POLYDIMETHYLSILOXANE CONTAINING COMPOSITION
The present invention relates to a liquid polymer film composition which contains one or more bactericidal, fungicidal, algicidal, yeasticidal or moldicidal agents, its application to substantially continuous surfaces such as glass, its incorporation into a wide range of other materials such as coatings, cleaning materials, building materials and to articles treated with the composition.
A great deal of time and effort in a wide range of technical research areas is devoted to overcoming the problems of infection and cress infection in medical, industrial, commercial, domestic and marine environments.
Many compositions are known which contain bactericidal, fungicidal, algicidal, yeasticidal and moldicidal agents. However, such compositions are often toxic to humans or animals or are difficult to use because of their toxicity when wet. Many of these products are unsuitable for mixing with other materials as they either affect the properties of the other material or their own properties are affected.
Furthermore, products such as disinfectants of the type often used in food preparation areas are only effective when wet and can damage substantially continuous surfaces such as glass by staining or etching the surface.
It is one object cf the present invention to provide a liquid polymer film composition which contains one or more bactericidal, fungicidal, algicidal, yeasticidal or moldicidal agents and which can be applied to substantially continuous surfaces such as glass without damaging the surface .
A further object cf the present invention is to provide a liquid polymer film composition as set out in the immediately preceding paragraph which can be incorporated into other materials such as coatings, surfaces, or cleaning agents to give those materials sterilizing properties.
A still further object of the present invention is to provide a liquid polymer film composition as set out in the two immediately preceding paragraphs which is an effective sterilizer when dry and imparts sterilizing properties to an object to which it is applied for many months.
In a first aspect the present invention provides a composition consisting essentially of a polymer composition capable of adhering to a substantially continuous surface.
In a second aspect the present invention provides a composition consisting essentially of a polymer composition capable of incorporation into a material.
The polymer composition preferably comprises a mixture of isopropanol, butyl acetate, sulphuric acid and polydimethylsiloxane .
Preferably there is 87 - 91% isoproponal which preferably acts as a carrier, 1 - 6% of butyl acetate which preferably acts as a drying agent, 1.5 - 3% sulphuric acid which preferably acts as a scavenger and 3 - 6% polydimethylsiloxane (all percentages are by volume) .
Preferably the coir.position includes at least one antibacterial agent and most preferably the composition includes two anti-bacterial agents, which may be the same or different.
The anti-bacterial agents suitable for use in the present invention may include amphoteric compounds, iodophores,
phenolic compounds, quaternary ammonium compounds, hypochlorites and nitrogen based heterocyclic anti-bacterial compounds .
Examples of amphcteric compounds include long chain N-alkyl derivatives of am no acids such as glycine, alanine and beta- amino butyric acid, particular examples being dodecyl beta- alanine, dodecyl eta-aminobutyric acid, dodecylamino-di (aminoethylamino,] glycine and N- (3-dodecylarαino) propylglycine .
The term iodophores as used herein refers to complexes of iodine or triodiα with a carrier, such as a neutral polymer. The carrier typically is one which increases the solubility of iodine in water, provides a sustained release of the iodine and reduces the equilibrium concentrations of free iodine. Examples of polymeric carriers from which iodophore compositions can be made include polyvinylpyrolidone, polyether glycols such as polyethylene glycols, polyvinyl alcohols, polyacrylates, polyamides, polyalkylenes and polysaccharides . preferred iodophore is povidone iodine, in which the carrier s polyvinylpyrrolidone .
Examples of quaternary ammonium compounds include compounds of the general formula R
1R
2N
''
"R
3R
4X
~ wherein or one or two of the R groups are alkyl chains optionally substituted by an aryl group, or optionally interrupted by an aryl group or a heteroatorα such as oxygen, and the other R groups are the same or different and are
alkyl groups and in particular methyl groups. Examples of classes of quaternary ammonium compounds within this general formula include benzalkonium halides, aryl ring substituted benzalkonium halides such as ethyl-substituted benzalkonium halides (e.g. Barquat 4250 available from Lon
~a) , and twin chain quaternary ammonium compounds such as dialkyldimethyl ammonium compounds wherein the two non-methyl alkyl groups are selected from medium and
long chain alkyl groups such as octyl groups and dodecyl groups. Examples of quaternary ammonium compounds in which an alkyl group R contains an oxygen heteroatom include domiphen bromide, benzalkonium chloride, and methylbenzalkoniurα chloride .
Other examples cf quaternary ammonium compounds include alkylpyridinium compounds such as cetylpyridinium chloride and bridged cyclic ami o compounds such as the hexaminium compounds, e.g: - 3-chlorallyl) hexaminium chloride.
