate, sec-butyl acetate, amyl acetate (mixture of isomers), methylamyl acetate, 2-ethylhexyl acetate and iso-butyl isobutyrate, and mixtures thereof.

Suitable hydroxy and glycol esters include, but are not limited to, methyl glycol acetate, ethyl glycol acetate, butyl glycol acetate, ethyl diglycol acetate, butyl diglycol acetate, ethyl lactate, n-butyl lactate, 3-methoxy-n-butyl acetate, ethylene glycol diacetate, polysolvan O, 2-methylpropanoic acid-2,2,4-trimethyl-3- hydroxypentyl ester, methyl glycol, ethyl glycol, iso-propyl glycol, 3- methoxybutanol, butyl glycol, iso-butyl glycol, methyl diglycol, ethyl diglycol, butyl diglycol, iso-butyl diglycol, diethylene glycol, dipropylene glycol, ethylene glycol monohexyl ether and diethylene glycol monohexyl ether, and mixtures thereof.

Suitable polyols include, but are not limited to, ethylene glycol, propylene glycol, 1 ,3-butylene glycol, 1 ,4-butylene glycol, hexylene glycol, diethylene glycol, triethylene glycol and dipropylene glycol, and mixtures thereof.

Suitable ketones include, but are not limited to iso-butyl heptyl ketone, cyclohexanone, methyl cyclohexanone, methyl iso-butenyl ketone, pent-oxone, acetyl acetone, diacetone alcohol, iso-phorone, methyl butyl ketone, ethyl propyl ketone, methyl iso-butyl ketone, methyl amyl ketone, methyl iso-amyl ketone, ethyl butyl ketone, ethyl amyl ketone, methyl hexyl ketone, diisopropyl ketone, diisobutyl ketone, acetone, methyl ethyl ketone, methyl propyl ketone and diethyl ketone, and mixtures thereof.

Typically, although not essentially, the compositions of the invention do not comprise an ether. In a particular aspect, the compositions of the invention do not comprise dipropylene glycol methyl ether.

Preferred polar solvents for use in the compositions of the invention include, but are not limited to, water, ethanol, n-propanol, isopropanol, diethylene glycol and dipropylene glycol and mixtures thereof. However, in one aspect, the compositions of the invention are substantially free of alcohol. By substantially free we mean that the compositions comprise less than 1% by weight alcohol.

For example, the compositions may contain less than 1 % or less than 0.5% by weight of an alcohol such as isopropanol. As an example, compositions of the invention may comprise no isopropanol. The composition may comprises water or a mixture of water and one or more alcohols selected from the alcohols described above. In such mixtures, water is preferably the major component.

It is believed that in the compositions of the invention the majority (greater than 50%) of the component (i) and the component (ii) are present in colloids containing both of these components.

A colloid or colloidal dispersion is a heterogeneous mixture that visually appears to be a homogeneous solution. Some colloids are translucent because of the Tyndall effect, which is the scattering of light by particles in the colloid. Other colloids may be opaque or have a slight color. The colloids in the compositions of the present invention are typically not opaque.

In a colloid, the dispersed phase is made of tiny particles or droplets that are distributed evenly throughout the continuous phase. The size of the dispersed phase particles or droplets is typically between one nanometer and one micrometer. Heterogeneous mixtures with a dispersed phase in this size range may be called colloidal sols, colloidal emulsions, colloidal foams, colloidal suspensions or colloidal dispersions.

We use the term colloid herein to encompass various colloidal structures including but not limited to vesicles and micelles, which may for example be spherical or cylindrical.

The dispersed phase particles or droplets are largely affected by the surface chemistry present in the colloid. For example, colloidal particles often carry an electrical charge and therefore attract or repel each other. The charge of both the continuous and the dispersed phase, as well as the mobility of the phases are factors affecting this interaction.

The skilled person in the field of colloids would readily be able to select suitable materials for use as components (i) and (ii) based on the information provided in this specification on such materials, the anti-microbial agent with surfactant properties and polar solvent with which such a material forms the colloidal dispersion, and their knowledge of colloids (see, for example, http://en.wikipedia.org/wiki/Colloid).

It has been found that in use compositions of the invention which comprise at least components (i) and (ii) in for example the ratios set out above have an advantageous anti-microbial effect. For example, such compositions can have an enhanced kill rate when they are applied to a surface (so called "wet kill") and/or they can also have a residual anti-microbial effect in that they control, reduce or prevent the formation of new microbial colonies at the surface (so called "dry kill") and/or they are effective at significantly lower concentration of anti-microbial agent than previously known compositions.

The compositions of the invention are also resistant to washing with water and to wiping. This means that the compositions of the invention provide a residual anti- microbial effect even when the surface which has been treated is subsequently wiped and/or washed or rinsed with water.

Typically, component (i) is present in the compositions of the invention in an amount of from about 0.001 to about 50 % by weight of the compositions, such as from about 0.01 or about 0.02 to about 40 %, for example from about 0.05 to about 30 %, preferably from about 0.1 to about 20 % (e.g. from 0.2 to 15 % or 0.5 to 10 %).

For example, anti-microbial agent(s), such as PHMB, may be present in the compositions of the invention in an amount of from about 0.001 to about 20 % by weight of the compositions, such as from about 0.005 to about 5 % or about 10%, for example from about 0.01 to about 2 %, preferably from about 0.05 to about 1 % (e.g. from 0.1 to 0.5 %).

Typically, the component (ii) is present in the compositions of the invention in an amount of from about 0.001 to about 50 % by weight of the compositions, such as from about 0.002 to about 5 %, for example from about 0.003 to about 2 %, preferably from about 0.005 to about 1 % (e.g. from 0.008 to 0.8 % or 0.1 to 0,5 %). The amount of component (ii) will vary depending on a number of factors, such as the intended use of the composition, the nature of component (ii) and its properties (e.g. viscosity and volatility). Typically, the polar solvent component (Ni) is present in the compositions of the invention in an amount of from about 10 to about 99.999 % by weight of the compositions, such as from about 50 to about 99,999 %, for example from about 80 to about 99.99 %, preferably from about 90 to about 99.9 %, more preferably from about 95 to about 99.8 % (e.g. from 97 to 99.7 % or 97.5 to 99.6 %).

It will be appreciated that the actual concentration of components (i) and (ii) in a composition of the invention will depend on the intended use of that composition. For disinfecting uses, such as cleaning of hospital wards and equipment to help prevent the spread of disease such as MRSA, higher concentrations are required than for certain sanitising applications.

The present invention provides an anti-microbial composition comprising (A) colloids of components (i) and (ii) as defined above and (B) a polar solvent (iii). These colloids may optionally also comprise a hydrophobic material such as a siloxane.

It is believed that in the compositions of the invention the majority (greater than 50% preferably greater than 75%, more preferably greater than 90% and most preferably substantially all (at least 97%) or 100%) of the component (i) and the component (ii) are present in colloids containing both of these components. The composition may also contain some anti-microbial agent dissolved in the polar solvent.

Without wishing to be bound by theory, the inventors have found that there are very significant advantages associated with the compositions of the invention. It is thought that the colloidal nature of the compositions of the invention is responsible for one or more of these advantages.

In use the compositions of the invention act to substantially reduce or control the formation of microbial colonies on or at the surface to which they are applied. This means that not only do the compositions of the invention kill any microorganisms that are present on a surface when they are applied to that surface (so called "wet kill"), they also have a residual effect in that they prevent the formation of new microbial colonies at the surface (so called "dry kill"). It is believed that the non-ionic surfactant and the antimicrobial agent(s) (for example in the form of colloids) present in the compositions of the invention remain on the surface after the polar solvent has evaporated and that the presence of these components on the surface prevents bio-film formation/the growth of colonies of microorganisms. The residual effect can often be seen even after a treated surface has been washed or rinsed with water and sometimes even after numerous washings or rinsings.

