BACTERICIDAL COMPOSITIONS AND ARTICLES CONTAINING THEM

Abstract: The invention relates to bactericidal compositions comprising an isothiazolinone and a benzalkonium halide. Preferred compositions contain a mixture of 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one as the isothiazolinone and N-alkyl-N-benzyl dimethylammonium chloride as the benzalkonium halide. The invention also relates to liquid compositions (e.g. paints) and solid articles containing the bactericidal compositions, as well as solid articles such as filters and air-conditioning conduits coated with the compositions.

Description: BACTERICIDAL COMPOSITIONS AND ARTICLES CONTAINING THEM The present invention relates to bactericidal compositions, articles containing them, and processes for their preparation. A great deal of time and effort, in a wide range of technical fields is currently devoted to overcoming the problem of bacterial infection and contamination. In the office, and in the home, there are many everyday objects which are touched or handled on a regular basis by numerous people. Such items, if not cleaned properly and regularly, tend to harbour and accumulate dirt and germs and this can contribute to the spread of illness and disease. Disinfection achieved by the use of disinfectants is short-lived. Moreover, the disinfection of objects item by item is time-consuming and there is no easy way of telling whether the required standard of disinfection has been achieved. On many occasions filters are employed to regulate the flow of air between different locations. Hitherto, such filters have had only limited success in controlling the spread of bacterial infection from one location to another. Another field in which thorough disinfection is important, if not essential, is in the field of food processing, and a particular problem faced by the food processing industry is in keeping sterile the surfaces and materials with which food comes into contact. For example, it can be very difficult adequately to ensure that work surfaces, wall surfaces and claddings etc. are free from harmful bacteria which could cause food spoilage. Furthermore, although food packaging materials can be sterilised along with the food after packaging, it would undoubtedly be advantageous to be able to prevent bacterial contamination of the packaging materials in the first place. Bacterial contamination can be a significant problem in the context of air-conditioning, ventilation and air filtration systems. It will readily be appreciated that if pathogenic disease-causing bacteria find their way into the air-conditioning or ventilation shafts of a building, they will rapidly be circulated throughout the building thereby greatly increasing the likelihood of the spread of infection and disease. This can be a particular problem in hospitals, for example, where the weakened or suppressed immune systems of many patients will render them much more susceptible to infection. It would therefore be highly desirable to be able to provide a means of treating air-conditioning and ventilation systems, and their component parts such as trunking, conduits and air filtration systems, with anti-bacterial agents to reduce or eliminate the spread of pathogenic bacteria. Thus there exists a need to provide articles, objects and materials, particularly those associated with the food processing industry, and those associated with air- conditioning and ventilation of buildings, with a means of preventing bacterial contamination. It has been known previously to provide articles with an ability to resist bacterial contamination by incorporating a bactericidal compound or composition into the matrix of the material from which the article is formed. This approach is exemplified by International Patent application, publication number WO 90/11015 (HYGENICO), and the various documents cited therein. WO 90/11015 discloses the incorporating into the matrix of the article of a combination of an organoarsenic antibacterial agent such as 10,10-oxybisphenoxarsine (OBPA), with an alkylated diaminoalkane antibacterial agent such as a l-alkylamino-3-amino propane. However, this combination, although undoubtedly effective against a broad spectrum of both gram positive and gram negative bacteria, is not suited to use with items and articles destined to come into contact with food, and is not authorised for use in conjunction with such articles. A further problem with the combination of bactericidal agents disclosed in WO 90/11015 is that they have been found to be incompatible with certain additives