AU2006209795A1 - Biostatic polymer - Google Patents

Description

WO 2006/081617 PCT/AU2006/000130 1 TITLE: BIOSTATIC POLYMER FIELD OF THE INVENTION 5 This invention relates to a polymer composition which is biostatic or biocidal, and to a method for treating a surface to prevent microbial colony growth thereupon. The composition may be formed into a film, and the film will resist microbiological growth for a long period. 10 BACKGROUND OF THE INVENTION Any discussion of-the prior art throughout the specification should in no way be considered as an admission that such prior art is widely known or forms part of 15 common general knowledge in the field. It is well known that infection may be transmitted from one person to another by direct contact, by inhalation of air borne infectious particles, or by contact with infectious fluids. Infection is also commonly transmitted indirectly for example by contact with a surface that has itself become infected by contact with an infected 20 person, or with infected airborne particles, or fluids. For example hospital taps are a notorious for their potential to transmit infection and this has been to some extent alleviated by the use of elbow lever taps. But inside hospitals microbial agents such as bacteria, spores, viruses and fungi can also be indirectly transmitted by staff handling instruments, instrument sterilizing 25 baths, door handles, and by touching many other surfaces. Both inside and outside of hospitals infections are spread via contact with toilet cubicle surfaces, toilet flushing WO 2006/081617 PCT/AU2006/000130 2 buttons/levers, toilet doorhandles, telephone handsets, lift buttons, furniture and building surfaces, documents, and utensils to name but a few of countless examples. Surfaces of all of these typically harbour significant and rapidly growing colonies of microbes, moulds and the like. 5 The risk of infection from such like surfaces is reduced by regular cleaning with disinfectant solutions. However it is not practical to wipe such surfaces sufficiently often to provide effective disinfection. No disinfectants for application to surfaces have been sufficiently durable to maintain a biostatic surface for long periods in use. Attempts to incorporate 10 disinfectants into the surface for slow release have either not proven sufficiently durable, or have not been sufficiently effective or have been too toxic or expensive and none has been commercially successful. It is an object of the present invention to overcome or ameliorate at least one of the disadvantages of the prior art, or to provide a useful alternative. 15 BRIEF DESCRIPTION OF INVENTION According to a first aspect the invention provides a method effective for at least a week for prevention of microbial colony growth on a surface comprising the 20 step of covering the surface with a dry or substantially dry film formed from a composition comprising a polyvinyl alcohol and a quaternary ammonium compound. Preferred embodiments of the invention are effective for at least a week for prevention of microbial colony growth, and in some cases many months. According to a second aspect the invention provides a composition effective 25 for at least a week for prevention of microbial colony growth on a surface comprising WO 2006/081617 PCT/AU2006/000130 3 a dry or substantially dry film formed from a composition containing a complex formed between a polyvinyl alcohol and a quaternary ammonium compound. The present invention provides a polymeric material which can be coated onto a surface from a solution or emulsion and dried or allowed to dry to a dry film, 5 although in less preferred embodiments, the film is substantially dry but may retain some moisture. Preferably, the surface of the film remains biostatic for long periods. By biostatic is meant that microbial colonies (if any) on the surface do not grow or multiply. By "long periods" in this context is meant a period of at least a week, preferably weeks, months, and more preferably years. 10 Unless the context clearly requires otherwise, throughout the description and the claims, the words 'comprise', 'comprising', and the like are to be construed in an inclusive sense as opposed to an exclusive or exhaustive sense; that is to say, in the sense of "including, but not limited to". In preferred embodiments a composition according to the invention is coated 15 onto an inanimate surface (for example a bench top), by being wiped on as a film, or by being sprayed onto the surface. The composition may then be wiped off the inanimate surface and serves to (a) disinfect the surface to which it is applied, (b) cleans the surface and (c) leave a residual transparent residual film which is biostatic for at least a week, and preferably many weeks. The composition need not be wiped 20 off and in the case of for example of an air-conditioning duct interior, the sprayed composition may simply be left to dry. In other preferred embodiments an article may be coated (for example onto sheet material) by knife coating or calendering or spraying or by dipping it into a solution or emulsion of the polymer and drying the film or allowing the film to dry. In preferred embodiments of the invention the WO 2006/081617 PCT/AU2006/000130 4 quaternary ammonium compound is present in the range of from 0.5% to 75% w/w of the dried composition. The present inventors have discovered that a combination of a polyvinyl alcohol with from 0.5% to 75% w/w of a quaternary ammonium biocide results in a 5 composition which is biostatic, that is to say on which micro organisms do not grow. The composition may be used to form a film with which to coat a surface. and which is biostatic and remains so for long periods. The combination may optionally include adhesion promoters, vehicles, pigments and the like. Desirably, the film forming composition contains one or more surfactants 10 which are selected so as not to deactivate the quaternary ammonium compound and which due to their low surface tension ensure thorough wetting of an underlying inanimate substrate penetrating into any scratches or cracks. Preferred surfactants are selected from non-ionic, cationic or amphoteric surfactants. Conventional formulation wisdom teaches that a combination of a surfactant with a quaternary 15 ammonium compound would deactivate the quaternary compound and/or dry to a sticky surface which attracts dust and other proteinaceous residues which have a tendency to deactivate quaternary ammonium biocides. The present inventors have discovered that a complex is formed between the polyvinyl alcohol and the quaternary compound which is not sticky in the presence of 20 efficacious levels of quaternary compatible surfactants. Evidence for complex formation resides in a significant shift in the infra red spectrum of a the OH group peak from 3296" in pure polyvinyl alcohol to 3346 "' in mixtures with the quaternary ammonium biocide indicative of very significant levels of hydrogen bonding.

