AU777059B2

AU777059B2 - Antibacterial compositions

Info

Publication number: AU777059B2
Application number: AU54720/00A
Authority: AU
Inventors: Priscilla S. Fox; Earl P. Seitz Jr.; Timothy J. Taylor
Original assignee: Dial Corp
Current assignee: Dial Corp
Priority date: 1999-06-23
Filing date: 2000-06-08
Publication date: 2004-09-30
Anticipated expiration: 2020-06-08
Also published as: CA2371925A1; TWI284020B; CA2371925C; MXPA01013312A; JP2003502353A; EP1191843A2; BR0011860A; WO2000078275A3; AU5472000A; WO2000078275A2

Description

WO 00/78275 PCTIUS00/15729 1 ANTIBACTERIAL COMPOSITIONS FIELD OF THE INVENTION The present invention is directed to antibacterial compositions, like personal care compositions, including hand sanitizer gels, having improved antibacterial effectiveness. More particularly, the present invention is directed to antibacterial compositions comprising an antibacterial agent and a surfactant or a relatively low amount of a disinfecting alcohol, and that provide a substantial reduction, greater than 99%, in Gram positive and Gram negative bacterial populations within one minute.

BACKGROUND OF THE INVENTION Antibacterial personal care compositions are known in the art. Especially useful are antibacterial cleansing compositions, which typically are used to cleanse the skin and to destroy bacteria and other microorganisms present on the skin, especially the hands, arms, and face of the user.

Another class of antibacterial personal care compositions is the hand sanitizer gels. This class of compositions is used primarily by medical personnel to disinfect the hands and fingers. The hand sanitizer gel is applied to, and rubbed into, the hands and fingers, and the composition is allowed to evaporate from the skin. Wiping of the composition from th- skin is not necessary L=%aute the high alcohol content of present-day hand sani- WO 00/78275 PCT/US00/15729 2 tizer gels leads to a fast and essentially complete evaporation of the composition from the skin.

Antibacterial compositions in general are used, for example, in the health care industry, food service industry, meat processing industry, and in the private sector by individual consumers. The widespread use of antibacterial compositions indicates the importance consumers place on controlling bacteria and other microorganism populations on skin. It is important, however, that antibacterial compositions provide a substantial and broad spectrum reduction in microorganism populations quickly and without problems associated with toxicity and skin irritation.

In particular, antibacterial cleansing compositions typically contain an active antibacterial agent, a surfactant, and various other ingredients, for example, dyes, fragrances, pH adjusters, thickeners, skin conditioners, and the like, in an aqueous carrier. Several different classes of antibacterial agents have been used in antibacterial cleansing compositions. Examples of antibacterial agents include a bisguanidine chlorhexidine digluconate), diphenyl compounds, benzyl alcohols, trihalocarbanilides, quaternary ammonium compounds, ethoxylated phenols, and phenolic compounds, such as halo-substituted phenolic compounds, like PCMX p-chloro-m-xylenol) and triclosan 2,4,4'-trichloro-2'hydroxy-diphenylether). Presentday antimicrobial compositions based on such antibacterial agents exhibit a wide range of antibacterial activity, ranging from low tn high, depending WO 00/78275 PCTUS00/15729 3on the microorganism to be controlled and the particular antibacterial composition.

Hand sanitizer gels contain a high percentage of an alcohol, like ethanol. At the high percent of alcohol present in the gel, the alcohol itself acts as a disinfectant. In addition, the alcohol quickly evaporates to obviate wiping or rinsing skin treated with the sanitizer gel. Hand sanitizer gels containing a high percentage of an alcohol, about 40% or greater by weight of the composition, however, have a tendency to dry and irritate the skin.

Most commercial antibacterial compositions, however, generally offer a low to moderate antibacterial activity. Antibacterial activity is assessed against a broad spectrum of microorganisms, including both Gram positive and Gram negative microorganisms. The log reduction, or alternatively the percent reduction, in bacterial populations provided by the antibacterial composition correlates to antibacterial activity. A log reduction of is most preferred, a 1-3 reduction is preferred, whereas a log reduction of less than 1 is least preferred, for a particular contact time, generally ranging from 15 seconds to 5 minutes. Thus, a highly preferred antibacterial composition exhibits a 3-5 log reduction against a broad spectrum of microorganisms in a short contact time. Prior disclosures illustrate attempts to provide such antibacterial compositions, which, to date, do not provide the rapid, broad range control of microorganisms desired by consumers.

