WO2019097293A1 - Process for removal of biofilm - Google Patents
Process for removal of biofilm Download PDFInfo
- Publication number
- WO2019097293A1 WO2019097293A1 PCT/IB2018/001437 IB2018001437W WO2019097293A1 WO 2019097293 A1 WO2019097293 A1 WO 2019097293A1 IB 2018001437 W IB2018001437 W IB 2018001437W WO 2019097293 A1 WO2019097293 A1 WO 2019097293A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- acid
- biofilm
- solution
- process according
- dye
- Prior art date
Links
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Classifications
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N59/00—Biocides, pest repellants or attractants, or plant growth regulators containing elements or inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
- A61L2/16—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor using chemical substances
- A61L2/18—Liquid substances or solutions comprising solids or dissolved gases
- A61L2/186—Peroxide solutions
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
- A01N37/16—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing the group; Thio analogues thereof
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
- A01N37/18—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing the group —CO—N<, e.g. carboxylic acid amides or imides; Thio analogues thereof
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
- A01N37/18—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing the group —CO—N<, e.g. carboxylic acid amides or imides; Thio analogues thereof
- A01N37/20—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing the group —CO—N<, e.g. carboxylic acid amides or imides; Thio analogues thereof containing the group, wherein Cn means a carbon skeleton not containing a ring; Thio analogues thereof
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N2300/00—Combinations or mixtures of active ingredients covered by classes A01N27/00 - A01N65/48 with other active or formulation relevant ingredients, e.g. specific carrier materials or surfactants, covered by classes A01N25/00 - A01N65/48
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
- A01N25/02—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests containing liquids as carriers, diluents or solvents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2202/00—Aspects relating to methods or apparatus for disinfecting or sterilising materials or objects
- A61L2202/20—Targets to be treated
- A61L2202/25—Rooms in buildings, passenger compartments
Definitions
- the present invention relates to a process for removing dry surface biofilm from a surface.
- biofilms are composed of microorganisms attached to surfaces and encased in a hydrated polymeric matrix of their own synthesis.
- the matrix is composed of polysaccharides, proteins, and nucleic acids which are collectively termed“extracellular polymeric substances” (EPS).
- EPS extracellular polymeric substances
- the EPS matrix enables cells in a biofilm to stick together and is a key element in the development of complex, three- dimensional, attached communities. Water channels are dispersed throughout biofilms, allowing the exchange of nutrients, metabolites, and waste products.
- Biofilms form virtually anywhere there is water. Sites include inorganic natural and manmade materials above and below ground, on minerals and metals, including medical implant materials, and on organic surfaces such as plant and body tissues. Biofilm growth surfaces may act as an energy source, a source of organic carbon, or simply a support material.
- One common feature of biofilm environments is that they are periodically or continuously suffused with water.
- One common example of a biofilm dental plaque a slimy build-up of bacteria that forms on the surfaces of teeth. Similarly, the slimy layers often found on rocks in rivers and streams are also formed from biofilm.
- Nosocomial (hospital acquired) infections are the fourth leading cause of death in the U.S. with 2 million cases annually (or approximately 10% of American hospital patients) leading to more than $5 billion in added medical cost per annum. About 60- 70% of nosocomial infections are associated with some type of implanted medical device. It is estimated that over 5 million medical devices or implants are used per annum in the U.S. alone. Microbial infections have been observed on most, if not all, such devices, including: prosthetic heart valves, orthopaedic implants, intravascular catheters, artificial hearts, left ventricular assist devices, cardiac pacemakers, vascular prostheses, cerebrospinal fluid shunts, urinary catheters, ocular prostheses and contact lenses, and intrauterine contraceptive devices.
- biofilm needed a moist or wet environment in order to develop. Normally dry surfaces were thought not to form bacterial biofilm. However, a study by Vickery et al (Reference 1 ) showed that biofilm could be found on normally dry surfaces. These biofilms were found to contain multiple bacteria, including Pseudomonas spp., Staphylococcus aureus,
- Multiply Resistant Organisms persist in the environment, in the face of enhanced cleaning, as biofilms. Although detergents are good at removing patient soil and planktonic bacteria, they are less effective at removing biofilm, rendering current cleaning protocols less efficient.
