Patent Description:
The invention relates to a non-therapeutic method of disinfecting a surface containing or suspected to contain tuberculosis causing bacteria, wherein said method uses quaternary ammonium antimicrobial in combination with a water insoluble, di-substituted alkylamide solvent.

Quaternary ammonium compounds have been used as disinfectants for many years, and these compounds have broad spectrum antimicrobial activity. Although formulations containing higher concentrations of quaternary ammonium compounds are known to be effective against certain gram-positive and gram-negative bacteria, these formulations are typically not very effective against tuberculosis-causing bacteria.

<CIT> discloses an effective tuberculocide composition that comprises a quaternary ammonium salt and a minimum concentration of at least <NUM>% by weight of a glycol ether. In particular, the compositions have a weight ratio of glycol ether to quaternary ammonium salt of at least <NUM>:<NUM>, and preferably <NUM>:<NUM>. Although the compositions have tuberculocidal efficacy, glycol ethers are volatile organic compounds (VOCs), which are undesirable from an environmental standpoint. Moreover, stricter regulations limiting VOCs have been proposed, making it important to limit the use of glycol ethers.

<CIT> discloses an aqueous disinfectant composition effective against mycobacteria, wherein the composition comprises a germicidal cationic quaternary ammonium compound and a phenoxyalcohol or glycol ether solvent.

<CIT> discloses disinfectant cleaner compositions that are said to have tuberculocidal and mycobactericidal efficacy and/or efficacy against Norovirus, Adenovirus, and Polyomavirus. The compositions comprise a particular quaternary ammonium chloride, namely N-alkyl dimethyl benzyl ammonium chloride, in combination with bis(<NUM>-aminopropyl)alkylamine, in specific weight ratios.

<CIT> discloses a composition having tuberculocidal efficacy, wherein the composition comprises a quaternary ammonium compound, a guanidine derivative, and an alkylamine.

<CIT> discloses that a composition comprising a quaternary ammonium compound in combination with a chlorine bleach can be an effective disinfectant against mycobacteria.

<CIT> relates to aqueous hard surface cleaners, and in particular, to compositions that provide fast, effective cleaning of greasy soils even at relatively neutral (<NUM>-<NUM>) pH. <CIT> discloses hard surface aqueous cleaners useful for rapidly removing permanent ink. <CIT> describes a concentrated agricultural composition comprising an agriculturally active ingredient and a quaternary ammonium surfactant. <CIT> relates to softening detergent compositions containing a peroxyacid-bleaching compound, and a narrowly-defined amide softening agent. <CIT> discloses solvent-based coating remover compositions useful for removing paints, coatings, adhesives, sealants, and other hard-to-remove materials. <CIT> describes a disinfectant with antimicrobial activity in water against Mycobacterium tuberculosis. <CIT> relates to quaternary ammonium salt antimicrobial compositions, methods for treating bacterial infestations, and in particular mycobactericidal and tuberculocidal compositions comprising quaternary ammonium salts and glycol ethers. <CIT> discloses derivatives of aliphatic acid amides which are said to exhibit anti-microbial activity.

There is still a need for improved antimicrobial compositions that have tuberculocidal and mycobactericidal efficacy, and which have low toxicity, low VOC, and low impact on the environment.

In one aspect, this disclosure provides a non-therapeutic method of disinfecting a surface containing or suspected to contain tuberculosis causing bacteria, comprising the steps of:.

the N,N-di-substituted-alkylamide water insoluble solvent has the following chemical formula:
<CHM>
wherein:.

Some preferred embodiments of the method of disinfecting a surface containing or suspected to contain tuberculosis causing bacteria are set forth in claims <NUM> to <NUM>.

The compositions used in the method of the present technology comprise a biocidal quaternary ammonium compound and an N,N-alkyl di-substituted alkyl amide that together are an effective disinfecting agent against a variety of bacteria, including tuberculosis-causing bacteria. The compositions may also contain additional components, such as surfactants, solubilizers, pH adjusters, pH buffers, chelating agents, rheological modifiers, dyes, and fragrances. In some embodiments, the compositions are free of alcohols.

Suitable biocidal quaternary ammonium compounds for use herein have the general formula:
<CHM>.

Exemplary biocidal quaternary ammonium compounds within the general formula include alkyl trimethyl ammonium halide, dialkyl dimethyl ammonium halide, alkyl dimethyl benzyl ammonium halide, dialkyl methyl benzyl halide, alkyl dimethyl ethylbenzyl ammonium halide, and dialkyl methyl ethylbenzyl ammonium halide. Specific biocidal quaternary ammonium salts include didecyl dimethyl ammonium chloride, dioctyl dimethyl ammonium chloride, octyl decyl dimethyl ammonium chloride, (C<NUM>-C<NUM>)-alkyl dimethyl benzyl ammonium chloride, and (C<NUM>-C<NUM>)-alkyl dimethyl ethylbenzyl ammonium chloride. The biocidal quaternary ammonium compound need not be a single entity, but may be a blend of two or more biocidal quaternary ammonium compounds.

