Antimicrobial composition having efficacy against endospores

Abstract

A sporicidal composition has a moderately low pH and includes a glycosidase and the dissocia-tion product of at least one inorganic oxidizing agent. High effective solute concentrations can enhance the efficacy of the composition. The composition can be applied to a surface and allowed to absorb into an endospore, ultimately killing at least some of those bacteria in mature endospore form. Surfaces to be treated include inanimate (hard) surfaces via cleaning and medical devices such as endoscopes, typically via immersion.

Claims

1. A composition useful for treating surfaces susceptible to carry endospores, comprising: a) a solvent component that comprises water and one or more organic liquids, said solvent component exhibiting a δ.sub.p value of from 13.1 to 15.7 MPa.sup.½, and b) a solute component that comprises (1) a buffer provided by combining at least one carboxylic acid and conjugate base of at least one carboxylic acid, (2) dissociation product of from 4 to 18 g/L of one or more electrolyte oxidizing agents, each of said electrolyte oxidizing agents being a compound that comprises an anion selected from the group consisting of manganate, permanganate, peroxochromate, chromate, dichromate, and peroxymonosulfate, (3) from 0.05 to 1 g/L of a lysozyme, and (4) from 5 to 30 g/L of an ionic surfactant, said composition having a pH of from about 4.75 to about 6.5 and an effective solute concentration of at least 0.5 Osm/L.

2. The composition of claim 1 wherein said ionic surfactant is an anionic surfactant.

3. The composition of claim 1 wherein said one or more organic liquids comprises at least one glycol ether.

4. The composition of claim 1 wherein said solute component further comprises nonionic surfactant.

5. The composition of claim 4 wherein said ionic surfactant is an anionic surfactant.

6. The composition of claim 4 wherein said solute component further comprises dissociation products of one or more non-oxidizing electrolytes.

7. The composition of claim 2 wherein said solute component further comprises dissociation products of one or more non-oxidizing electrolytes.

8. The composition of claim 1 wherein said solute component further comprises dissociation products of one or more non-oxidizing electrolytes.

9. The composition of claim 8 wherein said composition is free of oxidizing acids.

10. The composition of claim 1 wherein said composition is free of oxidizing acids.

11. The composition of claim 1 wherein at least one of said one or more electrolyte oxidizing agents has an E.sup.0.sub.red value of at least +1.5 V.

12. A composition useful for treating surfaces susceptible to carry endospores, said composition being free of oxidizing acids and consisting of: a) a solvent component that comprises water and one or more organic liquids, said solvent component exhibiting a δ.sub.p value of from 13.1 to 15.7 MPa.sup.½, and b) a solute component that comprises (1) a buffer provided by combining at least one carboxylic acid and conjugate base of at least one carboxylic acid, (2) dissociation product of from 4 to 18 g/L of one or more electrolyte oxidizing agents, each of said electrolyte oxidizing agents being a compound that comprises an anion selected from the group consisting of manganate, permanganate, peroxochromate, chromate, dichromate, and peroxymonosulfate, (3) from 0.05 to 1 g/L of a lysozyme, (4) from 5 to 30 g/L of an anionic surfactant, and (5) a nonionic surfactant, said composition having a pH of from about 4.75 to about 6.5 and an effective solute concentration of at least 0.5 Osm/L.

13. The composition of claim 12 in which said effective solute concentration is at least 1.5 Osm/L.

14. The composition of claim 12 wherein said buffer comprises acetic acid and an alkali metal salt of acetic acid.

15. The composition of claim 12 wherein said buffer is provided by combining acetic acid and an alkali metal salt of acetic acid.

16. The composition of claim 12 wherein said solute component further comprises dissociation products of one or more non-oxidizing electrolytes.

17. The composition of claim 12 wherein said solute component comprises from 7 to 13 g/L of said one or more electrolyte oxidizing agents.

18. The composition of claim 12 wherein each of said electrolyte oxidizing agent compounds is inorganic.

19. The composition of claim 1 wherein each of said electrolyte oxidizing agent compounds is inorganic.

Description

DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS

(1) The composition will be described first in terms of its properties and components, many of which are widely available and relatively inexpensive, and then in terms of its use.

(2) The solvent component of the composition typically includes a significant amount of water. Relative to its overall volume, a composition often includes up to 20%, 25%, 30%, 33%, 35%, 40%, 45%, 50%, or even 55% (all v/v). On a per liter basis, a composition often includes from ˜50 to ˜500 mL, commonly from ˜75 to ˜475 mL, more commonly from ˜100 to ˜450 mL, usually from ˜125 to ˜425 mL, typically from ˜150 to ˜400 mL, and most typically 250±50 mL water. The water need not be specially treated (e.g., distilled and/or deionized), although preference certainly can be given to water that does not interfere with the intended antimicrobial effect of the composition.

