WO2014209222A1

WO2014209222A1 - Antimicrobial coating composition

Info

Publication number: WO2014209222A1
Application number: PCT/SG2013/000267
Authority: WO
Inventors: Ping Kwong Peter CHAN; Chin Peng Tan
Original assignee: Lanxess Butyl Pte. Ltd.
Priority date: 2013-06-27
Filing date: 2013-06-27
Publication date: 2014-12-31
Also published as: HK1201119A2; TW201542724A

Abstract

The present invention is directed to a coating composition, particularly an architectural coating composition, comprising antimicrobial agents based on zinc pyrithione and zinc oxide, a process for the manufacture of such coating compositions, and their use. Coating compositions comprising zinc pyrithione and zinc oxide as antimicrobial agents exhibit antiviral, antibacterial and/or antifungal activities and efficacies, rendering them suitable for creating hygienic surfaces. The antimicrobial efficacy of these coating compositions will have applications in areas where microbial transmission and infection potential are high. More specifically, the coating compositions comprising zinc pyrithione and zinc oxide exhibit a synergistic antiviral efficacy against the Coxsackievirus type A16 and Enterovirus type 71, viruses responsible for the transmission and infection of hand-foot-mouth disease in children. Additional antiviral or antimicrobial agents that can be used in the coating compositions of the invention include silver in the form of organic or inorganic silver salts.

Description

ANTIMICROBIAL COATING COMPOSITION

BACKGROUND OF THE INVENTION Field of the Invention

The present invention is directed to a coating composition comprising antimicrobial agents based on zinc compounds, architectural coatings comprising these compositions, a process for the

manufacture of such coating compositions and the use of zinc compounds as antimicrobial, and particularly antiviral, agents in coating compositions.

Description of Background Art

Antimicrobial coatings have been a subject of many investigations. Micro-organisms such as bacteria, viruses, fungi, mould and mildew deposited on surfaces can cause sickness and death in humans. These micro-organisms can cause sneezing and coughing, as well as major respiratory illnesses that may cause death. A surface can be temporarily sterilized with disinfectants; however, effective and durable antimicrobial surfaces are desirable. This requirement has become

increasingly urgent today with the development of drug resistant pathogens such as MRSA

(Methicillin Resistant Staphylococcus aureus) and C. difficile. One way to achieve effective and ^ durable antimicrobial surfaces is to apply antimicrobial coatings on walls and surfaces which frequently come into contact with humans.

An example investigation of antimicrobial coatings is described in US Patent Number 5,968,538: Anti-bacterial/antiviral coatings, coating process and parameters thereof. This patent describes a method for coating a substrate with an anti-pathogenic agent to render the substrate suitable for use as a barrier against pathogens. The coating can be made up of two or more than two layers, forming a dual or multilayered coating. The anti-pathogenic agent consists of the mixture of PVP-I and N-9, in a mixed ratio of from about 100:0 to about 0:100. PVP-1 is a polyvinyl-pyrrolidone- iodine complex whereas Nonoxynol 9, also known as N-9, is a nonylphenoxypoly (ethylene oxy) ethanol. It is claimed that a coating containing PVP-I, N-9, and various additives exhibits superior anti-HIV and antiviral / anti-bacterial activity. In a general formulation described in the patent, the coating is made up of an active ingredient solution and a pre-mix solution. The active ingredient solution consists of PVP-I and N-9 in a solvent blend ethanol product, whereas the pre-mix solution is essentially inert materials in ethanol solvent. Inert materials could include hydrophilic polymeric binders, pigments, fillers and other additives. The antiviral efficacies of coatings based on this general formulation were evaluated. Coatings were coated on table roll paper, tissue paper, medical packaging paper and medical / surgical material. The HIV-inactivating properties were evaluated in accordance with the test protocol set forth in "Evaluation of Antiviral Drugs and Neutralizing Antibodies to Human Immunodeficiency Virus by a Rapid and Sensitive Microfilter Infection Assay", J. Clin. Microbiology, 1988 Vol. 26:231 - 235. The test results indicated that HIV was completely inactivated upon contact with the coated samples. Silver ions are known as an antibacterial agent in coatings. Silver ions in such coatings may be contained in organic or inorganic silver salts, or colloidal or nano particulate silver or silver oxide. Despite their antibacterial efficacy, silver ions have a color stability problem. Coatings containing silver will usually turn blackish upon exposure to sunlight, even mild sunlight through windows. Due to this unaesthetic effect, silver based antibacterial agents are not widely accepted in coating applications for creating a hygienic surface.

There have been attempts to minimize the blackening effect caused by silver ions. An example has been reported in US Patent Application Publication US 2010/0204357 Al: Antimicrobial Coating Compositions, Related Coatings and Coated Substrates. This application describes antimicrobial coating compositions based on (a) a film-forming resin; (b) the antimicrobial agent from a porous solid comprising pores having antimicrobial metal ions; and (c) halogen counter ion-containing

"onium" compound. It is claimed that the coatings exhibit UV color stability comparable to UV color stability exhibited by the same composition that does not include (b) and (c). The resins include thermosetting and thermoplastic resins which include polyacrylic, polyurethane, silicon-based polymers, and polycarbodiimide. The antimicrobial agent is a porous solid comprising pores having antimicrobial metal ions disposed therein. A typical example of the porous solid is a zeolite prepared by an ion-exchange reaction in which non-antimicrobial ions present in the zeolite, such as sodium ions, calcium ions, potassium ions and iron ions, are partially or wholly replaced with antimicrobial metal ions. Examples of antimicrobial metal ions are ions of silver, copper, zinc or combinations thereof. The "onium compound" refers to a salt in which the positive ion (onium ion) is formed by the attachment of a proton to a neutral compound, examples are ammonium (NH₄ ⁺), phosphonium (PH₄ ⁺), sulfonium (H₃S⁺), fluoronium (H₂F⁺), chloronium (H₂CI⁺), bromonium (H₂Br⁺) and iodonium (Η₂ ). The purpose of the onium compound is to deplete the release of silver ion from the zeolite thus preventing discoloration of the composition. It is claimed that the coating compositions can be applied on various substrates, including cellulosic-containing materials (such as paper and plywood), metallic substrates and polymeric substrates. The coating compositions can be applied as a primer or primer surface, or as a topcoat. It is also claimed that the coating compositions have a wide variety of applications, which include surfaces of common objects accessible to the public such as doorknobs, children's toys and the like. The antimicrobial efficacy of an exemplary coating was demonstrated and the test results showed that coating compositions contain silver ion-exchanged in Type A zeolite as the antimicrobial agent had 100% efficacy of kill on P. aeruginosa and Listeria. Despite the claim, no antiviral efficacy for coating compositions containing silver ions was demonstrated in the report.

Zinc pyrithione is a coordination complex of zinc and the pyrithione molecule, also known as zinc salt of l-hydroxypyridine-2-thione; 2-pyridinethiol-l-ox-ide; 2-mercaptopyridine-N-oxide; or pyridinethione-N-oxide. Zinc pyrithione is well-known for its efficacy against microbes such as bacteria, fungi and algae. It has been widely used in shampoo as an antidandruff agent, and in marine coatings as an antifoulant. Other applications of zinc pyrithione include, but are not limited to, sealants, construction products, textiles, plastics and polyurethane products. It has been reported that zinc pyrithione has antiviral activity in laboratory tests; for example, in a published paper, "Antiviral activity of the zinc ionophorespyrithione and hinokitiol against picornavirus infections. Journal of virology, Vol. 83, No. 1, p. 58-64, 2009, Krenn et al has reported that the antiviral activity of zinc pyrithione is related to the zinc ionophore property of the pyrithione molecules. Although antiviral activity of zinc pyrithione has been demonstrated in other contexts, its use in a coating to create a durable antiviral surface has not been demonstrated.