- Another potential route to the development of dry surface biofilm on environmental high touch surfaces could be the deposition of proteinaceous solutions arising from various bodily fluids (sweat, saliva, blood) onto the environmental surface, thus allowing early colonisation by opportunistic biofilm forming micro- organisms. Repeated contact of the high touch surfaces may provide intermittent nutrients to the dry surface biofilm.
- Almatroudi modified the methodology used in ASTM E2562 to generate dry surface biofilm by incorporating prolonged periods of dehydration in between exposure of the sample coupons to growth media. In this way, the Almatroudi methodology attempts to replicate the conditions under which dry surface biofilm is thought to grow (ie exposure of the surface to occasional aqueous nutrients (cleaning chemicals, biological fluids etc) followed by extensive periods of desiccation).
- Described herein is a process of removing dry surface biofilm from both environmental surfaces (floors, walls etc) as well as from non-critical medical devices such as bedframes, infusion pump stands, infusion pump keyboards etc).
- biocidally effective is to be taken as meaning a substance that will effectively kill, inactivate or repel living or replicating organisms, including spores, bacteria, fungus, virus, yeasts and moulds.
- a solution of the composition described herein is particularly effective as a sporicide.
- a solution of the composition described herein is also effective against viral species, particularly blood borne viruses such as HIV, Hepatitis A, B and C.
- the invention will also be active against other viral species such as filoviruses (eg Ebola, Marburg) and arenavirus (Lassa), even in the presence of whole blood.
- filoviruses eg Ebola, Marburg
- Lassa arenavirus
- the fact that peracetic acid is not deactivated by catalase makes the composition particularly useful against these latter hemorrhagic fever inducing species.
- Figure 1 is a graph showing the variation in concentrations of hydrogen peroxide and peracetic acid with time following dissolution of the composition described herein in tap water.
- Figure 2 is a graph showing the variation in concentrations of peracetic acid with time following dissolution of differing weights of the composition described herein in tap water.
- Figure 3 is a graph showing the peracetic acid (PAA) concentration generated for various samples of sachets of the composition described herein, dissolved in tap water, at 10 minutes, 20 minutes and 30 minutes.
- PAA peracetic acid
- Figure 4 shows a Venn diagram outlining the differences in numbers of distinct upregulated proteins in various biofilms of Staphylococcus aureus.
- Figure 5 shows the results of a Crystal Violet assay for the removal of wet biofilm using differing cleaning products
- Figure 6 shows the log reduction obtained from a disinfectant according to Example 9, Chlorclean and sodium dicloroisocyanurate (SDIC) under both clean and dirty conditions.
- Figure 7 shows the protein removal from a dry surface for a disinfectant according to Example 9, 1000ppm chlorine (sodium hypochlorite) and 1000pm chlorine (SDIC).
- Figure 8 shows the bacterial reduction of a range of disinfectants against planktonic Staphylococcus aureus.
- Figure 9 shows the bacterial reduction of a range of disinfectants against dry surface biofilms formed by Staphylococcus aureus.
- US 15/035,633 the contents of which is incorporated herein by reference, describes a composition which, on dissolution in a solvent, generates a biocidally effective disinfectant solution comprising peracetic acid and hydrogen peroxide.
- the composition comprises a system to produce a visual indication of the formation of the peracetic acid. The indication is provided by a dye that is rapidly bleached in the presence of peracetic acid, whilst being substantially unaffected by the presence of hydrogen peroxide.
- An optional second dye may be incorporated, wherein the second dye is not substantially bleached by either peracetic acid or hydrogen peroxide.
- composition of‘633 is provided in a powder.
- composition of ‘633 is dissolved in water.
- composition of‘633 When the composition of‘633 is presented in powdered form, it may also contain a flow modifier to prevent clumping of the powder prior to dispersion and dissolution into the solvent, and a wetting agent to assist in the rapid dispersion and dissolution of the acetyl source into solution, preferably at ambient temperature. [46] The composition of ‘633 may also be packaged into a soluble sachet wherein the entire sachet and contents is placed into a solvent, preferably water, to generate the disinfectant, thus mitigating occupational exposure to the potentially harmful powder precursor.