commonly used in food-grade plastics materials, particularly PVC. It is an object of this invention to overcome the aforementioned problems and to provide a bactericidal composition which can be incorporated into an article to provide the article with the ability to resist bacterial infection, and which is compatible with food. It is a further object of the invention to provide anti-bacterial compositions and methods of treating the components of air-conditioning, ventilation and air filtration systems to prevent or reduce bacterial contamination of air passing therethrough. It has now been found that a combination of a benzalkonium-type disinfecting agent and an isothiazolinone disinfecting agent can meet the above criteria. Accordingly, in a first aspect the present invention provides a bactericidal composition containing an isothiazolinone and a benzalkonium halide. The isothiazolinone can be a substituted or unsubstituted isothiazolin-3-one, and particular examples of substituted isothiazolin-3-ones are these bearing a substituent such as halogen (e.g. a chloro-substituent ) in the 5-position. Advantageously the isothiazolinone is selected from 5-chloro-2-methyl-4-isothiazolin-3-one, or 2-methyl-4-isothiazolin-3-one, or a mixture thereof. Preferably the isothiazolinone is a mixture of the two aforesaid isothiazolinones. Examples of benzalkonium halides include N-alkyl-N-benzyl dimethylammonium chloride. The N-alkyl group typically contains from 12 to 16 carbon atoms and a particularly preferred benzalkonium c o m p o u n d i s a m i x t u r e o f N-C j4 alkyl-N-benzyl-dimethylammonium chloride, N-C22alkyl-N-benzyl-dimethylammonium chloride and N-C | galkyl-N-benzyl-dimethylammonium chloride, most preferably in the ratio 50:40:10. The weight ratio of the isothiazolinone to benzalkonium halide in the composition can vary, for example from about 1:500 to about 1:1. More usually, the weight ratio will lie in the range from about 1:300 to about 1:3. For example in one embodiment the weight ratio lies between about 1:30 and about 1:40. In another embodiment, the weight ratio lies between about 1:3 and 1:4. The term "weight ratio" as used herein refers to the dry weights of the component compounds. In a further aspect, the invention provides an article comprising a solid or liquid matrix containing a bactericidal composition as hereinbefore defined. The matrix can comprise between about 0.05% by weight and 10% by weight of the bactericidal composition, for example between about 0.2% and 5% by weight. For example, the matrix can be a solid polymeric matrix formed from any natural or synthetic plastics material such as ethylene vinyl acetate copolymer (EVA), polyvinylchloride (PVC), polyethylene, polypropylene, thermoplastic rubbers such as butadiene-based block copolymers, natural rubbers and derivatives thereof. It is preferred that the plastics material is thermoformable at a temperature of 160°C or less, and a particularly preferred plastics material is ethylene vinyl acetate (EVA) which can be thermoformed by heating to 120°C. It is preferred that the plastics materials should be thermoformable at temperatures of 160°C or less because this reduces the likelihood of thermal degradation of the bactericidal compositions occurring. Typical liquid matrices include paint bases, coatings, adhesives, varnishes and the like. Examples of solid articles formed from a matrix incorporating the bactericidal compositions are articles associated with food manufacture and processing and include packaging materials, work surfaces, food processing implements, food storage surfaces and containers, and cladding materials such as wall cladding. Other articles include filters and those which in everyday use are handled or touched frequently by people. Such articles include in- wall fans, filters, door handles, door touch plates, lavatory handles, lavatory seats, wall cladding materials, telephones and the like. Still further examples of solid articles incorporating the bactericidal compositions of the present invention are ducting panels, tubes and conduit and other component parts of air-conditioning and ventilation systems. An advantage of the compositions and articles of the present invention is that they are compatible with foodstuffs and are not toxic to the user. Nevertheless, the compositions exhibit bactericidal activity against both gram positive and gram negative bacteria, yeasts, moulds, and fungi. The compositions of the present invention can be mixed with polymeric and plastics materials and moulded by commonplace