Anti-microbial compositions are considered to have residual efficacy if, in the residual efficacy test described herein, they give a reduction in the number of microorganisms which is at least log 3.0. Preferably an anti-microbial composition having a residual effect and tested in this manner will give a log reduction of at least about 3.5, more preferably at least about 5.0 and most preferably about 7.0 or more, up to total kill or substantially total kill (zero survivors) under the test conditions described above.

In a particular aspect, the present invention provides anti-microbial compositions which have residual efficacy. By this we mean that these compositions when tested in accordance with the residual efficacy test described herein have an anti- microbial efficacy within the parameter set out in the paragraph above.

It has been found that the unique composition of the compositions of the invention (which may comprise colloids of the non-ionic surfactant and the antimicrobial agent(s)) results in increased anti-microbial efficiency (either in terms of higher initial rates of kill and/or in terms of residual efficacy) compared to the use of the anti-microbial agents alone. This is particularly surprising because the non-ionic surfactants used in the invention do not themselves have any antimicrobial properties. This means that the concentration of anti-microbial agent required in the compositions of the invention to give the desired effect can be lower than that required in many conventional anti-microbial compositions.

The prevention of the formation of a biofilm and the greatly reduced and attenuated colonies of microorganisms provides a substantially reduced risk due to infection or contamination. The anti-microbial compositions of the invention are typically able to break down biofilms that have already formed.

As the anti-microbial compositions of the invention physically disrupt the adhesion and attachment of a microorganism to a surface, which is a feature that is common to a wide range of microorganisms, including bacteria, fungi and moulds, the compositions are effective against a broad range of microorganisms. Thus, an advantage of the anti-microbial compositions of the invention is that they are able to prevent a broad range of microorganisms from adhering and attaching to the surface, and, therefore, from forming a biofilm. Large numerous colonies are also substantially prevented from forming. Thus, the ability of the colony to grow is substantially reduced or even prevented. The anti-microbial compositions of the invention are, therefore, general in their control of microorganisms.

The anti-microbial compositions of the invention can easily be incorporated into other materials, such as functional materials. When incorporated into such materials, these become anti-microbial in nature and the surface of the formulation will be modified so as to substantially prevent the microorganisms from adhering and attaching thereto.

Another advantage of the anti-microbial compositions is that they need not comprise combinations of materials that are highly toxic to mammals. The antimicrobial agents used in the anti-microbial compositions are typically well known and widely understood and tested anti-microbial agents. The efficacy of the known anti-microbial agents is amplified in the compositions of the invention. Therefore, anti-microbial agents that have a low toxicity can be used in the antimicrobial compositions. In contrast, new anti-microbial agents for known techniques of sanitization use "stronger", more toxic and/or little tested materials.

The anti-microbial compositions of the invention also do not comprise materials that produce highly persistent residues or rinsates or products that contain heavy metals and their salts. Thus, there is a greatly reduced risk of long term hazards associated with the anti-microbial compositions. The composition of the invention does not interfere with the biochemical reproductive pathways of the microorganisms it controls. The risk of resistance build up and the development of resistant strains is, therefore, low.

As general rule, the anti-microbial efficacy of the compositions of the invention increases with increasing concentration of the anti-microbial agents contained therein. However, the compositions of the invention can be surprisingly effective at low concentration of anti-microbial agents (i.e. high dilution by polar solvents) compared to known anti-microbial compositions of the same anti-microbial concentration. It has been found that the compositions of the invention can be effective when the total concentration of the anti-microbial agent(s) (i) is as low as from about 400 or less to about 30ppm such as from about 300 to about 50ppm for example about 200 to about 75ppm, or about 150 to about 100ppm (for example compositions comprising a total of about 95ppm of component (i) and about 5ppm of component (H)). This is very surprising as it is thought that in conventional anti-microbial compositions (such as those comprising quaternary ammonium compounds) the concentration of anti-microbial agent must be at least about 400ppm. This enhanced activity is believed to be associated with a variation in the nature of the colloidal structures as the concentration of components (i) and (ii) is varied.

The present invention provides compositions which comprise the low levels of anti-microbial agent described in the paragraph above and also provides more concentrated compositions, which contain higher levels of anti-microbial agent that can be diluted before or during use to provide the low levels of anti-microbial agent described in the paragraph above.

Compositions comprising this low level of anti-microbial agent are particularly useful for sanitization applications and for long term applications.

Compositions are considered to have anti-microbial efficacy if, in the suspension test with Escherichia coli K12 O Rough H48 described herein, they give a reduction in the number of micro-organisms which is at least about log 5.0. This is in accordance with the European standard (1276) for suspension tests. Compositions having anti-microbial efficacy can be considered to be those that when subjected to this test provide a reduction in the number of micro-organisms of at least about log 5.0 to total kill or zero survivors. Preferably an anti-microbial composition provides a reduction in the number of micro-organisms of at least about log 6.0 more preferably about 7.0 or more under the test conditions described above. Most preferably an anti-microbial composition provides substantially zero survivors or substantially total kill under the test conditions described above.

Thus, in a particular aspect, the present invention provides compositions having the low concentrations of anti-microbial agents mentioned above which have an anti-microbial efficacy when subjected to the suspension test with Escherichia coli K12 O Rough H48 described herein within the parameter set out in the paragraph above. The present invention also provides compositions which can be diluted to have those low concentrations of anti-microbial agent and which have an antimicrobial efficacy when subjected to the suspension test with Escherichia coli K12 O Rough H48 described herein within the parameter set out in the paragraph above when diluted to those concentrations.

Without being bound by theory, it is thought that the components (i) and (ii) which are thought to make up the colloidal dispersions in the compositions of the invention may form different colloidal structures depending on the concentration of those components in solution. These different structures may typically have a preferred range of concentration of components (i) and (ii) at which they are formed, the so-called critical micelle concentration.

The size and morphology of the colloidal structures in the compositions of the invention is thought to vary depending on factors such as the concentration of the ingredients that form colloids. For example, it is thought that when the compositions comprise from about 500,000ppm to about 5000ppm of component (i) and component (ii) (the combined amount of these components) the colloids typically have an average (mean) diameter of from about 1 to about 120 nm, for example from about 2 to about 100 nm, for example from about 5 to about 80nm, for example from about 10 or about 20nm to about 60nm.

It is believed that as the concentration of the components (i) and (ii) decreases below about 5000ppm to about 30ppm or about 50ppm or about IOOppm the size of the colloids changes and so does their morphology. Colloidal particle size measurements may be made using any suitable method, for example by Dynamic Light Scattering (e.g. using a Malvern Zetasizer).

It is believed that at lower combined concentrations of components (i) and (ii), such as from about 0.002 to about 5 % by weight of the compositions (e.g. 0.005 to about 1 %), the compositions are surprisingly effective as antimicrobials. This may be due to the presence of larger vesicles in the colloidal suspension compared to more concentrated solutions. These vesicles are thought to contain a greater number of anti-microbial molecules. Each vesicle may, therefore, have an enhanced anti-microbial effect.

The compositions of the invention do not give surfaces to which they are applied a greasy feel. Additionally, the compositions have a very good hand feel which makes them particularly suitable for uses such as hand sanitizing.

According to a further aspect of the invention, there is provided a formulation comprising an anti-microbial composition and at least one other functional material or substrate.

The formulations of the present invention typically comprise an anti-microbial composition as described above in combination with compatible ingredients which allow the formulation to perform its primary purpose. By this we mean for example that a detergent formulation of the invention (such as a washing up liquid) would contain ingredients to provide the necessary cleaning properties together with an anti-microbial composition as described above.

Suitable functional materials or substrates include plastics, fibres, coatings, films, laminates, adhesives, sealants, clays, china, ceramics, concrete, sand, paints, varnishes, lacquers, cleaning agents or settable or curable compositions such as fillers, grouts, mastics and putties.