- a solvent preferably water
- a composition comprising a hydrogen peroxide source, an acetyl donor, an acidifying agent, and a first dye that is bleached in the presence of peracetic acid, but not hydrogen peroxide.
- a second dye that is substantially bleach-stable may also be included in the composition of‘633.
- the first dye is a dye that is bleached in the presence of a biocidal concentration of peracetic acid
- the second dye is a dye that is bleached after several hours in the presence of a biocidal concentration of peracetic acid. The presence of the first dye in the solution acts as a visual indication that the solution has not yet achieved the desired biocidal
- the colour due to the first dye is discharged, the colour due to the second dye is left to provide an aesthetically pleasing colouration.
- the composition of‘633 is in powder form, it is dissolved in a solvent, preferably water, to form the peracetic acid-containing solution.
- composition of ‘633 may also optionally contain wetting agents, sequestering and chelating agents, and other ingredients, such as bleach-stable fragrances, corrosion inhibitors, powder flow modifiers, rheology modifiers etc.
- composition of ‘633 is prepared by combining the ingredients together.
- the composition of‘633 is in powder form.
- composition of‘633 may be presented in kit form, where the hydrogen peroxide source, part (a), is stored separately to a mixture of the acetyl source and peracetic acid bleachable dye, parts (b) and (c).
- the hydrogen peroxide source is mixed with the acetyl source/peracetic acid bleachable dye mixture, in solution.
- the composition of ‘633 is dissolved in a solvent and to produce a broad spectrum disinfectant solution which is efficacious against spores, bacteria fungus, virus, yeasts and moulds.
- the disinfectant solution is particularly efficacious against spore forming bacteria such as Clostridium difficile.
- the disinfectant may be used to disinfect surfaces, including hard surfaces, and instruments.
- the disinfecting composition described in the‘633 document is a powder- based formulation comprising a hydrogen peroxide donor, and acetyl donor, along with acidifying agents, wetting agents, along with optional ingredients such as additional sequestrants and perfumes.
- compositions of‘633 also contain a peracetic acid (PAA) bleachable dye to serve as an indicator as to when a biocidally active concentration of peracetic acid has been generated.
- a biocidally active concentration of peracetic acid is defined as a concentration of peracetic acid above 1300ppm.
- the present invention is directed to a process for removing dry surface biofilm from a surface.
- a process for removing dry surface biofilm from a surface which process comprises:
- the powder-based formulation may be in the form of a tablet.
- the composition may also contain disintegrants.
- An example of a tabletted formulation is given in example 16 of‘633.
- composition of‘633 as used in the process of the present invention, contains the following ingredients:
- Examples of a hydrogen peroxide source which may be used in the composition of ‘633 and in the present invention include, but are not limited to, sodium perborate, sodium percarbonate, urea peroxide, povidone-hydrogen peroxide, calcium peroxide, and combinations thereof.
- a dilute solution of hydrogen peroxide in water may also be used as a hydrogen peroxide source, if a two part product is intended. In this case, the hydrogen peroxide solution should preferably contain less than 8% hydrogen peroxide, thus negating classification as a Class 5.1 Dangerous Good.
- the dilute solution of hydrogen peroxide may also contain additional stabilising ingredients, such as 1 - hydroxyethylidene -1 ,1 ,-diphosphonic acid, (sold as Dequest 2010), or other strongly chelating additives, such as ethylenediamine tetraacetic acid (EDTA).
- additional stabilising ingredients such as 1 - hydroxyethylidene -1 ,1 ,-diphosphonic acid, (sold as Dequest 2010), or other strongly chelating additives, such as ethylenediamine tetraacetic acid (EDTA).
- EDTA ethylenediamine tetraacetic acid
- the peroxide solution may optionally contain pH buffering agents.
- acetyl donors which may be used in the composition of ‘633 and in the present invention include, but are not limited to, tetraacetylethylenediamine (TAED), N-acetyl caprolactam, N-acetyl succinimide, N-acetyl phthalimide, N-acetyl maleimide, penta-acetyl glucose, octaacetyl sucrose, acetylsalicylic acid, tetraacetyl glycouril, and combinations thereof.