Another zinc compound, zinc oxide, has also been known for its antibacterial and antifungal activities. Other antimicrobial applications of zinc oxide include, but are not limited to, antibacterial cream, anti-rash cream, and other medical remedies. Zinc oxide has also been known to have antiviral activities and has been used in a variety of formulations to treat viral infections; for example, US Patent 6638915 Bl describes a method of making and using a mixture containing a combination of zinc oxide, aspartic acid, and high fructose corn syrup, as an antiviral remedy.

However, the use of zinc oxide as an antiviral agent in coatings to create a durable hygienic surface has not been explored.

It is an object of the present invention to provide antimicrobial surfaces, particularly antiviral surfaces. One way to achieve effective and durable antimicrobial surfaces is to apply antimicrobial coatings to surfaces, including walls, which frequently come into contact with humans. Accordingly, it is a further object of the present invention to provide antimicrobial coating compositions, including architectural coating compositions.

According to the Centers for Disease Control and Prevention, "hand, foot, and mouth disease is spread from person to person by direct contact with the infectious viruses that cause this disease. These viruses are found in the nose and throat secretions (such as saliva, sputum, or nasal mucus), fluid in blisters, and stool of infected persons. The viruses may be spread when infected persons touch objects and surfaces that are then touched by others." (See http://www.cdc.gov/hand-foot- mouth/about/transmission.html)

It is a further object to provide antiviral coatings such as to prevent the spread of Coxsackievirus type A16 and Enterovirus type 71 (the viruses responsible for the transmission and infection of hand-foot- mouth disease in children) among other microbial pathogens.

SUMMARY OF THE INVENTION

Accordingly, and from a first aspect, the present invention resides in a coating composition comprising zinc pyrithione and zinc oxide, wherein the zinc pyrithione and zinc oxide are present as an antimicrobial agent, and the zinc pyrithione and zinc oxide are present in an amount sufficient to provide antimicrobial properties to the coating.

The Applicant has found that compositions comprising a combination of zinc pyrithione and zinc oxide as antimicrobial agents exhibit antiviral, antibacterial and/or antifungal activities and efficacies, rendering them suitable for creating hygienic surfaces. More specifically, compositions comprising zinc pyrithione and zinc oxide exhibit a synergistic antiviral efficacy against Coxsackievirus type A16 and Enterovirus type 71, viruses responsible for the transmission and infection of hand- foot-mouth disease in children, and are particularly suitable for use in architectural coating compositions.

Preferably, the coating composition according to this first aspect is a coating composition wherein the zinc pyrithione and zinc oxide together provide antiviral properties to the coating composition. Preferably, the coating is an architectural coating, such as a paint.

Additional antiviral or antimicrobial agents that can be used in the compositions of the invention include, but are not limited to, silver in the form of organic or inorganic silver salts.

From a further aspect, the present invention resides in a process for manufacturing an architectural coating composition comprising:

- forming a mill base; and

introducing to the mill base a mixture comprising an antimicrobial agent, wherein said antimicrobial agent comprises zinc pyrithione and zinc oxide, to form an architectural coating composition.

From another aspect, the present invention is directed to use of zinc pyrithione and zinc oxide in combination as an additive for maintaining or increasing antimicrobial properties, particularly antiviral properties, of an architectural coating composition. From yet another aspect, the present invention is directed to a method of treating an architectural surface, comprising applying to said surface a coating composition in accordance with the first aspect of the invention.

Microorganisms, microbes or microbials are microscopic organisms which may be smaller than a cell (subcellular) or which may comprise a single cell (unicellular), cell clusters, or multi-cellular relatively complex organisms. Microorganisms, microbes or microbials include bacteria, fungi, algae, protozoa, microscopic plants, animals such as rotifers and planarians, and viruses. The term

"antimicrobial" therefore refers to microbicidal properties which include microbe inhibition and killing, leading to a reduction in number of microbes. The term "antimicrobial" also encompasses microbistatic properties which include retardation of microbial growth, wherein numbers of microbes may remain more or less constant.

The term "virus" refers to the microscopic organisms studied by microbiologists as particles or infectious agents that can replicate only inside the living cells of another organism as the host. Viruses infect all types of organisms, from animals and plants to bacteria and archae. Types of virus include, but are not limited to, Adenovirus, Herpesvirus, Poxvirus, Coxsackievirus, Enterovirus, Influenza A (H1N1) virus and Influenza A (H5N1) virus.

The term "bacteria" refers to organisms which are made up of just one cell. They are capable of multiplying by themselves, as they have the power to divide. Bacteria exist everywhere, inside and on human bodies and other surfaces. Most of them are completely harmless, and some of them are very useful, but some bacteria can cause diseases. The disease causing bacteria include, but are not limited to, Escherichia coli, Staphylococcus aureus and Methicillin Resistant Staphylococcus aureus.

The term "fungi" refers to a member of large group of eukaryotic organisms that includes microorganisms such as yeasts, moulds and mushrooms. These organisms are classified as a kingdom, Fungi, which is separate from plants, animals and bacteria. Many fungi are parasites on plants, animals and to humans as well. They can cause serious diseases in humans, several of which may be fatal if untreated. These include, but are not limited to, aspergilloses, candidoses and coccidiodomycosis. Furthermore, persons with immuno-deficiencies are particularly susceptible to disease by genera such as Aspergillus, Candida, Cryptoccocus, Histoplasma and Pneumocystis. Other fungi can attack eyes, nails, hair, and especially skin, the so-called dermotophytic and keratinophilic fungi, and cause local infections such as ringworm and athlete's foot. Fungal spores can also be a cause of allergies, and systemic infection of tissues and organs.

Accordingly, by antimicrobial, it is meant that the compositions of the invention may have antiviral, antibacterial and/or antifungal activities and efficacies. The coating compositions of the present invention may be used as a coating for a wall, or for another surface such as furniture, flooring, door knobs, toys, medical equipment and household items, and are preferably architectural coating compositions. The surface to be coated may include, but is not limited to, plaster, wood, metal, paper, cardboard, fabrics, concrete, linoleum, ceramics, rubber, plastic or glass. The coating compositions may be applied as a primer or primer surface, or as a topcoat, and may be either water based or solvent based. The term 'solvent based' herein is used in contrast to 'water based' and is to be understood to exclude water as a main solvent.

Preferably, the coating composition is water based. As used herein water-based coating

compositions are those compositions comprising water as a main solvent or a carrier. The coating compositions according to the invention may be used as architectural coatings. The coating compositions according to the present invention may be paint compositions, such as paint compositions providing a decorative or protective coating to surfaces, and include but are not limited to: emulsion or latex paints based on polyacrylic or modified polyacrylic emulsion, silicon emulsion or blends of emulsions; alkyd paints based on short, medium or long oil alkyd resins; polyester coatings; polyurethane coatings including water based and solvent based, 1-K (one component) and 2-K (two component) types; polyacrylic coatings based on solvent-based or water- based dispersions ; epoxy coatings including solvent-based and water-based types; and/or polyurea coatings.

The coating composition of the present invention may be an architectural coating composition for interior or exterior use. Preferably, the composition of the present invention is employed for interior use. By interior use is meant use on walls or surfaces that are not exposed to the exterior or outside of a structure or building. Interior use occurs in an environment in which the climate is controlled, i.e., an environment not routinely exposed to weather elements such as extremes of temperature or humidity, rain, wind or snow. Optionally, the coating composition of the present invention may also be employed for exterior use. Exterior use occurs on the outside of a structure or building in an environment which may be exposed to weather elements such as extremes of temperature or humidity, rain, wind or snow.