(3) The solvent component of the composition often includes at least one organic liquid and, in some embodiments, preference is given to those organic liquids with δ.sub.p values lower than that of water (δ.sub.p≈16.0 MPa.sup.1/2). Where an organic liquid or liquids is present in the solvent component, the δ.sub.p value of the overall solvent component generally is less than 16.0, no more than 15.6, no more than 15.2, no more than 15.0, no more than 14.6 or no more than 14.0 MPa.sup.1/2. In some embodiments, the δ.sub.p value of the overall solvent component can range from 13.1 to 15.7 MPa.sup.1/2, from 13.3 to 15.6 MPa.sup.1/2, from 13.5 to 15.5 MPa.sup.1/2, and even from 13.7 to 15.4 MPa.sup.1/2.

(4) The organic liquid(s) often is/are present at concentrations of up to 60%, commonly 5 to 50%, more commonly 10 to 45%, even more commonly 15 to 40%, and typically 20 to 35% (all w/v, based on total volume of solvent component).

(5) The amount of a given organic liquid (or mixture of organic liquids) to be added to water can be calculated using formula (I) if a targeted δ.sub.p value is known. Similarly, a projected δ.sub.p value can be calculated using formula (I) if the amount of organic liquid(s) and their individual δ.sub.p values are known.

(6) The solvent component can consist of, or consist essentially of, only water or only one or more organic liquids, with preference being given to mixtures of species of the same genus of organic liquids, e.g., two ethers or two alcohols rather than one ether and one alcohol. In certain preferred embodiments, the solvent component can consist of, or consist essentially of, water and an organic liquid, preferably one having a δ.sub.p value less than 15.5 MPa.sup.1/2. In yet other embodiments, the solvent component can consist of, or consist essentially of, water and two or more organic liquids, with the resulting solvent component having δ.sub.p value that can be calculated using formula (I); again, preference is given to mixtures of species of the same genus of organic liquids, e.g., two ethers or two alcohols rather than one ether and one alcohol.

(7) With respect to organic liquids that can be employed in the solvent component, those which are miscible with one another and/or water are preferred. Non-limiting examples of potentially useful organic liquids include ketones such as acetone, methyl butyl ketone, methyl ethyl ketone and chloroacetone; acetates such as amyl acetate, ethyl acetate and methyl acetate; (meth)acrylates and derivatives such as acrylamide, lauryl methacrylate and acrylonitrile; aryl compounds such as benzene, chlorobenzene, fluorobenzene, toluene, xylene, aniline and phenol; aliphatic alkanes such as pentane, isopentane, hexane, heptane and decane; halogenated alkanes such as chloroform, methylene dichloride, chloroethane and tetrachloroethylene; cyclic alkanes such as cyclopentane and cyclohexane; and polyols such as ethylene glycol, diethylene glycol, propylene glycol, hexylene glycol, and glycerol. When selecting such organic liquids for use in the solvent component of the composition, possible considerations include avoiding those which contain a functional group that will react with either the acid(s)/base(s) or salt(s) employed in the composition and favoring those which possess higher regulatory pre-approval limits.

(8) Preferred organic liquids include ethers and alcohols due to their low tissue toxicity and environmentally friendliness. These can be added at concentrations up to the solubility limit of the other ingredients in the composition.

(9) Ether-based liquids that can be used in the solvent component include those defined by the following general formula
R.sup.1(CH.sub.2).sub.xO—R.sup.2—[O(CH.sub.2).sub.z].sub.yZ  (II)
where x is an integer of from 0 to 20 (optionally including, where 2≤x≤20, one or more points of ethylenic unsaturation), y is 0 or 1, z is an integer of from 1 to 4, R.sup.2 is a C.sub.1-C.sub.6 linear or branched alkylene group, R.sup.1 is a methyl, isopropyl or phenyl group, and Z is a hydroxyl or methoxy group. Non-limiting examples of glycol ethers (formula (II) compounds with Z═OH) that can be used in the solvent component are set forth below in Table 2.

(10) TABLE-US-00002 TABLE 2 Representative glycol ethers, with formula (II) variables and δ.sub.p values ~δ.sub.p R.sup.1 x R.sup.2 y z (MPa.sup.1/2) ethylene glycol monomethyl ether CH.sub.3 0 (CH.sub.2).sub.2 0 — 9.2 ethylene glycol monoethyl ether CH.sub.3 1 (CH.sub.2).sub.2 0 — 9.2 ethylene glycol monopropyl ether CH.sub.3 2 (CH.sub.2).sub.2 0 — 8.2 ethylene glycol monoisopropyl ether (CH.sub.3).sub.2CH 0 (CH.sub.2).sub.2 0 — 8.2 ethylene glycol monobutyl ether CH.sub.3 3 (CH.sub.2).sub.2 0 — 5.1 ethylene glycol monophenyl ether C.sub.6H.sub.5 0 (CH.sub.2).sub.2 0 — 5.7 ethylene glycol monobenzyl ether C.sub.6H.sub.5 1 (CH.sub.2).sub.2 0 — 5.9 diethylene glycol monomethyl ether CH.sub.3 0 (CH.sub.2).sub.2 1 2 7.8 diethylene glycol monoethyl ether (DGME) CH.sub.3 1 (CH.sub.2).sub.2 1 2 9.2 diethylene glycol mono-n-butyl ether CH.sub.3 3 (CH.sub.2).sub.2 1 2 7.0 propylene glycol monobutyl ether CH.sub.3 3 (CH.sub.2).sub.3 0 — 4.5 propylene glycol monoethyl ether CH.sub.3 1 (CH.sub.2).sub.3 0 — 6.5 propylene glycol monoisobutyl ether (CH.sub.3).sub.2CH 1 (CH.sub.2).sub.3 0 — 4.7 propylene glycol monoisopropyl ether (CH.sub.3).sub.2CH 0 (CH.sub.2).sub.3 0 — 6.1 propylene glycol monomethyl ether CH.sub.3 0 CH.sub.2CH(CH.sub.3) 0 — 6.3 propylene glycol monophenyl ether C.sub.6H.sub.5 0 CH.sub.2CH(CH.sub.3) 0 — 5.3 propylene glycol monopropyl ether (PGME) CH.sub.3 2 CH.sub.2CH(CH.sub.3) 0 — 5.6 triethylene glycol monomethyl ether CH.sub.3 0 (CH.sub.2).sub.2 2 2 7.6 triethylene glycol monooleyl ether CH.sub.3 17* (CH.sub.2).sub.2 2 2 3.1 *includes unsaturation at the 9 position

