WO2010015801A2

WO2010015801A2 - Biocidal composition

Info

Publication number: WO2010015801A2
Application number: PCT/GB2009/001851
Authority: WO
Inventors: Paul Reip
Original assignee: Intrinsiq Materials Limited
Priority date: 2008-08-04
Filing date: 2009-07-27
Publication date: 2010-02-11
Also published as: GB0814237D0; TW201010614A; WO2010015801A3

Abstract

The invention relates to compositions including one or more particles, the particles may comprise a compound of formula MnXy where M is selected from calcium, aluminium, zinc, nickel, tungsten, copper, silicon, boron, carbon and combinations thereof; and X is selected from oxygen, nitrogen, carbon, phosphate, hydrogen phosphate, dihydrogen phosphate, carbonate, silicate, sulphate, nitrate, nitrite and combinations thereof; wherein n is in the range 1 to 3 and y is in the range 1 to 4; and a noble metal selected from copper, ruthenium, rhodium, palladium, silver, rhenium, osmium, iridium, platinum, gold, mercury and combinations thereof. Additional particles may be present which comprise a noble metal but which are substantially free of compounds of formula MnXy. The particles may be prepared by inserting a compound of formula MnXy and a noble metal into a plasma stream and cooling a resultant vapour upon exit from the plasma stream. The compositions including the particles may be used as biocides which have two or more of virucidal, bacterial and fungicidal effects.

Description

Biocidal Composition

Field

The invention relates to biocidal compositions, to processes for the preparation of these compositions and to uses thereof. In particular, the invention relates to a particulate biocidal composition with at least two properties selected from antiviral, antibacterial and antifungal properties.

Background

There is increasing concern about the presence of micro-organisms in the environment which could be damaging to human health. Such micro-organisms include bacteria, viruses and fungi. Of particular concern is the transmission of virulent pathogenic micro-organisms including bacteria such as Methicillin-resistant Staphylococcus aureus (MRSA), Pstudomonus aeruginosa (F. aeruginosa) and Escherichia coli (E. coli); viruses such as, the SARS Coronovirus (SARS-CoV), the avian influenza virus H5N1 , and the Human immunodeficiency virus (HIV). It can also be desirable to limit the growth of fungal species such as Candida albicans (C albicans) and Saccharomyces cerevisiae (S. cerevisiae).

Accordingly, there is an ongoing desire for new methods of preventing the growth of such micro-organisms and their transmission through the provision of new biocidal and/or biostatic products. Such products would beneficially have utility in reducing the transmission pathogenic micro-organisms through direct contact; or indirect contact as a result of interaction with surfaces in our surroundings, organisms in found in water, airborne organisms or organisms carried in vectors such as mosquitoes or meat.

It is known that some metals have bactericidal properties. For instance silver and copper ions are used in water treatment where they cause lysis of gram-negative bacteria such as Legionella, through disruption of the cell walls. These metals are often used in fine particulate form to maximise the surface area of the metal exposed to the environment. This minimises the amount of metal which must be used to achieve the desired bactericidal effect. However, there are problems associated with these products, for instance, it is necessary to balance the amount of metal used with the rate of consumption. The more metal is present, the higher the cost of the product, yet the less metal present the greater the rate of consumption or passivation by reaction with other chemicals. The problem of passivation is intrinsic to the use of such metals as they are often naturally reactive and prone to forming oxides, hydroxides or other salts. These side reactions inhibit the bactericidal effect of the metals. In addition, it is difficult to thermally process silver and copper containing materials without degradation or reaction and as such their utility in articles which require high temperature processing is limited.

Further, silver, copper and gold are known to migrate from their site of intended activity, leaching into their surrounds. This is undesirable as not only is the biocidal benefit of the metal lost, but neighbouring materials become contaminated. As a result, these elements are prohibited from use as biocides in some jurisdictions.

It would be advantageous to overcome or ameliorate some or ail of the above problems.

Nanoparticles have found use in pharmaceutical formulations to improve the solubility and/or biological activity of drug substances. Nanoparticles have also been used for medical purposes. For example, silver nanoparticles have been used to kill bacteria (Furno et al J. Antimicrob Chemother, 54(6), 1019-24 (2004)).

The application of nanoparticles as antiviral agents is discussed in WO 2007/093808 (Queen Mary & Westfield College et al.) which describes the use of nanoparticle metal salts for the reduction and prevention of virus transmission. In this document compounds of formula MnXy are described where M is (i) a metal selected from the group consisting of Calcium, Aluminium, Zinc, Nickel, Tungsten, or Copper; or (ii) a non-metal selected from the group consisting of Silicon, Boron or Carbon; in which n is equal to 1, 2, or 3, and X is (iii) a non- metal selected from the group consisting of Oxygen, Nitrogen, or Carbon; or (iv) an anion selected from the group consisting of phosphate, hydrogen phosphate, dihydrogen phosphate, carbonate, silicate, sulphate, nitrate, nitrite; in which y is equal to 0, 1, 2, 3, or 4; for reducing and/or preventing virus transmission. However, the disclosure of this document is limited to antiviral agents and fails to address the combined need for antiviral agents, antibacterial agents and antifungal agents. GB 0715728.2 (Qinetiq Nanomaterials Limited) also teaches the use of metals, in particular tungsten, in antiviral applications. A tungsten compound is provided of formula WnXy wherein X is a non-metal, a metalloid or an anion and wherein n is equal to 1 or 2 and y is equal to 0, 1, 2 or 3. This document teaches that more than one form of biocide may be achieved by mixing the tungsten compounds disclosed (antiviral) with secondary compounds known to have antimicrobial or antifungal properties. These combinations of compounds can be applied to a variety of articles without loss of biocidal activity.