Examples of interior and exterior uses of the composition in architectural coatings include, but are not limited to, wood coatings for furniture, wood finishes and flooring; wall coatings for interior walls of residential houses, hospitals, retirement centers, physician's offices, dental centers, veterinary offices, schools, government facilities and other public or residential places; and light duty metal coatings for door knobs, metal surfaces of elevators and mail boxes. Zinc pyrithione and zinc oxide used in the compositions of the present invention may be of regular particle size, typically on the order of about 20 microns, preferably on the order of 15 to 20 microns in particle size. As the particles may be regular in size but irregular in shape, the particle size refers to the longest width cross-section of a particle. Both zinc pyrithione and zinc oxide in the compositions of the present invention may have particle size distributions wherein preferably at least 99.5 wt , more preferably at least 99.9 wt%, and most preferably 99.99 wt% of each of zinc pyrithione and zinc oxide is composed of particles of particle size of less than 45 microns. Zinc pyrithione used in the compositions of the present invention may have a particle size distribution wherein at least 99 wt% of the zinc pyrithione is composed of particles of particle size less than 20 microns, or wherein at least 90 wt% of the zinc pyrithione may be composed of particles of particle size less than 10 microns.

Nano-sized zinc pyrithione and zinc oxide particles, with particle sizes in the range of 1 to 100 nanometers, are also embraced in the compositions of the present invention and may exhibit enhanced antimicrobial efficacies. Without wishing to be bound by theory, smaller particle sizes result in a larger surface area-to-volume and surface area-to-weight ratio; therefore nano-sized particles are expected to be more effective than larger particles, because of their relatively larger surface area available to come into contact with microbes for a given quantity of material.

Zinc oxide and zinc pyrithione for use in the present invention may be sourced from Arch Chemicals,

Hangzhou Trigger Chemical Co. Ltd and Xuancheng Jingrui New Material Co., Ltd. Zinc pyrithione for use in the present invention may also be prepared from solution-based reactions of sodium pyrithione and zinc chloride, with a precipitate of zinc pyrithione collected as the product. Zinc oxide for use in the present invention may also be manufactured by using the renowned French process.

In this process, metal zinc is vaporized, and then reacts with oxygen in the air to give zinc oxide.

Nano-sized zinc pyrithione and nano-sized zinc oxide for use in the present invention may be made through dissolution of regular particle sized material into solvent or water medium, followed by a subsequent recrystallization step. Particle sizes may be assessed by means known to those skilled in the art, such as measurement by TEM (Transmission Electron Microscopy).

Use of either zinc oxide or zinc pyrithione alone in coating compositions is associated with several drawbacks. High loading of zinc pyrithione, for example, may result in coating films turning yellow, particularly when contacted with acidic materials, while high loading of zinc oxide may result in gellation if the composition is water-based. The compositions of the invention comprising both zinc pyrithione and zinc oxide in combination show high antiviral efficacy in particular, due to a synergistic effect from these two active ingredients. This antiviral efficacy is demonstrated in the detailed description of the invention below. The antimicrobial agents used in the coating composition in accordance with the present invention may be provided in the form of a powder or in the form of an aqueous dispersion. The antimicrobial agents contain zinc pyrithione and zinc oxide, which may be present in a combined amount of between 5 wt% to 55 wt%, more preferably between 24 wt% to 38 wt , and most preferably between 20 wt% to 30 wt%, based on the combined weight of zinc pyrithione and zinc oxide relative to the total weight of antimicrobial agent in the form of powder or in the form of aqueous dispersion. Typically, the antimicrobial agents containing zinc pyrithione and zinc oxide are provided as an aqueous dispersion.

Optionally, coating compositions comprising the antimicrobial agent of the present invention may comprise additional antiviral or antimicrobial agents. Additional antiviral or antimicrobial agents may include, but are not limited to, silver in the form of, for example, organic or inorganic silver salts, colloidal or nano-particulate silver or silver oxide. By nano-particulate it is meant particle sizes in the range of 1 to 100 nanometers. The coating composition comprising the antimicrobial agent of the present invention may comprise between about 0.01 wt% and 1.0 wt% of a formulated silver ion product, relative to the total weight of the coating composition. Preferably, the formulated silver ion product is provided in powder form. Preferably, the formulated silver ion product comprises between 0.1 wt% to 5.0 wt% silver ion, preferably between 0.5 wt% to 2.0 wt% silver ion, relative to the total weight of the formulated silver ion product.

Formulated silver ion products for use in the present invention may be supplied for example by AglON Technologies, Inc., American Elements, and Molecular Products Limited. A formulated silver ion product for use as a silver-based antimicrobial agent in the present invention may be, for example, a silver-based product using zeolite as the carrier.

As used herein, the total weight of a coating composition refers to the total combined weight of solid, non-volatile, and volatile components present in the coating composition as prepared and before drying, wherein volatile components are those that are removed by evaporation when the coating composition is dried to form a coating, preferably an architectural coating. Volatile components in an architectural coating composition may include water and solvent. Unless otherwise specified, the weight percentage (wt%) of a given component herein is based on the total weight of the coating composition as prepared and before drying, as defined above. The coating compositions of the present invention may comprise the aforementioned antimicrobial agents. As these agents are added in a certain percentage by weight during the preparation of the architectural coating compositions, the weight percentages of zinc pyrithione and zinc oxide relative to the total weight of the coating compositions are determined by multiplying their weight percentages in the antimicrobial agent by the weight percentage in which the antimicrobial agent is added to the coating composition, as known to those skilled in the art. Preferably, the

aforementioned antimicrobial agents may be added in an amount between 0.05 and 2.0 wt% of the coating composition, preferably between 0.25 and 1.0 wt%, relative to the total weight of the coating composition.

The coating compositions preferably comprise between 0.006 wt% and 0.24 wt%, preferably between 0.03 wt% and 0.12 wt%, of each of zinc pyrithione and zinc oxide, relative to the total weight of the coating composition. As a lower limit, the coating composition may comprise 0.006 wt%, or 0.03 wt% of each of zinc pyrithione and zinc oxide in the coating composition, relative to the total weight of the coating composition. As an upper limit, the coating composition may comprise 0.03 wt%, or 0.12 wt%, or 0.24 wt% of each of zinc pyrithione and zinc oxide in the architectural coating composition, relative to the total weight of the coating composition. When present in these amounts, zinc pyrithione and zinc oxide may provide antimicrobial properties, particularly antiviral properties, to the coating. Antibacterial and antifungal properties may also be provided. Formulated silver ion product may be added in an amount between 0.01 and 1.0 wt%, preferably in an amount between 0.05 wt% and 0.5 wt%, relative to the total weight of the coating compostion. The coating composition comprising the antimicrobial agent of the present invention may comprise between about 1 and 100 ppm silver ion, preferably between about 5 and 50 ppm by weight silver ion relative to the total weight of the coating composition, as defined above. Zinc pyrithione and zinc oxide may be present in the coating composition in an amount to provide antimicrobial properties to the coating. In contrast to the "total weight" of the coating composition, which refers to the as-prepared composition prior to drying as defined above, the "dry weight" of a coating composition refers to the total combined weight of the solid and non-volatile components of the coating composition, or to the weight of the coating composition following removal of its volatile components through drying of the composition to form a coating, preferably an architectural coating. Preferably zinc oxide and zinc pyrithione may be present in an amount of from 0.012 wt% to 0.48 wt%, more preferably in an amount of from 0.06 wt% to 0.24 wt%, relative to the dry weight of the coating composition or coating. Preferably, silver ion may be present in an amount of from 10 to 100 ppm, relative to the dry weight of the coating composition or coating. Coating compositions according to the present invention may contain other additives and materials, including, but not limited to one or more of rheology modifiers, neutralizing agents, dispersants, defoamers, surfactants, white spirits, fillers, pigments, film formers, anti-freeze agents, in-can preservatives, paint film preservatives, coalescent solvents and water as a carrier. A filler, sometimes called extender, is a substance practically insoluble in the application medium and it is used to reduce cost, to increase volume or to alter technical properties such as appearance, durability, and rheology. A pigment is an inorganic or organic substance which is insoluble in the application medium and is used to provide colour and other properties such as opacity, hardness, durability and corrosion resistance. A film former is a polymer dispersion used to enable an emulsion paint to form a film. An in-can preservative is a chemical agent used to prevent microbial growth in the coating compositions during the wet stage, i.e., when the coating composition is still wet and in a container. Paint film preservatives refer to chemical agents used to prevent microbial infestation, particularly mould, mildew, fungus and algae onto the dry films. The active ingredients in paint film preservatives contain may include fungicides and / or algaecides. In a particularly preferred formulation, the architectural coating composition includes each of a rheology modifier, dispersant, defoamer, pigment, filler, film former, in-can preservative, fungicide for interior and exterior coating, algaecide or algaecide/fungicide combination for exterior coating, carrier and antimicrobial agent. Neutralizing agent, surfactant and anti-freeze agent may also be included. In the aforementioned coating composition comprising the antimicrobial agent of the present invention, the composition may contain the following other additives and materials. These include, but are not limited to, surfactants, dispersants, defoamers, rheology modifiers, neutralizing agents, fillers, pigments, paint film preservatives and coalescent solvents.