- TAED tetraacetylethylenediamine
- N-acetyl caprolactam N-acetyl succinimide
- N-acetyl phthalimide N-acetyl maleimide
- penta-acetyl glucose octaacetyl sucrose
- acetylsalicylic acid tetraacetyl glycouril
- acetyl donor is a
- a preferred acetyl donor is TAED, more particularly, a micronized grade of TAED, such as B675, obtainable from Warwick Chemicals (UK).
- acidifying agents which may be used in the composition of ‘633 and in the present invention include, but are not limited to, citric acid,
- the acidifying agent is a solid.
- The‘first dye’ is a peracetic acid bleachable dye.
- peracetic acid bleachable dyes which may be used in the composition of‘633 and in the present invention include Amaranth (C.l. 16185), Ponceau 4R (C.l. 16255), FD&C Yellow 6 (C.l. 15985), any other 1 -arylazo-2-hydroxynaphthyl dye, and combinations thereof.
- the peracetic acid bleachable dye is preferably relatively rapidly bleached in the presence of peracetic acid, but not hydrogen peroxide. By“relatively rapidly” is meant that the colour of the dye is bleached within about 10 minutes.
- the peracetic acid has reached a biocidally effective concentration in the solution.
- substantially discharged is meant that the colour in the solution, generated by the peracetic acid bleachable dye, is entirely, or almost entirely, discharged.
- the first dye is Amaranth Red (C.l. 16185) and the second dye is C.l. Acid Blue 182.
- Amaranth Red is bleached rapidly by only peracetic acid, whilst being relatively resistant to bleaching by hydrogen peroxide. This is a particularly unexpected finding, as
- Amaranth Red is used as an indicator in a commercially available powder-based detergent called Virkon, a product produced and marketed by Antec Ltd. In the case of Virkon, as long as the red colouration due to Amaranth is present, the Virkon solution is still actively biocidal. According to the Virkon product brochure,“VIRKON 1 % solutions are stable for 7 days but should be discarded when the pink colour fades”.
- Virkon is comprised of a mixture of potassium monoperoxysulfate, sodium chloride, sulfamic acid, plus other ingredients such as surfactants, perfumes, as well as Amaranth.
- the Virkon powder mix undergoes the Haber-Willstatter Reaction, producing a mix of biocidal species including the potassium monoperoxysulfate, chlorine, N-chlorosulfamic acid, hypochlorous acid.
- the document goes on to state that Virkon contains“a pink dye (amaranth colour, EEC No. 123). In addition to being aesthetically pleasing, this serves a very practical purpose - it indicates whether the VIRKON solution is active.
- the second dye which may optionally be included in the composition of ‘633, as used in the present invention is a substantially bleach-stable dye. It is recognised that peracetic acid will be capable of bleaching most dyes, and therefore reference to a“substantially bleach-stable” dye is to be taken as meaning that the dye is capable of imparting colour to the peracetic acid/hydrogen peroxide solution for at least 2 hours, preferably about 4 to 6 hours, at room temperature.
- substantially bleach-stable dyes which may be used in the composition of ‘633 and in the present invention include, but are not limited to, Acid Blue 182, Acid Blue 80, Direct Blue 86, Acid Green 25 (C.l. 61570) and combinations thereof.
- the first dye is Amaranth Red (C.l. 16185) and the second dye is C.l. Acid Blue 182.
- the colour of the solution upon dissolution of the composition is red, generated by the Amaranth.
- the red colour discharges at around 5-7 minutes, at which time the peracetic acid is at a biocidally effective concentration, leaving a blue colour, generated by the Acid Blue 182.
- the blue colour is aesthetically pleasing, and has the added benefit of making the solution more visible when disinfecting a surface or object.
- a wetting agent may be included in the composition to facilitate dispersion of the acetyl source into solution on initial dilution, thus assisting in its dissolution.
- the wetting agent is preferably comprised of a solid surfactant capable of lowering the surface tension of the solvent, preferably water, thus allowing the acetyl source to wet and disperse.
