Liquid sporicidal compositions

Abstract

Liquid sporicidal disinfectant and sterilant compositions including formic acid, a solvent / diluent and one or more of hydrogen peroxide and peracetic acid. The liquid sporicidal compositions comprise three primary embodiments or aspects of a) a low amount of hydrogen peroxide and a low amount of formic acid, or b) very low amount of peracetic acid and a low amount of formic acid, or c) a low amount of hydrogen peroxide, a very low amount of peracetic acid, and a low amount of formic acid, each of which have been found to provide antimicrobial efficacy against bacterial spores. Such compositions have exceedingly high log10 reductions of bacterial spores that are achieved in relatively short contact times and advantageously are suitable for use on many surfaces, such as floors, in cleanroom environments, and in healthcare settings to process medical equipment.

Description

International Patent ApplicationDOCKET NO.: ASCO.20018-WO-PCT1LIQUID SPORICIDAL COMPOSITIONSCROSS-REFERENCE TO RELATED APPLICATION

[0001] This application claims the benefit of priority to U.S. Provisional Patent Application Serial No. 63 / 730,658 entitled “LIQUID SPORICIDAL COMPOSITIONS,” filed December 11, 2024, the disclosure of which is incorporated herein in its entirety by reference.FIELD OF THE INVENTION

[0002] The present invention relates to liquid sporicidal disinfectant and sterilant compositions including formic acid, a solvent / diluent and one or more of hydrogen peroxide and peracetic acid. The liquid sporicidal compositions comprise three primary embodiments or aspects of a) a low amount of hydrogen peroxide and a low amount of formic acid, or b) very low amount of peracetic acid and a low amount of formic acid, or c) a low amount of hydrogen peroxide, a very low amount of peracetic acid, and a low amount of formic acid, each of which have been found to provide antimicrobial efficacy against bacterial spores. Such compositions have exceedingly high logio reductions of bacterial spores that are achieved in relatively short contact times and advantageously are suitable for use on many surfaces, such as floors, in cleanroom environments, and in healthcare settings to process medical equipment.BACKGROUND OF THE INVENTION

[0003] Hydrogen peroxide and peracetic acid are known antimicrobial agents that are effective against vegetative bacteria. Bacterial sporicidal efficacy can be achieved either by each compound alone, or in combination.

[0004] However, hydrogen peroxide does not provide antimicrobial efficacy against bacterial spores when used in concentrations below 10 wt.%. Moreover, higher concentrations increase safety risks to users regarding shipping, during use and also are considered to have increased combustibility. Peracetic acid has limited sporicidal efficacy at low concentrations, that is at or less than about 500 parts per million, and high concentrations thereof are known to be irritants to mucosal membranes. Accordingly, the individual use thereof with regard to antimicrobial agents such as sporicides has been limited.

[0005] U.S. Patent No. 5,900,256 relates to aqueous acidic disinfecting and sterilizing compositions for medical instruments, which may include brass, copper, aluminum, stainless steel,International Patent ApplicationDOCKET NO.: ASCO.20018-WO-PCT1 plastic and ceramic components. The compositions contain hydrogen peroxide, peracetic acid, a corrosion inhibitor system, a surfactant and a stabilizer. These compositions are reportedly effective as a disinfectant and / or sterilant either at room temperature or when heated.

[0006] U.S. Patent No. 6,049,002 relates to a method for the preparation of aqueous solutions containing performic acid formed by reaction of formic acid and hydrogen peroxide in the presence of a catalyst, the catalyst being a compound containing at least one ester group and / or group (a) differing from a carboxylic acid group and an alcoholic group, preferably a carboxylic acid ester, and also to aqueous solutions containing performic acid, formic acid, hydrogen peroxide, and a compound containing at least one ester group and / or group (a) differing from a carboxylic acid group, and the use of such solutions.

[0007] U.S. Patent No. 6,211,237 relates to disinfecting agents that contain up to 5 wt.% performic acid, hydrogen peroxide and peracetic acid. The agents can be obtained by addition of a source of formic acid such as formic acid, a water-soluble salt of the same or a lower formic ester, to an aqueous phase containing 5 to 50 wt.% hydrogen peroxide and 1 to 15 wt.% peracetic acid and, in the case of the addition of a salt, additionally a mineral acid. Preferred agents result from the addition of 0.1 to 1 mole sodium formate or formic acid, per kg of the agent to be produced, to an equilibrium peracetic acid containing mineral acid with 0.5 to 6 wt.% peracetic acid.

[0008] U.S. Patent No. 10,609,925 relates to a two component disinfectant composition comprising: (A) a peracetic acid-generating component comprising acetic acid, hydrogen peroxide and an organic phosphonic acid; and (B) a stabilizer component comprising an alkaline agent and a chelating agent, wherein the chelating agent is selected from the group consisting of N,N- bis(carboxymethyl)-L-glutamic acid, methylglycine diacetic acid, nitrilotri acetic acid, and alkali metal salts thereof, and a mixture of two or more thereof and to the aqueous disinfectant solution obtainable by mixing and diluting components (A) and (B) in water. A method of disinfecting surface and instruments, particularly flexible endoscopes, using said aqueous disinfectant solution is disclosed.