Surfactants include, but are not limited to, one or more of disodium alkyl amido polyethoxy sulfosuccinate; sodium alkyl naphthalene sulfonate; nonyl phenoxy polyethyleneoxy ethanol; octyl phenoxy polyethyleneoxy ethanol; complex fatty ethers; dodecylbenzene sulfonate; sodium tridecyl ether sulfate; sodium dodecyl sulfate; and organic salts of quaternary ammonium hydroxide.

Surfactants may be present in a preferred range of 0.1 to 3 wt%, based on the total weight of the coating composition. Dispersants include, but are not limited to, one or more of solutions of high molecular weight block copolymers with pigment affinity groups; solutions of acrylate copolymers with basic pigment affinity groups; alkylammonium salts of high molecular weight copolymers; alkylolammonium salts of copolymers with acidic groups; salts of unsaturated polyamine amides and lower molecular weight acidic polyesters; solutions of polyamine amides of unsaturated polycarboxylic acids; and solutions of phosphoric acid salts of long chain carboxylic acid polyamine amides. Dispersants may be present in a preferred range of 0.1 to 3 wt%, based on the total weight of the coating composition. Defoamers include, but are not limited to, one or more of solutions of polysiloxanes; emulsions of siloxylated polyethers and hydrophobic particles; emulsions of siloxylated polyethers; solutions of foam destroying polymers; polyether modified polydimethylsiloxanes; and emulsions of paraffin based mineral oils and hydrophobic components. Defoamers may be present in a preferred range of 0.1 to 3 wt%, based on the total weight of the coating composition.

Rheology modifiers include, but are not limited to, one or more of attapulgite; ethylcellulose such as hydroxyethyl cellulose, hydroxybutyl methylcellulose, hydroxypropyl methylcellulose; quaternary ammonium bentonite complex; alkali soluble rheology modifiers based on acid / acrylic copolymer emulsions; hydrophobically modified alkali soluble rheology modifiers based on acid / acrylic copolymer backbones and including an ethoxylated hydrophobe; hydrophobically modified ethoxylated urethane rheology modifiers based on polymers synthesized from an alcohol, a diisocyanate and a polyethylene glycol; and rheology modifiers based on hydrophobically modified polyether polyols. Rheology modifiers may be present in a preferred range of 0.1 to 3 wt%, based on the total weight of the coating composition. Anti-freeze agents include, but are not limited to, ethylene glycol, propylene glycol, dipropylene glycol. Anti-freeze agents may be present in a preferred range of from 0.1 to 10 wt%, based on the total weight of the coating composition.

In-can preservatives include, but are not limited to, isothiazolinones, formaldehyde, and any forms of formaldehyde condensate or formaldehyde releaser. Specific examples of isothiazolinones are mixture of 5-chloro-2-methyl-2H-isothiazol-3-one and 2-methyl-2H-isothiazol-3-one; and 1,2- benzisothiazolin-3-one. In-can preservatives may be present in a preferred range of from 1 to 500 ppm, depending on the type of in-can preservatives used, based on the total weight of the coating composition.

Neutralizing agents include, but are not limited to, one or more of amines such as amino methyl propanol; alkyl alkanolamines such as 2, 2'-(butylimino) diethanol; 2-[(3-aminopropyl) methylamino] ethanol; dimethylamino hydroxypropane; and solutions of potassium methyl siliconante.

Neutralizing agents may be present in a preferred range of 0.1 to 3 wt%, based on the total weight of the coating composition.

Fillers include, but are not limited to, one or more of barium sulphate, calcium carbonate, clay, kaolin, talc, silica, mica and gypsum. Fillers may be present in a preferred range of 1 to 50 wt%, based on the total weight of the coating composition. Pigments include, but are not limited to, one or more of titanium dioxide, carbon black, red iron oxide, ultramarine blue and phthalocyanine pigments. Pigments may be present in a preferred range of 1 to 50 wt%, based on the total weight of the coating composition.

Paint film preservatives include fungicides, including, but not limited to, one or more of isothiazolinones, carbamates, pyrithiones, aldehydes, ketones, quinones, amines, amidines, guanidimes, hydrazo and azo compounds, aromatic carbonitriles, carboxylic esters, carboxamides and carboximides, benzimidazoles, quinoxalines, imidazoles, triazoles, pyrimidines, triazines, halogenated and nitrated alcohols and phenols, perhaloalkyl mercaptan derivatives, phosphoric and phosphonic esters, tetrahydro-l,3,5-thiadiazinethiones, thiocyanates and isothiocyanates, thiophenes, antibiotics and active plant substances. Specific examples of highly suitable fungicides are methyl-lH-benzimidazol-2-ylcarbamate (carbendazim), 2-n-octylisothiazolin-3-one (OIT), 4,5- dichloro-octylisothiazolin-3-one (DCOIT), 3-iodo-2-propynyl N-butylcarbamate (IPBC), and chlorothalonil.

Paint film preservatives include algaecides, including, but not limited to, one or more of triazines, Ν,Ν-dimethylureas, uracils and pyrithiones. Specific examples of algicides are IM-t-butyl-N-ethyl-6- methylthio-l,3,5-triazine-2,4-diyldiamine (terbutyrn), 3-(3,4-dich!orophenyl)-l,l-dimethyl urea (DCMU), 2-chloro-4,6-bis(isopropylamino)-s-triazine, 2-methylthio-4-butylamino-6- cyclopropylamino-s-triazine, 4-butylamino-2-chloro-6-ethylamino-s-triazine, 3-(4-isopropylphenyl)- 1,1-dimethylurea, and 3-t-butyl-5-chloro-6-methyluracil. Paint film preservatives may be present in a preferred range of 0.1 to 5 wt%, based on the total weight of the coating composition.

Coalescent solvents include, but are not limited to, one or more of propylene glycol methyl ether, dipropylene glycol methyl ether, propylene glycol diacetate, propylene glycol methyl ether acetate, dipropylene glycol dimethyl ether and other glycol ethers. Coalescent solvents may be present in a preferred range of 0.1 to 10 wt%, based on the total weight of the coating composition. Film formers include, but are not limited to, acrylic polymer emulsions, such as Primal AC-268. Primal AC-268 is a product of Dow Chemical Company. Film formers may be present in a preferred range of 1 to 90 wt%, based on the total weight of the coating composition.

Preferably, the coating composition comprising the antimicrobial agent according to the present invention exhibits a maximum fineness of 50 μητι, as measured in accordance with ASTM D1210. Preferably, the coating composition exhibits a specific gravity of 1.42 - 1.48, as measured in accordance with ASTM D3505. Preferably, the coating composition has a solids content of 56.0 - 60.0 wt%, as measured in accordance with ASTM 2832. Preferably, the coating composition exhibits a viscosity of 75-110 KU, most preferably of 85 - 91 KU, wherein KU are Kreb's units, as measured with a Stormer viscometer and in accordance with ASTM D-562.