moulding methods such as injection moulding, vacuum forming, rotomoulding and the like without substantial loss of bactericidal activity. For example, the compositions can be incorporated into a plastics material and moulded to a shape that can be used to replace, cover, fit over, or fit into any product which is regularly handled by significant numbers of people. For example, the matrix can be moulded into a shape to fit over or into any household or office products such as a door knob, door touch plate, lavatory handle, lavatory seat as well as cladding panels, for example panels made of glass reinforced plastic (GRP) and polyvinylchloride (PVC), work surfaces, containers and food packaging materials. In another aspect, the invention provides a method of preparing a moulded article, which method comprises forming a bactericidal composition containing a benzalkonium halide and an isothiazolinone as hereinbefore defined, mixing the composition with a polymeric or plastics material and moulding said mixture to form the article. The bactericidal compositions typically are added to the polymeric or plastics materials as liquid compositions comprising a carrier liquid, most preferably a non-aqueous carrier liquid. Suitable carriers include glycols such as the alkylene and polyalkylene glycols, e.g. diethylene glycol, hexylene glycol and polyethylene glycol. A preferred glycol is diethylene glycol. The compositions of the present invention can be used to treat air filters, for example filters of the type used in air-conditioning and ventilation systems. Filter membranes used in such systems typically are formed from polypropylene or paper and can be treated with liquid compositions according to the present invention to impart anti-bacterial properties to the filter membranes. Typically, the liquid compositions of the invention will be sprayed on to the filter in the form of an aqueous solution, the water then being allowed to evaporate. As an alternative to spraying, the filter membranes may be dipped in the solution. It is preferred that the aqueous solution used for treating the filter membranes also contain a non-volatile liquid carrier such as the glycols, e.g. alkylene and polyalkylene glycols referred to above. By incorporating such non-volatile liquid carriers into the compositions, following initial evaporation of the water, the anti¬ bacterial compositions remain on the filter in solution form, and it has been found that in this form they are much more effective in killing bacteria. It will be appreciated that the filter should be loaded with a sufficient quantity of the composition to provide the desired anti-bacterial effect, whilst ensuring that the loading of non-volatile carrier liquid is not so great as to cause clogging of the filter. The bactericidal compositions of the invention may also be incorporated into surface coating material such as paints. For example, the compositions may be incorporated into standard paint bases, e.g. oil-based paints or emulsion paints and the resulting bactericidal paints used to treat surfaces in areas where it is desired to reduce or eliminate bacterial contamination. For example, paints incorporating the bactericidal compositions of the present invention may be used to treat the inner surfaces of air conduits and pipes used in air-conditioning and ventilation systems. In a further aspect, the invention provides articles such as panels and conduits for air-conditioning and ventilation systems, coated with a paint composition comprising the bactericidal compositions of the present invention. In a still further aspect, the invention provides a method of treating an air-conditioning system or ventilation system in a building to provide the air- conditioning system or ventilation system with anti¬ bacterial properties, which method comprises coating the surfaces of ventilation shafts, conduits and pipes, and any air filters making up the system with a composition or compositions comprising a bactericidal composition as hereinbefore defined. The articles of the present invention, in addition to containing the bactericidal compositions, can also contain one or more other substances such as other bactericidal agents, biocidal agent, algaecidal and fungicidal agents. Such other substances typically are incorporated into the mixture prior to moulding. An advantage of the compositions and articles of the present invention is that whereas it has previously been considered that disinfectants only normally work in a wet environment, and cease to work when the disinfectant dries