However, the impact of virus outbreaks of SARS, avian flu and human influenza; and the ongoing problems in eliminating MRSA from our hospitals and the concern resulting therefrom, show how limited the current repertoire of defences are against infection. Accordingly there is a need for improved means to prevent the growth and/or transmission bacteria, viruses and fungi.

Summary

There is provided in a first aspect of the invention the use of a composition including particles which comprise: a) a compound of formula MnXy where M is selected from calcium, aluminium, zinc, nickel, tungsten, copper, silicon, boron, carbon and combinations thereof; and X is selected from oxygen, nitrogen, carbon, phosphate, hydrogen phosphate, dihydrogen phosphate, carbonate, silicate, sulphate, nitrate, nitrite and combinations thereof; wherein n is in the range 1 to 3 and y is in the range 1 to 4; and b) a noble metal selected from copper, ruthenium, rhodium, palladium, silver, rhenium, osmium, iridium, platinum, gold, mercury and combinations thereof; as a biocide, wherein the biocidal effect of the composition comprises two or more of virucidal, bactericidal and fungicidal effects.

The above composition provides a particle in which an inorganic matrix supports the noble metal. The presence of this matrix has been found to result in a composition which when used exhibits a biocidal effect at dilutions greater than would be expected through use of the noble metal alone. As discussed above, the biocidal effect of the inventive composition is selected from two or more of virucidal, bactericidal and fungicidal. In many cases, the composition will have antiviral properties and at least one of antibacterial and antifungal properties. For instance, the biocidal effect of the composition may comprise virucidal and bactericidal effects; virucidal and fungicidal effects; or virucidal, bactericidal and fungicidal effects. Alternatively, a composition exhibiting a combination of bactericidal and fungicidal effects is also envisaged.

The biocidal effect may include an antiviral effect (H5N1, Feline calicivirus) combined with an antibacterial effect (S. aureus, MRSA, P. aeruginosa and E. coli) and/or an antifungal effect (C. albicans and S. cerevisiae). The fungicidal use of the composition is typically in the control of yeasts. The provision of a single composition for use as a multi-organism biocide is advantageous as it is often difficult to prepare compositions which are virucidal and/or bactericidal and/or fungicidal due to the very distinct and different nature of viruses, bacteria and fungi. This is particularly the case when attempting to combine antiviral properties with antibacterial and/or antifungal properties. General purpose biocides are often composed of several ingredients, each of which are intended to attack a particular organism. Preparing a biocide in this way can give rise to problems of stability (the different active ingredients are often not mutually stable) and raises the cost of the product as more than one active must be included. The compositions described herein go some way to alleviating this problem.

In a second aspect of the invention there is provided a biocidal composition including particles of at least two different constitutions, a first particulate constitution and a second particulate constitution, the first particulate constitution comprising: a) a compound of formula MnXy where M is selected from calcium, aluminium, zinc, nickel, tungsten, copper, silicon, boron, carbon and combinations thereof; and X is selected from oxygen, nitrogen, carbon, phosphate, hydrogen phosphate, dihydrogen phosphate, carbonate, silicate, sulphate, nitrate, nitrite and combinations thereof; wherein n is in the range 1 to 3 and y is in the range 1 to 4; and b) a noble metal selected from copper, ruthenium, rhodium, palladium, silver, rhenium, osmium, indium, platinum, gold, mercury and combinations thereof; and the second particulate constitution comprising: a noble metal selected from copper, ruthenium, rhodium, palladium, silver, rhenium, osmium, iridium, platinum, gold, mercury and combinations thereof; wherein the second particulate constitution is substantially free of compounds of formula MnXy where M is selected from calcium, aluminium, zinc, nickel, tungsten, copper, silicon, boron, carbon and combinations thereof; and X is selected from oxygen, nitrogen, carbon, phosphate, hydrogen phosphate, dihydrogen phosphate, carbonate, silicate, sulphate, nitrate, nitrite and combinations thereof; wherein n is in the range 1 to 3 and y is in the range 1 to 4.

In a third aspect of the invention there is provided a process for the preparation of a biocidal composition inserting a compound of formula MnXy and a noble metal into a plasma stream and cooling a resultant vapour upon exit from the plasma stream; wherein

M is selected from calcium, aluminium, zinc, nickel, tungsten, copper, silicon, boron, carbon and combinations thereof; X is selected from oxygen, nitrogen, carbon, phosphate, hydrogen phosphate, dihydrogen phosphate, carbonate, silicate, sulphate, nitrate, nitrite and combinations thereof; n is in the range 1 to 3 and y is in the range 1 to 4; and the noble metal is selected from copper, ruthenium, rhodium, palladium, silver, rhenium, osmium, iridium, platinum, gold, mercury and combinations thereof.

In a fourth aspect of the invention there is provided an article or surface coated or impregnated with a biocidal composition including particles comprising: a) a compound of formula MnXy where M is selected from calcium, aluminium, zinc, nickel, tungsten, copper, silicon, boron, carbon and combinations thereof; and X is selected from oxygen, nitrogen, carbon, phosphate, hydrogen phosphate, dihydrogen phosphate, carbonate, silicate, sulphate, nitrate, nitrite and combinations thereof; wherein n is in the range 1 to 3 and y is in the range 1 to 4; and b) a noble metal selected from copper, ruthenium, rhodium, palladium, silver, rhenium, osmium, iridium, platinum, gold, mercury and combinations thereof; wherein a biocidal effect of the composition comprises two or more of virucidal, bactericidal and fungicidal effects.

A fifth aspect of the invention includes a use of a surface or article according to the fourth aspect of the invention for reducing and/or preventing one or more of (often two or more of) bacterial, viral or fungal transmission. A sixth aspect of the invention relates to the use of a biocidal composition as described in the second aspect as one or more of (often two or more of) an antiviral, antibacterial or antifungal agent.