(11) Cyclic and C.sub.1-C.sub.16 acyclic (both linear and branched, both saturated and unsaturated) alcohols, optionally including one or more points of ethylenic unsaturation and/or one or more heteroatoms other than the alcohol oxygen such as a halogen atom, an amine nitrogen, and the like, can be included in the solvent component of the composition. Non-limiting examples of representative examples are compiled in the following table.

(12) TABLE-US-00003 TABLE 3 Representative alcohols, with δ.sub.p values ~δ.sub.p (MPa.sup.1/2) 2-propenol 10.8 1-butanol 5.7 t-butyl alcohol 5.1 4-chlorobenzyl alcohol 7.5 cyclohexanol 4.1 2-cyclopentenyl alcohol 7.6 1-decanol 10.0 2-decanol 10.0 2,3-dichloropropanol 9.2 2-ethyl-1-butanol 4.3 ethanol 8.8 2-ethyl-hexanol 3.3 isooctyl alcohol 7.3 octanol 3.3 methanol 12.3 oleyl alcohol 2.6 1-pentanol 4.5 2-pentanol 6.4 1-propanol 6.8 2-propanol (IPA) 6.1

(13) For further information on organic liquid-containing solvent components, the interested reader is directed to U.S. Pat. Publ. No. 2016/0073628.

(14) The composition is somewhat acidic. Generally, the composition has a pH of no less than 4.5, and certain embodiments can have a pH of no less than 4.55, 4.60, 4.75, 4.80, 4.85, 4.90, 4.95 or even 5.00. The composition also generally has a pH of no more than 6.75, 6.50, 6.25, or even 6.00. Ranges of pH values employing each of the lower limits in combination with each of the upper limits are envisioned. The composition can have a pH value of 5.5±1.0, 5.6±0.8, 5.7±0.8, 5.75±0.8, 5.8±0.75, and 5.75±0.75.

(15) Acidity can be achieved by adding to the solvent component (or vice versa) one or more acids. Strong (mineral) acids such as HCl, H.sub.2SO.sub.4, H.sub.3PO.sub.4, HNO.sub.3, H.sub.3BO.sub.3, and the like or organic acids, particularly organic polyacids, may be used. Examples of organic acids include monoprotic acids such as formic acid, acetic acid and substituted variants (e.g., hydroxyacetic acid, chloroacetic acid, dichloroacetic acid, phenylacetic acid, and the like), propanoic acid and substituted variants (e.g., lactic acid, pyruvic acid, and the like), any of a variety of benzoic acids (e.g., mandelic acid, chloromandelic acid, salicylic acid, and the like), glucuronic acid, and the like; diprotic acids such as oxalic acid and substituted variants (e.g., oxamic acid), butanedioic acid and substituted variants (e.g., malic acid, aspartic acid, tartaric acid, citramalic acid, and the like), pentanedioic acid and substituted variants (e.g., glutamic acid, 2-ketoglutaric acid, and the like), hexanedioic acid and substituted variants (e.g., mucic acid), butenedioic acid (both cis and trans isomers), iminodiacetic acid, phthalic acid, and the like; triprotic acids such as citric acid, 2-methylpropane-1,2,3-tricarboxylic acid, benzenetricarboxylic acid, nitrilotriacetic acid, and the like; tetraprotic acids such as prehnitic acid, pyromellitic acid, and the like; and even higher degree acids (e.g., penta-, hexa-, heptaprotic, etc.). Where a tri-, tetra-, or higher acid is used, one or more of the carboxyl protons can be replaced by cationic atoms or groups (e.g., alkali metal ions), which can be the same or different.

(16) In certain embodiments, preference can be given to those organic acids which are, or can be made to be, highly soluble in water; acids that include groups that enhance solubility in water (e.g., hydroxyl groups), examples of which include tartaric acid, citric acid, and citramalic acid, can be preferred in some circumstances. In these and/or other embodiments, preference can be given to those organic acids which are biocompatible; many of the organic acids listed above are used in preparing or treating food products, personal care products, and the like.