[0009] European Patent No. 1,070,506 Bl relates to a method for disinfection of an endoscope by contacting the endoscope for preferably 5-15 minutes with an aqueous solution comprising preferably 1 wt.% of peracetic acid, up to 6 wt.% of hydrogen peroxide and 6 to 10 wt.% of acetic acid in a washing / disinfecting machine for endoscopes.SUMMARY OF THE INVENTIONInternational Patent ApplicationDOCKET NO.: ASCO.20018-WO-PCT1

[0010] A solution of a) a low amount of hydrogen peroxide and a low amount of formic acid, or b) a very low amount of peracetic acid and a low amount of formic acid, or c) a low amount of hydrogen peroxide, a very low amount of peracetic acid, and a low amount of formic acid, each in a solvent / diluent, have unexpectedly been found to provide a liquid sporicide that has excellent antimicrobial efficacy against bacterial spores. The use of such liquid sporicides, that is formic acid-hydrogen peroxide and / or peracetic acid, unexpectedly and synergistically yield logio reductions of at least 5 in significant short times of 10 minutes or less, 7 minutes or less, and desirably in 5 minutes or less as measured according to ASTM E2197-17el or ASTM E2315-03.

[0011] A liquid sporicidal composition, comprising: a) hydrogen peroxide in an amount of from about 2.0 wt.% to about 10 wt.%; and formic acid in an amount of from about 0.3 wt.% to about 4 wt.%; b) peracetic acid in an amount of from about 0.02 wt.% to about 0.1 wt.%; and formic acid in an amount of from about 0.2 wt.% to about 2.0 wt.%; or c) hydrogen peroxide in an amount of from about 0.1 wt.% to about 3.0 wt.%; peracetic acid in an amount of from about 0.02 wt.% to about 0. 1 wt.%; and formic acid in an amount of from about 0.2 wt.% to about 2.0 wt.%; and a solvent / diluent comprising water in a major amount by weight based on the total weight of the composition.BRIEF DESCRIPTION OF THE DRAWINGS

[0012] The invention will be better understood, and other features and advantages will become apparent from the detailed description of the invention, taken together with the drawings, wherein:

[0013] FIG. 1 is a graph showing average logio reduction of Bacillus suhtilis ATCC 19659 spores; 6.66 logs / carrier after 5 minutes of contact time using 304 stainless steel carriers for different compositions and concentrations of hydrogen peroxide and formic acid;

[0014] FIG. 2 is a graph showing average logio reduction of Bacillus subtilis ATCC 19659; 6.68 logs / carrier after 5 minutes of contact using 304 stainless steel carriers for different compositions and concentrations of hydrogen peroxide and one of formic acid, furoic acid, oxalic acid, propionic acid, lactic acid and acetic acid;

[0015] FIG. 3 A is a graph showing average logio 1 reductions of Bacillus subtilis 19659 spores, baseline = 7.04 log CFU / mL / 7.27 log CFU / mL after 5 minutes of contact with the indicated compositions, the compositions including 0.05 wt.% (500 ppm) of peracetic acid and one of formic acid, lactic acid, acetic acid and glycolic acid; FIG. 3B is a graph showing average logio reductions of Bacillus subtilis 19659 spores, at a baseline of 7.04 Log CFU / mL / 7.27 Log CFU / mL for 10International Patent ApplicationDOCKET NO.: ASCO.20018-WO-PCT1 minutes of contact with the indicated compositions, the compositions including 0.05 wt.% (500 ppm) of peracetic acid and different weight percentages of formic acid;

[0016] FIG. 4A is a graph showing logio reductions of Bacillus subtilis 19659 spores, baseline =7.26 Log CFU / mL at contact times of 5 minutes and 10 minutes utilizing 0.05 wt.% (500 ppm) of peracetic acid, various amounts of H2O2, and 1) 1 wt.% of succinic acid (Control), or 2) 0.9 wt.% of formic acid;

[0017]

[0018] FIG. 4B is a graph showing logio reductions of Bacillus subtilis 19659 spores, baseline =7.26 Log CFU / mL for 5 minutes of contact utilizing 0.05 wt.% (500 ppm) of peracetic acid, and different concentrations of hydrogen peroxide and one of succinic acid, furoic acid, lactic acid and formic acid;

[0019] FIG. 4C is a graph showing logio reductions of Bacillus subtilis 19659 spores, baseline =7.26 Log CFU / mL for 5 minutes of contact with 0.05 wt.% (500 ppm) of peracetic acid, and different concentrations of hydrogen peroxide and one or more of succinic acid, furoic acid, lactic acid, and formic acid;

[0020] FIG. 5 is a graph showing excipients negatively altering the activity of a peracetic acid (0.05 wt.%) / H2O2 (1 wt.%) combination against spores of Bacillus subtilis PS533;

[0021] FIG. 6 illustrates comparative images of coupon substrates photographed after having an application of a composition of the present invention having 1 wt.% hydrogen peroxide with 0.9 wt.% formic acid a) alone and b) with a corrosion inhibitor, 0.25 wt.% benzotri azole, after one application, as well as after one application followed by a 10 second static rinse; and

[0022] FIG. 7A is a graph showing logio reductions of Bacillus subtilis 19659 spores, baseline = 7.24 Log CFU / mL at 5 minutes of contact utilizing 0.05 wt.% (500 ppm) of peracetic acid, the indicated amounts of hydrogen peroxide, and the indicated amounts of various acids including acetic acid, formic acid, propionic acid, and glycolic acid;