The plastics may be in the form of films, sheets, stabs and molded plastic parts.

Suitable plastics materials may be prepared from polyesters such as polyethylene terephthalate, polybutylene terephthalate, polyamides such as Nylon, polyimides, polypropylene, polyethylene, polybutylenes, polymethylpentene, polysiloxane, polyvinyl alcohol, polyvinylacetate, ethylene-vinylacetate, polyvinyl chloride, polyvinylidene chloride, epoxy, phenolic and polycarbonate cellulosics, cellulose acetate, polystyrene, polyurethane, acrylics, polymethyl methacrylate, acrylonitrile, butadiene-styrene copolymer, acrylonitrilestyrene-acrylic copolymers, acetals, polyketones, polyphenylene ether, polyphenylene sulphide, polyphenylene oxide, polysfulfones, liquid crystal polymers and fluoropolymers, amino resins, thermo plasties, elastomers, rubbers such as styrene butadiene rubber and acrylonitrile butadiene rubber, polyacetal (polyoxymethylene), and blends and copolymers thereof.

Formulations comprising an anti-microbial composition of the invention and a plasties material as the functional material may, for example, be used to form products such as automobile parts, shower curtains, mats, protective covers, tape, packaging, gaskets, waste containers, general purpose containers, brush handles, sponges, mops, vacuum cleaner bags, insulators, plastic film, indoor and outdoor furniture, tubing, insulation for wire and cable, plumbing supplies and fixtures, siding for housing, liners, non-woven fabrics, kitchen and bathroom hardware, appliances and equipment, countertops, sinks, floor covering, tiles, dishes, conveyer belts, footwear including boots, sports equipment and tools.

Suitable fibres may be prepared from acetate, polyester such as PET and PTT, polyolefins, polyethylene, polypropylene, polyamides such as Nylon, acrylics, viscose, polyurethane, and Rayon, polyvinyl alcohol, polyvinyl chloride, polyvinylidene chloride, polysaccharide, and copolymers and blends thereof.

Formulations comprising the anti-microbial composition and a fibre as the funcitional material, may for example, be used in applications such as mattress cover pads and filling, pillow covers, sheets, blankets, fibrefill for quilts and pillows, curtains, draperies, carpet and carpet underlay, rugs upholstery, table cloths, napkins, wiping cloths, mops, towels, bags wall covering fabrics, cushion pads, sleeping bags and brush bristles. The fibres are also suitable for use in automotive and truck upholstery, carpeting, rear decks, trunk liners, convertible tops and interior liners. Furthermore, the fibres are suitable for use in umbrellas, outerwear, uniforms, coats, aprons, sportswear, sleepwear, stockings, socks, hosiery caps, and undergarment and inner liners for jackets, shoes, gloves and helmets, trim for outerwear and undergarments as well as brush bristles, artificial leather, filters, book covers, mops, cloth for sails, ropes, tents, and other outdoor equipment, tarps and awnings.

Coatings suitable for use in the formulations include water-borne, solvent-borne, 100% solids and/or radiation cure coatings. The coatings may be liquid or powder coatings.

Suitable coatings, films and laminates include alkyds, amino resins, such as melamine formaldehyde and urea formaldehyde, polyesters, such as unsaturated polyester, PET, PBT, polyamides such as Nylon, polyimides, polypropylene, polyvinylacetate, ethylene-vinylacetate, polyvinyl chloride, polyvinylidene chloride, epoxy, phenolic and polycarbonate cellulosics, cellulse acetate, polystyrene, polyurethane, acrylics, polymethyl methacrylate, acrylonitrile-butadiene-styrene copolymer, acrylonitrile-styreneacrylic copolymers, acetals, polyketones, polyphenylene ether, polyphenylene sulphide, polyphenylene oxide, polysulfones, liquid crystal polymers and fluoropolymers, thermoplastic elastomers, rubbers such as styrene butadiene rubber, acrylonitrile butadiene rubber, polyacetal (polyoxymethylene), and blends and copolymers thereof.

Formulations comprising the anti-microbial composition and coatings as the functional material may, for example, be used on walls, wall boards, floors, concrete, sidings, roofing shingle, industrial equipment, natural and synthetic fibres and fabrics, furniture, automotive and vehicular parts, packaging, paper products (wall coverings, towels, book covers) barrier fabrics, and glazing for cement tile and for vitreous china used in plumbing fixtures such as toilets, sinks, and countertops.

Adhesives and sealants suitable for use in the formulations include hot-melt, aqueous, solvent borne, 100% solids and radiation cure adhesives and sealants.

Suitable adhesives and sealants include alkyds, amino resins such as melamine formaldehyde and urea formaldehyde, polyesters such as unsaturated polyester, PET, PBT, polyamides such as Nylon, polyimide polypropylene, polyethylene, polybutylene, polymethylpentene, polysiloxane, polyvinyl alcohol, polyvinylacetate, ethylene-vinylacetate, polyvinyl chlorides such as plastisol, polyvinylidene chloride, epoxy, phenol and polycarbonate, cellulosics, cellulose acetate, polystyrene, polyurethane, acrylics, polymethylmethacrylate, acrylonitrile-butadienestyrene copolymer, acrylonitrile-styrene-acrylic copolymers, acetals, polyketones, polyphenylene ether, polyphenylene sulphide, polyphenylene oxide, polysulfones, liquid crystal polymers and fluoropolymers, thermoplastic elastomers, rubbers (including styrene butadiene rubber) acrylonitrile butadiene rubber, CR), polyacetal (poiyoxymethylene), and blends and copolymers thereof.

Formulations comprising the anti-microbial composition and an adhesive or sealant as the functional material may, for example, be used in the manufacture of wood and plastic composites, adhesives for ceramic tiles, wood, paper, cardboard, rubber and plastic, glazing for windows, grout, sealants for pipes, adhesives, sealants and insulating materials for appliances, bathrooms, showers, kitchens, and construction.

Formulations comprising the anti-microbial composition and clay, china, ceramics, concrete, sand or grout as the functional material may, for example, be used in toilets, sinks, tile, flooring, stucco, plaster, cat littler, drainage and sewerage pipe.

The anti-microbial composition can be combined into a very wide variety of functional compounds for the manufacturing, contracting and construction industries. The nature of the anti-microbial composition may be varied according to the particular functional compounds and the number and nature of microorganisms present in the particular functional compound.

There is also a need to provide formulations for a variety of applications and uses, particularly cleaning applications that have anti-microbial properties and that address one or more of the problems set out above. However, it is not a straight forward matter to do this. There are regulations such as the Biocidal Products Directive (Directive 98/8/EC) which regulates the use of anti-microbial agents both in terms of the nature and the amount of a given anti-microbial agent that may be used. Additionally, the potential reactivity of an anti-microbial agent once in a formulation is important as some anti-microbial agents are rendered inactive by chemical reaction. Even where an anti-microbial agent is not deactivated by chemical reaction it may have its activity suppressed by other components of the formulation. The present inventors have surprisingly found that the foregoing deficiencies can be overcome by the inclusion of certain anti-microbial compositions in formulations to which it is desired to provide anti-microbial properties. It has also been found that formulations prepared in this manner have some surprising and unexpected properties.

In particular, the present invention provides formulations comprising an antimicrobial composition suitable for a variety of consumer applications. The formulations that are within the scope of the present invention are surfactant containing formulations, for example surfactant based formulations. These surfactant containing formulations, for example surfactant based formulations, may comprise at least one non-ionic, anionic, cationic and/or amphoteric surfactant. In a particular aspect of the invention the formulation comprises at least one non-ionic and/or amphoteric surfactant. However, formulations free of or substantially free of amphoteric surfactants are also envisaged. For example, formulations and compositions which comprise a polymeric biguanide such as PHMB may be free of or substantially free of amphoteric surfactants. Typically the formulations are free of or substantially free of anionic surfactant.