(17) The composition advantageously need not include an oxidizing acid to have lethal efficacy against endospores. Many oxyacids, such as perchloric, chloric, chlorous, hypochlorous, persulfuric, sulfuric, sulfurous, hyposulfurous, pyrosulfuric, di sulfurous, thiosulfurous, pernitric, nitric, nitrous, hyponitrous, perchromic, chromic, dichromic, permanganic, manganic, perphosphoric, phosphoric, phosphorous, hypophosphorus, periodic, iodic, iodous, etc., are considered to be oxidizing acids. Organic oxidizing acids include, but are not limited to, peracetic acid, peroxalic acid and diperoxalic acid.

(18) If an oxidizing acid is included in the composition, those which have relatively high pK.sub.a values (i.e., are not considered to be particularly strong acids) and positive standard potentials (E.sup.0.sub.red) are preferred. The former permits production of a composition that has a pH value that is not too low, i.e., below ˜1.5, preferably not below ˜1.75, more preferably not below ˜2, and most preferably not below ˜2.2, so that the composition can be used without extreme protective measures by those charged with handling and applying them to surfaces. The latter permits the acid to have sufficient oxidizing capacity to permit overcoming or avoidance of certain endospore defenses such as, for example, oxidation of disulfide linkages and protein polymers on the endospore coat, which allows the outer spore coat to be breached.

(19) Preferred pK.sub.a values are greater than ˜1, greater than ˜1.5, greater than ˜2, greater than ˜2.5, greater than ˜3, greater than ˜3.5, greater than ˜4, greater than ˜4.5, greater than ˜5, and even greater than ˜5.5. Acids with lower pK.sub.a values can be used if other steps are taken to ensure compliance with required or desired properties of the composition such as pH range (discussed above) and effective solute concentration (discussed below).

(20) Preferred E.sup.0.sub.red values are those which are at least +0.20 V, at least +0.25 V, at least +0.33 V, at least +0.40 V, at least +0.50 V, at least +0.60 V, at least +0.67 V, at least +0.75 V, at least +0.80 V, at least +0.90 V, at least +1.00 V, at least +1.10 V, at least +1.20 V, or even at least +1.25 V.

(21) Some oxidizing acids are not particularly stable in aqueous solutions. Accordingly, where a composition with an oxidizing acid is desired, preparing the oxidizing acid in vitro can be advantageous. For example, to a solvent component of a composition can be provided acetic acid and hydrogen peroxide which, when contacted, reversibly form peracetic acid.

(22) The amount of any given acid employed can be determined from the target pH of a given composition and the pK.sub.a value(s) of the chosen acids in view of the type and amounts of compound(s), if any, utilized to achieve the desired effective solute concentration in the composition. (More discussion of osmolarity and the types of osmolarity-adjusting compounds appears below.)

(23) Also present in the solute component of the composition is an electrolyte oxidizing agent that does not contain any active hydrogen atoms when subjected to the Zerewitinoff determination. Non-limiting examples of potentially useful electrolyte, preferably inorganic, oxidizing agents include compounds which include anions such as manganate, permanganate, peroxochromate, chromate, dichromate, peroxymonosulfate, and the like. (Some of these electrolytes can impact pH, so a composition formulated to have a given pH might require adjustment after addition of the oxidizing agent(s).) Preferred are those compounds having E.sup.0.sub.red values of at least +1.25 V, preferably at least +1.5 V, more preferably at least +1.75 V, even more preferably at least +2.0 V and most preferably at least +2.25 V.

(24) Electrolyte oxidizing agents generally can be added at up to their individual solubility limits, although the maximum amount generally is on the order of 30 g/L total composition. Exemplary ranges of electrolyte oxidizing agent(s) are ˜2 to ˜25 g/L, ˜3 to ˜21 g/L, ˜4 to ˜18 g/L, ˜5 to ˜16 g/L and ˜6 to ˜14 g/L. Exemplary amounts of electrolyte oxidizing agent(s) are 17.5±12 g/L, 15±9 g/L, 12.5±6 g/L and 10±3 g/L. Utilizing lower amounts of electrolyte oxidizing agents generally results in an increase in biocompatibility of the composition.

(25) Once the acid(s) and oxidizing agent(s) are added to a solvent component that contains water (or vice versa), each at least partially dissociates.

(26) In certain embodiments, the acid(s) and oxidizing agent(s) can provide a relatively high effective solute concentration to the composition. Often, efficacy increases as effective solute concentration (osmolarity) increases. The presence of an abundance of solutes ensures that a sufficient amount are present to induce a high osmotic pressure across the cortical membrane, leading to lysis. This efficacy is independent of the particular identity or nature of individual compounds of the solute component, although smaller molecules are generally more effective than larger molecules due to solvent capacity (i.e., the ability to (typically) include more small molecules in a given amount of solvent component than an equimolar amount of larger molecules) and ease of transport across cortical membranes.