WO 00/78275 PCT/US00/15729 4 It should be noted that high log reductions have been achieved at pH values of 4 and 9, but such log reductions are attributed at least in part to these relatively extreme pH values. Compositions having such pH values can irritate the skin and other surfaces, and, therefore, typically are avoided. This is especially the case for hand sanitizer compositions which typically are not wiped or rinsed from the skin after use. It has been difficult to impossible to achieve a high log reduction using an antibacterial composition having a neutral pH of about 5 to about 8, and especially about 6 to about 8, without simultaneously incorporating a high percentage of an alcohol.

For example, WO 98/01110 discloses compositions comprising triclosan, surfactants, solvents, chelating agents, thickeners, buffering agents, and water. WO 98/01110 is directed to reducing skin irritation by employing a reduced amount of surfactant.

Fendler et al. U.S. 5,635,462 discloses compositions comprising PCMX and selected surfactants. The compositions disclosed therein are devoid of anionic surfactants and nonionic surfactants.

WO 97/46218 and WO 96/06152 disclose compositions based on triclosan, organic acids or salts, hydrotropes, and hydric solvents.

EP 0 505 935 discloses compositions containing PCMX in combination with nonionic and anionic surfactants, particularly nonionic block copolymer surfactants.

WO 00/78275 PCT/US00/15729 WO 95/32705 discloses a mild surfactant combination that can be combined with antibacterial compounds, like triclosan.

WO 95/09605 discloses antibacterial compositions containing anionic surfactants and alkylpolyglycoside surfactants.

WO 98/55096 discloses antimicrobial wipes having a porous sheet impregnated with an antibacterial composition containing an active antimicrobial agent, an anionic surfactant, an acid, and water, wherein the composition has a pH of about 3.0 to about N.A. Allawala et al., J. Amer. Pharm.

Assoc.--Sci. Ed., Vol. XLII, no. 5, pp. 267-275, (1953) discusses the antibacterial activity of active antibacterial agents in combination with surfactants.

A.G. Mitchell, J. Pharm. Pharmacol., Vol.

16, pp. 533-537, (1964) discloses compositions containing PCMX and a nonionic surfactant that exhibit antibacterial activity. The compositions disclosed in the Mitchell publication exhibit antibacterial activity in at least 47 minutes contact time, thus the compositions are not highly effective.

With respect to hand sanitizer gels, Osborne et al. U.S. Patent No. 5,776,430 discloses a topical antimicrobial cleaner containing chlorhexidine and an alcohol. The compositions contain about to 60%, by weight, denatured alcohol and about 0.65 to 0.85%, by weight, chlorhexidine. The composition is applied to the skin, scrubbed into the skin, then rinsed frnm the skin.

WO 00/78275 PCT/US00/15729 6 European Patent Application 0 604 848 discloses a gel-type hand disinfectant containing an antimicrobial agent, 40% to 90% by weight of an alcohol, and a polymer and a thickening agent in a combined weight of not more than 3% by weight. The gel is rubbed into the hands and allowed to evaporate to provide disinfected hands. As illustrated in EP 0 604 848, the amount and identity of the antibacterial agent is not considered important because the hand sanitizer gels contain a high percentage of an alcohol to provide antibacterial activity. The disclosed compositions often do not provide immediate sanitization and do not provide residual antibacterial efficacy.

Prior disclosures have not addressed the issue of which composition ingredient in an antibacterial composition provides bacterial control.

Prior compositions also have not provided an effective, fast, and broad spectrum control of bacteria at a neutral pH of about 5 to about 8, and especially at about 6 to about 8.

An efficacious antibacterial composition has been difficult to achieve because of the properties of the antibacterial agents and the effects of a surfactant on an antibacterial agent. For example, several active antibacterial agents, like phenols, have an exceedingly low solubility in water, triclosan solubility in water is about 5 to ppm (parts per million). The solubility of the antibacterial agent is increased by adding surfactants to the composition. However, an increase in solubility of the antimicrobial acyt. in tuiii, the amount of antibacterial agent in the composi- WO 00/78275 PCT/US00/15729 7 tion, does not necessarily lead to an increased antibacterial efficacy.