out, the articles of the present invention continue to exhibit bactericidal activity in the dry state. Thus the articles of the invention do not required repeated wiping down with disinfectant in order to prevent the build-up of bacteria. Moreover, the bactericidal activity appears to extend a short distance out from the surface of the article, to form a "halo" of bactericidal activity and it is speculated that this may be due to slow leaching of one or both bactericidal agents from the matrix. The composition and articles of the present invention are bactericidal against a wide range of gram positive and gram negative bacteria, such as Bacillus cereus. Bacillus subtilis, Brevibacterium ammoniagenes, Brucella abortus, Klebsiella pneumoniae, Lactobacillus casei, Proteus vulgaris, Listeria monocytogenes, Pseudomonas aeruginosa, Salmonella gallinarum, Salmonella typhosa, Staphylococcus aureus, Streptococcus faecalis, Flavobacterium species, Bacillus species, Escherichia species, Aeromonas species, Achromobacter species and Alcaligenes species. The compositions and articles of the present invention also have activity against fungi such as Cephalosporium species, Cladosporium species, Fusarium species, Paecilomyces species, Penicillium species Streptomyces species, Trichophyton interdigitale, Chaetorarium globesu , Aspergillus niger, and Ceniphora puteana, yeasts such as Monilia albicans and Saccharomyces cerevisiae, and algae such as Chlorella pyrenoidosa and Anabaena cylindrica The preparation and properties of the compositions and articles of the present invention will now be illustrated, but not limited, by the following examples. EXAMPLE 1 One volume of a solution obtained from Thor Chemicals, Ch e a d 1 e hu 1 me , Cheshire, UK containing 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one in polyethylene glycol, the combined weights of the isothiazolinones constituting 1.5% by weight of the solution, was blended with one volume of a solution of 50% N-alkyl-N-benzyl-dimethylammonium chloride (N-alkyl = 50% C 14 , 40% C 12 , 10% C 10 ) in polyethylene glycol (obtained from Rhone Poulenc). The resulting mixture (0.24 kg) was blended with a conventional GRP resin to give a total weight of 8 kg resin/bactericidal mixture. Catalyst (1-1.5 weight %) was added to the resin in standard fashion, and the resulting mixture was spread over fibre-glass matting (12 kg) and allowed to harden to give GRP sheet. Microbiological Properties Samples of GRP prepared in accordance with Example 1 and measuring approximately 7x7cm and containing the bactericidal compositions were tested against control samples containing no bactericidal composition in the following manner. Surface contamination A duplicate sample of extruded glass fibre approximately 7x7cm was contaminated with Staph.aureus at a concentration of approximately 10° cfu/ml. Swabs, soaked in nutrient broth, were taken at 1 minute, 5 minutes, 10 minutes, 30 minutes and 1 hour. These were subcultured onto DST nutrient medium and incubated at 37"c for 18 hours. For samples including the bactericidal compositions of the invention, bactericidal activity was observed after 5 minutes. Numbers of organisms dropped rapidly after 5 minutes, indicating bacterial kill. EXAMPLE 2 A solution containing a mixture of 5-chloro-2-methyl-4-isothiazolin-3-one, 2 - me t hy l - 4 - i s o t h i a z o l i n - 3 - on e and N-alkyl-N-benzyl-dimethylammonium chloride (N-alkyl = 50% C 14 , 40% C j2 , 10% C j g) in polyethylene glycol prepared in accordance with Example 1 was mixed with EVA pellets in an amount corresponding to 5% by weight of the total weight of the solution/pellet mixture in such a way as to ensure thorough coating of the pellets with the mixture. The coated pellets were then introduced into the hopper of a conventional injection moulding machine and moulded into a variety of shapes and sizes. Articles formed by this method are found to have excellent bactericidal properties. EXAMPLE 3 Ten volumes of a solution obtained from Thor Chemicals, Cheadlehulme, Cheshire, UK containing 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one in polyethylene glycol, the combined weights of the isothiazolinones constituting 1.5% by weight of the solution, were blended with one volume of a solution of 50% N-alkyl-N-benzyl-dimethylammonium chloride (N-alkyl = 50% C 14 , 40% C 12 , 10% C 10 ) in polyethylene glycol (obtained from Rhone Poulenc). The resulting polyethylene glycol solution was mixed with EVA pellets and moulded into various products in the manner described in Example 