WO 2006/081617 PCT/AU2006/000130 5 In preferred embodiments the combination is prepared as an aqueous solution which dries to a clear hard film on which micro organisms will not grow. The solution may be applied by wiping, brushing spraying, dipping onto an inanimate surface and drying or allowing drying. Compositions according to the invention may 5 be formed into films for example on door handles, tap handles, toilet seats, telephone handsets, air conditioning ducts, bench tops, or the like. The term "polyvinyl alcohol" as herein used includes all resins made by the hydrolysis (saponification) of polyvinyl esters, for example polyvinyl acetate. The properties of the resins vary according to the degree of polymerization of the parent 10 polyvinyl ester and the extent of the hydrolysis (saponification degree). In the case of a polyvinyl alcohol prepared from polyvinyl acetate the structure of polyvinyl alcohol may be represented by

-CH

2 CHOH (CH 2 CHOH)m 15 where "1+m" is the degree of polymerization. On partial hydrolysis proportional amounts of residual CH 2 COO- groups are distributed along the chain in place of OH and the amount of such acetate groups expressed as a percentage is the acetate content. Thus in polyvinyl alcohol of 70% acetate content, 30% of the acetate groups 20 of the original polyvinyl acetate were hydrolysed to hydroxyl groups, and 70% remain as acetate groups. This may be referred to as 70% acetate content or as a 30% alcohol. In grades having above 90% alcohol (less than 10% acetate), the polyvinyl alcohol tends to be only readily soluble in hot water (above 90 0 C) although this also varies to an extent with degree of polymerization.