Examples of the formulations of the invention include, but are not limited to, surface cleaners such as those intended for use in bathrooms, kitchens, living areas, hard floor cleaners, carpet cleaners, furniture cleaners, glass/mirror cleaners; toilet care products including solid toilet cleaners such as rim devices and those designed to be placed in the cistern, liquid toilet cleaners excluding those comprising hypochlorite bleaches; dishwashing products such as washing up liquids and preparations from dishwashing machines such as dishwashing solids (eg powders and tablets) & liquids; laundry products such as solid detergents (eg powders and tablets), liquid detergents and fabric conditioners and "2 in 1" products comprising detergent and fabric conditioner; cleaning products intended for use outdoors such as those for cleaning for wood, stone, concrete or plastics, for example patio cleaner, garden furniture cleaners/treatments, BBQ cleaners, wall and fence cleaners/treatments, plant sprays such as those intended to remove insects such as aphides from plants; food sprays, such as those suitable for use in food preservation; personal care products such as bath and shower products; soaps, including liquid and solid soaps, hand sanitisers, deodorants and antiperspirants, haircare products including shampoos, for example anti-scalp odour shampoos, shampoos for the control of head lice eggs and anti- dandruff shampoos, hair conditioners, hair styling products such as hair mousses, gels and sprays, skin care products such as shaving products, cosmetics and products for hair removal; baby products including baby cleaning and cleansing products such as baby bath, soaps, wipes, moisturisers, nappy rash cream, products for cleaning surfaces that have regular & high incidence of infant & baby contact; first aid products and products for treating ailments and illnesses, including products for the topical treatment and/or prevention of minor infections such as athletes foot, spot/acne prevention/treatment products; foot hygiene products, including those for use on the foot and those for the treatment/deodourisation of foot ware, particularly sports foot wear; products for cleaning and/or deordourising vehicles such as cars.

The formulations of the invention comprise an anti-microbial composition as described above.

More particularly, the formulations of the invention comprise (A) at least one surfactant (referred to hereinafter as component (A) or the at least one formulation surfactant) and (B) an anti-microbial composition of the invention as described above.

The formulation surfactant (A) may be any suitable surfactant or combination of surfactants, for example at least one non-ionic, anionic, cationic and/or amphoteric surfactant. In a particular aspect of the invention the formulation surfactant (A) comprises at least one non-ionic and/or amphoteric surfactant.

The selection of the formulation surfactants (A) will depend on the nature of and the intended purpose of the formulation. Suitable surfactants for use in formulations intended for different purposes will be within the knowledge of the person of ordinary skill in the art. The pH of the formulations of the invention can vary within wide limits. Typically, the pH of a formulation of the invention will be similar to that of known formulations which are intended to be used for the same purpose or a similar purpose to a given formulation of the invention. For example, a formulation that is intended to come into contact with the skin or the hair, such as a hand wash formulation or a shampoo formulation or other personal care or first aid formulations as listed above will typically have a pH which will not irritate the skin, for example from about pH 5 to about pH 8, such as from about pH 5.5 to about pH 7.5. On the other hand formulations for use for purposes such as kitchen or bathroom cleaning may have a low pH, such as a pH of 3 or below, for example about 2.

In one preferred group of formulations of the invention the formulation surfactant (A) comprises at least one non-ionic surfactant. For example, the formulation surfactant (A) may consist essentially of at least one non-ionic surfactant or the formulation surfactant (A) may consist of at least one non-ionic surfactant. If the formulation surfactant (A) consists of at least one non-ionic surfactant it will not contain other types of surfactants, for example it will be free of amphoteric surfactants, anionic surfactants and cationic surfactants. Examples of non-ionic surfactants that can be used in these formulations are listed below.

In another preferred group of formulations of the invention the formulation surfactant (A) is an amphoteric surfactant. Amphoteric surfactants can be used alone or in combination with a non-ionic surfactant. If a combination of an amphoteric surfactant and a non-ionic surfactant is used the weight ratio of the two types of surfactant can vary within wide limits, for example from 1 % of amphoteric surfactant to 99% of non-ionic surfactant to 99% of amphoteric surfactant to 1 % of non-ionic surfactant, based on the total weight of the formulation surfactant (A). Preferably the amphoteric surfactant and the non-ionic surfactant are used in approximately equal amounts by weight.

In one aspect of the invention, preferred formulations comprise up to about 5% by weight ^'(based on the total weight of the formulation) amphoteric surfactant, although higher levels of amphoteric surfactant can be used in some formulations. As an example, the present invention provides formulations having a pH of from about 5 to about 8, more preferably from about 5.5 to about 7.5 and comprising an amphoteric surfactant and a non-ionic surfactant, wherein the amphoteric surfactant is present in an amount of up to about 5% by weight (based on the total weight of the formulation). In such formulations, the total amount of surfactant is not particularly limited and the total amount of surfactant may be an amount that is typical in the art for the particular type of formulation in question. Examples of preferred formulations comprising an amphoteric surfactant and a non-ionic surfactant have a total surfactant content of about 10% by weight, wherein no more that 5% by weight (based on the total weight of the formulation) is amphoteric surfactant.

Suitable cationic surfactants for use as the formulation surfactant (A) include but are not limited to distearyl dimethyl ammonium chloride, lauryl trimethyl ammonium chloride, alkyl trimethyl ammonium methosulfate, coco trimethyl ammonium chloride and cetyl pyridinium chloride.

Suitable non-ionic surfactants for use as the formulation surfactant (A) include those described above in relation to component (ii) and include but are not limited to ethylene oxide/propylene oxide block polymers, polyethoxylated sorbitan esters, fatty esters of sorbitan, ethoxylated fatty esters (containing from 1 to 25 units of ethylene oxide), polyethoxylated C₈-C₂₂ alcohols (containing from 1 to 25 units of ethylene oxide), polyethyoxylated C₆-C₂₂ alkylphenols (containing from 5 to 25 units of ethylene oxide), alkylpolyglycosides. Examples include but are not limited to nonyl phenol ethoxylate (9EO), Nonyl phenol ethoxylate (2EO), octyl phenol ethoxylate (10EO), C₁₂/C₁₄ synthetic ethoxylate (8EO), stearyl alcohol ethoxylate (7EO), cetostearyl alcohol ethoxylate (20EO), coconut fatty amine ethoxylate (10EO), sorbitan monolaurate ethoxylate, 80%PO/20%EO, coconut diethanolamide (shampoo foam booster), sorbitan monolaurate, sorbitan monolaurate 4EO, di-isopropyl adipate, alkyl poly glucosides, such as C_6-20, preferably C₈.io alkyl glucosides, eg Surfac APG (D-Glucopyranose oligomers C_8- io alkyl glucosides, CAS 161074-97-1 , available from Seppic, UK), and cetostearyl stearate. Other suitable non-ionic surfactants include Neodol 25-7 (C12/15 alcohol 7 ethoxylate (EO), CAS 68131-39-5), Surfac LM90/85 (C12/15 alcohol 9 ethoxylate (EO), CAS 68131-39-5), Surfac 65/95 (C9/11 alcohol 6.5 ethoxylate (EO), CAS 68439-45-2), Tomadol PF9 (C9/11 alcohol 6.0 ethoxylate (EO), CAS 68439-46-3), Surfac T80 Veg (Polysorbate 80, Polyoxyethylene sorbate mono oleate, CAS 9005-65-6), Tween 60 (Polysorbate 60, Polyoxyethylene sorbate mono stearate, CAS 9005-67-8), Tween 40 (Polysorbate 40, Polyoxyethylene sorbate mono palmitate, CAS 9005-66-7), Surfac T-20 (Polysorbate 20, Polyoxyethylene sorbate mono laurate, CAS 9005- 64-5), Surfac PGHC (Hydrogenated Castor oil 40EO, CAS 61788-85-0), Ninol 49- CE (Coconut diethanolamide, CAS 68603-42-9). Preferred non-ionic surfactants include those sold under the names Tomadol and Neodol.