(27) Any of a number of solutes can be used to increase the composition osmolarity, which increases the differential osmotic pressure across the bacterial cell wall membrane.

(28) One approach to achieving increased osmolarity of the composition is by adding large amounts of non-oxidizing electrolytes, particularly ionic compounds (salts); see, e.g., U.S. Pat. No. 7,090,882. Like the oxidizing acid and inorganic oxidizing agent, non-oxidizing electrolytes dissociate upon being introduced into a solvent component that includes water.

(29) Where one or more organic acids are used in the composition, one approach to increasing osmolarity without increasing the pH of the composition past a desired target involves inclusion of salt(s) of one or more the acid(s) or the salt(s) of one or more other organic acids. Such compounds, upon dissociation, increase the effective amount of solutes in the composition without greatly impacting the molar concentration of hydronium ions while, simultaneously, providing a buffer system in the composition.

(30) For example, where the composition includes an acid, a fraction up to a many fold excess (e.g., 3× to 10×, at least 5× or even at least 8×) of one or more salts of that (or another) acid also can be included. The identity of the countercation portion of the salt is not believed to be particularly critical, with common examples including ammonium ions and alkali metals. Where a polyacid is used, all or fewer than all of the H atoms of the carboxyl groups can be replaced with cationic atoms or groups, which can be the same or different. For example, mono-, di- and trisodium citrate all constitute potentially useful buffer precursors, whether used in conjunction with citric acid or another organic acid. However, because trisodium citrate has three available basic sites, it has a theoretical buffering capacity up to 50% greater than that of disodium citrate (which has two such sites) and up to 200% greater than that of sodium citrate (which has only one such site).

(31) One preferred acid/buffer precursor combination is acetic acid and an alkali metal salt of acetic acid, e.g., sodium acetate.

(32) Each buffer precursor, when added to a solvent component that contains water (or vice versa), at least partially dissociates.

(33) The solute component of the composition also includes at least one glycosidase. Preferred are those glycosidases which are active toward peptidoglycans. A particularly preferred glycosidase is lysozyme, which effectively hydrolyzes the glycosidic bond between N-acetylmuramic acid and the fourth carbon atom of N-acetylglucosamine.

(34) Surprisingly, the one or more glycosidases can be added at very low amounts and still provide significant enhancement to a composition's efficacy. They generally can be added at up to their individual solubility limits, although the maximum amount generally is on the order of 5 g/L total composition. Exemplary amounts of glycosidase(s) are on the order of at least 0.05, 0.1, 0.15, or 0.2 g/L up to 0.4, 0.5, 0.6, 0.7, 0.8, 0.9 or 1 g/L, with ranges employing combinations of each of the lower limits with each of the upper limits being contemplated.

(35) Regardless of how achieved, the effective solute concentration of the composition is at least 0.5, 0.75 or 1.0 Osm/L, generally at least 1.25 Osm/L, often at least 1.5 Osm/L, commonly at least 1.75 Osm/L, more commonly at least 2.0 Osm/L, typically at least 2.25 Osm/L, more typically at least 2.5 Osm/L. (As points of comparison, in biological applications, a 0.9% (by wt.) saline solution, which is ˜0.3 Osm/L, typically is considered to be have moderate tonicity, while a 3% (by wt.) saline solution, which is ˜0.9 Osm/L, generally is considered to be hypertonic.) In some embodiments, the composition has an effective solute concentration of at least ˜3.0, at least ˜3.25, at least ˜3.5, at least ˜3.75, or even at least ˜4.0 Osm/L, with the upper limit being defined by the solubility limit of the solutes in the solvent component; in some embodiments, the upper limit of effective solute concentration can range as high as 4.5, 4.75, 5.0, 5.25, 5.5, 5.75, 6.0, 6.25, 6.5, 6.75, 7.0, 7.2, 7.4, 7.6, 7.8, 8.0, 8.2, 8.4, 8.6, 8.8 or even ˜9 Osm/L. Effective solute concentration ranges involving combinations of any of the lower and upper limits set forth in this paragraph also are envisioned. Surprisingly, the effective solute concentrations of compositions according to the present invention, which are intended to be effective against (i.e., lethal to) endospores, need not be significantly higher than those described in U.S. Pat. Nos. 8,940,792 and 9,314,017 as well as U.S. Pat. Publ. Nos. 2010/0086576, 2013/0272922, 2013/0079407 and 2016/0073628, all of which are directed generally against planktonic bacteria and biofilms.

(36) Unlike many of the compositions described in the documents listed in the preceding paragraph, the present composition does not require inclusion of surfactant in the solute component, although certain preferred embodiments do include one or more wetting agents which include, but are not limited to, surfactants.

(37) Essentially any material having surface active properties in water can be employed, regardless of whether water is present in the solvent component of the composition, although those surface active agents that bear some type of ionic charge are expected to have enhanced antimicrobial efficacy because such charges, when brought into contact with a bacteria, are believed to lead to more effective bacterial membrane disruption and, ultimately, to cell leakage and lysis.