[0023] FIG. 7B is a graph showing logio reductions of Bacillus subtilis 19659 spores, baseline = 7.24 Log CFU / mL utilizing 0.05 wt.% (500 ppm) of peracetic acid with various indicated amounts of hydrogen peroxide, and various acids including acetic acid, formic acid, propionic acid, and glycolic acid, at 5 minutes of contact.DETAILED DESCRIPTION OF THE INVENTIONInternational Patent ApplicationDOCKET NO.: ASCO.20018-WO-PCT1

[0024] The liquid sporicidal compositions of the present invention which include formic acid and a synergistic amount of either hydrogen peroxide or peracetic acid, or a combination of hydrogen peroxide and peracetic acid, as well as a solvent and / or diluent, advantageously eradicate bacterial spores. A first embodiment of a liquid sporicide composition comprises relatively low amounts of hydrogen peroxide of less than about 10 wt.% based on the total weight of the compositions, and a unique weak acid, i.e. formic acid, in low amounts. The compositions of the first embodiment are desirably free of any peracetic acid. In a second embodiment, the liquid sporicidal compositions of the present invention comprise very small amounts of peracetic acid with low amounts of formic acid, wherein said compositions are desirably free of any hydrogen peroxide. A third embodiment of the present invention provides a liquid sporicidal composition comprising low amounts of hydrogen peroxide, very low amounts of peracetic acid, as well as low amounts of formic acid.

[0025] A key aspect of the present invention is that the various blends that utilize formic acid yield unexpected and improved synergistic results with regard to bacterial spores, fungal spores and vegetative bacteria. Examples of bacteria which form spores include those from the genera Bacillus and Clostridium. Examples of specific bacteria include, but are not limited to Bacillus cereus, Bacillus subtilis, and Clostridium sporogenes. An example of a fungus which forms spores is Chaetomium globosum. The compositions of the present invention also eliminate a wide range of vegetative bacteria, both gram negative and gram positive, such as, but not limited to genera including Staphylococcus aureus and Pseudomonas. The logio reduction or kill values of the compositions of the present invention are exceedingly high and desirably are in excess of 2 or 3 and preferably in excess of 4 or 5 as measured according to ASTM E2197-17el.

[0026] The compositions of the present invention can achieve desirable logic reductions in a relatively short period of time such as within 10 minutes, desirably within 7 minutes and preferably within 5 minutes as measured according to ASTM E2197-17el or ASTM E2315-03. As such, the compositions of the present invention are highly advantageous for use on many different surfaces that require disinfection. For example, the compositions are suitable for use in healthcare settings to process medical equipment and devices more quickly as compared to prior art formulations, which saves worker time and are highly economical for the processing entity. The compositions are also advantageous for environmental disinfection such as in cleanroom settings. The rapid killInternational Patent ApplicationDOCKET NO.: ASCO.20018-WO-PCT1 time lessens the need for reapplication of the composition to keep the surfaces wet to kill the organisms.

[0027] Compositions including Formic Acid and Hydrogen Peroxide

[0028] In compositions including formic acid and hydrogen peroxide, the hydrogen peroxide is present in amounts from about 2 wt.% to about 10 wt.%, desirably from about 3 wt.% to about 9 wt.%, and preferably from about 4 wt.% to about 7 wt.% based on the total weight of the composition. The formic acid is generally present in relatively low or small amounts of from about 0.3 wt.% to about 4.0 wt.%, desirably from about 0.5 wt.% to about 3.0 wt.%, and preferably from about 0.7 wt.% to about 1.5 wt.%.

[0029] This embodiment of the present invention is substantially free or free of peracetic acid. That is, if utilized, the amount of any peracetic acid is very, very low such as about 0.08 wt.% or less, desirably about 0.02 wt.% or less, and preferably nil, that is no peracetic acid is present whatsoever.

[0030] The compositions including formic acid and hydrogen peroxide also include at least one solvent and / or diluent and optionally other components as described herein below. Water is a preferred solvent / diluent that makes up a majority of the total weight of the composition.

[0031] Compositions including formic acid and hydrogen peroxide offer the advantages of having a relatively low odor, for example as compared to compositions including other carboxylic acids.

[0032] Examples illustrating effectiveness of compositions including formic acid and hydrogen peroxide

[0033] The following examples, with reference to Table 1 below and FIGS. 1 and 2, illustrate the advantages of compositions including formic acid and hydrogen peroxide as well as the unexpected effectiveness in view of comparative carboxylic acids having relatively similar amounts of carbon atoms.

[0034] Example sporicidal composition solutions of 6 wt.% hydrogen peroxide with 0.9 wt.% formic acid, and also 4 wt.% hydrogen peroxide with 0.9 wt.% formic acid were prepared and tested against Clostridium sporogenes. A comparative control formulation of 0.9 wt.% of formic acid was also tested.

[0035] Samples were prepared by diluting concentrated solutions of peroxide and formic acid (35% and 88% respectively) to the desired concentration in the total batch % of deionized waterInternational Patent ApplicationDOCKET NO.: ASCO.20018-WO-PCT1 while gently mixing. While the order of addition of the actives is of no consequence, for the examples, peroxide was added first followed by formic acid.

[0036] The results in Table 1 were achieved using the AOAC Sporicidal Test Method 966.04, Sporicidal Activity of Disinfectants. Spores were inoculated on Dacron suture loops.