The coating composition comprising zinc pyrithione and zinc oxide in accordance with the present invention exhibits particular efficacy against viruses. Such viruses include, but are not limited to, Adenovirus, Herpesvirus, Poxvirus, Coxsackievirus, Enterovirus, Influenza A (HlNl) virus and Influenza A (H5N1) virus genuses. The coating composition comprising zinc pyrithione and zinc oxide in accordance with the present invention exhibits particular efficacy against Coxsackievirus type A16 and Enterovirus type 71. These are common viruses causing hand-foot-mouth disease among children. Architectural coatings comprising the coating composition containing zinc pyrithione and zinc oxide exhibit a synergistic antiviral effect against these viruses in particular, as shown in

Example 1. Accordingly, the present invention includes a coating composition comprising zinc pyrithione and zinc oxide for use as an antiviral agent, preferably against Adenovirus, Herpesvirus, Poxvirus, Coxsackievirus, Enterovirus, Influenza A (HlNl) virus and Influenza A (H5N1) virus genuses, and most preferably against Coxsackievirus type A16 and Enterovirus type 71. Preferably, such use may include use in an architectural coating composition, more preferably said architectural coating composition may be a water-based architectural coating composition and/or an architectural coating composition for indoor use. It is to be understood that such architectural coating

compositions may comprise all optional and/or preferable features set forth above.

The coating composition comprising zinc pyrithione and zinc oxide in accordance with the present invention exhibits efficacy against bacteria, in accordance with Example 2 below. Such bacteria include, but are not limited to, Escherichia coli, Staphylococcus aureus, Methicillin Resistant

Staphylococcus aureus and Pseudomonas aeruginosa species. Accordingly, the coating compositions of the present invention comprising zinc pyrithione and zinc oxide may also be used for their antibacterial properties, preferably against Escherichia coli, Staphylococcus aureus, Methicillin Resistant Staphylococcus aureus and Pseudomonas aeruginosa species. Preferably, such use may include use as an architectural coating, more preferably said architectural coating may be a water- based architectural coating and/or an architectural coating for indoor use. It is to be understood that such architectural coating compositions may comprise all optional and/or preferable features set forth above. The coating composition comprising zinc pyrithione and zinc oxide in accordance with the present invention exhibits efficacy against fungi, in accordance with Example 3 below. Such fungi include, but are not limited to, Aspergillus niger, Alternaria alternata and Penicillium purpurogenum. Accordingly, the coating compositions of the present invention comprising zinc pyrithione and zinc oxide may also be used for their antifungal properties, preferably against Aspergillus niger, Alternaria alternata and Penicillium purpurogenum species. Preferably, such use may include use as an architectural coating composition, more preferably said architectural coating may be a water-based architectural coating composition and/or an architectural coating composition for indoor use. It is to be understood that such architectural coating compositions may comprise all optional and/or preferable features set forth above.

Optional and/or preferred features as set forth with regard to the first aspect of the invention may be incorporated into the other aspects of the invention, and vice versa.

As further described herein, the invention also resides in a process for manufacturing an

architectural coating composition comprising:

- forming a mill base; and

The architectural coating compositions may be manufactured using high speed dissolver, with or without the aid of industrial grinding equipment, such as one or more of a horizontal mill, basket mill or a ball mill. A working high speed dissolver system may consist of a mixing tank to contain materials that are going to be mixed, and a disperser shaft driven by a motor and attached to a mixing blade.

The mill base may be formed from a mixture comprising at least a carrier, a rheology modifier, a dispersant, a defoamer, a pigment, and a filler. Optionally, the mill base may further comprise a surfactant, a neutralising agent, and an anti-freeze agent. Other possible optional additional components in the mill base include dispersing aids and protective colloids. Where the singular is used in the above lists, the plural is also intended, and vice versa.

Preferably the carrier is water. The carrier may be present in the mill base in a preferred range of 5 to 50 wt%, based on the total weight of the coating composition.

Preferably the components of the mill base are agitated sufficiently to disperse the mill base mixture homogeneously, preferably for about 20 minutes. Preferably prior to the introduction of the mixture comprising an antimicrobial agent, the mixture forming the mill base is agitated at a speed of preferably about 800 to 1,000 rpm in a mixing tank, wherein the speed in rpm refers to the rotation speed of the disperser shaft.

The mixture comprising the antimicrobial agent may comprise several components in addition to the antimicrobial agent. The mixture comprising an antimicrobial agent may further comprise an in-can preservative and a paint film preservative, such as a fungicide, an algaecide and/or an

algaecide/fungicide combination. Fungicide is typically used in both interior and exterior coatings. Algaecide or algaecide/fungicide combination is typically used in exterior coatings. The mixture comprising an antimicrobial agent optionally comprises one or more of a film former, an anti-freeze agent, a defoamer, a rheology modifier, a coalescent solvent and/or additional carrier. Other possible optional components in the mixture comprising the antimicrobial agent include one or more of anti-mar and anti-slip agents, colorants, wetting agents, adhesion promoters, flow control agents, levelling agents, opacifiers and waxes. Where the singular is used in the above lists, the plural is also intended, and vice versa. Preferably, each of the components in the mixture comprising the antimicrobial agent is added to the mill base individually and in succession. A typical order of addition of the components in the mixture comprising the antimicrobial agent is shown in Table 1 of Example 1, with components numbered 9 - 16 being added individually and in succession to the mill base mixture, the mill base mixture comprising components numbered 1 - 8. Optionally, the mixture comprising the

antimicrobial agent may consist essentially of the antimicrobial agent dispersion or powder, that is to say, for example, component 14 in Table 1 of Example 1.

Preferably, following introduction to the mill base of the mixture comprising the antimicrobial agent, a coating precursor is formed. Preferably, prior to the formation of the coating precursor, additional carrier, in a preferred range of 0 to 10 wt%, based on the total weight of the coating composition, may be introduced to the mixture comprising the mill base and the antimicrobial agent. Preferably, additional carrier to make up the volume of the coating precursor is the last component to be added in the succession of components forming the mixture comprising the antimicrobial agent. Preferably, the coating precursor is dispersed at a speed of about 500 to 800 rpm, preferably for between 5 to 10 minutes, most preferably for about 5 minutes. Alternatively, the invention resides in a process for manufacturing an architectural coating composition comprising:

adding an antimicrobial agent to a coating composition;

allowing the antimicrobial agent to become uniformly dispersed in the coating composition, wherein said antimicrobial agent comprises zinc pyrithione and zinc oxide. It is to be understood that the process of manufacturing an architectural coating composition according to one aspect of the invention may include all optional and/or preferable features as set forth with regard to the other aspects of the invention. From another aspect, the present invention is directed to use of zinc pyrithione and zinc oxide in combination as an additive for maintaining or increasing antimicrobial properties, particularly antiviral properties, of an architectural coating composition. Antimicrobial properties may be one or more of antiviral, antibacterial and antifungal properties. Increased antimicrobial properties include microbial inhibition and killing, leading to a reduction in number of microbes. Maintained antimicrobial properties include microbial inhibition, wherein microbial numbers remain more or less constant between treated and untreated architectural coating compositions. Preferably said architectural coating composition may be a water-based architectural coating composition and/or an architectural coating composition for indoor use. It is to be understood that such architectural coating compositions may comprise all optional and/or preferable features set forth above.

Use of zinc pyrithione and zinc oxide in combination as an additive in an architectural coating composition in accordance with the present invention further encompasses use for preventing allergies in allergy-prone individuals, and use for preventing the transmission of disease-causing microbes. The invention further includes use for preventing infections with infectious diseases corresponding to said disease-causing microbes. Such infectious diseases include, but are not limited to, infections of hand-foot-mouth disease, particularly in humans, more particularly in children, due to Coxsackievirus type A16 and Enterovirus type 71; influenza infections from (H1N1) virus and (H5N1) virus genuses; Adenovirus, Herpesvirus, Poxvirus, Coxsackievirus and Enterovirus infections; infections of Escherichia coli, Staphylococcus aureus and Methicillin Resistant

Staphylococcus aureus; aspergilloses, candidoses, cocc/^'d/odomycosis; Cryptoccocal infection, Histoplasmosis and Pneumocystitis in immuno-compromised individuals; dermotophytic and keratinophilic fungal infections such as ringworm and athlete's foot; and systemic fungal infections of tissues and organs. Preferably said architectural coating composition is a water-based

architectural coating composition and/or an architectural coating composition for indoor use. It is to be understood that such architectural coating compositions may comprise all optional and/or preferable features set forth above.