Examples of phenolic compounds include methyl, halo- and aryl substituted phenolic compounds such as 2- phenylphenol, 2-benzyl-4-chlorophenol-, 2-cyclopentyl-4- chlorophenol, 4-t-amylphenol, 4-t-butylphenol, 4-chloro-2- pentylphenol, 6-chloro-2-pentylphenol, p-chloro-meta-xylenol, 2,4,4 trichloro-2- hydroxydiphenol, thymol { 2-i-propyl-3- methylphenol) , chlorothymol, 3-methyl-4-chlorophenol, 2,6, dichloro-4-n-alkyl phenols, 2, 4-dichloro-meta-xylenol, 2 , 4, 5-trichlorophenol and 2-benzyl-4-chlorophenol .
Examples of hypochlorites include alkali-metal and alkaline earth metal hypochlorites such as lithium hypochlorites, sodium hypochlorites, potassium hypochlorites, calcium hypochlorites, and chlorinated trisodium phosphate and their various hydrates. Other chlorine-containing or chlorine releasing agents include chlorine dioxide and its precursors, as well as 4-sulpho-dichloramido-benzoicacid (halazone), 1 , 3- dichloro-5-5-dimethylhydantoin (halane) , and various cliloroisocyanuric acid derivatives .
Examples of nitrogen-containing anti-bacterial agents include pyridine derivatives such as 4-pyrιdine carboxylic acid hydrazide, sodium 2-pyridinethiol -1-oxide (Sodium Omadine™) bis- (2-pyridylthic zinc 1, 1-dioxide (zinc Omadine), triazoles and imi azoles such as 2- ( 4-thiazolyl)
benzimidazole (Metasol T K-100); 12-benzisothiazoline-3-one (Proxcel™) 2-n-octyl-4-isothiazolin-3-one (Kathen™) , 2- bromo-2-nitro-l-3-propanediol) , (Bromonopol™) , 3- trifluomethyl-4, ' -dichlorocarbanilide (Irgasan™) quinacrine hydrochloride (Atabrine™) , ciprofloxacin and nalidixic acid and its various derivatives.
The anti-bacteria_ agent or combination of anti-bacterial agents selected will depend on the polymer composition and on the intended use cf the end product.
Preferably the anti-bacterial agent is contained in a nonvolatile carrier. The non-volatile carrier may be a glycol, an ester derivative cf a glycol or an ether derivative of a glycol. In particular, alkylene glycols and polyalkylene glycols such as diethylene glycol, hexylene glycol, propylene glycol and polyethylene glycol are used. The most preferred glycol carrier is diethylene glycol (DEG) .
Alternatively, the carrier may be an alcohol having a high number of carbon atoms, preferably at least six carbon atoms, more preferably at least eight carbon atoms and most preferably at least ten carbon atoms.
Preferably the composition further includes at least one surfactant. Preferably the surfactant includes an amphoteric, an ionic and a non-ionic surfactant. An example of such a surfactant is PERSIL™ washing up liquid manufactured by Lever Brothers .
The compound is preferably diluted with water to provide a final product.
The polymer composition acts as a key to introduce the antibacterial agents to the substantially continuous surface, to adhere them thereto to protect that surface and also to
incorporate the ar.ti-bacterial agents into other materials and especially to allow incorporation of the composition into oil or water based products.
In a third aspect the present invention provides materials incorporating the composition of the present invention.
Such materials may include coatings such as paints and varnishes, which may be oil based or water soluble. The composition may be incorporated into settable or curable compositions such as fillers, grouts, adhesives, mastics, putties and other materials which form a solid matrix over a period of time. Such compositions are prone to the growth of mold and fungus, particularly in damp environments such as bathrooms and kitchens .
The composition of the present invention may include a co- solvent or a co-diluent which evaporates readily. The co- solvent or co-diluent may be aqueous or non-aqueous, depending upon the nature of the material with which it is to be mixed.
The composition car. also be incorporated into plastics materials which cat then be used to manufacture food processing implements, work surfaces, packaging materials, containers, floor and wall cladding materials, bathroom and kitchen furniture.
When the composition is incorporated into materials including those detailed above the surfactant aids mixing of the material and the composition.
A fourth aspect c the present invention provides a substantially continuous surface coated with the composition of the present invention.
The surface is preferably glass, which may then be used in a variety of places such as hospitals, where sterility is of great importance.
The surface may alternatively be a metal, for example, door touch plates, doer and windov; furniture, metal kitchen furniture, especially that used in restaurants.