(38) Polar surfactants generally are more efficacious than non-polar surfactants, with ionic surfactants being most effective. For polar surfactants, anionic surfactants generally are the most effective, followed by zwitterionic and cationic surfactants, with smaller molecules generally being preferred over larger ones. The size of side-groups attached to the polar head can influence the efficacy of ionic surfactants, with larger size-groups and more side-groups on the polar head potentially decreasing the efficacy of surfactants.

(39) Potentially useful anionic surfactants include, but are not limited to, ammonium lauryl sulfate, dioctyl sodium sulfosuccinate, perfluorobutanesulfonic acid, perfluorononanoic acid, perfluorooctanesulfonic acid, perfluorooctanoic acid, potassium lauryl sulfate, sodium dodecylbenzenesulfonate, sodium laureth sulfate, sodium lauroyl sarcosinate, sodium myreth sulfate, sodium myreth sulfate, sodium pareth sulfate, sodium stearate, sodium chenodeoxycholate, N-lauroylsarcosine sodium salt, lithium dodecyl sulfate, 1-octanesulfonic acid sodium salt, sodium cholate hydrate, sodium deoxycholate, sodium dodecyl sulfate (SDS), sodium glycodeoxycholate, sodium lauryl sulfate (SLS), and the alkyl phosphates set forth in U.S. Pat. No. 6,610,314. SLS is a particularly preferred material.

(40) Potentially useful cationic surfactants include, but are not limited to, cetylpyridinium chloride (CPC), cetyl trimethylammonium chloride, benzethonium chloride, 5-bromo-5-nitro-1,3-dioxane, dimethyldioctadecylammonium chloride, cetrimonium bromide, dioctadecyldimethylammonium bromide, tetradecyltrimethyl ammonium bromide, benzalkonium chloride (BK), hexadecylpyridinium chloride monohydrate and hexadecyltrimethylammonium bromide.

(41) Potentially useful nonionic surfactants include, but are not limited to, sodium polyoxyethylene glycol dodecyl ether, N-decanoyl-N-methylglucamine, digitonin, n-dodecyl β-D-maltoside, octyl β-D-glucopyranoside, octylphenol ethoxylate, polyoxyethylene (8) isooctyl phenyl ether, polyoxyethylene sorbitan monolaurate, and polyoxyethylene (20) sorbitan cholamidopropyl) dimethylammonio]-2-hydroxy-1-propane sulfonate, 3-[(3-cholamidopropyl) dimethylammonio]-1-propane sulfonate, 3-(decyldimethylammonio) propanesulfonate inner salt, and N-dodecyl-N,N-dimethyl-3-ammonio-1-propanesulfonate.

(42) Potentially useful zwitterionic surfactants include sulfonates (e.g. 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate), sultaines (e.g. cocamidopropyl hydroxysultaine), betaines (e.g. cocamidopropyl betaine), and phosphates (e.g. lecithin).

(43) For other potentially useful materials, the interested reader is directed to any of a variety of other sources including, for example, U.S. Pat. Nos. 4,107,328, 6,953,772, 7,959,943, and 8,940,792.

(44) The amount(s) of wetting agent(s) to be added to the composition is limited to some extent by the target effective solute concentration and compatibility with other subcomponents of the solute component of the composition. The total amount of surfactant present in the composition can range from at least 0.1%, from at least 0.12%, from at least 0.15%, from at least 0.17% or from at least 0.18% up to 5%, commonly up to 4%, more commonly up to 3%, and typically up to 2.5%. At times, even lower maximum amounts of certain types of surfactants that can be present in a composition for a particular end use (without specific testing, review and approval) are mandated by governmental regulations.

(45) If more than one type of surfactant is employed, the majority preferably is an ionic surfactant, with the ratio of ionic-to-nonionic surfactant generally ranging from ˜2:1 to ˜10:1, commonly from ˜5:2 to ˜15:2, and typically from ˜3:1 to ˜7:1. Additionally, as is known in the art, a composition should not include surfactant types that are incompatible, e.g., anionic with cationic or zwitterionic with either anionic or cationic.

(46) The antimicrobial composition can include a variety of additives and adjuvants to make it more amenable for use in a particular end-use application with negatively affecting its efficacy in a substantial manner. Examples include, but are not limited to, emollients, fungicides, fragrances, pigments, dyes, defoamers, foaming agents, flavors, abrasives, bleaching agents, preservatives (e.g., antioxidants) and the like. A comprehensive listing of additives approved by the U.S. Food and Drug Administration is available as a zipped text file at http://www.fda.gov/Drugs/InformationOnDrugs/ucm113978.htm (link active as of filing date of this application).