From a final aspect, the invention resides in a method of treating an architectural surface, comprising applying to said surface a coating composition in accordance with the invention.

DETAILED DESCRIPTION OF THE INVENTION The invention will now be more fully described with reference to the following Examples, which are for the purpose of illustration only. EXAMPLES

In the Examples that follow, the antimicrobial agents used were as below:

Agent #1 is a water dispersion containing 12 wt% zinc pyrithione and 12 wt % zinc oxide, relative to the total weight of the dispersion. Agent #2 is a water dispersion containing 38 wt% zinc pyrithione, relative to the total weight of the dispersion.

Agent #3 is a water dispersion containing 12 wt% zinc oxide, relative to the total weight of the dispersion.

Agent #4 is a powder containing 1 wt% of silver ion, relative to the total weight of the powder. Example 1

Preparation of Coating:

A white colour water-based architectural coating was prepared comprising components in the quantities defined in Table 1 below. The components are numbered below in accordance with their sequence of addition in the preparation of the coating mixture, Sample 1. The coating contains zinc pyrithione and zinc oxide based antimicrobial agent, rheology modifier, neutralizing agent, dispersant, defoamer, surfactant, filler pigment, film former, anti-freeze agent, in-can preservative, coalescent solvent and water as carrier.

Table 1. Components and their Weight % in Sample 1

12 Acrysol TT-935 Rheology modifier 0.20

13 Biox P113 ln-can preservative 0.10

14 Agent #1 Antimicrobial agent 0.25

15 Coasol Coalescent solvent 3.00

16 Water Carrier 4.15

TOTAL 100.00

Explanatory Note: The raw material for component 13, BioxP113, is a 1.5% isothiazolinone solution.

Agent #1 is a water dispersion containing 12 wt% zinc pyrithione and 12 wt % zinc oxide. The final coating mixture Sample 1, which contains 0.25 wt% Agent #1, is therefore 0.03 wt% in each of zinc pyrithione and zinc oxide.

90 wt% of the zinc pyrithione contained in Agent #1 had a particle size of less than 10 micrometers. 99.99 wt% of the zinc oxide contained in Agent #1 had a particle size of less than 45 micrometers.

Firstly, 20 parts of water was charged in a mixing tank. Component 2 was added and dispersed at high speed at about 800 to 1,000 rpm for 5 minutes to form a homogeneous mixture. Component 3 was then added and dispersed at about the same speed for another 5 minutes. Thereafter, components 4 to 8 were added and dispersed at 1,000 rpm for 10 minutes. This preparation is referred to as the mill base.

Components 9 to 15 were then added to the mill base in sequence and dispersed at 500 to 800 rpm for 5 minutes. The remaining water was added to adjust the viscosity to the desired range. Upon completion of the process, adequate amounts of sample were collected to perform evaluation on other paint properties, such as fineness, appearance and tinting strength. These properties and their corresponding specifications appear in Table 2 below.

Table 2. Properties and their Specifications

Antimicrobial Efficacy Testing:

A modified JIS Z 2801:2000 test protocol: Test for Antimicrobial Activity and Efficacy (available from Japanese Industrial Standards Committee, Tokyo, Japan) was used to test for antiviral activity and efficacy of the paint film containing antimicrobial agents. The JIS Z 2801 protocol is a well-known worldwide as a standard test method in this field. The test procedures used are briefly summarized below.

Coatings in the following Experiments were prepared as above in Table 1; however, the final mixtures in these Samples contained different amounts of antimicrobial agents, as detailed below. The Samples were cast on a glass panel to form a film using a metal bar applicator at a 250 μιη gap. Upon drying at room temperature for seven days, the glass panel was cut into smaller pieces, approximately 50 mm x 50 mm. A control material (GP control) cut to the same size was used as the blank control. The control material, GP control, was a glass panel or a coated glass panel prepared as above with water in place of the suspended antimicrobial agent. The test and control were equilibrated to the exposure temperature prior to use. A carrier film was prepared to fit over the test and control materials. The film was approximately 40 mm x 40 mm and was cut from the side of a sterile Stomacher^® bag. A separate carrier film was prepared for each test and control carrier.

On the day of testing, the stock virus utilized in the assay was titred by 10-fold serial dilution and assayed for infectivity to determine the starting titre of the virus. One test carrier from each batch of test substance and one control carrier, contained in individual sterile petri dishes, were inoculated with a 100 μί aliquot for the test virus. The inoculum was covered with the carrier film and the film was pressed down so the test virus spread over the film, but did not spill over the edge of the film. The exposure time began when each sample was inoculated. The samples were transferred to a controlled chamber set to room temperature in a relative humidity of 50% for the duration of a specific time of exposure.

Following a specific exposure time, a 1.00 mL aliquot of test medium was pipetted individually onto each test and control carrier as well as the underside of the film used to cover each sample (side exposed to the test sample or control). The surface of each carrier was scraped with a sterile plastic cell scraper. The test medium was collected, mixed using vortex type mixer, and serial 10-fold dilutions were prepared.

Viral titres are expressed as -logi₀ of the 50 percent titration endpoint for infectivity (TCID₅₀), as calculated by the method of Spearman Karber and according to Equation 1 below. TCID_S0—— Log of 1st dilution inoculated

Log reduction was calculated according to Equation 2 below:

Log reduction = Virus Control TCID₅₀ - Test Substance TCID₅₀ (2) Beneficial Index is expressed as a percent reduction, and calculated according to Equation 3 below:

TCIDro test

Beneficial Index = % Reduction lOO (3)

TCID₅₀ virus controlj ment 1 An antiviral efficacy test was conducted using paint films of an untreated sample and an antiviral agent treated sample. The virus species used were Coxsackievirus type A16 and Enterovirus type 71. Viral titres on the paint film were evaluated after 2 hours and 4 hours of exposure. The results are shown in Table 3. The results showed that the treated sample is highly effective against

Coxsackievirus type A16, as indicated by 82.2% and 90.0% virus reduction after 2 hours and 4 hours exposure respectively, with reference to an untreated paint film. Thus the treated sample had a high beneficial index on Coxsackievirus type A16 virus. On the other hand, the treated sample showed rather weak initial efficacy against Enterovirus type 71: there was no beneficial index over the untreated sample when the paint films were exposed for 2 hours; however, there was slight virus reduction after exposure for 4 hours. The beneficial index of the treated sample was 43.8%, with reference to an untreated paint film at 4 hours exposure. In the Tables that follow, dosage % wt/wt indicates the weight percentage of the antimicrobial agent in the coating composition, based on the total weight of the coating composition.

Table 3. Results of antiviral efficacies of Control and Sample 1 on Coxsackievirus type A16 and Enterovirus type 71, tested upon 2 hours and 4 hours exposure.

Sample 1 was prepared in the manner described above. As noted above, Agent #1 is a water dispersion containing 12 wt% zinc pyrithione and 12 wt % zinc oxide. Sample 1, which contains 0.25 wt% Agent #1, is therefore 0.03 wt% in each of zinc pyrithione and zinc oxide.

Experiment 2 As Sample 1 showed only slight efficacy on Enterovirus type 71 in Experiment 1, another experiment (Experiment 2) was conducted using a paint sample containing a higher dosage of the same antiviral agent. In this experiment, Sample 2, containing 0.3 wt% of Agent #1, and therefore 0.036 wt% in each of zinc pyrithione and zinc oxide, was used with exposure time extended to 6 and 8 hours. An untreated paint was used as reference. The antiviral efficacy results are in Table 4. The results showed that on 6 hours exposure time, Sample 2 is effective against Enterovirus type 71, as indicated by 68.4% virus reduction with reference to the untreated paint film. Thus the beneficial index has increased as compared to Experiment 1 when lower antiviral agent was used and shorter exposure time was conducted. On 8 hour exposure, the beneficial index of Sample 2 increased further, as indicated by 82.2% virus reduction with reference to the untreated paint film. Table 4. Results of antiviral efficacies of Control and Sample 2 on Enterovirus type 71, tested upon 6 hours and 8 hours exposure.