The surface may alternatively be a plastics material, for example, toilet seats, bathroom furniture, work surfaces and kitchen implements . The surface may alternatively be a glazed ceramic surface such as floor and wall tiles.
The composition may be used in the components of ventilation and air conditioning systems, for example, the conduits, panels, grills and filters may incorporate or be coated with the composition of the present invention.
The polymer composition of the present invention adheres to substantially continuous surfaces without damaging them and as a result forms a coating layer on the surface which contains anti-bacterial agents, so that any bacteria present on or subsequently contacting the surface are eliminated.
The surfactant in this case acts to help the composition to spread over a substantially continuous surface and imparts cleaning and detergent properties to the composition.
The polymer composition works even when it is dry. This is believed to be because even when the surface appears to be dry a low concentraticr. of the anti-bacterial compound is still present as a solution in the non-volatile carrier.
The materials into which the composition of the present invention are incorporated may include other agents such as bactericidal agents, biocidal agents, algicidal agents,
fungicidal agents and moldicidal agents as well as other standard additives for the material in question.
The composition and articles of the present invention have anti-bacterial effect against a wide range of gram-positive and gram-negative bacteria, such as: Bacillus cereus, Bacillus subtilis, Brevibacterium amoniagenes, Brucella abortus, Klebsiella pneumonia, Lactobacillus casei, Proteus vulgaris, Listeria monocytogenes, Pseudomonas aeruginosa, Salmonella gall inaru , Salmonella typhosa, Staphylococcus aureus, Streptococcus faecalis, Flavobacterium species, Bacillus species, Eseherichia species, Aeromonas species, Anchromobacter 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, Trichopliytoninterdigitale, Chaetorariumglobesom, Aspergilluε niger, and Cenipliora putealla. yeasts such as Monilia albicans and Saccharomyces cerevisiae, and algae such as Chlorella pyrenoidosa and Anabaena cylindrica.
In a fifth aspect the present invention provides a method of imparting sterilizing properties to a substantially continuous surface by applying thereto a composition consisting essentially of a polymer film composition including at least one and preferably two anti-bacterial agents incorporated in a non-volatile carrier.
In a sixth aspect the present invention provides a method of imparting sterilizing properties to materials by incorporating therein a composition consisting essentially of a liquid polymer film composition including at least one and preferably two, anti-bacterial agents incorporated in a non-volatile carrier .
The composition preferably includes a surfactant, especially when the composition is incorporated into materials.
The composition may further include a preservative, and a co- solvent which readily evaporates off.
The present invention will be illustrated, merely by way of example, as follows:
Composition of the present invention (named 42AP)
1) Polymer composition (all percentages are by volume)
Isopropanol 87 - 91%
Butyl acetate 1 - 6%
Sulphuric acid 1.5 - 3%
Polydimethylsiloxane 3 - 6%
2 ) Surfactant composition
Anionic surfactant 15 - 30?
Non-ionic surfactant 1 - 5%
Amphoteric surfactant 1 - 5%
Ethanol 1 - 5%
Preservative 1 - 5%
3) First anti-bacterial agent composition
5-chloro-2-methyl-4-isothi azolin-3-l-ones 2-methyl-4-isothiazolin-3-ones; and 85% Diethylene glycol
4) Second anti-bacterial agent composition
Alkyldimethyl-benzylammonium chloride; and
50% Diethylene glycol
An example of the polymer film composition containing antibacterial agents is made by the following steps :-
a) Prepare the first and second anti-bacterial compositions and mix them together in a 1:1 ratio by volume;
b) Mix water with the anti-bacterial composition mixture in a 2:1 ratio by volume of water to anti-bacterial mixture.
c) Add 100ml of the dilute anti-bacterial agent mixture to 200ml of the surfactant composition;
d) Add 100ml of the polymer composition to the surfactant and anti-bacterial agent mixture;
e) Add 600ml of water to the mixture and mix well to give the polymer film composition of the present invention incorporating anti-bacterial agents.
This product can now be used on substantially continuous surfaces to impart an anti-bacterial film or it can be incorporated into a variety of other materials as herein before described. If the product is to be incorporated into oil based materials it will be used in its concentrated form (i.e. step e) will be omitted.
Examples of the Anti-bacterial Nature of the Composition of the Present Invention
Example 1
Two panes of glass were treated, i.e. coated with the active liquid polymer composition, which was allowed to dry. The coated glass panes were then placed m sealed bags. A further
untreated (control; pane of glass was also placed in a sealed bags . The panes cf glass were then stored for three weeks before being submitted for microbiological testing by P.H.L.S. Poole Hospital, Pcole Dorset. The micro-organism used in this test was Methicillin Resistant Staphylococcus aureus . (M.R.S.A.) .