Also described in a seventh aspect of the invention is a method for the reduction and/or prevention of one or more of (often two or more of) bacterial, viral and fungal transmission, the method comprising the use of the first aspect of the invention by application of the composition to an article or surface.

Composition

The composition of the invention will often comprise nanoparticles. By nanoparticle is meant particles having nanometric dimensions, and nanoparticles may have, for example, dimensions in the order of a few nanometres to a few micrometres. The nanoparticles may be of average particle size equal to or less than 2 μm, equal to or less than 200 nm, in many instances equal to or less than 20 nm. In many cases the composition will consist of nanoparticles with substantially all of the particles falling within the size range less than 2 μm, or the size range less than 200 nm, or the size range less than 20 nm. A common size range for the nanoparticles would be in the range of 1 to 500 nm prior to filtering, often 2 to 200 nm. However, where the particles have been filtered after production they may be present in the composition in the size range 2 to 50 nm, or even 2 to 20 nm.

For the purposes of this application the term "substantially all" is intended to mean 90% or above, typically 95% or above, most often 98% or above of the particles or other feature being described. The average particle size relates to the diameter at the widest point of the particle.

The specific surface area of the particles described may be in the range of from 150 m²/g to

*\ 7 7 about 1450 m /g, often, from 200 m /g to about 700 m /g, suitable values may comprise 150 m²/g, 640 m²/g, 700 m²/g. Voids present in the particles may be of the order of from 0.1 to about 0.8 ml/g, suitably of from 0.2 to about 0.7 ml/g, often about 0.6 ml/g.

The particles, including nanoparticles, are generally in the form of dry powders, but may also be in the form of liquids, sol-gels or polymers, as well as nanotubes. The particles may be agglomerated or in free association.

In many instances the compound of formula MnXy will be stoichiometric, in these cases n is equal to 1 , 2 or 3 and y is equal to 1 , 2, 3 or 4. In stoichiometric compounds, the values of n and y may vary depending upon the relative valencies of M and Y. However, non- stoichiometric compounds are also envisaged.

In general, the particles will have a structure in which the compound of formula MnXy and the noble metal are intimately mixed. For instance, analysis of a particle will reveal that

MnXy and the noble metal are evenly distributed throughout the particle. The particles may be substantially homogeneous. Alternatively, the particles may be prepared as layered

(core/shell) particles comprising an outer shell of noble metal and an inner core of the compound of formula MnXy either alone or mixed with the noble metal. In such examples at least a portion of the noble metal may be found on a surface of the particle; often the noble metal will at least partially coat the surface of the particle. For instance at least 10% of the surface area of the particle may be coated with noble metal, often at least 25%, or 50% of the surface area of the particle will be coated with noble metal. It may be desirable for the noble metal to coat in the range 50 - 100% of the surface area of the particle, perhaps in the range 70 - 100% or 85 - 100%.

The relative ratio of the compound of formula MnXy and the noble metal is variable in accordance with the identity of each component of the particle and the particular application for which the biocidal composition is to be used as would be appreciated by the person skilled in the art.

Where discussing the mixing and structure of the particles it will often be the case that at least 50% of the particles in any composition will have the property described above, in some instances in the range 80 - 100%, often 90 or 95 - 100% of the particles.

The composition may additionally include a second type of particle of second particulate constitution which differs from the constitution of the first type of particle. The second type of particle may be of size, shape and structure as described above. Particles of the second particulate constitution comprise a noble metal selected from copper, ruthenium, rhodium, palladium, silver, rhenium, osmium, iridium, platinum, gold, mercury and combinations thereof; wherein the particles are substantially free of compounds of formula MnXy where M is selected from calcium, aluminium, zinc, nickel, tungsten, copper, silicon, boron, carbon and combinations thereof; and X is selected from oxygen, nitrogen, carbon, phosphate, hydrogen phosphate, dihydrogen phosphate, carbonate, silicate, sulphate, nitrate, nitrite and combinations thereof; wherein n is in the range 1 to 3 and y is in the range 1 to 4.

As used herein the term "substantially free" is intended to mean that only trace levels of the compound of formula MnXy are present. For instance, the compound of formula MnXy may be present in the second particulate constitution in the range 0 - 1 wt%, often 0 - 0.5 wt%, more often 0 - 0.2 wt%, generally 0 - 0.1 wt%, in many instances compounds of formula MnXy will be absent from the second particulate constitution.

ϊt has surprisingly been found that the combination of particles of the first particulate constitution and particles of the second particulate constitution offers a greater biocidal effect when used in a biocidal composition than is observed where all of the particles are of substantially the same constitution. Most noticeably a bactericidal and fungicidal effect is observed at particle dilutions far higher than where substantially all of the particles contain both the matrix material formed from the compound of formula MnXy and the noble metal. Further, where both the compound of formula MnXy and the noble metal have independently observable biocidal effects, the combination of these two particle types may provide a biocidal effect which is synergistic in that it is greater than the sum of the two independently observed effects.

The relative ratio of particles of each constitution will depend upon the final properties required from the biocidal composition. For instance, if the bactericidal effect of the composition is required to be greater than the virucidal effect, it may be the case that the particles of the second particulate composition be present in a greater amount than the particles of the first particulate composition or vice versa. However, in general it is envisaged that where both particles are present, the composition will comprise in the range 40 - 60 wt% of each particle type, often 45 - 55 wt%, more often both particles will be present in substantially equal amounts. In some cases M may be a single element and X a single anion or metalloid or non-metal. In such cases, M is selected from calcium, aluminium, zinc, nickel, tungsten, copper, silicon, boron, and carbon; and X is selected from oxygen, nitrogen, carbon, phosphate, hydrogen phosphate, dihydrogen phosphate, carbonate, silicate, sulphate, nitrate, and nitrite.