Experiment 3

In Experiments 1 and 2, the antiviral agent used contained zinc pyrithione and zinc oxide together. In this experiment, Experiment 3, the antiviral efficacies of compounds containing a single active ingredient were studied. Paint samples containing zinc pyrithione alone (Sample 3) and containing zinc oxide alone (Sample 4) were used. In this experiment, the virus species used was Coxsackievirus type A16 and the exposure time was 4 hours. The efficacy results are in Table 5.

In Table 5 below, Agent #2 is a water dispersion containing 38 wt% zinc pyrithione. Agent #3 is a water dispersion containing 12 wt% zinc oxide. Sample 3 contains 0.16 wt% of Agent #2, therefore its zinc pyrithione content is 0.06 wt%. Sample 4 contains 0.5 wt% of Agent #3, therefore its zinc oxide content is 0.06 wt%. As noted above, Sample 1, which contains 0.25 wt% Agent #1, is 0.03 wt% in each of zinc pyrithione and zinc oxide.

Table 5. Results of anti-virus efficacy of Sample 1, Sample 3 and Sample 4 on Coxsackievirus type A16, tested on 4 hours exposure.

The test results showed that using the virus species Coxsackievirus type A16 and exposure time of 4 hours, Sample 3 (using zinc pyrithione alone) has an observed beneficial index of 43.8, Sample 4 (using zinc oxide alone) has an observed beneficial index of 82.2. Based on these empirical values, the expected beneficial index of a coating containing both zinc pyrithione and zinc oxide may be calculated. The following calculation of expected beneficial index (Equation 4) is based on the assumption that the beneficial index results from an additive effect of both active components:

Xa + Xb

Expected beneficial index of coating containing mixture of a + b

Xa Xb

= + (4)

Observed beneficial index of A Observed beneficial index of B wherein Xa is the fraction by mass of component 'a' relative to the total mass of active components in the mixed antiviral agent

A is a coating that contains the active component 'a' alone Xb is the fraction by mass of component 'a' relative to the total mass of active components in the mixed antiviral agent

B is a coating that contains the active component 'b' alone.

In this case, 'a' is zinc pyrithione and 'b' is zinc oxide. Consequently, using Formula (4), the expected beneficial index of Sample #1 would be calculated as 57.1, if the antiviral effect were a purely additive one.

Since the empirical value of the beneficial index of Sample #1 is 90.0 (see Table 5), and the ratio of actual beneficial index over the theoretical value is 1.6 (i.e. more than 1, see Table 5a below), there is evidence for a synergistic antiviral effect of the combination of zinc pyrithione and zinc oxide, the two active components.

Table 5a. Beneficial index of coating on Coxsackievirus type A16, tested on 4 hours exposure.

theoretical value was calculated using Formula (4)

If the ratio of actual / theoretical beneficial index = 1, the effect is additive

If the ratio of actual / theoretical beneficial index > I, the effect is synergistic

If the ratio of actual / theoretical beneficial index < 1, the effect is antagonistic

The results from the above experiments show that the combination of zinc pyrithione and zinc oxide based antiviral agent has a high antiviral efficacy, due to a synergistic effect from these two active components. The combination of active components exhibits an unexpectedly high beneficial index against Coxsackievirus type A16 and Enterovirus type 71, which are the common viruses causing hand-foot-mouth disease in children.

Experiment 4

Experiment 4 was conducted to compare the antiviral efficacy of silver-based and zinc pyrithione / zinc oxide-based antiviral agents- Experimental antiviral paint Sample 5, a paint sample

incorporated with silver-based antiviral agent, and Experimental antiviral paint Sample 6, a paint sample incorporated with lower dosage of zinc pyrithione / zinc oxide based antiviral agent, were used. Agent #1 was again a water dispersion containing 12 wt% zinc pyrithione and 12 wt % zinc oxide.

The virus species used was Enterovirus type 71. Viral titres on the paint film were evaluated after 6 hours of exposure. The efficacy results on Enterovirus type 71 are in Table 6. The results show that both Sample 5 (using silver based antiviral agent) and Sample 6 (using zinc pyrithone and zinc oxide as antiviral agent) have the same strength of antiviral efficacy against Enterovirus type 71. After 6 hours of exposure, both samples have a beneficial index of 82.2%, with reference to an untreated paint film. The zinc pyrithione and zinc oxide antiviral agent therefore shows the same efficacy as a silver based antiviral agent, which features the drawback of blackening. The zinc pyrithione / zinc oxide combination may therefore be used alone or in combination with the latter.

Table 6. Results anti-virus efficacies of Sample 5 and Sample 6 efficacy on Enterovirus type 71, tested on 6 hours exposure.

Example 2

Testing for antibacterial activities and efficacy

The JIS Z 2801:2000 test protocol was used to test antibacterial activity and efficacy of the paint film containing antimicrobial agents. For the antibacterial efficacy test, paint samples, with or without antibacterial agent, were coated on a waxy paper using an applicator of 500 μιτι thickness. After drying for seven days, 5 cm x 5 cm square-shaped paint film samples were cut out from the paint film using a cutter. Each square-shaped paint film sample was sterilized under UV light before conducting the test. The sterilized paint films were placed in the center of a sterilized petri dish, and surface was inoculated with 0.2 ml o Escherichia coli (ATCC No. 4157) inoculums. The E. coli inoculums contained 5.0 x 10⁵ - 2.0 x 10⁶ CFU/ml, wherein CFU is a colony forming unit. After inoculation, each test paint film sample was covered with a 4 cm x 4 cm square-shaped polyethylene (PE) film to ensure a thin layer of inoculums would contact the test paint film sample. After incubation at 37°C for 24 hours, the test paint film was washed with 20 ml of sterile water; and 0.5 ml of the washing water was inoculated onto the Nutrient Agar (NA) petri dish under aseptic conditions. The number of Echerichia coli colonies recovered from the paint film sample was counted after the petri dish had been incubated at 37°C for 1-2 days. The above procedures were repeated using two other bacteria, Staphylococcus aureus (ATCC No. 6538) and Methicillin Resistant Staphylococcus aureus (MRSA) (ATCC No. BAA-41). Experiment 5

This experiment, Experiment 5, has been conducted to evaluate the antibacterial efficacy of paint films containing Agent #1 at different dosages. The test results are in Table 7. The results show that at the end of the incubation period, heavy growth of the bacteria was seen on control paint film, as indicated by the large number of bacteria (as illustrated by colonies on the petri dish) recovered from the paint film with the respective washing solutions. All paint films from paint treated with Agent #1 have no bacterial growth.

This antibacterial efficacy test results indicate that Agent #1 in paint samples is effective in eliminating all the tested bacteria inoculated on the paint film.

Table 7: Antibacterial Efficacy Test with Escherichia coli on paint film dosed with Antimicrobial Agent #1.

Experiment 6

Another experiment, Experiment 6, was conducted to evaluate the antibacterial efficacy of paint films containing antimicrobial agents based on zinc pyrithione / zinc oxide and silver at various dosages. The test results are in Table 8. The antibacterial efficacy test results showed that at the end of the incubation period, heavy growth of the bacteria Pseudomonas aeruginosa was seen on paint films of the control samples, (PE film and the Blank) as indicated by the large number of bacteria (as illustrated by colonies on the petri dish) recovered from the paint film with the respective washing solutions, while no bacterial colonies were recovered in the respective washing solutions for the paint film treated with both antimicrobial agents, zinc pyrithione / zinc oxide and silver ion. This results indicate that, under the test conditions, the antibacterial agents are effective at the lowest tested dose (0.1% w/w), in eliminating Pseudomonas aeruginosa (ATCC 15442) bacteria inoculated on the paint film. It also indicates that both antimicrobial agents based on zinc pyrithione / zinc oxide and silver ion have antibacterial efficacy.