Without being bound to any particular theory, it is theorized that the addition of a surfactant increases antimicrobial agent solubility, but also typically reduces the availability of the antibacterial agent because a surfactant in water forms micelles above the critical micelle concentration of the surfactant. The critical micelle concentration varies from surfactant to surfactant.

The formation of micelles is important because micelles have a lipophilic region that attracts and solubilizes the antibacterial agent, and thereby renders the antibacterial agent unavailable to immediately contact bacteria, and thereby control bacteria in short time period one minute or less).

The antibacterial agent solubilized in the surfactant micelles will control bacteria, but in relatively long time frames. The antibacterial agent, if free in the aqueous solution and not tied up in the surfactant micelle is activated), is attracted to the lipophilic membrane of the bacteria and performs its function quickly. If the antibacterial agent is tied up in the surfactant micelle is not activated), the antibacterial agent is only slowly available and cannot perform its function in a time frame that is practical for cleaning the skin.

In addition, antibacterial agent that is solubilized in the micelle is readily washed from the skin during the rinsing process, and is not available to deposit on the skin tr pr.vide a resid- WO 00/78275 PCT/US00/15729 8 ual antibacterial benefit. Rather, the antibacterial agent is washed away and wasted.

With respect to sanitizers, hand sanitizer gels typically contain: at least 60% by weight ethanol or a combination of lower alcohols, such as ethanol and isopropanol, water, a gelling polymer, such as a crosslinked polyacrylate material, and other ingredients, such as skin conditioners, fragrances, and the like. Hand sanitizer gels are used by consumers to effectively sanitize the hands, without, or after, washing with soap and water, by rubbing the hand sanitizer gel on the surface of the hands. Current commercial hand sanitizer gels rely on high levels of alcohol for disinfection and evaporation, and thus suffer from disadvantages. Specifically, current hand sanitizer gels have a tendency to dry and irritate the skin because of the high levels of alcohol employed in the compositions. Also, because of the volatility of ethyl alcohol, the primary active disinfectant does not remain on the skin after use, thus failing to provide a persistent, or residual, antibacterial effect.

At alcohol concentrations below 60%, ethyl alcohol is not recognized as an antiseptic. Thus, in compositions containing less than 60% alcohol, an additional antibacterial compound must be present to provide antibacterial activity. Prior disclosures, however, have not addressed the issue of which composition ingredient in such an antibacterial composition provides bacterial control. Therefore, for formulations containing a reduced alcnhnl concentra tion, the selection of an antibacterial agent that provides both a rapid antibacterial effect and a persistent antibacterial benefit is difficult.

Accordingly, a need exists for an antibacterial composition that is highly efficacious against a broad spectrum of Gram positive and Gram negative bacteria in a short time period, and wherein the antibacterial activity is attributed primarily, or solely, to the presence of the active antibacterial agent in the composition. The present invention is directed to such antibacterial compositions.

Summary of the Invention The present invention relates to antibacterial compositions that provide a substantial reduction in Gram positive and Gram negative bacteria in less than about one minute.

More particularly, the present invention relates to antimicrobial compositions containing an active antibacterial agent, a surfactant, and water, wherein the antibacterial agent is present in the continuous aqueous phase (in contrast to being present in micelles), in an amount of at least 50% of saturation, when measured at room temperature. The present invention also relates to antimicrobial compositions containing an active antibacterial agent, a surfactant, water, and a hydric solvent and/or a hydrotrope, wherein the antibacterial agent is present in an amount of at least 25% of saturation, when measured at room temperature.

o o 20 According to a first aspect of the invention there is provided an antibacterial composition comprising: about 0.001% to about by weight, of a phenolic antimicrobial agent; about 0.1% to about 15%, by weight, of an anionic surfactant and optionally a further surfactant selected from the group consisting of a cationic surfactant, a nonionic 25 surfactant, an ampholytic surfactant, and mixtures thereof; 2% to about 30%, by weight, of a hydrotrope; 2% to about 25%, by weight, of a water-soluble hydric solvent; and water, wherein the antimicrnhil noynt ic nrpcpnt n -m t of.. t ast 4C^ An X ot L Ca V /0 0l sa i ai lu ll 30 concentration, when measured at room temperature, and wherein the pH of the composition is about 6 to about 8.