A disinfectant composition used in the method of the present technology, in the form of a concentrate, comprises from <NUM>% to <NUM>% by weight, based on the total weight of the composition, alternatively about <NUM>% to about <NUM>% by weight, alternatively about <NUM>% to about <NUM>% by weight of biocidal quaternary ammonium compound. In some embodiments, the amount of the biocidal quaternary ammonium compound is <NUM>% by weight of the total concentrate composition. A disinfectant composition used in the method of the present technology, in the form of a ready-to-use (or diluted) composition may comprise from about <NUM> ppm to about <NUM>,<NUM> ppm, alternatively about <NUM> ppm, about <NUM> ppm, about <NUM> ppm, about <NUM> ppm, about <NUM> ppm, or about <NUM> ppm to about <NUM> ppm, about <NUM> ppm, about <NUM> ppm, or about <NUM> ppm, of the biocidal quaternary ammonium compound, based on the total weight of the composition. In some embodiments, the amount of the biocidal quaternary ammonium compound is <NUM> ppm by weight of the ready-to-use disinfectant.

The water insoluble di-substituted alkylamide has the following general structure:
<CHM>
where R is a straight or branched, saturated or unsaturated, alkyl or alkene group having from <NUM> to <NUM>, preferably from <NUM> to <NUM> carbon atoms, n=<NUM> or <NUM>; and
R<NUM> and R<NUM> are independently an alkyl group having from <NUM> to <NUM> carbon atoms. In one embodiment, the water insoluble solvent is an N,N-dimethyl alkyl amide having from <NUM> to <NUM> carbon atoms in the alkyl group.

The disinfectant composition used in the method of the present technology, when in the form of a concentrate, comprises from <NUM>% to <NUM>% by weight, based on the weight of the composition, of N,N-di-substituted alkylamide, alternatively <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>%, or <NUM>% by weight to <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM> %, or <NUM>% by weight. When the disinfectant composition is a ready-to-use (or diluted) composition, the composition may comprise from <NUM> ppm to <NUM>,<NUM> ppm of N,N-di-substituted alkylamide, alternatively <NUM> ppm, <NUM> ppm, <NUM> ppm, <NUM> ppm, <NUM> ppm, or <NUM> ppm to <NUM> ppm, <NUM> ppm, <NUM> ppm or <NUM> ppm, based on the total weight of the composition.

It has been surprisingly found that the combination of one or more biocidal quaternary ammonium compounds, and one or more of the N,N-di-substituted alkylamides provides an effective disinfecting agent against a variety of microbes, including tuberculosis-causing bacteria, Pseudomonas aeruginosa (Pa), Staphylococcus aureus (Sa), and Salmonella enterica (Se). Disinfectant compositions used in the method of the present technology are also effective against other microorganisms, including viruses, mildews, and fungi. In addition, the compositions used in the method of the present technology are efficacious without the need for any additional antimicrobial active. Without being bound by theory, it is believed that the one or more biocidal quaternary ammonium compounds combined with one or more of the N,N-di-substituted alkylamides forms a synergistic mixture that provides efficacy against a wide variety of microbes, including tuberculosis-causing bacteria. The use of glycol ether or alcohol solvents, chlorine bleaches, and guanidine derivatives can therefore be avoided in the disinfectant compositions used in the method of the present technology.

The disinfectant compositions used in the method of the present technology are in liquid form and comprise a carrier in addition to the biocidal quaternary ammonium compound and the N,N-di-substituted alkylamide. Water, either de-ionized or regular tap water, is a suitable carrier, particularly for a Ready-to-Use formulation. Water can be used alone as the carrier, or in combination with other suitable carriers. In some embodiments, the disinfectant composition is a liquid concentrate formulation that contains no added water. In such concentrate formulations, glycerine can be used as an environmentally friendly filler/carrier, which surprisingly also provides phase stability for the concentrated formula. These concentrate formulations can be diluted with water at, for example, a <NUM>:<NUM> dilution ratio, and surprisingly still have efficacy against tuberculosis-causing bacteria, as well as a wide variety of other biocidal targets, such as other types of bacteria, viruses, fungi, and yeasts.