(47) The composition does not require the inclusion of an active antimicrobial agent (defined above) to be efficacious, but such materials optionally can be included. Non-limiting examples of potentially useful active antimicrobial additives include C.sub.2-C.sub.8 alcohols (other than or in addition to any used as an organic liquid of the solvent component) such as ethanol, n-propanol, and the like; aldehydes such as gluteraldehyde, formaldehyde, and o-phthalaldehyde; formaldehyde-generating compounds such as noxythiolin, tauroline, hexamine, urea formaldehydes, imidazolone derivatives, and the like; anilides, particularly triclocarban; biguanides such as chlorhexidine and alexidine, as well as polymeric forms such as poly(hexamethylene biguanide); dicarboximidamides (e.g., substituted or unsubstituted propamidine) and their isethionate salts; halogen atom-containing or releasing compounds such as bleach, ClO.sub.2, dichloroisocyanurate salts, tosylchloramide, iodine (and iodophors), and the like; silver and silver compounds such as silver acetate, silver sulfadiazine, and silver nitrate; phenols, bis-phenols and halophenols (including hexachlorophene and phenoxyphenols such as triclosan); and quaternary ammonium compounds.

(48) The following tables provide ingredient lists for exemplary compositions according to the present invention which are free of inorganic oxidizing acids, with amounts being provided in grams and with distilled water being added to bring the ingredients up to a volume of 1 L.

(49) TABLE-US-00004 TABLE 4 Formulations for exemplary compositions Formulation 1 Formulation 2 salt of organic acid  8-32 12-24 organic acid 125-200 140-180 ionic surfactant  5-30 15-25 nonionic surfactant 0-5 1-3 glycosidase 0.05-1   0.1-0.5 inorganic oxidizing agent  4-20  6-12 organic liquid 175-450 225-375

(50) Various embodiments of the composition have been provided by way of example and not limitation. As evident from the foregoing table, general preferences regarding features, ranges, numerical limitations and embodiments are, to the extent feasible and as long as not interfering or incompatible, envisioned as being capable of being combined with other such generally preferred features, ranges, numerical limitations and embodiments.

(51) A composition according to the present invention is intended to be, and in practice is, aggressively antimicrobial. Its intended usages are in connection with inanimate objects such as, in particular, hard surfaces, particularly those commonly found in healthcare facilities.

(52) The composition can be applied to inanimate objects, particularly hard surfaces, in a variety of ways including pouring, spraying or misting, via a distribution device (e.g., mop, rag, brush, textile wipe, etc.), and the like.

(53) Alternatively, certain objects are amenable to being immersed in a composition. This is particularly true of medical equipment designed for use with multiple patients such as, for example, dialysis equipment, any of a variety of endoscopes, duodenoscopes, etc., endoscopic accessories such as graspers, scissors and the like, manual instruments such as clamps and forceps, laparoscopic surgical accessories, orthopedic and spinal surgery hardware such as clamps and jigs, and the like. Because the composition of the present invention has a more moderate [H.sup.+] than treatments such as peracetic acid and bleach, it can achieve disinfection, high level disinfection or even sterilization without negative effects such as, e.g., polymeric degradation, metal corrosion, glass or plastic etching, and the like.

(54) Once applied to a surface or object, the various ingredients of the composition act on any endospores present and avoid or break down their various defenses. The contact time necessary for a composition to treat endospores (i.e., ensure that they cannot return to a vegetative state) can vary widely depending on the particular composition and its intended end use.

(55) A composition intended for use as an immersion bath for medical devices can achieve at least a 5.0, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, or 6.0 log reduction after a contact time of no more than 14,400 seconds, no more than 10,800 seconds, no more than 7200 seconds, no more than 5400 seconds, no more than 3600 seconds, no more than 3000 seconds, no more than 2700 seconds, no more than 2400 seconds, no more than 2100 seconds, no more than 1800 seconds, no more than 1500 seconds, no more than 1440 seconds, no more than 1380 seconds, no more than 1320 seconds, no more than 1260 seconds, or even no more than 1200 seconds. When tested in accordance with a variant of AOAC Official Method 966.04, Method II (substituting C. diff spores for B. subtilis, using stainless steel cylinders rather than porcelain, performing all incubations under anaerobic conditions, and using Brain-Heart infusion agar), certain embodiments can achieve a passing score after contact times of no more than 900, 600 or even 300 seconds.

(56) A composition intended to be applied to hard surfaces, particularly surfaces in a healthcare facility, is expected to be able to achieve at least a 3.0, 3.2, 3.4, 3.6, 3.8, 4.0, 4.2, 4.4, 4.6, 4.8 or 5.0 log reduction after a contact time of more than 1200 seconds, no more than 1050 seconds, no more than 900 seconds, no more than 840 seconds, no more than 780 seconds, no more than 720 seconds, no more than 660 seconds, or even no more than 600 seconds. When tested in accordance with ASTM E2197-11, embodiments of the composition are expected to achieve at least a 3 log reduction after a contact time of 600 seconds.

(57) After the composition has been allowed to contact a given object or surface for an appropriate time (in view of factors such as expected bacterial load, type of bacteria potentially present, importance of the object/surface, any pre-cleaning that might have been undertaken, the presence and amount of soil load, and the like), it can be left to evaporate or, preferably, rinsed away with water or a dilute saline solution.

(58) The following non-limiting, illustrative examples provide detailed conditions and materials that can be useful in the practice of the present invention. Throughout those examples, any reference to room temperature refers to ˜22° C.