Suitable amphoteric surfactants for use as the formulation surfactant (A) include but are not limited to C₆-C_2O alkylamphoacetates or amphodiacetates (such as cocoamphoacetates), Ci₀-Ci₈ alkyldimethyl betaines, Ci₀-Ci₈ alkyl amidopropyldimethyl betaines. Examples include but are not limited to coconut amphoteric surfactant cocoamidopropyl betaine (CAPB) (Surfac B4, CAS 61789-

40-9), coco imidazoline betaine, oleo amido propyl betaine, and tall oil imidazoline. A particularly preferred amphoteric surfactant is cocoamidopropyl betaine.

Other suitable surfactants include those that exhibit non-ionic or cationic type properties at pHs below about 8, for example between about pH 5 and about pH 7 or 8. It will be appreciated that the behaviour of such surfactants depends on factors such as their pKa and which surfactants are suitable for use in a given formulation will depend on the pH of the formulations. Examples of surfactants which exhibit properties that can vary with pH and that can be used in the formulations of the invention include but are not limited to amine oxides such as those having an average carbon chain length of from 8 to 20, eg 12 or 14 such as C10-C18 alkyldimethyl amine oxides and C₈-C₂2 alkoxyethyldihydroxyethylamine oxides, for example dimethyl laurylamine oxide (eg Surfac AO30 from Surfachem and manufactured by Stepan as Ammonyx LO), alkyl ether carboxylates and alkyl ether phosphates, such as those having an average chain length of from 8 to 12, eg 12 or 14 (eg Laureth 11 carboxylic acid, sold by Univar as Akypo RLM 100 and Laureth 4 phosphate, sold by Surfachem and manufactured by Schill and Seilacher as Silaphos MDE 124). These surfactants can be used in combination with other surfactants such as non-ionic surfactants. Preferred combinations of surfactants include but are not limited to CAPB and a non-ionic surfactant, such as an APG, an amine oxide and a non-ionic surfactant, such as an APG.

It will be appreciated that the compositions and formulations of the invention can comprise other ingredients commonly used in the art. The nature of any other ingredients used will depend on the nature and intended purpose of the composition or formulation. For example, the additional ingredients used in a bath/shower product are likely to be different to those used in a toilet care product, which will be different again from those used in a dishwashing or laundry product. The person of ordinary skill in the art will know which additional ingredients are suitable for use in compositions and formulations for different applications.

Additional ingredients that may be used in the formulations of the invention include but are not limited to water, antioxidants, thickeners, corrosion inhibitors, foam makers/boosters such as alkanolamides and amine oxides, eg alkyl amine oxides and ehtoxylated amine oxides and breakers, abrasives, chelating agents such as tetrasodium EDTA, sequesterants such as ethylenediaminetetraacetic acid (EDTA), nitrilotriacetic acid (NTA), tetrasodium EDTA, other acetic acid derivatives and mixtures thereof, salts such as sodium chloride and citrate salts, pH modifiers, for example acids such as citric, sulfamic, hydrochloric, phosphoric, nitric, lactic, formic, acetic or gluconic acids or other mineral or organic acids or bases such as sodium or potassium hydroxide and mono-, di- or tri- ethanoiamine, colorants, fragrances, emollients and hair and/or skin rejuvenating and/or protecting agents.

It is preferred that the compositions and formulations of the invention do not comprise a sequesterant. Thus, in a specific aspect, the compositions and formulations of the present invention are free of sequesterant. For example, the compositions and formulations of the invention are preferably free of one or more of ethylenediaminetetraacetic acid (EDTA), nitrilotriacetic acid (NTA), tetrasodium EDTA and other acetic acid derivatives.

The pH of the compositions and formulations of the invention will depend on the intended use for the compositions or formulations. For example, household cleaners may have a pH from 8 to 11 , for example 9 or 10. On the other hand compositions and formulations intended for use on the skin typically have a pH which is approximately neutral or similar to skin pH. The person of ordinary skill in the art will appreciate what pH is appropriate for compositions and formulations for different uses.

Some compositions and formulations of the invention are free of or substantially free of acids or bases. For example some compositions and formulations of the invention do not comprise a citrate or citric acid.. Other compositions and formulations may contain an acid or base as is appropriate for their intended use.

Typically the compositions and formulations of the invention do not comprise citrate salts such as sodium or potassium citrate.

For the avoidance of doubt, when we state herein that the formulations comprise a surfactant or is surfactant based we mean that the formulations comprise a surfactant in addition to the surfactant(s) present in the anti-microbial compositions of the invention used in those formulations.

It will be appreciated that the amount of formulation surfactant (A) in the formulations of the invention will depend on factors such as the intended purpose of the formulation. Typically, the formulations of the invention comprise from 1 to 30 % by weight of formulation surfactant (A), preferably from 2 to 25 % by weight. For household cleaning products the amount of surfactant (A) is typically from about 2 to 10% by weight. For dishwashing products the amount of surfactant (A) is typically from about 10 to 25 % by weight, for example from about 15 to 20 % by weight. For personal care products the amount of surfactant (A) is typically from about 10 to 20 % by weight for example from 15 to 20 % by weight. It will be appreciated that these percentages are examples only and that some products may comprise surfactant (A) in an amount outside the range specified for a given product type.

The anti-microbial compositions of the invention and formulations comprising them can typically degrade when submersed in water, to provide a rinsate/leachate of low toxicity and which has a short residence time in the environment. It is thought that the rinsate has a low toxicity because the anti-microbial agents are associated with the second compound and so the composition does not readily dissociate in the presence of water.

The formulation can be designed so that they are stable and effective in most manufacturing environments. The formulation is typically stable up to temperatures of 200⁰C.

The property of mobility of the product permits materials that are frequently washed or rinsed to be "recharged" with the anti-microbial composition during a routine act of cleaing or maintenance.

Typically, the anti-microbial composition is incorporated into a simple conventional detergent solution or added to a "final rinse" during cleaning. The anti-microbial composition will be drawn, due to the presence of its hydrophobic elements, into the surface of the product to be "recharge". The sanitization properties of the formulation are, therefore, restored without the need for re- manufacture or difficult treatment processes.

Any wash off or rinsates containing the anti-microbial composition or formulation diluted by such a re-charging solution and water would quickly dissociate into the biodegradable components as previously discussed.

According to a further aspect of the invention, there is provided the use of an antimicrobial composition of the invention to prevent the formation of colonies of microorganisms on a surface at which it is provided.

According to yet a further aspect of the invention, there is provided the use of a formulation to prevent the formation of colonies of microorganisms on a surface at which it is provided.

The invention also provides a process for making the compositions of the invention. The process comprises the steps of (A) mixing at least part of component (i) and component (ii); (B) adding the polar solvent to the mixture formed in step (A); and (C) agitating the resulting mixture until a clear solution is formed.

If component (i) is a solid, step (A) can be carried out in sufficient polar solvent to dissolve component (i). Alternatively, some materials which may be used as component (i) are commercially available in solution. In this case, these materials can be used in step (A) in their commercially available form.

Typically, the mixture used in step (A) comprises from about 1 to about 25% by weight of a polar solvent, more preferably from about 2 to about 8% by weight polar solvent. If the amount of solvent used in step (A) is too great, the colloids will not form. The person of ordinary skill in the art could readily determine an appropriate amount of solvent to use. If too much solvent is used the initial cloudy solution will not become clear (the clear solution is thought to be associated with the formation of colloids). The polar solvent typically used in step (A) is water, although other polar solvents may be used alternatively or additionally.

Typically, the process to produce the compositions of the invention is carried out at room temperature with stirring. In step (A) the mixture is initially cloudy because the component (ii) has limited solubility in the polar solvent.