One or more optional components can be included in the disinfectant compositions depending on the end use. For example, one or more surfactants can be added to the compositions to improve cleaning, detergency, and/or microbiocidal efficacy. Surfactants are particularly useful in one-step disinfecting formulations, since no pre-cleaning step is needed to first remove dirt and filth. Surfactants also help to wet the surface and thereby enable the combination of biocidal quaternary ammonium compound and N,N-di-substituted alkylamide to kill microorganisms more effectively. In the disinfectant compositions, surfactants also help to solubilize the water insoluble N,N-di-substituted alkylamide solvent, and any water insoluble fragrances. The surfactants can be non-ionic or amphoteric/zwitterionic surfactants, or combinations thereof. Examples of useful nonionic surfactants that can be used in the disinfectant composition include fatty alcohols having from <NUM> to <NUM>, preferably <NUM> to <NUM> carbon atoms in the alkyl chain, further ethoxylated with from <NUM> to <NUM>, preferably <NUM> to <NUM> ethylene oxide units. Such non-ionic surfactants could also include some propylene oxide units, provided there are sufficient ethylene oxide units to maintain water solubility of the surfactant. Although less preferred, ethoxylated alkyl phenols could also be used as a surfactant. Particularly useful non-ionic surfactants include, for example, Bio-Soft® N1-<NUM> (ethoxylated C11 alkyl 9EO alcohol), available from Stepan Company, Northfield, Illinois. Examples of useful amphoteric/zwitterionic surfactants include alkyl amine oxides, betaines, and sarcosinates. The surfactant is included in the composition in an amount such that the weight ratio of combined biocidal quaternary ammonium compound and surfactant(s) to di-substituted alkylamide is <NUM>:<NUM> to <NUM>:<NUM>, preferably <NUM>:<NUM> to <NUM>:<NUM>.

Other components or additives can also be included in the disinfectant compositions for use in the methods of the invention. Additional components can include pH adjustment agents, hydrotropic or other solubilizing agents for obtaining and maintaining a clear single phase concentrate or ready-to-use composition, electrolytes for enhancement of surfactant detergency, chelators for improvement of surfactant detergency and of cationic surfactant efficacy, fragrances for different attractive smells, dyes for pleasing color, and other functional ingredients.

In some embodiments, the final pH of a commercial product for use in the methods of the invention is more easily controlled within specification by including one or more water soluble primary amines as organic alkaline pH buffers in the formulation. Suitable primary amine buffers include <NUM>-aminoethanol and <NUM>-amino-<NUM>-methyl-<NUM>-propanol. When a Ready-To-Use formulation is made with water, any pH buffer agent with a pKa of larger than <NUM> (preferably larger than <NUM>) can be used instead of the water soluble organic primary amines. The weight ratio of buffer to quaternary ammonium compound is in the range of <NUM>:<NUM> to <NUM>:<NUM>, preferably <NUM>:<NUM> to <NUM>:<NUM>.

Compositions used according to the present technology can be supplied in different forms depending on the desired end use. In some embodiments, the composition is in a ready-to-use (RTU) form that can be used without dilution. In accordance with other embodiments of the present technology, the composition comprising the biocidal quaternary ammonium compound and N,N-di-substituted alkylamide is a dilutable concentrate product. A dilutable concentrate product is a product that needs to be diluted with a diluent (e.g., water) in a ratio of, for example but not limited to, <NUM>:<NUM>, <NUM>:<NUM>, <NUM>:<NUM>, or <NUM>:<NUM> before it can be applied to articles or surfaces to be disinfected. Suitable dilution ratios for the present compositions in concentrate form range from <NUM>:<NUM> to <NUM>:<NUM>, alternatively, <NUM>:<NUM> to <NUM>:<NUM>, alternatively, <NUM>:<NUM> to <NUM>:<NUM>. Depending on the intended dilution ratio, the concentration of actives in the dilutable concentrate product can vary.

In some embodiments of the present invention the disinfectant composition is envisioned to be used as a spray. The disinfectant composition may be used as a spray in an RTU formulation, or a concentrate formulation can be used as a spray using, for example, a <NUM>:<NUM>, <NUM>:<NUM>, <NUM>:<NUM>, or a <NUM>:<NUM> dilution of the disinfectant composition. In some embodiments, the composition may be used in a wipe. In other embodiments, the composition may be used, for example, in a wipe used with an applicator pad. In some embodiments, the composition used in the method of the present application is envisioned to be a concentrate that can be packaged, for example, in a packet or pod that can be added to water at an appropriate dilution ratio.

Also disclosed is a non-inventive method of cleaning a hard surface by providing a disinfectant composition as specified above at its end use concentration, and contacting at least one soiled surface or substrate with the composition for a set period of time and then removing the composition or soil from the surface or substrate.

Further, disclosed is a non-inventive general method of disinfecting a hard surface by providing a disinfectant composition as specified above at its end use concentration and contacting the at least one surface to be disinfected with the composition. In some embodiments, the surface to be disinfected is contacted for a specific amount of time, for example, for about <NUM> minutes or less, alternatively for about <NUM> minutes or less, and then the composition is removed from the surface.