According to a second aspect of the invention there is provided an antibacterial composition comprising: about 0-0.001% to about by weight, of a phenolic antimicrobial agent; [R:\LIBH]581037.doc:aak about 0.1% to about 15%, by weight, of an anionic surfactant and optionally a further surfactant selected from the group consisting of a cationic surfactant, a nonionic surfactant, an ampholytic surfactant, and mixtures thereof; about 2% to about 30%, by weight, ofa hydrotrope; s about 2% to about 25%, by weight, of a water-soluble hydric solvent; and water, wherein the composition has a log reduction against Gram positive bacteria of at least 2 after 30 seconds of contact, as measured against S. aureus, and has a log reduction against Gram negative bacteria of at least 2.5 after 30 seconds of contact, as measured o0 against E. coli, and wherein the composition has a pH of about 6 to about 8.

According to a third aspect of the invention there is provided a method of reducing a bacteria population on a surface comprising contacting the surface with a composition of the first aspect of the invention for 30 seconds to achieve a log reduction of at least 2 against S. aureus and a log reduction of at least 2.5 against E. coli, then rinsing the composition from the surface.

According to a fourth aspect of the invention there is provided a method of reducing a bacteria population on a surface comprising contacting the surface with a composition of the second aspect of the invention for 30 seconds to achieve a log reduction of at least S 20 2 against S. aureus and a log reduction of at least 2.5 against E. coli, then rinsing the composition from the surface.

According to a fifth aspect of the invention there is provided an antibacterial composition comprising: about 0.001% to about by weight, of a phenolic antimicrobial agent; 25 about 0.1% to about 15%, by weight, of an anionic surfactant and optionally a further surfactant selected from the group consisting of a cationic surfactant, a nonionic surfactant, and mixtures thereof; about 2% to about 30%. hy weight, of P hydrotrope seleQted from the group consisting of sodium cumene sulfonate, ammonium cumene sulfonate, ammonium xylene sulfonate, potassium toluene sulfonate, sodium toluene sulfonate, sodium xylene sulfonate, toluene sulfonic acid, xylene sulfonic acid, sodium polynaphthalene sulfonate, sodium polystyrene sulfonate, sodium methyl naphthalene sulfonate, disodium succinate, and mixtures thereof; 0% to about 25%, by weight, of a water-soluble hydric solvent; and water, fR:\LIBH]581037.doc:aak 11 wherein the composition has a pH of about 6 to about 8, and wherein the antimicrobial agent is present in an amount of at least 25% of saturation concentration, when measured at room temperature.

According to a sixth aspect of the invention there is provided an antibacterial composition comprising: about 0.001% to about by weight, of a phenolic antimicrobial agent; about 0.1% to about 15%, by weight, of an anionic surfactant and optionally a further surfactant selected from the group consisting of a cationic surfactant, a nonionic surfactant, and mixtures thereof; about 2% to about 30%, by weight, of a hydrotrope selected from the group consisting of sodium cumene sulfonate, ammonium cumene sulfonate, ammonium xylene sulfonate, potassium toluene sulfonate, sodium toluene sulfonate, sodium xylene sulfonate, toluene sulfonic acid, xylene sulfonic acid, sodium polynaphthalene sulfonate, sodium polystyrene sulfonate, sodium methyl naphthalene sulfonate, disodium succinate, and mixtures thereof; about 0% to about 25%, by weight, of a water-soluble hydric solvent; and water, wherein the composition has a pH of about 6 to about 8, and wherein the :composition has a log reduction against Gram positive bacteria of at least 2 after 20 seconds of contact, as measured against S. aureus, and has a log reduction against Gram negative bacteria of at least 2.5 after 30 seconds of contact, as measured against E. coli.

According to a seventh aspect of the invention there is provided a method of reducing a bacterial population on a surface comprising contacting the surface with a composition of the fifth or sixth aspect of the invention for 30 seconds to achieve a log 25 reduction of at least 2 against S. aureus and a log reduction of at least 2.5 against E. coli, then rinsing the composition from the surface.

•Also disclosed herein are antimicrobial compositions containing an active antibacterial agent, a disinfecting alcohol, a gelling agent and water, wherein the antibacterial agent is present in an amount of at least 50% of saturation, when measured at room temperature. Further disclosed herein are antimicrobial compositions containing an active antibacterial agent, a disinfecting alcohol, a gelling agent, a hydrotrope, and water, wherein the antibacterial agent is present in an amount of at least 25% of saturation, when measured at room temperature.