In many examples M and X will be selected to provide a compound of formula MnXy which is physically robust and stable to high temperature. It will often be the case that M comprises tungsten as tungsten compounds are stable to high temperature and have been found by the inventors to have a substantial bactericidal and fungicidal effect even when exposed to harsh conditions during processing. X may be carbon and/or oxygen. Often M is tungsten and X is carbon so that MnXy comprises tungsten carbide, in other words MnXy may be selected from WC, W₂C and combinations thereof.

Often the noble metal will be independently selected from silver, copper, gold and combinations thereof. The combination of tungsten carbide and copper, silver or a combination thereof has been found to offer a particularly effective biocidal effect for antiviral and antibacterial use.

Preparation

Particulate compositions can be prepared by, for instance, gas phase synthesis or sol-gel processing. In gas phase synthesis, particles, often nanoparticles, may be generated by evaporation and condensation (nucleation and growth) in a subatmospheric inert-gas environment. Various aerosol processing techniques may be used to improve the production yield of nanoparticles. These include synthesis by combustion flame, plasma, laser ablation, chemical vapor condensation, spray pyrolysis, electrospray and plasma spray.

Ball and other forms of milling can also be used to produce particles, including nanoparticles. In milling techniques the ultimate particle size depends upon factors including the size, morphology and composition of the grinding medium, process variables, design, and operation of the mill.

Where it is desirable to minimise the size variation between particles produced, gas phase synthesis is a reliable way of achieving this. The uniformity of particle size is typically achieved by using a combination of rigorous control of nucleation-condensation growth and avoidance of coagulation by diffusion and turbulence as well as by the effective collection of particles and their handling afterwards. The stability of the collected particle powders against agglomeration, sintering, and compositional changes can be ensured by collecting the particles in liquid suspension.

One production method that is suitable for the production of nanoparticles is the Tesima® process (described in WO 01/78471 and WO 01/58625) where a high temperature DC plasma (a plasma torch) is used to a generate plasma stream within a gas envelope. The gas envelope may be inert, comprising argon or helium for instance; or may contain a reactive gas, for instance hydrogen. Hydrogen may be present in the range 0 to 20 wt%, 1 to 10 wt%, or 2 to 5 wt%. Materials (either pre-produced feedstock or mixed feedstock), or liquids, can be placed into the plasma causing rapid vaporisation. The resultant vapour then exits the plasma where it may be cooled by quantities of cold gas. These gases can be inert (such as argon or helium), air, or can include trace components to develop the chemistry /morphology/size that is required. The rapid cooling (greater than 100,000 degree per second) then freezes the particle for subsequent cooling and collection using a combination of techniques that can include solid or fabric filters, cyclones and liquid systems. The materials can also be collected directly into containers under either inert gas or into various liquids.

The invention includes a process comprising inserting a compound of formula MnXy and a noble metal into a plasma stream and cooling the resultant vapour upon exit from the stream. The plasma stream may, in some instances, be a thermal plasma stream. In this process, the compound of formula MnXy and the noble metal may combined before insertion into the plasma stream, at the point of insertion into the plasma stream, or not at all. Further, the noble metal may, in some instances, be combined with the compound formula MnXy after the compound formula MnXy has been exposed to the plasma stream but prior to cooling the resultant vapour. This results in particles with a core of the compound formula MnXy which is at least partially coated in the noble metal.

Often, the compound of formula MnXy and the noble metal are co-fed into a thermal plasma torch as described above. Typically, the raw materials from which the particles are created will be in fine particulate form. This may require a pre-treatment step, such as a grinding step, to prepare the raw materials for reaction. In many instances particles of the raw materials will be of size less than 10 μm diameter, often in the range l μm - 5 μm, or the range 2 μm - 4 μm. Utilising the raw materials in fine particulate form increases the surface area available for reaction and hence reaction rate. A more intimate mixing of components is also facilitated. However, it has been found that using particles of size less than 1 μm or 2 μm can impair processing as the new materials begin to bind or clump together. This reduces the flow rate of material through the processing equipment and increases the risk that pipework will become clogged causing production to cease whilst the processing equipment is cleaned.

In some instances the noble metal will be at least partially combined with a compound of formula MnXy prior to particle formation. In some examples the noble metal will be substantially entirely combined with a compound of formula MnXy prior to particle formation, for instance by using a milling process. Alternatively, both the compound of formula MnXy and the noble metal could be at least partially or substantially entirely dissolved in an alternative solvent prior to particle formation. As used herein the terms "at least partly" and "substantially entirely" are intended to have their common general meanings in the art. For instance "substantially entirely", as used herein, is intended to mean that only a very small amount of solute remains visible on the macroscopic scale as a separate phase from the solute-solvent solution.

The particles may be formed by simple blending of the compound of formula MnXy and the noble metal. Alternatively, milling processes may be used as described above. Such milling generally results in a mechanical joining of the compound of the formula MnXy and the noble metal.

The use of a thermal plasma torch facilitates the production of particles of substantially uniform size with a high surface area which is stable to high temperature. This allows the resulting biocidal composition to be used in applications where the processing is at high temperature, for instance, it provides a possible application in the incorporation of the biocidal composition into plastics products creating a product with surfaces which are intrinsically hostile to microorganisms. It has surprisingly been found that the preparation of particles by inserting a compound of formula MnXy and a noble metal into a plasma stream and cooling the resultant vapour upon exit from the stream produces particles which when used in a biocidal composition offer a greater biocidal effect than is observed with other preparation techniques, for instance mechanical milling. Most noticeably a bactericidal and fungicidal effect is observed at particle dilutions far higher than where the particles are formed using milling or other techniques which simply co-mingle the compound of formula MnXy and the noble metal.