[0037] Table 1 - AOAC Carrier Test Results for H2O2 with Formic Acid Formulations vs. Formic Acid Control (the remaining amount was water)

[0038] As apparent from the above, at contact times of approximately 10 minutes, complete kills of Clostridium sporogenes spores were obtained by the hydrogen peroxide-formic acid liquid sporicidal compositions of the present invention. As evident from Table 1, the formic acid control comparative example showed that formic acid alone did not kill any Clostridium sporogenes spores.

[0039] Further examples of the unexpected and synergistic results of the compositions based on formic acid and hydrogen peroxide of the present invention without the need for any other carboxylic acid are shown in FIG. 1, wherein various low amounts of hydrogen peroxide namely from 1 wt.% to 6 wt.%, were utilized with 0.9 wt.% of formic acid.

[0040] The examples illustrated in FIG. 1 were prepared by diluting concentrated solutions of hydrogen peroxide and formic acid (35 % and 88% respectively) to the desired concentration in the total batch weight % of deionized water while gently mixing. While the order of addition of the actives is of no consequence, for these examples, peroxide was added first followed by formic acid. For the results shown in FIG. 1 testing was performed with Bacillus subtilis ATCC 19659. The test method utilized was ASTM E2197-17el, Standard Quantitative Disk Carrier Test Method for Determining Bactericidal, Virucidal, Fungicidal, Mycobactericidal, and Sporicidal Activities of Chemicals, ASTM International, West Conshohocken, PA, 2017, www.astm.org. ThreeInternational Patent ApplicationDOCKET NO.: ASCO.20018-WO-PCT1 replicates were used since the results showed dramatic differences such that an additional two replicates were not necessary for statistical significance. 6.66 logs per carrier were utilized, wherein the carriers were 304 stainless steel coupons. Results were measured after 5 minutes of contact time.

[0041] As apparent from FIG. 1, compositions containing about 3 wt.% of hydrogen peroxide with formic acid yielded logio reduction of about 2, with 6 wt.% of hydrogen peroxide yielding average logio reduction well in excess of 5, which is considered a complete kill, as the limit of detection within the test is lOOcfu / mL.

[0042] Proof the efficacy of the hydrogen peroxide-formic acid combination of the present invention was unique and unexpected amongst different short chain carboxylic acids is illustrated in FIG. 2, wherein a 6 wt.% solution of hydrogen peroxide and 0.9 wt.% of formic acid was tested and compared with the exact same solution except that in lieu of formic acid, other acids, namely furoic acid, oxalic acid, propionic acid, lactic acid, and acetic acid were utilized. The same testing procedure and sample preparation method as described for FIG. 1 were also utilized.

[0043] As set forth in FIG. 2 the example composition of the present invention including 6 wt.% hydrogen peroxide and 0.9 wt.% formic acid achieved an extremely high logio kill or reduction of at least 5.5, whereas the various other acids yielded an exceedingly low logio reductions of 0.1 or less. Thus, as noted above, the liquid sporicidal compositions of the present invention exhibit excellent, unexpected sporicidal efficacy, whereas the other carboxylic acids showed essentially no sporicidal efficacy at 5 minutes of contact.

[0044] One of ordinary skill in the art would hypothesize that adding a corrosion inhibitor to the compositions of the present invention would be beneficial. However, it has been unexpectedly discovered that the compositions of the present invention when combined with corrosion inhibitors actually leave undesirable residue on generally any surface that would benefit therefrom, including but not limited to, cleanroom surfaces, floors, and surfaces of devices the compositions are expected to disinfect and sterilize. FIG. 6 illustrates comparative images of coupon substrates photographed after having an application of a composition of the present invention a) alone and b) with a corrosion inhibitor benzotriazole after one application, as well as after one application followed by a 10 second static rinse. For this test, one milliliter of the composition was spread on the surface of a three-inch by six-inch stainless-steel coupon and allowed to dry. Therefore, asInternational Patent ApplicationDOCKET NO.: ASCO.20018-WO-PCT1 described further hereinbelow, the compositions of each embodiment of the present invention are preferably free of corrosion inhibitors.

[0045] Compositions including Formic Acid and Peracetic Acid

[0046] Another important embodiment of the present invention is the utilization of compositions including the specific combination of very low amounts of peracetic acid with low amounts of formic acid that have been found to also yield excellent antimicrobial efficacy against bacterial spores, fungal spores and vegetative bacteria. The various types of bacteria and spores that are set forth hereinabove, and hereby fully incorporated by reference, can be eradicated by the peracetic acid and formic acid liquid sporicidal compositions of the present embodiment. Effective logio reduction values have been obtained generally within 10 minutes, within 7 minutes or even within 5 minutes in some cases depending on the concentration of formic acid and peracetic acid, as well as the type of bacteria, spore, etc.

[0047] Suitable amounts of peracetic acid range from about 200 parts per million (ppm) to about 1,000 ppm (0.02 wt.% - 0. 1 wt.%), desirably from about 300 ppm to about 750 ppm (0.03 wt.% - 0.075 wt.%), and preferably from about 400 ppm to about 600 ppm (0.04 wt.% - 0.06 wt.%).

[0048] The amount of formic acid is from about 0.2 to about 2.0 wt.%, desirably from about 0.4 to about 1.5 wt.%, and preferably from about 0.5 or 0.6 to about 1.2 wt.%.

[0049] In this embodiment of the present invention, hydrogen peroxide is not utilized. That is, the liquid sporicidal composition is substantially free or free of any hydrogen peroxide, whereby generally less than 1.0 wt.%, desirably about 0.1 wt.% or less, and preferably nil, that is no hydrogen peroxide is utilized whatsoever in combination with the peracetic acid and formic acid solution.