2. Articles formed by this method are found to have excellent bactericidal properties. EXAMPLE 4 The polyethylene glycol solution of Example 3 was diluted with water (one volume polyethylene glycol solution:eight volumes of water), and the resulting solution was sprayed on to a standard polypropylene air filter. Following evaporation of the water, there resulted an air filter having excellent anti-bacterial properties. EXAMPLE 5 Two volumes of the polyethylene glycol solution of Example 3 were mixed with ten volumes of a standard oil- based HMG grey primer paint manufactured by Marcel Guest, to give an anti-bacterial paint composition. A galvanised metal air conduit of the type used in air-conditioning and ventilation systems was treated with a phosphoric acid composition to prime the galvanised metal surface, and the primed surface was then coated with the anti-bacterial paint composition. Air-conditioning systems and building ventilation systems incorporating trunking treated in accordance with this example, and incorporating air filters treated in accordance with Example 4 provide excellent protection against the spread of pathogenic disease-carrying bacteria through buildings. It will readily be apparent that numerous modifications and alterations could be made to the exemplified composition and article without departing from the principles underlying the invention, and all such modifications and alterations are intended to be with the scope of this application. EXAMPLE 6 Five volumes (100cm 3 ) of a 16.5% w/v solution of a mixture of 5-chloro-2-methyl-4-isothiazolinone-3-one and 2-methyl-4-isothiazolinone-3-one in diethylene glycol were mixed with one volume (20cm 3 ) of a 50% w/v solution of N-alkyl-N-benzyl-dimethylammonium chloride (N-alkyl = 50% C 14 , 40% C 12 , 10% C 10 ) in diethylene glycol to give a bactericidal compositions which was then used to prepare a bactericidal paint. For oil based paints, the bactericidal composition was added to a conventional oil paint base at a concentration of 5cm 3 per 100cm 3 of paint. For emulsion paints, the bactericidal compos; ..on was diluted with water to a strength of 4:1 or 8:1 (water:bactericidal composition), and the resulting aqueous composition was added to a conventional emulsion paint base at a concentration of 10cm 3 100cm 3 of paint. EXAMPLE 7 One volume of a 16.5% of w/v solution of a mixture of 5-chloro-2-methyl-4-isothiazolinone-3-one and 2-methyl-4-isothiazolinone-3-one in diethylene glycol were mixed with one volume (20cm 3 ) of a 50% w/v solution of N-alkyl-N-benzyl-dimethylammonium chloride (N-alkyl = 50% C j4 , 40% C 1 , 10% CJ Q ) in diethylene glycol to give a bactericidal composition. The bactericidal composition (20cm 3 ) was then diluted with water to a strength of 4:1 or 8:1 (water:bactericidal composition) and the resulting solution was used to spray or dip conventional polypropylene filter elements .

Claims: CLAIMS A bactericidal composition containing an isothiazolinone and a benzalkonium halide. A bactericidal composition according to Claim 1 wherein the isothiazolinone is a substituted or unsubstituted isothiazolin-3-one. A bactericidal composition according to Claim 2 wherein the isothiazolin-3-one bears a substituent in the 5-position. A bactericidal composition according to Claim 2 wherein the substituent in the 5-position is a halogen such as chlorine. A bactericidal composition according to any one of the preceding claims wherein the isothiazolinone is selected from 5-chloro-2-methyl-4-isothiazolin-3-one or 2-methyl-4-isothiazolin-3-one or a mixture thereof. A bactericidal composition according to Claim 5 wherein the isothiazolinone is a mixture of 5-chloro- 2-methyl-4-isothiazolin-3-one and 2-methyl-4- isothiazolin-3-one. 7. A bactericidal composition according to any one of the preceding claims wherein the benzalkonium halide is an N-alkyl-N-benzyl dimethylammonium chloride. 8. A bactericidal composition according to Claim 7 wherein the N-alkyl group contains from 12 to 16 carbon atoms. 9. A bactericidal composition according to Claim 8 wherein the benzalkonium halide compound is a mixture of N-C 14 alkyl-N-benzyl-dimethylammonium chloride, N-C2 2 alkyl-N-benzyl-dimethylammonium chloride and N-C j galkyl-N-benzyl-dimethylammonium chloride. 10. A bactericidal composition according to Claim 9 wherein the N-C-^alkyl, N-C2alkyl and N^galkyl- substituted N-benzyl-dimethylammonium chlorides are present in the ratio 50:40:10. 11. A bactericidal composition according to any one of the preceding claims wherein the weight ratio of the isothiazolinone to benzalkonium halide varies from about 1:500 to about 1:1. 