Typically step (A) is complete when the solution becomes clear. It is thought that this clear solution contains colloids or micelles of the components (i) and (ii).

If an anti-microbial agent that is not soluble in the polar solvent is used, it should be added in step (A) so that it may form part of the colloids.

In step (A) the components may be mixed in any manner suitable (for example to maximize the formation of colloidal structures (e.g. micelles and vesicles)). This may be achieved by slow addition of a component (i) to component (ii) or visa versa and then mixing (for example stirring overnight). The rate of addition of the components often needs to be regulated to prevent "shock" which can prevent adequate mixing and/or colloid formation. It would be a routine matter for the person of ordinary skill in the art to determine a suitable rate of addition. The mixing/blending steps can also use techniques such as ultrasonic mixing/blending. The present invention provides compositions obtainable by the process set out above.

The compositions of the invention may be prepared in a concentrated form (i.e. with little or no polar solvent) and diluted with polar solvent (e.g. water) when used.

The following are non-iimiting examples of compositions of the invention.

A composition comprising an anti-microbial composition comprising (i) an antimicrobial component selected from (I) the combination of at least two quaternary ammonium compounds, and a polymeric biguanidine, such as PHMB and (II) a polymeric biguanide only such as PHMB, (ii) at least one non-ionic surfactant, (iii) at least one polar solvent, typically water.

Preferably the non-ionic surfactant is an alcohol ethoxylate such as one sold under the Tomadol or Neodol name.

The following are non-limiting examples of formulations of the invention:

A formulation comprising:

(A) at least one non-ionic surfactant;

(B) an anti-microbial composition comprising (i) an anti-microbial agent selected from (I) the combination of at least two quaternary ammonium compounds, and a polymeric biguanidine, such as PHMB and (II) a polymeric biguanide only such as PHMB (ii) at least one non-ionic surfactant, (iii) at least one polar solvent, typically water; and optionally other compatible ingredients as described above; the formulation preferably being substantially free of anionic surfactant.

(A) may, for example, comprise one or more non-ionic surfactants only, ie the formulation does not comprise other surfactants such as amphoteric surfactants.

In one aspect, the anti-microbial agent does not comprise an isothiazalone. A formulation comprising:

(A) at least one non-ionic surfactant and at least one amphoteric surfactant provided that the total amount of amphoteric surfactant is 5% by weight or less based on the total weight of the formulation; (B) an anti-microbial composition comprising (i) an anti-microbial agent selected from (I) the combination of at least two quaternary ammonium compound, and a polymeric biguanidine such as PHMB, and (II) a polymeric biguanide only such as PHMB (ii) at least one non-ionic surfactant (iii) at least one polar solvent, typically water; and optionally other compatible ingredients as described above; the formulation preferably being substantially free of anionic surfactant.

In one aspect, the formulation does not comprise an isothiazalone.

A formulation having a pH of about 8 or less, such as from about 5 to about 8 and comprising:

(A) at least one surfactant which exhibits non-ionic or cationic type properties at a pH below about 8;

(B) ■ an anti-microbial composition comprising (i) an anti-microbial agent selected from (I) the combination of at least two quaternary ammonium compound, and a polymeric biguanidine such as PHMB and (II) a polymeric biguanide only such as PHMB (ii) at least one non-ionic surfactant, (iii) at least one polar solvent, typically water; and optionally other compatible ingredients as described above; the formulation preferably being substantially free of anionic surfactant.

In one aspect, the formulation does not comprise an isothiazalone.

The formulations of the present invention can be made by introducing an amount of an anti-microbial composition as described above into a pre-prepared initial formulation. For example, an anti-microbial composition could be introduced into a suitable commercially available detergent composition. Alternatively, the anti-microbial composition may be incorporated into a formulation by addition during one of the steps in the process for making the formulation (ie without the formation of an initial formulation).

The method that is used to make a particular formulation of the invention may depend on the nature of the formulation and the conditions under which it is made: However, regardless of the method by which the formulation is made it is essential that the anti-microbial composition is pre-formed before it is mixed with any of the other components of the formulation.

Brief Description of the Figure.

Figure 1 illustrates the affect that the concentration of the non-ionic surfactant

Tomadol has on the residual efficiency of PHMB.

The invention is illustrated by the following examples.

Testing Method

Evaluation of bactericidal activity using suspension test with Escherichia co// K12 O Rough H48

Residual Efficacy Testing using Escherichia coli K12 O Rough H48

The aim of the test is to evaluate the residual efficacy of products of the invention against Escherichia coli K12 O Rough H48 using typical household conditions.

Media and Materials

10 g tryptone +

LB is sterilized by Luria broth (LB) 5 g yeast extract + autoclaving. 10 g NaCI / L water

15 g agar +

10 g tryptone + LBA is sterilized by

Luria broth Agar (LBA)

5 g yeast extract + autoclaving.

10 g NaCI / L water

30 mL Tween 80 +

NF is sterilized by Neutralising solution (NF) 30 g saponine + autoclaving. 1 g histidine + 1 g cysteine / L water

10 g tryptone +

5 g yeast extract +

1O g NaCI +

Luria broth + LB+NF is sterilized by

30 mL Tween 80 +

Neutralising solution (LB+NF) autoclaving.

30 g saponine +

1 g histidine +

1 g cysteine / L water

Sterile desalted water

Sterilized by means of Millipore filter. Used with

Bovine albumin solution 3 % BSA other liquids in final concentration of 0.3 % BSA

Incubator 37^°C

Stopwatch

Ceramic tiles, glazed (10 cm x 10 cm)

Professional Care Wipes, viskose free

Drigalsky spatula

Vortex mixer

Variable pipette and sterile tips

100mm Petri dishes

300ml Flasks

Test Organisms

Escherichia colϊ K12 O Rough H48

The test organism was kept on LBA plates at 4°C. One colony was used to inoculate a 100ml Flask of LB and incubated at 37°C for 16 hours to reach stationary phase. For log phase cultures, 4ml LB were inoculated with one colony and incubated at 37°C for 16 hours. 1 ml of the bacterial suspension was then added to 100ml LB and grown to an OD₆oo of approximately 0.375. Serial dilutions of each organism were then performed using LB and plated onto LBA plates to determine the number of colony forming units per ml.

Validation of Test Conditions

1. Validation of Selected Experimental Conditions 1ml of Bovine Albumin solution (BSA) was placed in a test tube with 1 ml of bacterial test suspension containing approximately 3.0x10⁸ cfu/ml and incubated at the test temperature of 20⁰C for 2 minutes. At the end of this time 8 ml of LB was added. This mixture was incubated for the test contact time of 10 minutes. The solution was then diluted to 3.0x10³ and 3.0x10² cfu/ml. 0.1 ml of these test solutions were pipetted in triplicate and plated on 12-15mls of LBA, which is equivalent to 3.0x10² and 3.0x10¹ cfu. The plates were incubated at 37°C for 24 hours. Test result should be equal to or greater than 0.05 times bacterial suspension.

2. Neutraliser Toxicity Validation

9ml of Neutraliser (NF) was placed in a test tube and mixed with 1 ml of a bacterial suspension containing approximately 3.0x10⁸ cfu/ml. The mixture was incubated at 20⁰C for 10 minutes. The suspension was diluted to 3.0x10³ and 3.0x10² cfu/ml using LBA. 0.1 ml was then pipetted onto triplicate plates containing 12-15mls of LBA. The plates were incubated at 37⁰C for 24 hours. Test result should be equal to or greater than 0.05 times bacterial suspension.

3. Dilution- Neutralisation Validation

1 ml of Bovine albumin solution (BSA) was placed in a test tube with 1 ml of LB and incubated at 20⁰C for 5 minutes. 1ml was then taken and added to 8ml

Neutraliser (NF). After 5 minutes incubation, 1 ml of the bacterial suspension was added. The mixture was left at 20⁰C for 10 minutes. The suspension was diluted to 3.0x10³ and 3.0x10² cfu/ml using LB and 0.1ml was then plated in triplicate onto 12-15mls of LBA. The plates were incubated at 37°C for 24 hours. Test result should be equal to or greater than 0.5 times of Neutraliser Toxicity

Validation.