There is also disclosed herein a liquid, antibacterial composition comprising: (a) about 0.001% to about 10%, by weight, of an antibacterial agent; about 0.1% to about [R:\LIBI]581037.doc:aak Ila by weight, of a surfactant selected from the group consisting of a C 8 -C 18 alkyl sulfate, a C 8

-C

18 fatty acid salt, a C8-C 18 alkyl ether sulfate having one or two moles of ethoxylation, a'C 8

-C]

8 alkamine oxide, a C 8

-C

18 alkyl sarcosinate, a C 8

-C

18 sulfoacetate, a

C

8

-C

18 sulfosuccinate, a C 8

-C

18 alkyl diphenyl oxide disulfonate, a C8-C 1 8 alkyl carbonate, a C 8

-C

18 aipha-olefin sulfonate, a methyl ester sulfonate, and mixtures thereof; and water, wherein the antibacterial agent is present in the composition in an amount of at least 50% of saturation concentration, when measured at room temperature.

goo* oooe [RA\LIBH]581037.doc:aak 12 Also disclosed herein is an antibacterial composition, wherein the composition comprising: about 0.001% to about 10%, by weight, of an antimicrobial agent; about 0.1% to about 40%, by weight, of a surfactant selected from the group consisting of an anionic surfactant, a cationic surfactant, a nonionic surfactant, an ampholytic surfactant, and mixtures thereof; about 0% to about 30%, by weight, of a hydrotrope; about 0% to about 25%, by weight, of a water-soluble hydric solvent; and water, wherein the composition contains at least one of the hydrotrope and hydric solvent, and wherein the antimicrobial agent is present in the composition in an amount of at least of saturation concentration, when measured at room temperature.

There is further disclosed herein an antibacterial composition, wherein the composition comprises: 0.001% to about 10%, by weight, of an antimicrobial agent; 0 to about 10%, by weight, of a surfactant selected from the group consisting of an anionic surfactant, a cationic surfactant, a nonionic surfactant, an ampholytic surfactant, and mixtures thereof; 0% to about 40%, by weight, of a hydrotrope; 0% to about 60%, by weight, of a water-soluble hydric solvent; and water, wherein the composition contains at least one of the hydrotrope and hydric solvent in an amount sufficient to solubilize the antimicrobial agent, and wherein the antimicrobial agent is present in the composition in an amount of at least 25% of the saturation concentration, when measured at room temperature.

Also disclosed herein is a liquid, antibacterial composition comprising: about 0.05% to about by weight, of an antibacterial agent; 9b) about 1% to about 40%, by weight, of a disinfecting alcohol, like a CI. alcohol: about 0 01% to about 5%0 by weight of a gelling agent, like a colloidal or polymeric gelling agent; and water, 30 wherein the antibacterial agent is present in the composition in an amount of at least of saturation concentration, when measured at room temperature.

[R:\bH]58 1037speci.doc:aak 13 There is also disclosed herein an antibacterial composition, wherein the composition comprises: about 0.05% to about by weight, of an antimicrobial agent; about 1% to about 40%, by weight, of a disinfecting alcohol; about 0.01% to about by weight, of a gelling agent; 0.1% to about 30%, by weight, of a hydrotrope; and water, wherein the antimicrobial agent is present in the composition in an amount of at least 25% of saturating concentration, when measured at room temperature.

Also disclosed herein is an antibacterial composition, wherein the composition comprises: about 0.05% to about by weight, of an antimicrobial agent; about 1% to about 40%, by weight, of a disinfecting alcohol; and water, is wherein the composition contains the disinfecting alcohol and an optional polyhydric solvent in an amount sufficient to solubilize the antimicrobial agent, and wherein the antimicrobial agent is present in the composition in an amount of at least of saturating concentration, when measured at room temperature.

Further disclosed herein is an antibacterial composition that exhibits a log reduction 20 against Gram positive bacteria S. aureus) of at least 2 after 30 seconds of contact.

There is also disclosed herein an antibacterial composition that exhibits a log reduction against Gram negative bacteria E. coli) of at least 2.5 after 30 seconds of S* contact.

Also disclosed herein is an antibacterial composition that exhibits a substantial log 25 reduction against Gram positive and Gram negative bacteria, and has a pH of about 5 to S. about 8.