[0050] As noted above with respect to the hydrogen peroxide-formic acid liquid sporicidal composition, the peracetic acid-formic acid liquid sporicidal composition contains at least a solvent and / or diluent, preferably water, optionally one or more other solvents and / or diluents and optionally also various types of one or more different additives described herein, hereby fully incorporated by reference for this embodiment.

[0051] Examples including Compositions Comprising Formic Acid and Peracetic Acid

[0052] In accordance with the present invention, the following examples serve to illustrate but not to limit the present invention set forth factual data as to the unexpected and synergistic results obtained with regard to logio reduction or kill factor with respect to bacterial spores.International Patent ApplicationDOCKET NO.: ASCO.20018-WO-PCT1

[0053] FIG. 3 A relates to examples wherein 0.05 wt.% (500 ppm) of peracetic acid was used in an aqueous solution with various different amounts of formic acid, acetic acid, glycolic acid or lactic acid to eradicate Bacillus subtilis spores.

[0054] The examples illustrated in FIG. 3A were created by first adding acetic acid, formic acid, glycolic acid or lactic acid to deionized water, followed by a nonionic surfactant, in particular 1 wt.% of an alcohol ethoxylate with 8 moles of ethoxylation and 13 carbon atoms, and then peracetic acid to bring the composition to its total, final weight while gently mixing the compositions. For the results shown in FIG. 3A testing was performed with Bacillus subtilis ATCC 19659. The test method utilized was ASTM E2315-03, 2003 (2008), “Standard Guide for Assessment of Antimicrobial Activity Using a Time-Kill Procedure,” ASTM International, West Conshohocken, PA, 2008, DOI: 10.1520 / E2315-03R08.

[0055] As apparent from FIG. 3A, compositions containing 0.9 wt.% formic acid and 0.05 wt.% peracetic acid yielded logic reduction of greater than 3.5. Lower amounts of formic acid, namely about 0.44%, exhibited roughly equivalent logio reductions as compared to utilization of 2% acetic acid or 2% glycolic acid at roughly 4% times of the 0.44 wt.% of formic acid utilized. Results were measured after 5 minutes of contact time. FIG. 3B is a graph showing average logio kill reductions of Bacillus subtilis 19659 spores, at a baseline of 7.04 Log CFU / mL / 7.27 Log CFU / mL for 10 minutes of contact with the indicated compositions, the compositions including .05 wt.% of peracetic acid and different weight percentages of formic acid. The compositions were created as described above with reference to FIG. 3 A and the same test method was utilized. The results show that for the longer contact period of 10 minutes, the composition containing .44 wt.% formic acid achieves an excellent logio reduction of about 5.0. The 0.09 wt.% formic acid-containing composition achieved a log reduction of less than 3.

[0056] Compositions including Formic Acid, Peracetic Acid and Hydrogen Peroxide

[0057] Another important embodiment of the present invention is the combination of low amounts of formic acid with very low amounts of peracetic acid and low amounts of hydrogen peroxide that also yield unexpected and synergistic results with regard to logio reduction of bacterial spores, fungal spores and vegetative bacteria. The various types of bacteria and spores that are set forth herein above, and hereby fully incorporated by reference, can be eradicated by the formic acid, peracetic acid, and hydrogen peroxide-containing liquid sporicidal composition of the present invention. Effective logio reductions values have been obtained generally within 10 minutes,International Patent ApplicationDOCKET NO.: ASCO.20018-WO-PCT1 within 7 minutes, or even within 5 minutes, depending upon the concentration of formic acid, peracetic acid, and hydrogen peroxide, as well as the type of bacteria, spore, etc.

[0058] The amount of formic acid ranges from about 0.2 wt.% to about 2.0 wt.%, desirably from about 0.4 wt.% to about 1.5 wt.%, and preferably from about 0.6 wt.% to about 1.2 wt.%.

[0059] The amount of peracetic acid is from about 0.02 wt.% to about 0.1 wt.%, desirably from about 0.03 wt.% to about 0.075 wt.%, and preferably from about 0.04 wt.% to about 0.06 wt.%.

[0060] The amount of hydrogen peroxide ranges generally from about 0.1 wt.% to about 3.0 wt.%, desirably from about 0.4 wt.% to about 2.0 wt.%, and preferably from about 0.5 wt.% to about 1.0 wt.%.

[0061] The compositions of this embodiment contain at least a solvent and / or diluent, preferably water, and optionally one or more other solvents and / or diluents.

[0062] Examples including Compositions Comprising Formic Acid, Peracetic Acid and Hydrogen Peroxide.

[0063] FIG. 4A illustrates a comparison of weak acid impact on the antimicrobial efficacy of systems that contain a combination of peracetic acid, varying amounts of hydrogen peroxide and either 1 wt.% succinic acid or 0.9 wt.% formic acid at different contact times. Blends of 0.05 wt.% (500 ppm) peracetic acid with various amounts of hydrogen peroxide and 1 wt.% succinic acid or 0.9 wt.% formic acid were compared and tested with regard to killing Bacillus subtilis. The compositions were made by adding nonionic surfactant, in particular, 1 wt.% of an alcohol ethoxylate with 8 moles of ethoxylation and 13 carbon atoms, to water, followed by succinic acid, or formic acid, and then the hydrogen peroxide. The peracetic acid was thereafter added to yield the final composition utilized for testing. Solutions were mixed during preparation and each component solubilized prior to adding the following component. For the results shown in FIG. 4A testing was performed with Bacillus subtilis ATCC 19659. The test method utilized was ASTM E2315-03, 2003 (2008). Results were measured at 5 minutes or 10 minutes of contact time.