WO 2006/081617 PCT/AU2006/000130 6 The term "polyvinyl alcohol" as used herein includes all suitable grades, degrees of saponification and degrees of polymerization. Polyvinyl alcohols may also be made by hydrolysing polyvinyl esters other than acetates, and the same principles apply to the polyvinyl alcohols so formed 5 which may also be used in the invention. However, preferred embodiments of the invention utilize polyvinyl alcohol having an average degree of hydrolysis of greater than 96 mole % hydrolysis, since such compositions are more resistant to removal from a surface to which they are applied by cold or warm water and are less likely to be removed from a treated surface onto the skin by human contact. 10 Quaternary Ammonium compounds for use in the invention The invention has been exemplified by reference to n-alkyl dimethyl benzyl ammonium chloride (also known as benzalkonium chloride) as the highly preferred quaternary biocide. Alkyl benzyl quaternary biocidal compounds are preferred; 15 however those skilled in the art will recognise that other biocidal quaternary ammonium antimicrobial compounds may be used in the present invention. It is preferred that the biocidal quaternary ammonium antimicrobial compound is selected from the group having a general formula: R1 20 N-- R"" X 20R" WO 2006/081617 PCT/AU2006/000130 7 Wherein R' R" R'" R"" are alkyl radicals that may be the same or different, substituted or unsubstituted, branched or unbranched, and cyclic or acyclic. X is any anion but preferably a halogen, more preferable chlorine or bromine. Highly preferred antimicrobial compounds are mono-long chain, tri-short 5 chain, tetralkyl ammonium compounds, di-long-chain, di-short chain tetralkyl ammonium compounds and mixtures thereof. By "long" chain is meant about C 6 - C 30 alkyl, and by "short" chain is meant C 1 - C 5 alkyl, preferably C1 - C 3, or benzyl, or C 1 - C 3 alkylbenzyl. Examples include monoalkyltrimethyl ammonium salts such as cetyltrimethyl ammonium bromide (CTAB), monoalkyldimethylbenzyl 10 compounds or dialkylbenzyl compounds. Quat. biocides such as chlorhexadine gluconate may be employed. The most highly preferred compounds for use in the invention have at least one benzyl radical which may be a substituted benzyl. Examples include C 8 - C 22 dimethyl benzyl ammonium chloride, C 8 - C 22 dimethyl ethyl benzyl ammonium 15 chloride and di- C 6 - C 20 alkyl dimethyl ammonium chloride The quaternary ammonium compound is incorporated for broad spectrum (gram positive and gram negative) antibacterial properties. Although the quaternary ammonium compound may comprise from 0.5%to 75% w/w of the dried film composition, it is preferred to employ more than 2% w/w 20 of the dried film composition. Desirably the composition includes one or more surfactants which are compatible with (i.e. do not deactivate) the quaternary ammonium compound. Surfactants selected from non-ionic, cationic and amphoteric surfactants are preferred for example non ionic surfactants such as C12 to C18 straight chain alcohol or 25 ethoxylated alcohols or cocamine oxides. However other examples include branch WO 2006/081617 PCT/AU2006/000130 8 chain and aromatic ethoxylated surfactants. An example of a suitable cationic surfactant is polyethylene glycol-2-cocamine and an example of a suitable amphoteric surfactant is coco-betaine. 5 Examples of the invention Example 1 Manufacture of composition according to the invention. A composition was manufactured having the composition shown in table 1: The following procedure was employed:. 10 * About one quarter of the amount of water required (about 724 Kg) was placed into a cleaned and sanitized water jacketed mixing tank. * The mixer was started. Polyvinyl alcohol was added slowly * The temperature was raised to 80-90 0 C while stirring * Mixing was continued for another hour or until the Polyvinyl alcohol was 15 dissolved at this temperature. " The tank was then cooled while mixing in the remaining water. " The solution was cooled to below 40 "C and the Teric LA8 added. e The combination was mixed for 5 minutes and then the quaternary compound (Barquat MB-80) was added. The combination was stirred for a further 10 20 mins, the pH adjusted to 7.0 and make up water added as required.

WO 2006/081617 PCT/AU2006/000130 9 Table 1 composition 3000 litre Batch size 3015 kg Density 1.005 g/mL Generic name Trade name %w/w (kg) Water Water 96 2894.4 Polyvinyl alcohol generic 1.5 45.225 Alcohols, C12-15, ethoxylated Teric LA8 0.2 6.030 n-Alkyl (40%C12, 50%C14, 10% C16) dimethyl benzyl ammonium chloride (80% solution) Barquat MB-80 1.5 45.225 Sodium hydroxide or NaOH (10%) or hydrochloric acid HCl (10%) to pH 6.5 - 7.5 to pH 7 Water Water to 100% To 3015 kg 5 The polyvinyl alcohol has a degree of saponification in the range 80%- 95%, more usually about 87.5% and a viscosity of 3.0-3.7 MPa.s(cp) The composition according to the invention was spread on a metal (aluminium) surface using a knife coater and allowed to dry to form a clear film. The dry film was inoculated with Pseudomonas Originosa ATCC 15442 (6.1 log 10 concentration). After 1 hour it was found that the population had reduced to less than 1 log. After 24 hours the population had reduced to zero. After 7 days the population WO 2006/081617 PCT/AU2006/000130 10 was zero. After 30 days the micro-organism population on the surface was still zero. These tests are ongoing and the inventors are confident that the surfaces will maintain the bacteriostatic properties for a very long period. The results achieved using Aspergillus Niger ATCC16404 were the same or 5 better showing resistance to colonization by both bacteria and fungi. The same results were achieved by casting films containing only the polyvinyl alcohol and the quat in ratios of from 0.5% up to 75%. Compositions according to examples 2 and 3 below were also made using the above method with similar results. 10 Example 2 Water 95.6.0% w/w Polyvinylalcohol 1.2% w/w (low molecular weight; % hydrolysis 96.5% - 99.0%) 15 Ethoxylated C12 to C18 straight chain alcohol 0.2% w/w Benzalkonium chloride 3.0% w/w Adjust pH to 7.0 with NaOH or HCl Water QS 100% 20 WO 2006/081617 PCT/AU2006/000130 11 Example 3 Water 96.0% w/w Polyvinylalcohol 1.5 % w/w 5 (low molecular weight; % hydrolysis 96.5% - 99.0%) Ethoxylated C12 to C18 straight chain alcohol 0.2% w/w Benzalkonium chloride 1.2% w/w Adjust pH to 7.0 with NaOH or HC Water QS 100% 10 Films made from compositions according to Examples 1, 2, and 3 were all deemed to be effective for prevention of microbial colony growth in accordance with method AOAC 955.17 after 1, 7, and 30 days. 15 Example 4 Water 7 7 .5% w/w Polyvinylalcohol 8 .0 % w/w (low molecular weight; % hydrolysis 96.5% - 99.0% 20 TericBL8 1.0% w/w Benzalkonium chloride 8 .0% w/w Phenoxy ethanol 1.0% w/w EDTA 4 Na 0.5%w/w Water QS 100% 25 WO 2006/081617 PCT/AU2006/000130 12 Biostatic properties of a dry film made from a composition according to example 4 wiped onto an inanimate surface were tested according to ASTM E2180 -01 immediately after drying (t=0); after 7 days; and after 30 days with the following results: 5 Time (t) Result 0 Total kill 7 days Total kill 30 days Total kill Compositions according to the invention may be coated on and are effective 10 on a wide range of surfaces including without limitation paper, textiles, plastics, metals, glass, and ceramics. These materials may be coated onto articles, (for example paper cups or food containers, or onto other surfaces. Those skilled in the art will be able to select combinations of polyvinyl alcohols and quaternary ammonium compounds for use in the invention based on the 15 teaching hereof and to select appropriate ratios according to intended end product use. The invention extends to include the combination, solutions of the combination in appropriate solvents, and films formed from the combination with or without solvents.