Without being bound by theory, this may be because the particles made using plasma torches are of dual composition. More particularly, the particles produced have at least two different constitutions, a first particulate constitution and a second particulate constitution, the first particulate constitution including the noble metal and the matrix material of formula MnXy, the second particulate constitution including the noble metal without the matrix material. Specifically, the first particulate constitution comprises: a) a compound of formula MnXy where M is selected from caicium, aluminium, zinc, nickel, tungsten, copper, silicon, boron, carbon and combinations thereof; and X is selected from oxygen, nitrogen, carbon, phosphate, hydrogen phosphate, dihydrogen phosphate, carbonate, silicate, sulphate, nitrate, nitrite and combinations thereof; wherein n is in the range 1 to 3 and y is in the range 1 to 4; and b) a noble metal selected from copper, ruthenium, rhodium, palladium, silver, rhenium, osmium, iridium, platinum, gold, mercury and combinations thereof; and the second particulate constitution comprises: a noble metal selected from copper, ruthenium, rhodium, palladium, silver, rhenium, osmium, iridium, platinum, gold, mercury and combinations thereof; wherein the second particulate constitution is substantially free of compounds of formula MnXy where M is selected from calcium, aluminium, zinc, nickel, tungsten, copper, silicon, boron, carbon and combinations thereof; and X is selected from oxygen, nitrogen, carbon, phosphate, hydrogen phosphate, dihydrogen phosphate, carbonate, silicate, sulphate, nitrate, nitrite and combinations thereof; wherein n is in the range 1 to 3 and y is in the range 1 to 4. Particles prepared using other methods, in particular milling, are thought to be of unitary structure with each particle including both the compound of formula MnXy and the noble metal.

Further, where both the compound of formula MnXy and the noble metal have independently observable biocidal effects, the combination of these two substances may provide a biocidal effect which is synergistic in that it is greater than the sum of the two independently observed effects.

The composition may be formulated for use in an appropriate carrier, coating or solvent such as water, methanol, ethanol, acetone, water soluble polymer adhesives, such as polyvinyl acetate, epoxy resin, polyesters etc. as well as coupling agents and antistatic agents. Solutions of biological materials may also be used such as phosphate buffered saline (PBS) or simulated biological fluid (SBF).

The concentration of particles may lie in the range of 0.001 - 20 wt%, often 0.01 - 10 wt%, on occasion 0.1 - 5 wt%.

Alternatively, the particles may be included in a composition in powder form. They may be coated onto or impregnated into a surface or article, or mixed with an absorbent powder such as Fuller's earth or sand.

Use

The reduction and/or prevention of the spread of pathogenic micro-organisms includes the prevention of infection of a subject with the virus, bacterium or fungus; in addition to the prevention of transmission from a first location to a second location, or the prevention of transmission through a barrier material. The subject may be a human or a non-human animal, suitably a non-human mammal. The invention may therefore find application in the field of human medicine and animal veterinary medicine as well as in the field of infection control in a non-medical context, such as a prophylactic against the transmission and/or spread of micro-organisms. The compositions described can be applied to enclosed ventilation fabrics for public buildings, hospitals, and to vehicles such as cars, trains, ships and aeroplanes. The compositions may also find use in medical applications, such as in filtering materials, i.e. in filtration of biological fluids such as plasma, blood, milk or semen to inactivate any viruses, bacteria and/or fungi present.

The antiviral particles may be coated onto fabrics and surfaces of different products such as furniture, paints/coatings, book covers and computer keyboards to produce products with biocidal properties. Such products will provide a low cost route to a safer environment for hospitals, children, patients and the elderly. Further uses may include air ventilation systems for enclosed environments such as passenger aeroplanes, for instance preventing the entry or outlet of airborne viruses.

An article of the invention may be coated or impregnated with the biocidal composition described above. The composition will work most effectively where at least one coated or impregnated surface of the article cυmes into direct contact with the micro-organisms to be removed. For example, protective clothing may comprise fabrics and/or fibres coated with the antiviral composition and the exposed surfaces of filters may be coated with the composition. Similarly, a counter top could be impregnated with or coated in the biocidal composition to produce a surface which is intrinsically hostile to micro-organisms. Such a surface could be used in hospitals to help improve the safety of surgical procedures or domestically to reduce the transmission of disease through the presence of pathogenic micro-organisms around the home.

The coating and impregnation processes which may be used are those common in the art and would be well known to the person skilled in the art. They include spray coating, extrusion- lamination, co-extrusion, electro-spray coating, dipping or plasma coating.

In addition to coating or impregnating the article itself, the components of the article may be pre-treated with the composition. For instance, an article may be composed of fibres coated with the biocidal composition. Such articles will often be selected from filters, face masks, surgical masks, respirator masks, hats, hoods, trousers, shirts, gloves, boiler-suits and surgical gowns. Medical and veterinary devices and prophylactic devices may also be used. Alternatively, surfaces that are routinely contacted by people, especially in_^communal areas such as toilets, doors, switches etc. may be coated and/or impregnated with the composition. Similarly, areas of food preparation and utensils or equipment used therein may be coated with a compound according to the invention.

Filters may be prepared from any suitable natural or artificial material. The filter may be an air filter. An air filter is a device which removes contaminants, often solid particles from air. Air filters are often used in diving air compressors, ventilation systems and any other situation in which air quality is important, such as in air-conditioning units. An air filter includes devices which filter air in an enclosed space such as a building or a room, as well as apparatus or chambers for handling viral materials. Other articles which perform a protective function such as curtains or screens may therefore also be considered as air filters.

Air filters may be composed of paper, foam, cotton filters, or spun fibreglass filter elements. Alternatively, the air filter may use fibres or elements with a static electric charge. There are four main types of mechanical air filters: paper, foam, synthetics and cotton.

An example of pleated-paper air filters designed for in-duct use with home heating, ventilation and air-conditioning (HVAC) systems is the 3M "Filtrete" product.