- the acetyl source is TAED and, in the absence of a wetting agent, a highly micronized grade of TAED such as B675 will tend to float on the surface of the solvent, and thus be slow to dissolve, resulting in slow production of peracetic acid.
- wetting agents which may be used in the composition of the invention include, but are not limited to, sodium dodececyl sulphate, sodium alkylbenzenesulphonate, Pluronic PE6800, Hyamine 1620 etc, and combinations thereof.
- a pH buffer may be included in the composition of‘633, as used in the present invention, to reduce the variation of pH with time. Since the formation of peracetic acid from the acetyl source, preferably TAED, requires the pH to be at, or above, the pKa of peracetic acid (8.2), the pH of the solution should be buffered between 8.00 and 9.00, preferably between 8.00 and 8.40.
- Suitable pH buffers which may be included in the composition of the invention include, but are not limited to, phosphate, borate, bicarbonate, TAPS (3-
- composition of‘633, as used in the present invention may include ingredients capable of complexing metal ions such as calcium and
- chelating and sequestering agents which may be used in the composition of the invention include, but are not limited to, sodium citrate, citric acid, phosphoric acid, sodium tripolyphosphate, EDTA, NTA, etc and combinations thereof.
- a flow modifier may be added to improve the flow characteristics of the composition of ‘633, as used in the present invention, when in a powder formulation. This is particularly useful if the powder is intended for supply in a unidose package (eg an individual sachet or water soluble pouch), as good powder flow will allow accurate dosing of the blended powder into the individual packs.
- powder flow modifiers which may be used in the composition of ‘633 and in the present invention include, but are not limited to, fumed silica, precipitated silica, micronized polyethylene glycol 6000, micronized lactose, talc, magnesium stearate etc, and combinations thereof.
- the flow modifier is a hydrophilic fumed silica, for example Aerosil 200 (Evonik Industries).
- Aerosil 200 Aerosil 200 (Evonik Industries).
- precipitated silica such as Tixosil 38
- the precipitated silica grades are less preferred as they produce a strong haze in the final disinfectant solution, by virtue of the larger particle size of the precipitated form over the fumed form.
- composition of‘633, as used in the present invention may also contain perfumes to mask the odour of peracetic acid.
- the perfume used should preferably be stable to hydrogen peroxide and peracetic acid.
- the acetyl donor is TAED
- the hydrogen peroxide source is sodium percarbonate
- the first dye is Amaranth Red
- the composition is in a powder formulation, which is dissolved in water.
- a deep red cloudy solution is formed by the rapid dissolution of the Amaranth Red dye and the suspension of undissolved TAED.
- the TAED dissolves into the water, and the red colouration is discharged as peracetic acid is generated by the reaction of the TAED with hydrogen peroxide produced by dissolution of the sodium percarbonate. After about 7-10 minutes, the solution will be clear, and all of the red colouration discharged.
- a second dye that is substantially bleach-stable may also be included in the composition of ‘633, as used in the process of the present invention.
- the substantially bleach-stable dye bleaches over the course of 4-6 hours, along with the Amaranth.
- a preferred second dye, which is slowly bleached, is C.l. Acid Blue 182.
- Dye premix A mixture of 78.00g of TAED B675 (Warwick Chemicals), 17.00g Amaranth dye and 5.00g of C.l. Acid Blue 182 dye were mixed and ground together using a pestle and mortar to give a homogenous brownish powder. Once mixed, the dye premix blend was stored in a well-sealed container prior to use.
- a solution of the disinfectant was prepared by dissolving 7.50g of the powder blend into 500ml of artificial hard water containing 340ppm CaCCh (prepared as described in SOP Number: MB-22-00: Standard Operating Procedure for
- Disinfectant Sample Preparation published by the US Environmental Protection Agency Office of Pesticide Programs, and hereafter referred to as AOAC Hard Water).
- the solution was stirred at room temperature.
- the red colour due to the Amaranth was observed to be discharged at around 5-7 minutes, leaving a blue solution.
- 10ml aliquots taken at regular intervals after 10 minutes, and the pH were also recorded. The aliquots were titrated to determine hydrogen peroxide and peracetic acid concentration.