[0064] As illustrated in FIG. 4A, each of the compositions including peracetic acid, hydrogen peroxide and formic acid achieved excellent logio reductions of greater than 5 at 5 minutes of contact time. The 1 wt.% succinic acid-containing compositions had poor logio reductions at 5 minutes of contact time. At 10 minutes of contact time, none of the succinic acid-containing compositions performed as well as the combinations of peracetic acid , formic acid, and hydrogen peroxide which maintained the logio reductions of greater than 5.International Patent ApplicationDOCKET NO.: ASCO.20018-WO-PCT1

[0065] Blends of 0.05 wt.% (500 ppm) peracetic acid with various amounts of hydrogen peroxide and formic acid or succinic acid or furoic acid or lactic acid were compared and tested with regard to killing Bacillus subtilis and the results thereof are set forth in FIG. 4B. The compositions were prepared as described hereinabove with respect to FIG. 4A. As apparent from FIG. 4B, formulations containing peracetic acid and hydrogen peroxide with a low carbon atom carboxylic acid, i.e. succinic acid or lactic acid, yield very little or essentially no improvement with regard to reduction logio of Bacillus subtilis spores at 5 minutes of contact time. Compositions including peracetic acid, hydrogen peroxide and furoic acid achieved logio reductions of about 4. Formulations of the present invention containing peracetic acid, hydrogen peroxide, and formic acid yielded a logio reduction of excess of 5 with respect to Bacillus subtilis 19659 spores, baseline 7.26 Log CFU / mL. The test method utilized was ASTM E2315-03, 2003 (2008).

[0066] Blends of 0.05 wt.% (500 ppm) peracetic acid with various amounts of hydrogen peroxide and formic acid or succinic acid or furoic acid or lactic acid were compared and tested and prepared as described hereinabove with respect to FIG. 4A with regard to killing Bacillus subtilis and the results thereof are set forth in FIG. 4C. As evident from FIG. 4C, only the compositions including acetic acid, hydrogen peroxide and lactic acid achieved logio reductions of greater than 5.0 at 5 minutes of contact time.

[0067] As apparent from FIG. 7A, amounts of hydrogen peroxide of 0.1, 0.25, 0.5, and 1.0 wt.% were tested with 0.05 wt.% of peracetic acid and 1.0 wt.% of acetic acid, glycolic acid or propionic acid. The same weight percentages of hydrogen peroxide and peracetic acid were tested with 0.9 wt.% formic acid. The 5-minute test revealed that none of the acetic acid examples, propionic acid examples, or glycolic acid examples yielded logio reductions above 1.0, whereas the present invention combination had a logio reductions of at least 5.0! Accordingly, unexpected and synergistic results of the three-component hydrogen peroxide-peracetic acid-formic acid liquid sporicidal compositions of the present inventions were very effective in eradicating bacterial spores. The test method utilized was ASTM E2315-03, 2003 (2008). Compositions were prepared as described hereinabove with respect to FIG. 1 A.

[0068] FIG. 7B illustrates a time kill study utilizing Bacillus subtilis 19659 spores, baseline equals 7.24 log CFU / mL. Log reductions are plotted at 5 minutes of contact time for compositions including 0.05 wt.% peracetic acid, various concentrations of hydrogen peroxide and 1 wt.% of acetic acid or formic acid or propionic acid or glycolic acid. The test method utilized was ASTMInternational Patent ApplicationDOCKET NO.: ASCO.20018-WO-PCT1E2315-03, 2003 (2008). The compositions were prepared as described hereinabove with respect to FIG. 1A.

[0069] As evident from FIG. 7B, only the inventive examples of the present invention including peracetic acid, hydrogen peroxide and formic acid achieved logio reductions greater than 5 at 5 minutes of contact.

[0070] Additional Components

[0071] Solvents / Diluents

[0072] The liquid sporicidal compositions of the present invention that contain formic acid along with one or more of hydrogen peroxide and peracetic acid contain a solvent and / or diluent. A liquid is considered a solvent when a component is required to be dissolved at a particular ambient temperature. A liquid is considered a diluent when it dilutes the concentration of a component utilized. For purposes of the application, the terms are used interchangeably.

[0073] In a preferred embodiment, water is utilized as a solvent or diluent. Water is present in a maj or amount by weight based on the total weight of the composition. In some embodiments water may be the only additional component besides the formic acid and one or more hydrogen peroxide and peracetic acid.

[0074] Thus, it should be clear that some embodiments of the present invention are compositions consisting of i) formic acid, ii) one or more of hydrogen peroxide and peracetic acid and iii) water.

[0075] In further embodiments solvents / diluents in addition to water can be utilized, such as, but not limited to, glycol ethers, carboxylate esters, and propanoate esters. Any solvents other than water are in amounts of from about 0.1 wt.% to about 1.5 wt.% and preferably from about 0.1 wt.% to about 0.5 wt.% based upon the total weight of the liquid sporicidal composition. Specific examples of optional solvents / diluents include phenoxyethanol, PPG-2 methyl ether, methylacetate, and ethyl propionate.