Test Method

1. Pretreatment of Carrier Carriers were cleaned / disinfected with isopropanol (70 % v/v) by spraying. Excess isopropanol was used to cover the entire surface completely. Excess isopropanol was removed by running off. Further drying was allowed for a period of 10 minutes.

2. 1^st Inoculation of Carrier 1^st challenge of tile surface with ~10⁶ CFU bacteria. Application volume is set at 10 μl_. If residual amounts of isopropanol remain some of applied bacteria might be killed. The applied volume of 10 μL was spread over entire tile surface by means of sterile plastic spatula (Drigalsky spatula). Challenged tile is allowed to dry over a period of 50 minutes.

3. Product Application to Carrier

1 mL of disinfecting product was applied to a pretreated carrier surface. Applied disinfecting product was spread over entire surface by means of sterile plastic spatula (Drigalsky spatula). Surface treatment with excess disinfecting product was done over a period of 10 minutes. Pretreated carriers were stored overnight in a clean place, covered with Professional Care Wipes.

4. Inoculation of Carrier

Inoculation of tile surface was done by using ~10⁶ CFU bacteria. Application volume was set at 10 μL. If residual amounts of isopropanol remain some of applied bacteria might be killed. The applied volume of 10 μL was spread over entire tile surface by means of sterile plastic spatula (Drigalsky spatula). Challenged tile was allowed to dry over a period of 50 minutes.

5. Rinsing with Water

Tile surface was rinsed with 10 mL sterile water (water_miιiipored). After rinsing tile was dried for up to 1 hr or till surface was visibly dry.

6. Dry wear cycle Wear cycles are used as an abrasive step. A dry wear cycle was done by moving a cork block wrapped with Professional Care Wipe back and forth. Normal hand pressure was applied. Professional Care Wipes of non viscose type, do not adsorb quaternary ammonium compounds or PHMB. 7. Wet Wear Cycle

Wetting of Professional Care Wipes was done by spraying water_mjHj_Pored onto wipes. Spraying was done by triggering one time from about 30 cm. Wet wear cycles were used as an abrasive step. A Wet wear cycle was done by moving a cork block wrapped with wetted (water_mnijp_Ored) Professional Care Wipe back and forth. Normal hand pressure was applied. The wetted surface was allowed to dry for at least 10 minutes.

8. Final Inoculation of Carrier The tile is challenged with ~10⁶ CFU bacteria. The application volume was set at 10 μl_. The applied volume was spread over entire tile surface by means of sterile plastic spatula (Drigalsky spatula). The challenged tile was allowed to dry over a period of 5 to 10 minutes. Surviving bacteria were dissolved by applying 500 μL LB + NF. The applied LB + NF was spread over entire tile surface by means of sterile plastic spatula (Drigalsky spatula, single use version). The neutralizer had no killing effect on surviving bacteria, but inactivates the disinfecting product on tiles. To dissolve surviving bacteria the tile was incubated at room temperature for 30 minutes. Dissolved surviving bacteria were collected by means of sterile plastic spatula (Drigalsky spatula).

9. Determination of Survivors

The collected liquid was sampled by means of a sterile pipette. 100 μL of sample was applied to 900 μL of LB + NF. Serial dilution in LB + NF up to 10^"4 100 μL of sample was carried out and the dilutions are transferred to agar plates.

Test Method - Total Procedure

# DAY PROCEDURE

1 1 Preparation of bacteria culture (overnight culture)

2 Pretreatment of carrier (tiles); see Step 1

3 2 1^st Inoculation of Carrier; see Step 2

4 Product Application to Carrier; see Step 3

5 Wet wear cycle; see Step 7

6 3 Dry wear cycle;; see Step 6

7 Rinsing with water_mini_POred ; see Step 5

8 4 Inoculation of carrier; see Step 4 9 Dry wear cycle; see Step 6

10 Final inoculation of carrier; see Step 8

11 5 Determination of survivors; see Step 10

This test procedure uses 10⁸ CFU/mL This means that of log 8 reduction in the number of micro-organisms is equivalent to zero survivors.

Using this test procedure, compositions which have a residual efficacy can be identified. Anti-microbial compositions are considered to have residual efficacy if, in this test, they give a reduction in the number of micro-organisms which is at least log 3.0. Preferably an anti-microbial composition having a residual effect and tested in this manner will give a log reduction of at least about 3.5, more preferably at least about 5.0 and most preferably about 7.0 or more under the test conditions described above.

Materials Used PHMB Vantocil TG from Arch Chemicals.

Neodol Shell Neodol 91-5 and 91-8 from Surfachem.

Tomadol Tomadol 900 from Tomah (US).

APG Surfac APG PC (personal care grade) purchased from

Surfachem, BAC Thor Acticide BAC50M.

DDQ Bardac 2240 from Lonza.

Natrosol Natrosol 250HR from Aqualon (Hercules)

Examples The following are representative of antimicrobial compositions in accordance with the present invention.

Example 1

The composition produced in this experiment was diluted as necessary to provide the compositions that were subjected to the test procedure described above.

The results obtained are shown in Figure 1.

Figure 1 shows how the concentration of the non-ionic surfactant, Tomadol affects the residual anti-microbial efficacy of PHMB. In the absence of Tomadol no residual effect was observed but good residual efficiency was observed with 5% Tomadol.

Example 2

Five prototype aqueous-based household cleaner formulations (A-E) were prepared and tested for residual efficacy against E.coli K12 0 Rough H48 DSM No.11250 as described above. Each of the formulations A to D had a pH in the range of about pH9 to about pH10 (pH was buffered with a sodium carbonate (0.04%)/biacarbonate (0.06%) buffer) and contained lemon fragrance, yellow colouring and were thickened with hydroxyethylcellulose (Natrosol®, 0.4%). Formulations E and F contained no added colouring, fragrance or thickening agents. Formulations G, and H were based on a commercial product Vantocil HFC® (Arch Chemicals Inc.) which contains a benzalkonium chloride, PHMB, non-ionic surfactants, colour and perfume.

It is apparent from the results of Example 2 that compositions of the invention comprising a non-ionic surfactant and an antimicrobial component comprising at least two quaternary ammonium compounds or an antimicrobial component comprising PHMB only provide effective residual antimicrobial efficacy.

In comparison with formulations comprising a single quaternary ammonium compound, with or without PHMB (A, B, G and H), those formulations having more than one quaternary ammonium antimicrobial component showed improved residual antimicrobial efficacy.

Claims

1. An anti-microbial composition comprising (i) an antimicrobial component; (ii) a non-ionic surfactant; and (iii) a polar solvent, wherein the antimicrobial component (i) comprises (I) (a) at least two quaternary ammonium compounds and optionally (b) one or more additional anti-microbial agents, or (II) at least one polymeric biguanide as the only anti-microbial agent and wherein the composition is substantially free of anionic surfactant.

2. A composition according to claim 1 , comprising a component (b) which is at least one polymeric biguanidine.

3. A composition according to claim 1 or 2 comprising polyhexmethylene biguanide (PHMB).

4. A composition according to any one of the preceding claims wherein the ratio of (ii) to (i) is from about 100:1 to about 0.1 :1.