Claims (22)

1. A method effective for at least a week for prevention of microbial colony 5 growth on a surface comprising the step of covering the surface with a dry or substantially dry film formed from a composition comprising a polyvinyl alcohol and a quaternary ammonium compound.

2. A method according to claim 1 wherein the film is formed on an inanimate 10 surface.

3. A method according to claim 1 or claim 2 wherein the film is formed in situ by coating the surface with a solution or emulsion comprising a polyvinyl alcohol and a quaternary ammonium compound and then causing or allowing it to dry or 15 substantially dry.

4. A method according to any one of the preceding claims wherein the film is effective for prevention of microbial colony growth thereon for at least four weeks. 20

5. A method according to any one of the preceding claims wherein the polyvinyl alcohol has a hydrolysis range of greater than 96 mole %

6. A method according to any one of the preceding claims wherein the quaternary ammonium compound comprises from 0.5%to 75% w/w of the dried film 25 composition

7. A method according to any one of the preceding claims wherein the quaternary ammonium compound is an alkyl benzalkonium compound 30

8. A method according to any one of the preceding claims wherein the quaternary ammonium compound is an n-alkyl dimethyl benzyl ammonium halide.

9. A method according to any one of the preceding claims wherein the polyvinyl alcohol forms a complex with the quaternary compound WO 2006/081617 PCT/AU2006/000130 14

10. A method according to any one of the preceding claims wherein the composition further includes a surfactant which does not inactivate the quaternary compound 5

11. A method according to claim 10 wherein the surfactant is a C12 to C 18 straight chain alcohol

12. A composition effective for at least a week for prevention of microbial colony 10 growth on a surface comprising a dry or substantially dry film formed from a composition containing a complex formed between a polyvinyl alcohol and a quaternary ammonium compound.

13. A composition according to claim12 further comprising a surfactant which 15 does not inactivate the quaternary compound.

14. A composition according to claim 12 or claim 13 wherein the polyvinyl alcohol has an average degree of hydrolysis of greater than 96 mole % 20

15. A composition according to any one of claims 12 to 14 wherein the quaternary ammonium compound comprises from 0.5%to 75% w/w of the dried film composition

16. A composition according to any one of claims 12 to 15 wherein the quaternary 25 ammonium compound is an alkyl benzalkonium compound

17. A composition according to any one of claims 12 to 16 wherein the quaternary ammonium compound is an n-alkyl dimethyl benzyl ammonium halide. 30

18. A composition according to any one of claims 12 to 17 wherein the composition comprises polyvinyl alcohol and a quaternary ammonium compound in an aqueous solution or emulsion. WO 2006/081617 PCT/AU2006/000130 15

19. A composition according to any one of claims 13 to 18 wherein the surfactant is a non-ionic, cationic or amphoteric surfactant

20. A composition according to any one of claims 13 to 19 wherein the surfactant 5 comprises a C12 to C18 straight chain alcohol or ethoxylated alcohol

21. A method substantially as herein described with reference to any one of the examples 10

22. A composition substantially as herein described with reference to any one of the examples