- a quantity of the powder blend from Example 1 was taken, and packaged into individual sachets prepared from heat sealed PVA water soluble film.
- the sachets were prepared by heat sealing two sheets of 50 micron thick PVA film (width 4.65cm, length 8cm), together to form an envelope, dispensing approximately 8.2g powder into each envelope and then sealing the open side to give the finished filled sachet.
- a single sachet was then taken and added to a stirred quantity of tap water (500ml). The sachet was observed to wrinkle in the water, and then to burst open, releasing the contained powder into the water to give a deep red solution.
- Example 1 A quantity of the powder blend according to Example 1 was taken, and packaged into individual sachets prepared from heat sealed PET-paper-Aluminium- PP laminate.
- the sachets were prepared by heat sealing a sheet of laminate 6cm wide to form a cylindrical tube, and then sealing across the tube to form a stick, which was then dosed with the powder blend via an auger doser. The open end of the filled tube was then sealed to give a stick pack.
- the mean gross weight of each stick pack was found to be 8.88g, with a standard deviation of 0.27 (see Table 8).
- the packaging material was found to weigh 0.88g, thus giving a mean net weight for the powder of 8.00g.
- sample sachets were taken from various parts of a production run and added to 500ml of tap water. The hydrogen peroxide and the peracetic acid content at 10, 20 and 30 minutes for each solution were then determined.
- the powder formulation can also be modified for the production of tablets capable of generating peracetic acid on dissolution into water.
- a means to facilitate the disintegration of the tablet is incorporated into the tablet formulation. This also assists the slower dissolution of the tablet due to the compression required to generate the tablet.
- Disintex 200 (ISP Technologies Inc) were found to be impractical for use, as the cross-linked polymer adsorbed the dyes strongly, and thus gave highly coloured particulate material in the final solution.
- a preferred means of disintegrating the tablet is to include additional sodium carbonate into the formulation, along with additional acidifying agent.
- sulfamic acid is used as the acidifying agent as this lacks a pKa above 2. If citric acid is used as an acidifying agent in the tablet formulation, then gas formation, hence tablet disintegration, is slowed down once the solution reached a pH of around 6 due to the third pKa of citric acid.
- a powder blend according to Table 10 was produced by mixing the ingredients together to produce a homogenous mix. In order to achieve adequate tablet formulation, the mixture was not sieved, and care was taken not to reduce the particle size of the soda ash, sodium percarbonate and the sulfamic acid.
- the material was tableted using a single punch tablet press, fitted with a 20mm die set to give tablets with a mean weight of 3.72g.
- the mean thickness of the tablets was 9.1 mm, with a thickness to weight ratio of 0.41 .
- Dry surface biofilm was produced in the surfaces of coupons following the method described by Almatroudi et al. in Reference 4.
- Staphylococcus aureus ATCC 25923 biofilm was grown on 24 removable, sterile Pyrex coupons in an intensively cleaned, brushed and steam sterilised (121 °C for 20 min) CDC biofilm reactor (BioSurface Technologies Corp, Bozeman, USA).
- the biofilm generator was located in an air-conditioned laboratory and filter-sterilised room air (average relative humidity 66%) was pumped across the media surface at an airflow rate of 3 l/min using an aquarium air pump.
- Biofilm development was initiated by inoculation of about 10 colony forming units (CFU) of S. aureus at the beginning of the first batch phase.
- CFU colony forming units
- all biofilms were grown in 5% TSB at 35 °C and subjected to shear by baffle rotation at 130 rpm/min producing turbulent flow.
- the disinfectant powder comprised a blend of a hydrogen peroxide source (sodium percarbonate) and an acetyl source (tetraacetylethylenediamine (TAED)), along with acidifying agents (citric acid) and sequestrants (monosodium phosphate, sodium tripolyphosphate), along with a peracetic acid bleachable dye (amaranth).
- TAED tetraacetylethylenediamine
- the formulation used is given in Table 13.
- the sachet was added to 500ml water and stirred at room temperature for 10-15 minutes, after which time the colouration provided by the peracetic acid bleachable dye was discharged. At this point the solution will contain between 1500 and 2000ppm peracetic acid, along with about 1000-1300ppm hydrogen peroxide.