Also disclosed herein are consumer products based on an antibacterial composition of the present invention, for example, a skin cleanser, a body plach, a surgical scrub, a wound care agent, a hand sanitizer gel, a disinfectant, a mouth wash, a pet shampoo, a 30 hard surface sanitizer, and the like.

[R:\UbHj581 I37speci.doc:aak 14 There is further disclosed herein a method of reducing the Gram positive and/or Gram negative bacteria populations on animal tissue, including human tissue, by contacting the tissue, like the dermis, with a composition of the present invention for a sufficient time, such as about 15 seconds to 5 minutes, to reduce the bacteria level to a s desired level, and to provide a residual control of bacterial levels. The composition can be wiped or rinsed from the skin. In some embodiments disclosed herein, the composition is allowed to remain on the skin until the volatile components of the composition evaporate.

The above and other novel aspects and advantages of the present invention are illustrated in the following, non-limiting detailed description of the preferred embodiments.

io oooo o•i o• 4o:I [R:\LibH]581037speci.doc:aak WO 00/78275 PCT/US00/15729 15 DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Personal care products incorporating an active antibacterial agent have been known for many years. Since the introduction of antibacterial personal care products, many claims have been made that such products provide antibacterial properties.

However, to be most effective, an antibacterial composition should provide a high log reduction against a broad spectrum of organisms in as short a contact time as possible. It also would be beneficial if the antibacterial compositions provided a residual bacterial control.

As presently formulated, commercial liquid antibacterial soap compositions provide a poor to marginal time kill efficacy, rate of killing bacteria. Table 1 summarizes the kill efficacy of commercial products, each of which contains about 0.2% to by weight, triclosan (an antibacterial agent), and a surfactant.

Table 1 Time Kill Efficacy of Commercial Liquid Hand Soaps Organism (Log Reductions after Product 1 Minute Contact Time) Gram Positive Gram negative Gram negative S. aureus B. coli K. pneum.

Commercial 1.39 0.00 0.04 Product A Commercial 2.20 0.00 0.01 Product B Commercial 1.85 0.00 0.00 Product C WO 00/78275 PCTIUS00/15729 16 Antibacterial hand sanitizer compositions typically do not contain a surfactant and rely upon a high concentration of an alcohol to control bacteria. The alcohols evaporate and, therefore, cannot provide residual bacterial control. The alcohols also can dry and irritate the skin.

Present-day products especially lack efficacy against Gram negative bacteria, such as E.

coli, which are of particular concern to human health. The present invention, therefore, is directed to antibacterial compositions having an exceptionally high broad spectrum antibacterial efficacy, as measured by a rapid kill of bacteria time kill), which is to be distinguished from persistent kill.

The present antibacterial compositions provide significantly improved time kill efficacy compared to prior compositions, for example, prior sanitizer compositions that incorporate a high percentage of an alcohol, 40% or greater, by weight. The basis of this improved time kill is the discovery that the antimicrobial efficacy of an active agent can be correlated to the rate at which the agent has access to an active site on the microbe. The driving force that determines the rate of agent transport to the site of action is the difference in chemical potential between the site at which the agent acts and the external aqueous phase.

Alternatively stated, the microbicidal activity of an active agent is proportional to its thermodynamic activity in the external phase. Accordingly, thermodynamic activity, as opposPed tn crnentratin, iz the more important variable with respect to WO 00/78275 PCT/US00/15729 17 antimicrobial efficacy. As discussed more fully hereafter, thermodynamic activity is conveniently correlated to the percent saturation of the active antibacterial agent in the continuous aqueous phase of the composition.

Many compounds have a solubility limit in aqueous solutions termed the "saturation concentration," which varies with temperature. Above the saturation concentration, the compound precipitates from solution. Percent saturation is the measured concentration in solution divided by the saturation concentration. The concentration of a compound in aqueous solution can be increased over the saturation concentration in water by the addition of compounds like surfactants, solvents, and hydrotropes.

Surfactants not only increase the solubility of compounds in the continuous aqueous phase of the composition, but also form micelles, and can solubilize compounds in the micelles.