Polyester fibre can be used to make web formations used for air filtration. Polyester can be blended with cotton or other fibres to produce a wide range of performance characteristics. In some cases polypropylene may be used. Tiny synthetic fibres known as micro-fibres may be used in many types of high efficiency particulate air (HEPA) filters. High performance air filters may use oiled layers of cotton gauze.

Alternatively, the filter may be used to filter liquids. Such filters may be composed of any suitable fibre as described above. Filters used to filter liquids may be used to filter potable liquids for human or animal consumption, water for general domestic use, fluids for medical use, such as plasma or saline solutions, or pharmaceutical formulations for injection, or other biological liquids which may come into contact with a patient.

Articles of protective clothing are suitable composed of fibres which are coated with a composition of particles as defined above. The article of protective clothing may be a face mask. Such masks may cover the whole face of the user of a part thereof, suitably the external areas of the nose and/or mouth of the wearer.

The article of protective clothing may be prepared from any suitable fibre or fabric and may comprise natural and/or artificial fibres. Suitable natural fibres include cotton, wool, cellulose (including paper materials), silk, hair, jute, hemp, sisal, flex, wood, bamboo, metal or carbon. Suitable artificial fibres include polyester, rayon, nylon, Kevlar®, lyocell

(Tencel®), polyethylene, polypropylene, polyimide, polymethyl methacrylate, poly(carboxylato phenoxy) phosphazene (PCPP), fibre glass (glass) or ceramics. The article of clothing may be selected from the group consisting of face masks (surgical masks, respirator masks), hats, hoods, trousers, shirts, gloves, skirts, boiler suits and surgical gowns

(scrubs). Such clothing may find particular use in a hospital where control of infection is of paramount importance.

In aspects of the invention relating to articles of protective clothing or filters, it should be noted that the articles of cioihing or filters may be made of mixed fibres from any source as described above.

Assessment of Biocidal Effect

The biocidal effect of the particles and compositions described herein is at least two-fold. Specifically, the compositions of the invention exhibit at least two of an antiviral effect, an antibacterial or an antifungal effect.

As used herein the term "micro-organism" is intended to include viruses, bacteria and fungi; generally these will be pathogenic micro-organisms, often virulent micro-organisms.

Transmission

The reduction and/or prevention of virus, bacterial and/or fungal transmission may be defined as a reduction on microbial titre of at least 90% following administration of a composition of nanoparticles as defined herein to a preparation of one or more of these microbes. Preferably the reduction on titre is at least 93%, 94% or 95%, most preferably 98%, 99% or 100%. Reduction and/or prevention of transmission is demonstrated by the inactivation of the microbe upon contact with the particles. A reduction in titre of 70% or less is not an effective reduction sufficient to avoid infection. The present invention provides a means for reducing titre such that infection is prevented or avoid to a significant extent.

The titre is a quantification of the number of microbes in a given sample. The tires may be performed by using the Hemagglutination Assay (HA). The HA assay is particularly suitable for virus detection because viral families have surface or envelope proteins that are able to agglutinate animal Red Blood Cells (RBC) and bind to N-acetylneuraminic acid residues on the cell surface of the RBCs. The RBC will form a type of lattice following viral binding which can be quantitated.

The HA procedure is an easy, simple and rapid method and can be applied to large amounts of samples. The detailed conditions depend on the type of microbe. For instance, some viruses bind RBCs only at certain pH values, others at certain ionic strengths. However, these are well known to the person skilled in the art and can be readily identified according to the microbe in question. A microbe dilution will be applied to a RBC dilution for a suitable period of time under appropriate conditions. Subsequently, the formation of lattices will be counted and the titre calculated.

Alternatively, a bioluminescent assay may be used. For instance, the bacterial contamination of water may be determined by incubation of the water, filtration of the resulting bacterial suspension, release of bacterial ATP using a reagent such as dimethyl sulfoxide and detection of ATP concentration using luminescent techniques.

The titre may also be determined using a β-D-glucan assay. This assay is performed on incubated blood or plasma samples. A limulus amebocyte lysate is added to the sample and the change in optical density determined using spectro-photometric techniques. β-D-glucan assays are often used to obtain fungal and bacterial titres.

The present invention may provide a means to reduce the viral titre of a virus, preferably the virus is selected from Influenza, Measles, Coronavirus, Mumps, Marburg, Ebola, Rubella, Rhinovirus, Poliovirus, Hepatitis A, Smallpox, Chicken-pox, Severe Acute Respiratory Syndrome virus or SARS virus, HIV and associated non-human animal immunodeficiency retroviruses such as Simian Immunodeficiency Virus (SIV), Rotavirus, Norwalk virus and Adenovirus. Norwalk virus includes its surrogate Feline calicivirus virus. Influenza viruses include both human and avian forms of the virus.

Unless otherwise stated each of the integers described in the invention may be used in combination with any other integer as would be understood by the person skilled in the art.

Further, although all aspects of the invention preferably "comprise" the features described in relation to that aspect, it is specifically envisaged that they may "consist" or "consist i essentially" of those features outlined in the claims.

Unless otherwise indicated all percentages appearing in the specification are percentages by weight of the element being described. In addition, unless otherwise stated, all numerical values appearing in this application are to be understood as being modified by the term "about".