[0076] The amount of water comprises the remaining weight of the compositions after the amounts of the formic acid and one or more of hydrogen peroxide and peracetic acid, any other optional solvents / diluents and any other additives are taken into consideration. In other words, water constitutes the remaining weight amounts to add up to 100% of the total weight of the various liquid sporicidal compositions of the present invention.

[0077] Nonionic SurfactantsInternational Patent ApplicationDOCKET NO.: ASCO.20018-WO-PCT1

[0078] In some embodiments of the present invention, nonionic surfactants are present in the liquid sporicidal compositions. Examples of suitable nonionic surfactants are well known in the art and include for example 1 wt.% of an alcohol ethoxylate with 8 moles of ethoxylation and 13 carbon atoms. When present, the nonionic surfactant may be utilized in amounts that range from about 0.1 wt.% to about 5 wt.% and preferably from about 0.5 wt.% to about 2 wt.% based on the total weight of the composition.

[0079] Excluded / Minimal Components

[0080] C2-C6 Carboxylic Acids

[0081] Surprisingly, it has been found that the utilization of hydrogen peroxide in combination with formic acid yields synergistic and very improved unexpected antimicrobial efficacy against bacterial spores, whereas homologs of low carbon atom carboxylic acids, other than formic acid, having from 2 to about 6 carbon atoms for example, carboxylic acids such as furoic acid, oxalic acid, propionic acid, lactic acid, acetic acid, glycolic acid, succinic acid, and citric acid yield relatively low activity.

[0082] Since the other low carbon atom carboxylic acids (C2-C6) yield very little, if any, antimicrobial effects, they are not used in compositions comprising formic acid and one or more of hydrogen peroxide and peracetic acid. Hence, the compositions of the present invention including formic acid and one or more of hydrogen peroxide and peracetic acid are preferably free of carboxylic acids having from 2 to about 6 carbon atoms, meaning the amount of any such acids are about 1.0 wt.% or less, desirably about 0.5 wt.% or less, and preferably nil, that is no such acids are used, based on the total, i.e. 100 wt.% of the liquid sporicidal compositions of the present invention. It should be noted that one of ordinary skill in the art would recognize that some acetic acid is inherently present in peracetic acid, but no acetic acid is intentionally added to the compositions of the present invention.

[0083] Corrosion Inhibitors

[0084] It has been found that the use of various types or classes of chemical compounds, such as corrosion inhibitors in combination with the formic acid-hydrogen peroxide and / or peracetic acid liquid sporicidal compositions of the present invention can actually lower log reductions, i.e. a decrease in the logio values of Bacillus subtilis as compared to compositions without the compounds. Examples of corrosion inhibitors include one or more of the following: a lower alkyl benzotri azole, hydroxybenzotriazole, lower alkyl hydroxybenzotriazole, carb oxybenzotri azole,International Patent ApplicationDOCKET NO.: ASCO.20018-WO-PCT1 sodium tolytriazole, lower alkyl carboxybenzotriazole, benzimidazole, lower alkyl benzimidazole, hydroxybenzimidazole, lower alkyl hydroxybenzimidazole, carboxybenzimidazole, lower alkyl carboxybenzimidazole, mercaptobenzothiazole, lower alkyl mercaptobenzothiazole, hydroxymercaptobenzothiazole, lower alkyl hydroxymercaptobenzothiazole, carboxymercaptobenzothiazole, lower alkyl carboxymercaptobenzothiazole, sodium gluconate, sodium benzoate, butyl benzoate, monoethanolamine, triethanolamine, morpholine, sorbitol, erythritol, sodium phosphate, sodium tripolyphosphate, tetrasodium pyrophosphate, sodium molybdate, sodium nitrite, sodium bisufite, sodium metabisulfite, chromates, borates, and combinations thereof. As used herein, the term "lower alkyl" refers to a hydrocarbon group having from one to six carbon atoms, in a linear or branched chain, saturated or unsaturated. If utilized, the amounts thereof are exceedingly small. Thus, the formic acid-hydrogen peroxide and / or peracetic acid sporicide solutions of the present invention are free of any one or more corrosion inhibitors meaning that if any amount thereof is utilized, it is exceedingly small, that is less than about 0.5 wt.% or less, desirably less than 0.01 wt.% or less, or nil, that is no such one or more corrosion compounds whatsoever, based on the total weight, i.e. 100 wt.%, of the liquid sporicidal compositions of the present invention.

[0085] Amphoteric Surfactants

[0086] Another class of compounds that are not utilized in association with the liquid sporicidal compositions or solutions of the present invention include various one or more amphoteric surfactants such as sodium laurimino dipropionate, sodium octylaminopropionate, disodium capryloampho dipropionate, and the like. That is, the liquid formic acid-hydrogen peroxide and / or peracetic acid solutions or compositions of the present invention are free of such compounds, meaning that the use of any amphoteric surfactants, if utilized is extremely small, generally less than about 0.5 wt.%, desirably less than 0.1 wt.% and preferably nil, that is no one or more amphoteric surfactants whatsoever, based on the total, i.e. 100 wt.% of the liquid sporicidal compositions of the present invention.

[0087] FIG. 5 illustrates excipients, namely corrosion inhibitors and amphoteric surfactants, e g. negatively altering the activity of a peracetic acid and hydrogen peroxide combination against spores of Bacillus subtillis PS533.