Method
A broth culture of a wild strain of methlcillin-resistant staphylococcus aureaus (MRSA) was grown,, in peptone saline diluent for 20 - 24 hours.
Serial decimal dilutions were then prepared in peptone saline diluent and a surface drop (Miles and Misra) count performed on blood agar. Plates were incubated at 30°C for 18 hours, colonies counted and counts estimated for each dilution.
Two dilutions (1 and 3) were used for inoculation. Dilution 1 contained 14,000 organisms per 20μl and dilution 3 contained 140 organisms per 20μl. Volumes of 20μl of each dilution were applied to each cf the three plates and left in contact for a range of times fret. 0 seconds to 6 hours.
After the designated time the liquid from each inoculation was aspirated and pipetted onto the surface of a blood agar plate. If the inoculum had dried, 20μl of sterile distilled water was applied, carefully mixed and then aspirated. The aspirate was spread over the agar surface using a sterile spreader. Plates were incubated at 30°C for 18 hours and then colonies counted.
Results
Counts obtained are shown in the tables. Plate 1 showed a reduction in count over 5 minutes with no recovery after 10 minutes. For the r.eavier inoculum of 14,000 organisms, this
represents a four log reduction within 10 minutes and a 97.98% reduction within 5 minutes. Plate 2 showed a 3.5 log or 99.95% reduction within 1 minute and a four log reduction (100%) within 2 minutes.
It will be noted that there was a slight reduction on the control plate with time; this was most likely due to the effect of drying, as all inocula had dried out after 1-1.5 hours .
Conclusion
The treatment used for plate 2 resulted in 100% reduction of an inoculum of 14,000 MRSA organisms within 2 minutes and 99.95% reduction within 1 minute.
The treatment used for plate 1 resulted in 100% reduction of an inoculum of 14,000 MRSA organisms within 10 minutes and 97.98% reduction within 5 minutes.
-13-
Example 2
Approximately 50 ml of clear colourless liquid (42AP) was submitted for microbiological testing Joy P.H.L.S Poole Hospital, Poole, Dorset in a clear plastic screwtop bottle. The concentration was said to be 15 ml liquid polymer diluted to 50 ml.
Method
A 1 ml volume of the liquid was inoculated with 20μl of an undiluted overnight broth of MRSA; this inoculum was estimated to contain 107-108 organisms. Using a fresh sterile pipette tip each time, a 20μl volume was immediately withdrawn and another 20μl volume withdrawn after 1, 2, 5, 10, 30 and 60 minutes . This volume was spread over the surface of a blood agar plate which was then incubated at 30°C for 20 hours. After incubation plates were examined for the presence of colonies .
Results
No colonies of MRSA were recovered on any plate.
Conclusion
An inoculum of approximately 107 organisms was killed within 10 seconds when added to 1 ml of ' D' stage 1 surface preparation (where D is 42AP) .
Example 3
A detergent/cleaner called Enviroclene was obtained from H. Marcel Guest Ltd., Manchester, in a concentrated form. 30ml of the concentrate was diluted 15:1 with water and mixed by
conventional methods. 30ml of 42AP concentrate was then added to the diluted detergent/cleaner. After mixing, the product (a clear mobile liquid) was then submitted for microbiological testing by Microbac Analytica Ltd Consett Co. Durham.
Example 4
A detergent/cleaner called Deep-Clean was obtained from MGM Ltd Southampton in a concentrated form. 30ml of concentrate was diluted 15-1 with water and mixed by conventional methods. 30ml of 42AP concentrate was then added to the diluted detergent/cleaner. After mixing, the product (a light pink coloured mobile liquid) was then submitted for microbiological testing by Microbac Analytica Ltd Consett, Co. Durham.
Example 5
A detergent/cleaner called MGMx was obtained from MGM Ltd Southampton in a concentrated form. 30ml of concentrate was diluted 15-1 with water and mixed by conventional methods. 30ml of 42AP concentrate was then added to the diluted detergent/cleaner. After mixing, the product (a light straw coloured mobile liquid) was then submitted for microbiological testing by Microbac Analytica Ltd Consett Co. Durham.
The principle of the test requires that the product under test, diluted in hard water, shall demonstrate at least a 105 reduction in viable count when tested under simulated clean conditions (0.3 g/1 bovine albumin) and dirty conditions (3 g/1 bovine albumin) .