- the resultant solution was found to be active against a range of bacteria, viruses, spores and fungi for approximately 8 hours after dissolution.
- Example 10 initial screening study using TOC to assess removal of dry surface biofilm.
- TOC Total Organic Carbon
- Fabrisan is marketed as a carpet spotter. Its ingredients include sodium citrate, sodium dodecyl sulfate, and Tea Tree Oil. The formulation is according to Example 3 of US patent no. 5610189
- Matrix is marketed as a wet surface biofilm remover.
- the formulation is according to Australian patent no. AU2001275599B2, and its efficacy against normal
- Zip Strip is a floor stripper intended to remove polymeric sealants form vinyl floors.
- the formulation comprises a highly alkaline solution of surfactants, butyl glycol, and ethanolamine.
- Phensol is a phenolic disinfectant comprising a blend of o-phenylphenol and benzyl chlorophenol with the sodium salt of a (C10-16) Alkylbenzenesulfonic acid.
- a 12 day dry surface biofilm was grown on Pyrex glass coupons as described in Example 8. Three coupons, coated in dry surface biofilm were then placed into 25ml of each test product solution. Three coupons were also placed in 25ml of MilliQ water to serve as a negative control. A 1 M solution of sodium hydroxide was used as a positive control.
- the washed tiles were then scraped, and eluted with 5ml of 95% ethanol into a 28ml vial, which was then closed and stood overnight to elute the adsorbed Crystal Violet.
- the absorbance of the solutions were then read via a spectrophotometer.
- each rod was placed into 30ml of 1 M sodium hydroxide solution to elute off all remaining protein. Aliquots from each solution were then taken and tested for protein using a Bicinchroninic Acid (BCA) assay, using a micro BCA test kit (Sigma Aldrich).
- BCA Bicinchroninic Acid
- Example 9 gives a significantly higher reduction of protein than Matrix when tested against 12 day dry surface biofilm.
- Example 9 The efficacy of protein removal from coupons coated in 12 day dry surface biofilm using Example 9, 1000ppm sodium hypochlorite solution and Chlorclean, (a sodium diisocyanurate (SDIC) tablet formulated with adipic acid and a sodium toluenesulfonate and marketed as a 2-in-1 Hospital Grade Disinfectant with detergent action by Helix Solutions (Canning Vale South, Western Australia) were assessed as described in Example 1 1 . Both chlorine solutions were shown to give 10OOppm, available chlorine. In this test a 10 minute contact time was used. Percentage reductions were calculated from the positive control (Milli-Q water). [155] As can be seen in Table 18, Example 9 gives the highest protein reduction. Chlorclean, a formulated SDIC tablet marketed as a 2-in-1 cleaning/disinfecting product was also observed to be more efficacious than sodium hypochlorite solution.
- SDIC sodium diisocyanurate
- Each test product was dissolved in water.
- Coupons coated in 12-day dry surface biofilm were produced as per Example 8. 2ml of each test solution, followed by 2 ml of water were added to the wells in a tissue culture plate.
- the disinfectant according to Example 9 was tested against planktonic S. aureus, and compared to two commercially obtained oxidising disinfectants, Chlorclean and Oxivir Tb (Diversey Australia Pty Ltd, Smithfield, NSW, Australia), a ready to use solution comprising 0.5% hydrogen peroxide, formulated with other proprietary ingredients.
- the disinfectant products were diluted using artificial hard water prepared by dissolving 0.304g anhydrous CaC and 0.065g anhydrous MgC in distilled water to make one litre of hard water.
- Table 22 shows the products tested, and the concentrations of active materials in the test samples.
- Disinfectant efficacy in the absence of soil was tested by mixing 1 ml of test disinfectant with 1 ml of hard water and immediately adding 10mI of Tryptone Soy Broth (TSB) containing approximately 10 9 planktonic bacteria for 5 minutes contact time. 1 ml neutralizer (1 % Na-thiosulphate, 6 % Tween 80, 5% BCS and 10% BSA in PBS) was then added.