Examples

In order that the invention may be more readily understood, it will be described by way of example only, by reference to the accompanying figures, of which:

Figure 1 is an EDX spectrum of Area 1 showing densely packed particles. This spectrum provided background data against which individual particles could be analysed;

Figure 2 is a spot mode spectrum illustrating the elemental composition of Area 1;

Figures 3a - 3d are enlarged EDX spectra of Area 1 illustrating the presence of silicon, silver, copper and tungsten-containing particles;

Figure 4 is an EDX spectrum of Area 2, a selection of elemental maps were acquired from this region;

Figures 5a - 5c are enlarged EDX spectra of Area 2 illustrating the presence of silver, copper and tungsten-containing particles; Figure 6 is an EDX spectrum of Area 3, a selection of elemental maps were acquired from this region;

Figures 7a - 7d are enlarged EDX spectra of Area 3 illustrating the presence of silicon, silver, copper and tungsten-containing particles; Figure 8 is an EDX spectrum of Area 4, a selection of elemental maps were acquired from this region;

Figures 9a - 9d are enlarged EDX spectra of Area 4 illustrating the presence of silicon, silver, copper and tungsten-containing particles; Figure 10 is an EDX spectrum of Area 5, a selection of elemental maps were acquired from this region;

Figure 1 1 is an enlarged EDX spectrum of Area 5 illustrating the presence of copper- containing particles;

Figure 12 is a spot mode spectrum illustrating the elemental composition of the particle identified in the enlarged EDX spectrum shown in Figure 1 1 ;

Figure 13 is an EDX spectrum of Area 6, spot mode spectra were acquired from this region;

Figures 14a and 14b are spot mode spectra illustrating the elemental composition of particles appearing in Area 6;

Figure 15 is an EDX spectrum of Area 7, spot mode spectra were acquired from this region; Figures 16a and 16b are spot mode spectra illustrating the elemental composition of particles appearing in Area 7;

Figure 17 is an EDX spectrum of Area 8, spot mode spectra were acquired from this region; and

Figure 18 is a spot mode spectrum illustrating the elemental composition of a particle appearing in Area 8.

Transmission Electron Microscopy (TEM) was used to analyse a series of silver/copper and tungsten carbide containing particles. The particles were produced using the Tesima® process. The feedstock comprised:

The nanoparticles were dispersed onto a perforated carbon aluminium grid by ultra-sonic agitation of the powder in ethanol followed by pipette dispersion onto the grid. The solution was allowed to settle for two minutes to avoid any large clusters being taken into the pipette. Micrographs were produced using a Philips Techni F20 at 200 Kv with a probe diameter of less than 5 run. Elemental EDX maps and spectra in spot mode were then acquired. All images are in bright field and were acquired in STEM mode. Area 1

Aluminium, silicon, silver, copper, tungsten, oxygen and carbon were detected in this area (as shown in Figures 1 and 2). Further analysis of the EDX maps (Figures 3a - 3d) showed the presence of particles containing a combination of silicon, copper and tungsten. Discrete silver particles were also observed (30 - 50 nm). These are illustrated on the maps. Accordingly, particles of formula MnXy and a noble metal may be present, as are particles comprising noble metals only.

Area 2

The EDX spectra of Area 2 show the presence of particles composed of single elements, examples of these are illustrated on the silver and tungsten maps (Figures 4 and 5a-c). In addition, regions comprising two or more elements are present, these regions may be particles composed of more than one element and may contain compounds of formula MnXy.

Area 3

As with Area 2, particles which may be single element particles were observed (including tungsten and the noble metals silver and copper). However, in Area 3 more of the particles comprise two or more elements present in combination (Figures 6 and 7a-d) making possible the presence of compounds of formula MnXy and noble metals within a single particle.

Area 4

Figures 8 and 9a-d illustrate the particle distribution of Area 4. Silver particles are present in this region and possibly individual tungsten and silicon-containing particles. Where present, copper is primarily co-located with tungsten indicating the possible presence of particles containing tungsten compounds of formula MnXy and the noble metal copper, and particles containing a noble metal (silver) alone. Area 5

Area 5 (Figures 10 - 12) provides evidence for individual copper containing particles in the composition. A spot mode spectrum was obtained of one of these particles (the particle highlighted in the example), the predominant element appearing in the spectrum is copper. Analysis of this area also indicates the presence of oxidised compounds (possibly compounds of formula MnXy) as oxygen levels are unevenly distributed within the sample.

Area 6

The spectra acquired for this area (Figure 13) clearly show the presence of a particle containing copper and silicon (Figure 14a, possibly with copper present in elemental form), and a particle containing tungsten, copper and silicon (Figure 14b, possibly a combination of a compound of formula MnXy and a noble metal).

Area 7

The spectra acquired for this area (Figure 15) show the presence of a particle containing silicon, copper and tungsten (Figure 16a, possibly a combination of a compound of formula MnXy and a noble metal), and a particle containing silver and copper (Figure 16b).

Area 8

The spectrum of the particle shown in Figure 17 indicates that this particle contains copper, tungsten and silicon (Figure 18, possibly a combination of a compound of formula MnXy and a noble metal).

General Observations

It was observed that silver particles were present as discrete particles in the size range less than 10 nm. Occasional larger silver particles of size in the range 30 - 50 nm were present. Copper and Tungsten containing particles were generally of size range 20 - 50 nm, these elements often appeared mixed within a single particle although discrete particles of each element were also observed. Aluminium and silicon were also present mixed within single particles.

Claims

1. Use of a composition including particles which comprise: a) a compound of formula MnXy where M is selected from calcium, aluminium, zinc, nickel, tungsten, copper, silicon, boron, carbon and combinations thereof; and X is selected from oxygen, nitrogen, carbon, phosphate, hydrogen phosphate, dihydrogen phosphate, carbonate, silicate, sulphate, nitrate, nitrite and combinations thereof; wherein n is in the range 1 to 3 and y is in the range 1 to 4; and b) a noble metal selected from copper, ruthenium, rhodium, palladium, silver, rhenium, osmium, iridium, platinum, gold, mercury and combinations thereof; as a biocide, wherein the biocidal effect of the composition comprises two or more of virucidal, bactericidal and fungicidal effects.

2. A use according to claim 1 wherein the particles comprise nanoparticles of average particle size equal to or less than 2 μm.

3. A use according to claim 2 wherein the particles comprise nanoparticles of average particle size equal to or less than 20 nm.