While the original procedure determines that the test should be undertaken at 20°C, concern has been expressed that the temperature does net adequately reflect the temperatures experienced during application of the product.
In most food processing companies, the environment is controlled in such a way as to discourage the growth of pathogenic micro-organisms and working temperatures are usually well below the 20°C specified in the suspension test methodology. As most chemical/biochemical reactions occur more rapidly at higher temperatures, it has been suggested that biocides which work effectively at 20°C may display reduced efficacy at lower temperatures.
Initial testing on a number of products has indicated that the biocidal activity is adversely affected at 10°C.
The following tests were undertaken to determine the efficiency at 10°C.
Test Samples :
The three samples comprised Environclene FS Active Polymer D, Deep-Clene FA Active Polymer D and MGMX FS Active Polymer D which are subsequently diluted with potable water to provide a 1% working concentration. Prior to testing, all samples were stored at room temperature, in dark conditions. The samples were tested on 9th January 1997.
(Active polymer D is 42AP) . Sample and storage details are summarised in Table 1.
Methodology:
The method used to assess the bactericidal activity of the samples is detailed in Appendix I of the Bacterial Activity Suspension Test specified by European Standard (E'inal Draft) Pr EN 1276: November 1995.
The test conditions were as described in Appendix 1, Section 5,5,2,2 (Dilution neutralisation method) with the following modifications :
(i) Temperature:
The tests were undertaken at 10°C only. The temperature was controlled throughout the test procedure at 10°C±1°C using a temperature controlled coolant waterbath.
(ii) Bacterial strains:
Only one organisms, Pseudomonas aeruginosa, was used for the purpose of this test.
The neutraliser selected from Annex B of the appended method comprised 30 g/1 Polysorbate 80 and 3 g/1 Lecithin.
The experimental conditions are summarised in Table 2.
Verification of Methodology:
Several control procedures were undertaken to ensure that the materials used did not affect the validity of the final result. (Appendix 1, section 5.6.2.)
Results :
The results of the tests are shown in Table 3. All of the formulations, when exposed to the test organism, Pseudomonas aeruginosa, for five minutes at 10°C, reduced the viable count by, greater than 10: as specified in the method. In all cases total kill was achieved.
Conclusions :
According to the test procedure, Enviroclene FS Active Polymer D, Deep-clene FS Active. Polymer D and MGMX FS Active Polymer D, possess the required bacterial activity specified by the Suspension Test at 10°C.
BACTERIAL ACTIVITY SUSPENSION TEST
TABLE 1 - SAMPLE AND STORAGE DETAILS
Identification of the samples:
Name of Products: Enviroclene FS Active Polymer D Deep-clene FS Active Polymer D MGMX FS Active Polymer D
Manufacturer: Research Holdings Ltd.
Date of Delivery: 18/11/96
Storage Conditions Room Temperature and Darkness
Product Diluent Recommended by the Potable Water Manufacturer for use:
Active Substance (ε and their Concentrations: Neat
BACTERIAL ACTIVITY SUSPENSION TEST
TABLE 2 - TEST METHOD AND EXPERIMENTAL CONDITIONS
Test Method and its Validation:
Method: Dilution Neutralisation:
Neutraliser: 30 g/1 Polysorbate, 80 3 g/1 Lecithin
Product Diluent Used Sterile Hard Water During the Test: 300 mg/Kg CaC03
Product Test Concentration: As received
Contact Time: 5 min ± 10 seconds
Test Temperature: 10"C ± 1°C
Interfering Substance: 0.3 g/1 of Bovine Albumin
(Clean Conditions
Interfering Substance: 3.0 g/1 of Bovine Albumin
(Dirty Conditions
Stability of the Mixture:
(interfering substance and Precipitate absent throughout product diluted in hard water) the test
Temperature of Incubators: 37CC ± 1°C
Bacterial Strain Used: Pseudomonas aeroginosa NCTC
10332
BACTERIAL ACTIVITY SUSPENSION TEST
TABLE 3 - TEST RESULTS
Enviro-clene FS Deep-clene FS MGMX FA Active Active t'olymei Z Active Polyme Folymer D
Initial Concentration 8 x 108 8 x 108 8 x 108 of Microorganism
(cfu/ml)
Experimental 5x 106 8x 106 8x 106
Concentration
(cfu/ml)
Pass Level :80 <80 <80 (cfu/(ml)
Actual Count at 37°C Clean Conditions (Average of Duplicate Plates)
Actual Count 37°C Dirty Conditions (Average of Duplicate Plates)
Pass/Fail Pass Pass Pass