In Table 8 below, Agent #4 is a powder containing 1 wt% of silver ion. Table 8: Antibacterial Efficacy Test with Pseudomonas aeruginosa on paint films dosed with Antimicrobial Agent #1 and Agent #4.

Agent #4 in a dosage % wt/wt of 0.1%, 0.2% and 0.3% and 0.5% corresponds to 10 ppm, 20 ppm and 30 ppm and 50 ppm respectively of silver ion relative to the total weight of the coating composition. Example 3

Experiment 7

Tests for antifungal activities and efficacy

Two types of fungal growth resistance efficacy tests were employed for the antimicrobial paint films. These were the Zone of Inhibition Test and the Humidity Cabinet Test.

Zone of Inhibition Test

In the Zone of Inhibition Test, the paint samples, with or without biocides, were coated on a filter paper using an applicator of 200 μηι thickness. After drying at room temperature for 7 days, a 3.5 cm diameter circle shape paint film sample was cut from each of the coated paint film. Each circle- shape paint film was placed in the center of a petri dish of Potato Dextrose Agar (PDA) inoculated with a sufficient quantity of Aspergillus niger (ATCC No. 6275) spores collected from culture. After incubation in darkness at 28°C for 7 to 10 days, the petri dishes were checked for zone of fungal growth inhibition. The above procedures were repeated using fungi species of Alternaria alternata and Penicillium purpurogenum. In the Zone of Inhibition test, the 'zone of inhibition' is measured as the distance (in cm) from the edge of the paint film to the outer edge of the clear zone, i.e, the zone that is clear of fungal growth. All samples tested had no zone of inhibition, but some also showed no fungal growth. Results are given in Table 9 below.

Humidity Cabinet Test

In the Humidity Cabinet Test, the paint samples, with or without biocides, were painted on wooden tongue depressor panels and the panels were left to air-dry for 24 hours. This was followed by second coat of painting. The wooden panels were then left to air dry for 7 days at room ambient temperature. After the 7 days air drying, the panels were inoculated with a sufficient quantity of Aspergillus niger (ATCC No. 6275) spores suspended in phosphate buffer solution; the fungal spore suspension was applied onto the dried coated wooden panels with a sterile cotton swab. The inoculated panels were then hung in a high humidity-incubating chamber at room temperature

(about 28°C) in darkness. Fungal growth on the paint film was evaluated after 14 days of incubation. The above procedures were repeated using fungi species of Alternaria alternata and Penicillium purpurogenum.

The test results from both the Zone of Inhibition Test and Humidity Cabinet Test are in Table 9. The results showed that zinc pyrithione alone is effective against Alternaria alternata and Penicillium purpurogenum, as demonstrated by the efficacy of 0.30 wt% of Agent #2, equivalent to 1,140 ppm of zinc pyrithione. (The paint sample contained 0.30 wt% of Agent #2. Agent #2 contains 38 wt% zinc pyrithione. The zinc pyrithione content in the paint is therefore 0.30% x 38% = 1,140 ppm.)

When the combination of zinc pyrithione and zinc oxide is used, efficacy against Alternaria alternate and Penicillium purpurogenum can be achieved with a lower content of zinc pyrithione, as demonstrated by the efficacy of 0.50 wt% of Agent #1, equivalent to 600 ppm of zinc pyrithoine. (The paint sample contained 0.50 wt% of Agent #1 which means it contains 0.5% x 12% = 600 ppm of zinc pyrithione.) The test results also showed that zinc pyrithione, with or without zinc oxide, is not completely effective against Apergillus niger.

The test results further showed that silver based antimicrobial agent has no fungal growth resistance efficacy.

In Table 9 below, the following symbols are used:

Zone of Inhibition Test rating scale:

A = Paint film had no zone of inhibition but had no fungal growth

B = Paint film had no zone of inhibition and had partial fungal growth

C = Paint film with heavy fungal growth

Humidity Chamber Test rating scale:

0 = No growth; 1 = Very slight growth; 2 = Slight growth 3 = Moderate growth; 4 = Heavy growth.

Table 9: Fungal growth resistance efficacy on antimicrobial agent based on zinc pyrithione / zinc oxide (Agent #1), zinc pyrithione (Agent #2) and silver ion (Agent # 4)

Blank C C C 4 4 4

Latex 0.05% C C c 4 4 4

Agent #4

paints 0.07% C C c 4 4 4

0.09% C C c 4 4 4

In the Table above, Agent #1 in a dosage % wt/wt of 0.10%, 0.30% and 0.50% corresponds to 120 ppm, 360 ppm and 600 ppm, respectively, in each of zinc pyrithione and zinc oxide relative to the total weight of the coating composition. Agent #2 in a dosage % wt/wt of 0.10%, 0.30% and 0.50% corresponds to 380 ppm, 1,140 ppm and 1,900 ppm respectively in zinc pyrithione relative to the total weight of the coating composition. Agent #4 in a dosage % wt/wt of 0.05%, 0.07% and 0.09% corresponds to 5 ppm, 7 ppm and 9 ppm respectively of silver ion relative to the total weight of the coating composition.

The various Examples provided above are by way of instruction only and should not be construed to limit the disclosed embodiments of the invention.

Claims

A coating composition comprising zinc pyrithione and zinc oxide, wherein the zinc pyrithione and zinc oxide are present as an antimicrobial agent, and the zinc pyrithione and zinc oxide are present in an amount sufficient to provide antimicrobial properties to the coating.

A coating composition according to claim 1, wherein the zinc pyrithione and zinc oxide are present in an amount sufficient to provide antiviral properties to the coating.

A coating composition according to claim 1 or 2, wherein the coating is an architectural coating.

A coating composition according to any one of claims 1 to 3, wherein the coating is a paint.

A coating composition according to any one of claims 1 to 4, wherein the zinc pyrithione and zinc oxide are each present in an amount of between 0.006 wt% and 0.24 wt% relative to the total weight of the coating composition.

A coating composition according to any one of claims 1 to 5 wherein the zinc pyrithione and zinc oxide are each present in an amount of between 0.03 wt% and 0.12 wt% relative to the total weight of the coating composition.

A coating composition according to any one of claims 1 to 6, wherein at least 99.5 wt% of each of zinc pyrithione and zinc oxide is composed of particles of particle size of less than 45 microns.

A coating composition according to any one of claims 1 to 7, wherein the zinc pyrithione and zinc oxide are present as nano-sized zinc pyrithione and zinc oxide particles.

A coating composition according to any one of claims 1 to 8, wherein the composition is a paint composition, preferably selected from emulsion or latex paints based on polyacryiic or modified polyacryiic emulsion, silicon emulsion or the blends of emulsions; alkyd paints based on short, medium or long oil alkyd resins; polyester coatings; polyurethane coatings including water based and solvent based, 1-K (one component) and 2-K (two component) types; polyacrylic coatings based on solvent-based or water-based dispersion polyacrylic; epoxy coatings consisting of solvent-based and water-based types; and/or polyurea coatings.

10. A coating composition according to any one of claims 1 to 9, wherein the composition further comprises silver in the form of an organic or inorganic silver salt, colloidal or nanoparticulate silver or silver oxide.

A coating composition according to claim 10, wherein the composition comprises between about 5 and 50 ppm silver ion, relative to the total weight of the coating composition.

A process for manufacturing an architectural coating composition comprising:

forming a mill base; and

13. Use of zinc pyrithione and zinc oxide in combination as an additive for maintaining or increasing antimicrobial properties, particularly antiviral properties, of an architectural coating composition.

14. Use of zinc pyrithione and zinc oxide in combination as an additive according to claim 13, wherein said use is for preventing infections with infectious diseases, particularly hand-foot- mouth disease due to Coxsackievirus type A16 and/or Enterovirus type 71.

A method of treating an architectural surface, comprising applying to said surface a coating composition according to any one of claims 1 to 10.