- TBS Tryptone Soy Broth
- Disinfectant efficacy in the presence of soil was tested by mixing 1 ml of test disinfectant with 1 ml of 5% bovine calf serum in hard water and immediately adding 10mI of Tryptone Soy Broth (TSB) containing approximately 10 9 planktonic bacteria for 5 minutes contact time for 5 minutes contact time prior to the addition of 1 ml of neutralizer.
- TBS Tryptone Soy Broth
- 1 ml neutralizer (1 % Na-thiosulphate, 6 % Tween 80, 5% BCS and 10% BSA in PBS
- Disinfectant efficacy in the absence of soil was tested by mixing 1 ml of test disinfectant with 1 ml of hard water and immediately adding a biofilm coated coupon for 5 minutes contact time. 1 ml neutralizer (1 % Na-thiosulphate, 6 % Tween 80, 5% BCS and 10% BSA in PBS) was then added.
- Positive control coupons had a mean of 2.6 x10 6 CFU/ coupon.
- Example 9 In the absence of biological soil, and with a five minutes contact time, example 9 was observed to give a 6.42 logio reduction, whilst the diluted Proxitane sample gave only a 2.04 logio reduction.
- the chlorine-based disinfectants, SDIC and Chlorclean reduced biofilm viability by 2.85 logio and 2.82 logio respectively.
- Oxivir was found to give approximately a 1 logio reduction whereas the unformulated hydrogen peroxide gave essentially a zero logio reduction under both clean and dirty conditions.
- Example 9 Under dirty conditions (ie in the presence of an organic soil), Example 9 again gave a 6.42 logio reduction.
- SIDC tablets were the next best performers, although they killed significantly less biofilm bacteria (3 Logio) than Example 9, and only in the absence of soil.
- Oxivir Tb killed approximated 1 Logio of the biofilm bacteria while hydrogen peroxide solution had no effect. It is noted however that Oxivir’s manufacturer’s recommended contact time for killing bacteria is 10 not five minutes as used in the study and this could explain its lower performance. However, even a contact time of 5 minutes is probably excessive given the way that dry hospital surfaces are cleaned. The majority of disinfectants have no residual effect and remain active only when wet.
- Example 9 formulated additives
- diluted Proxitane no additives
- the activity of Example 9 against DSB may be governed not only by the active ingredients (hydrogen peroxide and peracetic acid), but also by other factors such as the added surfactants or excipients, chelating agents or its solution pH.
- Surfactants may increase diffusion of the active ingredients into the biofilm (due to a lowering of the solution surface tension, and hence improved wetting of the biofilm surface).
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Abstract
Description
Claims
Priority Applications (7)
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EP18879396.2A EP3709807A4 (en) | 2017-11-16 | 2018-11-07 | Process for removal of biofilm |
AU2018367884A AU2018367884B2 (en) | 2017-11-16 | 2018-11-07 | Process for removal of biofilm |
CA3082443A CA3082443C (en) | 2017-11-16 | 2018-11-07 | Process for removal of biofilm |
KR1020207016865A KR102392343B1 (en) | 2017-11-16 | 2018-11-07 | How to remove biofilm |
NZ764703A NZ764703A (en) | 2017-11-16 | 2018-11-07 | Process for removal of biofilm |
CN201880085662.XA CN111818797A (en) | 2017-11-16 | 2018-11-07 | Biofilm removal method |
PH12020550610A PH12020550610A1 (en) | 2017-11-16 | 2020-05-11 | Process for removal of biofilm |
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AU2018367884B2 (en) | 2017-11-16 | 2020-10-22 | Whiteley Corporation Pty. Ltd. | Process for removal of biofilm |
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CA3082443A1 (en) | 2019-05-23 |
CN111818797A (en) | 2020-10-23 |
EP3709807A1 (en) | 2020-09-23 |
PH12020550610A1 (en) | 2021-02-22 |
CA3082443C (en) | 2022-05-17 |
AU2018367884B2 (en) | 2020-10-22 |
KR102392343B1 (en) | 2022-04-29 |
AU2018367884A1 (en) | 2019-08-22 |
KR20200084035A (en) | 2020-07-09 |
NZ764703A (en) | 2022-05-27 |
EP3709807A4 (en) | 2021-09-22 |
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