12. A bactericidal composition according to claim 11 wherein the weight ratio is in the range from about 1:300 to about 1:3. 13. A bactericidal composition according to Claim 12 wherein the weight ratio is between about 1:30 and about 1:40. 14. A bactericidal composition according to Claim 12 wherein the weight ratio is between about 1:3 and 1:4. 15. An article comprising a solid or liquid matrix containing a bactericidal composition as defined in any one of claims 1 to 14. 16. An article according to Claim 15 wherein the matrix comprises between about 0.05% by weight and 10% by weight of the bactericidal composition. 17. An article according to Claim 16 wherein the matrix comprises between about 0.2% and 5% by weight. 18. An article according to any one of claims 15 to 17 wherein the matrix is a solid polymeric matrix formed from a natural or synthetic plastic material. 19. An article according to Claim 18 wherein the solid polymeric matrix is formed from a material selected from ethylene vinyl acetate copolymer (EVA), polyvinylchloride (PVC)), polyethylene, polypropylene, thermoplastic rubbers such as butadiene-based block copoly ers, natural rubbers and derivatives thereof. 20. An article according to Claim 18 or Claim 19 wherein the plastics material is thermoformable at a temperature of 160°C or less. 21. An article according to Claim 20 wherein the plastics material is ethylene vinyl acetate (EVA). 22. An article according to any one of Claims 15 to 18 in which the liquid matrix is a paint base, coating, adhesive, varnish or the like. 23. A solid article according to any one of Claims 15 to 21 which is an article selected from packaging materials, work surfaces, food processing implements, food storage surfaces and containers, and cladding materials such as wall cladding. 24. An article according to any one of Claims 15 to 21 which is a filter. 25. An article according to any one of Claims 15 to 21 which is selected from ducting panels, tubes and conduits and other component parts of air-conditioning and ventilation systems. 26. A method of preparing a moulded article, which method comprises forming a bactericidal composition containing a benzalkonium halide and an isothiazolinone as defined in any one of Claims 1 to 14, mixing the bactericidal composition with a polymeric or plastics material and moulding said mixture to form the article. 27. A method of forming a moulded article according to Claim 26, wherein the bactericidal composition comprises the benzalkonium halide and the isothiazolinone and a non aqueous carrier liquid. 28. A method according to Claim 27 wherein the carrier liquid comprises a glycol such as an alkylene or polyalkylene glycol. 29. A method according to Claim 28 wherein the glycol is selected from diethylene glycol, hexylene glycol and polyethylene glycol. 30. A method of imparting bactericidal properties to an air filter by treating the air filter with a bactericidal composition according to any one of claims 1 to 14. 31. A method according to Claim 30 wherein the bactericidal composition is sprayed on to the filter in the form of an aqueous solution, or the filter is dipped into the said solution. 32. A method according to Claim 31 wherein the aqueous solution contains a non-volatile liquid carrier such as a glycol. 33. A bactericidal composition as defined in any one of claims 1 to 14, said composition also comprising a liquid carrier such as a glycol. 34. A bactericidal composition according to Claim 33 wherein the glycol is a alkylene or polyalkylene glycol. 35. A bactericidal composition according to Claim 34 wherein the alkylene or polyalkylene glycols are selected from diethylene glycol, hexylene glycol and polyethylene glycol. 36. A paint composition incorporating a bactericidal composition as defined in any one of claims 1 to 14 and 33 to 35. 37. A method of treating an air-conditioning system or ventilation system in a building to provide the air- conditioning system or ventilation system with anti¬ bacterial properties, which method comprises coating the surfaces of ventilation shafts, conduits and pipes, and any air filters making up the system with a composition or compositions comprising a bactericidal composition as defined in any one of claims 1 to 14 and 33 to 35.

Inventors: WOOLARD TREVOR, WOOLARD, TREVOR
Applicants: HOLE TRISTAN, WOOD IAN, WOOLARD TREVOR, HOLE, TRISTAN, WOOD, IAN, WOOLARD, TREVOR
Application year: 1995
Main classification: A01N43
IPC codes: A01N43, C08K5, C09D5