[0088] PeracidsInternational Patent ApplicationDOCKET NO.: ASCO.20018-WO-PCT1

[0089] Yet another advantage of the present invention is that unexpected and improved synergistic results are obtained with regard to bacterial spore reduction are achieved without the use of any peracids containing 1, or from 3 to 5 carbon atoms. That is, the present invention is generally free of said peracids so that if utilized, very low amounts of peracids such as about 0.10 wt.% or less, desirably about 0.02 wt.% or less, and preferably nil, that is no such Ci or C3-C5 peracids whatsoever are utilized, based on the total, i.e. 100 wt.% of the liquid sporicidal compositions of the present invention.

[0090] Mineral acids / Strong acids

[0091] Another important aspect of the present invention is that the superior log kill properties with regard to various liquid sporicidal compositions were obtained without the use of any mineral or strong acids. Mineral acids include sulfuric acid, phosphoric acid, pyrophosphoric acid, polyphosphore acid, hydrochloride acid, and the like. Strong acids include nitric acid, hydrochloric acid, perchloric acid, hydrobromic acid, hydroiodic acid, and the like. Such mineral or strong acids are not utilized since they pose increased safety hazards and are corrosive to surfaces. The same are a health and safety issue since such strong acids are dangerous to animals including human beings. The various embodiments of the present invention are thus free of such strong and / or mineral acids, meaning that any amount of thereof is 1.0 wt.% or less, desirably about 0.05 wt.% or less, and preferably nil, that is no utilization of strong and / or mineral acid whatsoever based upon the total, i.e. 100 wt.% of the liquid sporicidal composition of the present invention.

[0092] For the avoidance of doubt, the compositions and methods of the present invention encompass all possible combinations of the components, including various ranges of said components, disclosed herein. It is further noted that the term ‘comprising’ does not exclude the presence of other elements. However, it is also to be understood that a description of a product comprising certain components also discloses a product consisting of these components. Similarly, it is also to be understood that a description on a process comprising certain steps also discloses a process consisting of these steps.

[0093] While in accordance with the patent statues, the best mode and preferred embodiment have been set forth, the scope of the invention is not limited thereto, but rather by the scope of the attached claims.

Claims

International Patent ApplicationDOCKET NO.: ASCO.20018-WO-PCT1WHAT IS CLAIMED IS:

1. A liquid sporicidal composition, comprising: a) hydrogen peroxide in an amount of from about 2.0 wt.% to about 10 wt.%; and formic acid in an amount of from about 0.3 wt.% to about 4 wt.% based on the total weight of the composition; b) peracetic acid in an amount of from about 0.02 wt.% to about 0.1 wt.%; and formic acid in an amount of from about 0.2 wt.% to about 2.0 wt.% based on the total weight of the composition; or c) hydrogen peroxide in an amount of from about 0.1 wt.% to about 3.0 wt.%; peracetic acid in an amount of from about 0.02 wt.% to about 0.1 wt.%; and formic acid in an amount of from about 0.2 wt.% to about 2.0 wt.% based on the total weight of the composition; and a solvent / diluent comprising water in a major amount by weight based on the total weight of the composition.

2. The composition according to claim 1, wherein the composition achieves a logio reduction of Bacillus subtilis ATC 19659 spores of at least 2, 3, 4 or 5 after five minutes of contact time as measured according to ASTM E2197-17el or ASTM E2315-03.

3. The composition according to any of claims 1-2, wherein the composition is free of peracids having from 1 to 5 carbon atoms.

4. The composition according to any of the previous claims, wherein the composition is free of carboxylic acids having from 2 to about 6 carbon atoms.

5. The composition according to any of the previous claims, wherein the composition is free of corrosion inhibitors.

6. The composition according to any of the previous claims, wherein the composition is free of mineral acids and strong acids.International Patent ApplicationDOCKET NO.: ASCO.20018-WO-PCT17. The composition according to any of the previous claims, wherein the composition is free of amphoteric surfactants.

8. The composition according to any of the previous claims, wherein the composition is a), wherein the hydrogen peroxide is present in an amount from 3 wt.% to 9 wt.% and wherein the formic acid is present in an amount from 0.5 wt.% to 3.0 wt.%.

9. The composition according to claim 8, wherein the hydrogen peroxide is present in an amount from 4 wt.% to 7 wt.% and wherein the formic acid is present in an amount from 0.7 wt.% to 1.5 wt.%, and wherein the composition a) is free of peracetic acid.

10. The composition according to any of claims 1-7, wherein the composition is b), wherein the peracetic acid is present in an amount from 0.03 wt.% to 0.075 wt.% and wherein the formic acid is present in an amount from 0.4 wt.% to 1.5 wt.%.

11. The composition according to claim 10, wherein the peracetic acid is present in an amount from 0.04 wt.% to 0.06 wt.% and wherein the formic acid is present in an amount from 0.5 wt.% to 1.2 wt.%, and wherein the composition b) is free of hydrogen peroxide.

12. The composition according to any of claims 1-7, wherein the composition is c), wherein the peracetic acid is present in an amount from 0.03 wt.%. to 0.075 wt.%, wherein the hydrogen peroxide is present in an amount from 0.4 wt.% to 2.0 wt.%, and wherein the formic acid is present in an amount from 0.4 wt.% to 1.5 wt.%.

13. The composition according to claim 12, wherein the formic acid is present in an amount from 0.5 wt.% to 1.2 wt.%, wherein the peracetic acid is present in an amount from 0.04 wt.% to 0.06 wt.% and wherein the hydrogen peroxide is present in an amount from 0.45 wt.% to 1.0 wt.%.

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