EXAMPLES

Examples 1-2: Control and Comparative

(59) A 0.01 M phosphate-buffered saline solution was prepared by adding one phosphate-buffered saline tablet (Sigma-Aldrich Corp.; St. Louis, Mo.) to 200 mL distilled water. This solution was covered and stored at room temperature.

(60) VIRASEPT™ disinfectant (Ecolab USA; St. Paul, Minn.) was kept at room temperature in its as-purchased form and used without modification.

Examples 3-6

(61) Four compositions were prepared by adding to 100 mL glass vessels each of the following ingredients (amounts in grams):

(62) TABLE-US-00005 buffer precursor (sodium acetate) 1.49 acid (acetic acid) 16.63 organic liquid (DGME) 30.0 anionic surfactant (SDS) 1.75 nonionic surfactant (polyoxyethylene (20) 0.2 sorbitan monooleate)
The compositions also included electrolyte oxidizing agent (KHSO.sub.5), glycosidase (lysozyme), and sodium hydroxide, with the varying amounts (in grams) tabulated below. Sodium hydroxide solution (50% w/v in water) was dropwise added to upwardly adjust the pH of the compositions to the values shown in the following table.

(63) TABLE-US-00006 TABLE 5 Ex. 3 Ex. 4 Ex. 5 Ex. 6 KHSO.sub.5 0.8 0.8 1.0 1.0 lysozyme 0.015 0.03 0.03 0.03 NaOH 3.75 3.75 3.75 8.33 pH 6 6 6 5

(64) After the aforementioned pH adjustment, sufficient distilled water was added to bring each composition to 100 mL.

(65) The comparative and inventive compositions were allowed to contact C. difficile endospores (ATCC 43598) for ˜10 minutes using the procedure of ASTM E2197-11, with their efficacy being reported in Table 6 below as log reductions in the number of viable endospores after the noted contact time.

(66) Testing also was performed on steel cylinders according to a variant of AOAC Official Method 966.04, Method II, a brief description of which follows: To a 20 mL beaker containing 10 mL of the type of C. diff suspension described in the U.S. Environmental Protection Agency's “Standard Operating Procedure for Production of Spores of Clostridium difficile for Use in the Efficacy Evaluation of Antimicrobial Agents” (SOP #MB-28-00), a sufficient number of steel cylinders were added so as to provide 10 per test to be run. Cylinders were permitted to sit in this suspension for 10-15 minutes before being removed, placed in a petri dish and dried under a vacuum for 24 hours. Each composition was provided in duplicate (i.e., two vessels of each composition), with a maximum of 5 inoculated cylinders placed in a vessel containing 10 mL of tested composition. Compositions were tested at both 30 and 60 minutes, with each time duration involving duplicate tested compositions. After being exposed to a tested composition for the predetermined time, each cylinder was transferred sequentially to a primary subculture tube containing 10 mL room temperature pre-reduced Dey/Engley neutralizing broth and, within one hour of all tested cylinders being transferred to a primary tube, a secondary subculture tube containing 10 mL reinforced clostridial medium (Becton Dickinson and Co.; Franklin Lakes, N.J.—38 g in 1 L distilled water, autoclaved at 121° C. for ˜15 minutes, then pre-reduced in an anaerobic chamber for ˜24 hours). Each type of subculture tube was incubated for 21 days at 36°±1° C.

(67) This same procedure also was performed with 2-loop coils of black, braided, polyester surgical sutures (USP size, metric size 6.0) instead of steel cylinders. A recommended method of preparing such coils is described in the aforementioned AOAC test.

(68) Results are recorded as positive or negative growth which, in the following table, is presented in the form of x/y where x is the number of cylinders with positive growth and y is the total number of cylinders tested.

(69) TABLE-US-00007 TABLE 6 Test results ASTM E2197-11 AOAC (steel) AOAC (suture) (log reduction) 30 min. 60 min. 30 min. 60 min. Ex. 1 (control) — 19/20  10/10  20/20  10/10  Ex. 2 3.87 1/20 0/10 6/20 3/10 (comparative) Ex. 3 3.75 0/20 0/10 0/20 0/10 Ex. 4 3.56 (a) (a) (a) (a) Ex. 5 3.19 9/20 5/10 0/20 1/10 Ex. 6 3.66 0/10 0/10 0/20 0/10 (a) not tested due to results of preliminary evaluation of Ex. 3

(70) Each of the exemplary compositions had at least some efficacy against C. difficile endospores, with the best results being achieved with Example 3 (pH≈6, lowest amounts of electrolyte oxidizing agent and glycosidase) and Example 6 (pH≈5, slightly higher amounts of electrolyte oxidizing agent and glycosidase). The composition of Example 4 is expected to provide results at least as good as those of Example 3.

(71) The efficacy results of these compositions compare favorably with those of the comparative composition (Example 2), a commercial disinfectant that contains H.sub.2O.sub.2, peroxyacetic acid and octanoic acid and has a [H.sup.+] two to three orders of magnitude greater, i.e., pH of 3.0±0.5 according to its material safety data sheet.

(72) Thus, despite being significantly less acidic than the comparative, the compositions of Examples 3-6 had efficacies roughly equivalent to that of a commercial disinfectant.