The saturation of an active antibacterial agent in any composition, including a surfactant-containing composition, ideally can be expressed as: saturation [C/C,]x00% wherein C is the concentration of antibacterial agent in the composition and C. is the saturation concentration of the antibacterial agent in the composition at room temperature. While not wishing to be bound by any theory, applicants believe that the continuous aqueous phase of a surfactant-containing composition is in equilibrium with the micellar pseudophase of said composition, and further that any dissolved species, such as an antibac- WO 00/78275 PCT/USOO/15729 18 terial active agent, is distributed between the aqueous continuous phase and the micellar pseudophase according to a partition law. Accordingly, the percent saturation, or alternatively the relative thermodynamic activity or relative chemical potential, of an antibacterial active agent dissolved in a composition is the same everywhere within the composition. Thus, the terms percent saturation of the antibacterial agent "in a composition," "in the aqueous continuous phase of a composition," and "in the micellar pseudophase of a composition" are interchangeable, and are used as such throughout this disclosure.

Maximum antibacterial efficacy is achieved when the difference in thermodynamic activities of the active antibacterial agent between the composition and the target organism is maximized when the composition is more "saturated" with the active ingredient). A second factor affecting antibacterial activity is the total amount of available antibacterial agent present in the composition, which can be thought of as the "critical dose." It has been found that the total amount of active agent in the continuous aqueous phase of a composition greatly influences the time in which a desired level of antibacterial efficacy is achieved, given equal thermodynamic activities. Thus, the two key factors affecting the antibacterial efficacy of an active agent in a composition are: its availability, as dictated by its thermodynamic activity, i.e., percent saturation in the continuous aqueous phase of a composition, and the total amoin- nf ;riIable active agent in the solution.

WO 00/78275 PCT/US00/15729 19 An important ingredient in antibacterial cleansing compositions is a surfactant, which acts as a solubilizer, cleanser, and foaming agent.

Surfactants affect the percent saturation of an antibacterial agent in solution, or more importantly, affect the percent saturation of the active agent in the continuous aqueous phase of the composition. This effect can be explained in the case of a sparingly water-soluble antibacterial agent in an aqueous surfactant solution, where the active agent is distributed between the aqueous continuous) phase and the micellar pseudophase. For antibacterial agents of exceedingly low solubility in water, such as triclosan, the distribution is shifted strongly toward the micelles a vast majority of the triclosan molecules are present in surfactant micelles, as opposed to the aqueous phase).

The ratio of surfactant to antibacterial agent directly determines the amount of active agent present in the surfactant micelles, which in turn affects the percent saturation of the active agent in the continuous aqueous phase. It has been found that as the surfactant:active agent ratio increases, the number of micelles relative to active molecules also increases, with the micelles being proportionately less saturated with active agent as the ratio increases. Since the active agent in the continuous phase is in equilibrium with active agent in the micellar pseudophase, as the saturation of antibacterial agent in the micellar phase decreases, so does the saturation of the antibacterial acent in the continuous phase. The converse is also true.

WO 00/78275 PCT/IUS00/15729 20 Active agent solubilized in the micellar pseudophase is not immediately available to contact the microoganisms, and it is the percent saturation of active agent in the continuous aqueous phase that determines the antibacterial activity of the composition. The active agent present in the surfactant micelles, however, can serve as a reservoir of active agent to replenish the continuous aqueous phase as the active agent is depleted.

To summarize, the thermodynamic activity, or percent saturation, of an antibacterial agent in the continuous aqueous phase of a composition drives antibacterial activity. Further, the total amount of available active agent determines the ultimate extent of efficacy. In compositions wherein the active agent is solubilized by a surfactant, the active agent present in surfactant micelles is not directly available for antibacterial activity. For such compositions, the percent saturation of the active agent in the composition, or alternatively the percent saturation of the active agent in the continuous aqueous phase of the composition, determines antibacterial efficacy.

The present compositions are. antibacterial compositions having an improved effectiveness against both Gram negative and Gram positive bacteria, and that exhibit a rapid bacteria kill. In one embodiment, as illustrated below, an antibacterial composition of the present invention comprises: (a) about 0.001% to about 10%, by weight, of an antibacterial agent; about 0.1% to about 40%, by weight, of a surfactant; an optional hvdrio solvent; an optional hydrotrope; and water.

WO 00/78275 PCT/IS00/15729 21 In another embodiment, an antibacterial composition of the present invention comprises: (a) about 0.05% to about by weight, of an antibacterial agent; about 1% to about 40%, by weight, of a disinfecting alcohol; about 0.01% to about by weight, of a gelling agent; an optional hydrotrope; and water. The present compositions also can contain an optional polyhydric solvent.