The methods of contacting a surface with the disinfectant composition to clean and/or disinfect a hard surface are contemplated to be used with, for example, but not limited to, a mop, a sponge, a rag, a towel, a wipe, an automatic floor cleaning device, a manual floor cleaning device, a wet pad applicator, and the like.

The presently described technology and its advantages will be better understood by reference to the following examples. These examples are provided to describe specific embodiments of the present technology. By providing these specific examples, it is not intended to limit the scope of the present technology. It will be understood by those skilled in the art that the full scope of the presently described technology encompasses the subject matter defined by the claims appended to this specification.

The bacteria used in the examples include:.

The following materials are used in the examples:.

Table <NUM> lists <NUM> Ready-To-Use formulations, and <NUM> concentrated formulation with a dilution rate of <NUM>:<NUM> by <NUM> ppm hard water. This screen test against tuberculosis-containing bacteria is conducted at test conditions of <NUM> minute contact time and <NUM>% soil load. The method, Quantitative Modification to the AOAC Germicidal Spray Test Tuberculocidal, is developed by and proprietary to MicroBac.

Table <NUM> shows that compositions that comprise the dialkylamide water insoluble solvent (Hallcomid® M-<NUM>-<NUM>) demonstrate effective killing of TB at quaternary ammonium compound amounts of <NUM>% or <NUM>%, but Formulation <NUM> with the water soluble solvent <NUM>,<NUM>-diethoxy-<NUM>-propanol, fails the efficacy test, even at <NUM>% solvent.

Table <NUM> shows the <NUM>:<NUM> dilution from the concentrated formulation of Example <NUM> passed the core reference organisms (Sa, Pa, and Se) by the current EPA UDT method at the <NUM> ppm hard water, <NUM> minute contact time and <NUM>% soil load.

Table <NUM> shows the <NUM>:<NUM> dilution of the Example <NUM> formulation, with <NUM>% quaternary ammonium compound and <NUM>% N,N-dimethylalkylamide, passed the efficacy test against <NUM> core reference organisms, Pa, Sa, and Se, at a <NUM> minute contact time.

The Example <NUM> formulation, at <NUM>:<NUM> dilution, was also tested for efficacy against several different organisms in the presence of <NUM> ppm hard water and a <NUM>% soil load. The organisms tested, the test contact time in minutes, and the efficacy results are set forth in Table <NUM>.

Fungi/Yeast: AOAC Germicidal Spray Products as Disinfectants Test (as above) modified for fungi.

The results in Table <NUM> show that the Example <NUM> formulation of the present technology has efficacy against a wide variety of organisms.

Additional example formulations according to the present technology were prepared and tested for efficacy against Pa. In Examples <NUM>, <NUM>, and <NUM>, concentrated formulations were prepared that contained the same components and amounts as in the Example <NUM> concentrate, except that Example <NUM> used a different dialkylamide, Hallcomid®-M-<NUM>, instead of the dialkylamide of Example <NUM>, and Examples <NUM> and <NUM> used different quaternary ammonium compounds, BTC®<NUM> and BTC®<NUM>, respectively, instead of the quaternary ammonium compound used in Example <NUM>. The efficacy of each of the Example <NUM>, <NUM>, and <NUM> formulations was tested at a <NUM>:<NUM> dilution using the AOAC Germicidal Spray Test (Official Method <NUM>) in the presence of <NUM> ppm hard water and a <NUM>% soil load. The results are shown in Table <NUM>.

The Table <NUM> results show that different combinations of quaternary ammonium compounds and dialkylamides, within the scope of the present technology, can be formulated into compositions having bacteriocidal efficacy.

Claim 1:
A non-therapeutic method of disinfecting a surface containing or suspected to contain tuberculosis causing bacteria, comprising the steps of:
(a) providing a disinfectant composition comprising:
(i) from <NUM>% to <NUM>% by weight of a biocidal quaternary ammonium compound;
(ii) from <NUM>% to <NUM>% by weight of an N,N-di-substituted alkylamide water insoluble solvent; and
(iii) a carrier to <NUM>% by weight of the composition;
(b) contacting the surface with an effective amount of the disinfectant composition, wherein
the N,N-di-substituted-alkylamide water insoluble solvent has the following chemical formula:
<CHM>
wherein:
R is a straight or branched, saturated or unsaturated, alkyl or alkene group having from <NUM> to <NUM> carbon atoms;
R<NUM> and R<NUM> are independently an alkyl group having from <NUM> to <NUM> carbon atoms; and
n is <NUM> or <NUM>, and
wherein the method is not a method for treatment of the human or animal body by therapy.