4. A use according to any preceding claim wherein the compound of formula MnXy is non-stoichiometric.

5. A use according to any preceding claim wherein the compound of formula MnXy and the noble metal are intimately mixed within at least 80% of the particles.

6. A use according to any preceding claim wherein at least a portion of the noble metal may be found on a surface of at least 80% of the particles.

7. A use according to any of claims 1 to 4 wherein the noble metal at least partially coats the surface of the particle.

8. A use according to any preceding claim wherein the composition additionally includes particles comprising a noble metal selected from copper, ruthenium, rhodium, palladium, silver, rhenium, osmium, iridium, platinum, gold, mercury and combinations thereof; wherein the additional particles are substantially free of compounds of formula MnXy where M is selected from calcium, aluminium, zinc, nickel, tungsten, copper, silicon, boron, carbon and combinations thereof; and X is selected from oxygen, nitrogen, carbon, phosphate, hydrogen phosphate, dihydrogen phosphate, carbonate, silicate, sulphate, nitrate, nitrite and combinations thereof; wherein n is in the range 1 to 3 and y is in the range 1 to 4.

9. A use according to any preceding claim wherein the compound of formula MnXy is stable to high temperature.

10. A use according to any preceding claim wherein M comprises tungsten.

1 1. A use according to any preceding claim wherein X comprises carbon and/or oxygen.

12. A use according to any preceding claim wherein MnXy is selected from WC, W₂C and combinations thereof.

13. A use according to any preceding claim wherein the noble metal is selected from silver, copper, gold and combinations thereof.

14. A biocidal composition comprising particles of at least two different constitutions, a first particulate constitution and a second particulate constitution, the first particulate constitution comprising: a) a compound of formula MnXy where M is selected from calcium, aluminium, zinc, nickel, tungsten, copper, silicon, boron, carbon and combinations thereof; and X is selected from oxygen, nitrogen, carbon, phosphate, hydrogen phosphate, dihydrogen phosphate, carbonate, silicate, sulphate, nitrate, nitrite and combinations thereof; wherein n is in the range 1 to 3 and y is in the range 1 to 4; and b) a noble metal selected from copper, ruthenium, rhodium, palladium, silver, rhenium, osmium, iridium, platinum, gold, mercury and combinations thereof; and the second particulate constitution comprising: a noble metal selected from copper, ruthenium, rhodium, palladium, silver, rhenium, osmium, iridium, platinum, gold, mercury and combinations thereof; wherein the second particulate constitution is substantially free of compounds of formula MnXy where M is selected from calcium, aluminium, zinc, nickel, tungsten, copper, silicon, boron, carbon and combinations thereof; and X is selected from oxygen, nitrogen, carbon, phosphate, hydrogen phosphate, dihydrogen phosphate, carbonate, silicate, sulphate, nitrate, nitrite and combinations thereof; wherein n is in the range 1 to 3 and y is in the range l to 4.

15. A process for the preparation of a particulate biocidal composition, the process comprising inserting a compound of formula MnXy and a noble metal into a plasma stream and cooling a resultant vapour upon exit from the plasma stream, wherein:

M is selected from calcium, aluminium, zinc, nickel, tungsten, copper, silicon, boron, carbon and combinations thereof;

X is selected from oxygen, nitrogen, carbon, phosphate, hydrogen phosphate, dihydrogen phosphate, carbonate, silicate, sulphate, nitrate, nitrite and combinations thereof; n is in the range 1 to 3 and y is in the range 1 to 4; and the noble metal is selected from copper, ruthenium, rhodium, palladium, silver, rhenium, osmium, iridium, platinum, gold, mercury and combinations thereof.

16. A process according to claim 15 wherein the noble metal is at least partially dissolved in a compound of formula MnXy prior to insertion into the plasma stream.

17. A process according to claim 15 or claim 16 wherein the plasma is in a gaseous envelope and the vapour is cooled by gas.

18. A process according to any of claims 15 to 17 wherein the compound of formula MnXy and the noble metal are co-fed into a thermal plasma torch.

19. An article or surface coated or impregnated with a biocidal composition including particles comprising: a) a compound of formula MnXy where M is selected from calcium, aluminium, zinc, nickel, tungsten, copper, silicon, boron, carbon and combinations thereof; and X is selected from oxygen, nitrogen, carbon, phosphate, hydrogen phosphate, dihydrogen phosphate, carbonate, silicate, sulphate, nitrate, nitrite and combinations thereof; wherein n is in the range 1 to 3 and y is in the range 1 to 4; and b) a noble metal selected from copper, ruthenium, rhodium, palladium, silver, rhenium, osmium, iridiurn, platinum, gold, mercury and combinations thereof; wherein a biocidal effect of the composition comprises two or more of virucidal, bactericidal and fungicidal effects.

20. An article according to claim 19, wherein the article is composed of fibres coated with the biocidal composition.

21. An article according to claim 19 or claim 20 selected from filters, face masks, surgical masks, respirator masks, hats, hoods, trousers, shirts, gloves, boiler-suits and surgical gowns.

22. Use of a composition, surface or article according to any of claims 14 and 19 to 21 for reducing and/or preventing two or more of bacterial, viral or fungal transmission.

23. Use of a biocidal composition according to claim 14 as two or more of an antiviral, antibacterial or antifungal agent.

24. A method for the reduction and/or prevention of two or more of bacterial, viral and fungal transmission, the method comprising the use of any of claims 1 to 13 by application of a composition to an article or surface.

25. Use, composition, article or method according to any of claims 1 to 13 and 19 to 21 wherein the fungicidal effect is on yeast.

26. A composition, article, surface, use or method substantially as described herein.

27. A composition or method for the reduction and/or prevention of bacterial, viral and/or fungal transmission substantially as described herein.