5. A composition according to any one of the preceding claims wherein at least one of the quaternary ammonium compounds has the formula

wherein R-i, R₂, R3 and R₄ represent, independently a substituted or unsubstituted and/or straight chain or branched and/or interrupted or uninterrupted alkyl, aryl, alkylaryl, arylalkyl, cycloalkyl, heterocyclyl or alkenyl group or two or more of R₁, R₂, R3 and R₄ together with the nitrogen atom form a substituted or unsubstituted heterocyclic ring, and wherein the total number of carbon atoms in the groups R-i, R₂, R₃ and R₄ is at least 4; wherein the substituents for the groups R-i, R₂, R₃ and R₄ are selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, heterocyclyl, substituted heterocyclyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, alkylaryl, substituted alkylaryl, arylalkyl, substituted arylalkyl, F, Cl, Br, I, -OR', -NR¹R", -CF₃, -CN, -NO₂, -C₂R¹, -SR', -N₃, -C(=O)NR'R", -NR'C(=O) R", -C(=O)R', -C(=O)OR', -OC(=O)R', -O(CR'R")_rC(=O)R', O(CR'R")_rNR"C(=O)R\ -O(CR'R")_rNR"SO₂R', -OC(=O)NR'R", -NR'C(=O)OR", - SO₂R', -SO₂NR¹R", and -NR¹SO₂R"; wherein R¹ and R" are individually hydrogen, Ci-C₈ alkyl, cycloalkyl, heterocyclyl, aryl, or arylalkyl, and r is an integer from 1 to 6, or R' and R" together form a cyclic functionality; wherein the term "substituted" as applied to alkyl, alkenyl, heterocyclyl, cycloalkyl, aryl, alkylaryl and arylalkyl refers to the substituents described above, starting with F and ending with -NR¹SO₂R"; and wherein X^' is halide or sulphonate.

6. A composition according to claim 5 wherein the quaternary ammonium compound has the formula (CH₃)n(A)mN⁺X^', wherein each A is independently as defined for R-i, R₂, R₃ and R₄, n is from 1 to 3 and m is from 1 to 3 provided that the sum of. n and m is 4.

7. A composition according to claim 6 wherein each A is independently a C_6- ₂₀ substituted or unsubstituted and/or straight chain or branched and/or interrupted or uninterrupted alkyl, aryl, alkylaryl, arylalkyl or cycloalkyl group.

8. A composition according to claim 6 or 7 wherein each A is independently a C_6-2O substituted or unsubstituted and/or straight chain or branched and/or interrupted or uninterrupted alkyl, aryl, alkylaryl group.

9. A composition according to claim 8 wherein the quaternary ammonium compound is selected from Cetrimide, dodecyltrimethylammonium bromide, tetradecyltrimethylammonium bromide, hexadecyltrimethylammonium bromide.

10. A composition according to claim 7 wherein n = 2 and m = 2 and each A is the same or different and is a straight chain, unsubstituted and uninterrupted C_8-12 alkyl group or a benzyl group.

11. A composition according to claim 5 or 6 wherein the quaternary ammonium compound is a benzalkonium halide or an aryl ring substituted derivative thereof.

12. A composition according to claim 11 wherein the benzalkonium halide has the formula:

wherein R is as defined for R₁, R₂, R₃ and R₄.

13. A composition according to claim 12 wherein R is a C_8--I₈ alkyl group or a mixture of C_8-I8 alkyl groups.

14. A composition according to claim 13 wherein R is a mixture of straight chain, unsusbtituted and uninterrupted C_8-18 alkyl groups.

15. A composition according to any of claims 5 to 14 wherein one or more of R-_I, R₂, R3 and R₄ is interrupted by a heteroatom selected from oxygen, nitrogen, sulphur, and a phosphorus-containing moiety.

16. A composition according to claim 1 , wherein at least one of the quaternary ammonium compounds is selected from domiphen bromide and benzethonium chloride, benzyldimethyl-n-tetradecyl-ammonium chloride, benzyldimethyl-n- dodecyl-ammonium chloride, n-dodecyl-n-tetradecyldimethyl-ammonium chloride and benzyl-C₁₂-C₁₆-alkyl-dimethyl-ammonium chloride, benzyl-cocoalkyl-dimethyl- ammonium chloride, di-n-decyldimethylammonium chloride, and Maquat A.

17. A composition according to claim 1 comprising polyhexamethylene biguanidine (PHMB) as component (II).

18. A composition according to any one of the preceding claims which additionally comprises a hydrophobic material.

19. A composition according to claim 18, wherein the hydrophobic material is selected from siloxanes, polysiloxanes and mixtures thereof.

20. A composition according to claim 19, wherein the hydrophobic material is. a siloxane of formulae (H₃C)[Si0(CH₃)₂]nSi(CH3)3, and/or (H₃C)[SiO(CH₃)H]_nSi(CHs)₃ wherein n is from 1 to 24.

21. A composition according to claim 20 wherein the siloxane is selected from hexamethyl disiloxane, octamethyl trisiloxane, decamethyl tetrasiloxane, dodecamethyl pentrasiloxane and mixtures thereof.

22. A composition according to any of the preceding claims wherein the polar solvent is selected from water, alcohols, esters, hydroxy and glycol esters, polyols and ketones, and mixtures thereof.

23. A composition according to claim 22 wherein the polar solvent is selected from water, ethanol, n-propanol, isopropanol, diethylene glycol and dipropylene glycol and mixtures thereof.

24. A composition according to any one of the preceding claims comprising colloids which comprise components (i) and (ii).

25. A composition according to any one of the preceding claims which on application to a surface acts to substantially reduce or control the formation of microbial colonies on or at the surface.

26. A process for preparing a composition according to any one of the preceding claims comprising (A) mixing together at least part of the antimicrobial component (i) and (ii) a non-ionic surfactant; and (B) adding (iii) a polar solvent to the product of step (A) and (C) agitating the resulting mixture until a clear solution is formed.

27. A process of claim 26 wherein in step (A), component (ii) is mixed with a concentrated solution of component (i) in a polar solvent.

28. A process of claim 26 or 27 wherein step (C) comprises sonication and/or stirring.

29. A composition obtainable by a process as defined in any one of claims 26 to 28.

30. A formulation comprising:

(A) at least one surfactant; and (B) a composition as defined in any one of claims 1 to 25 and 29.

31. A formulation according to claim 30, wherein the surfactant (A) comprises at least one non-ionic surfactant and/or at least one amophoteric surfactant.

32. A formulation according to claim 30 or 31, which does not comprise an anionic surfactant.

33. A formulation according to any one of claims 30 to 32 wherein the surfactant (A) consists essentially of at least one non-ionic surfactant.

34. A formulation according to claim 31 , wherein the surfactant (A) comprises at least one non-ionic surfactant and at least one amphoteric surfactant, provided that the total amount of amphoteric surfactant is 5% or less based on the total weight of the formulation.

35. A formulation according to any one of claims 30 to 32, wherein the surfactant (A) comprises an amine oxide.

36 A formulation according to any one of claims 30 to 35 in the form of a surface cleaner, a toilet care product, a dishwashing product, a laundry product, an outdoor cleaning product, a food spray, a personal care product, a baby product, a first aid product, a foot hygiene product or a car cleaning product.

37. A formulation according to any one of claims 30 to 36 which on application to a surface acts to substantially reduce or control the formation of microbial colonies on or at the surface.

38. A process for preparing a formulation as defined in any one of claims 30 to 37 which comprises mixing an anti-microbial composition with the other components of the formulation, wherein the anti-microbial composition has been prepared by a process according to claim 26.

39. A process according to claim 38, wherein the anti-microbial composition is mixed with a pre-prepared surfactant containing formulation.

40. The use of an anti-microbial composition according to any one of claims 1 to 25 or 29 or a formulation according to any one of claims 30 to 37 to provide anti-microbial properties to a surfactant containing formulation.

41. The use of a composition according to any one of claims 1 to 25 or 29 or a formulation according to any one of claims 30 to 37 to substantially reduce or control the formation of microbial colonies on or at a surface.

42. An anti-microbial composition, or formulation or use of the invention generally as herein described.

43 An anti-microbial composition or use generally as herein described with reference to the Examples.

44. A process for preparing an anti-microbial composition of the invention generally as herein described.