The compositions can further include a hydrotrope and additional optional ingredients disclosed hereafter, like polyhydric solvents, pH adjusters, dyes, skin conditioners, vitamins, and perfumes. The present compositions are free of surfactants, i.e., contain 0% to about by weight, of compounds that exhibit surface activity. The compositions also are mild, and provide a persistent kill because it is not necessary to rinse or wipe the compositions from the skin.

The compositions of these embodiments, and all other embodiments, have a percent saturation of antibacterial agent in the continuous aqueous phase of at least about 25%, when measured at room temperature. The compositions exhibit a log reduction against Gram positive bacteria of about 2 after seconds contact. The compositions exhibit a log reduction against Gram negative bacteria of about after 30 seconds contact.

The following illustrates important, nonlimiting embodiments of the present invention.

WO 00/78275 PCT/US00/15729 22 A. Antibacterial Compositions Containing an Antibacterial Agent and a Surfactant In one embodiment of the present invention, the antibacterial compositions comprise an active antibacterial agent, a surfactant, and water.

The compositions of embodiment A exhibit a rapid bacteria kill even in the absence of a hydric solvent and a hydrotrope. The presence of a hydric solvent and/or a hydrotrope does not adversely affect the antimicrobial properties of the composition, but such optional ingredients are not necessary ingredients. The compositions can further include additional optional ingredients disclosed hereafter, like pH adjusters, dyes, and perfumes.

1. Antibacterial Agent An antibacterial agent is present in a composition of the present invention in an amount of about 0.001% to about 10%, and preferably about 0.01% to about by weight of the composition. To achieve the full advantage of the present invention, the antibacterial agent is present in an amount of about 0.05% to about by weight, of the composition.

The antibacterial compositions can be ready to use compositions, which typically contain 0.001% to about preferably 0.01% to about and most preferably about 0.05% to about of an antibacterial agent, by weight of the composition.

The antibacterial compositions also can be formulated as coeiiuiLraces that are diluted before use WO 00/78275 PCT/US00/15729 23 with one to about 100 parts water to provide an end use composition. The concentrated compositions typically contain greater than about 0.1% and up to about 10%, by weight, of the antibacterial agent.

S Applications also are envisioned wherein the end use composition contains greater than by weight, of the antibacterial agent.

As discussed above, the absolute amount of antibacterial agent present in the composition is not as important as the amount of available antibacterial agent in the composition. The amount of available antibacterial agent in the composition is related to the identity of the surfactant in the composition, the amount of surfactant in the composition, and the presence of optional ingredients in the composition.

To achieve the desired bacteria kill in a short contact time, like 15 to 60 seconds, the continuous aqueous phase of the composition contains an amount of antibacterial agent that is at least about and preferably at least about 75%, of the saturation concentration of the antibacterial agent in water, when measured at room temperature. To achieve the full advantage of the present invention, the continuous aqueous phase is about 95% to 100% saturated with the antibacterial agent. The amount of antibacterial agent present in the continuous aqueous phase can be defined as the total amount of antibacterial agent in the composition, less any antibacterial agent present in surfactant micelles.

The method of determining percent saturation of antibacterial agent in the composition is disclosed hereafter.

WO 00/78275 PCT/US00/15729 24 The antimicrobial agents useful in the present invention are phenolic compounds exemplified by the following classes of compounds: (a) 2-Hydroxydiphenyl compounds (OH) m wherein Y is chlorine or bromine, Z is SO 2 H, NO 2 or alkyl, r is 0 to 3, o is 0 to 3, p is 0 or 1, m is 0 or 1, and n is 0 or 1.

In preferred embodiments, Y is chlorine or bromine, m is 0, n is 0 or 1, o is 1 or 2, r is 1 or 2, and p is 0.

In especially preferred embodiments, Y is chlorine, m is 0, n is 0, o is 1, r is 2, and p is 0.

A particularly useful 2-hydroxydiphenyl compound has the structure: Cl -Cl OH C1 having the adopted name, triclosan. and avai lhe commercially under the tradename IRGASAN DP300, from WO 00/78275 WO 0078275PCTIUSOO/15729 25 Ciba Specialty Chemicals Corp., Greensboro, NC.

Another useful 2-hydroxydiphenyl compound is 2,2'- 5'-dibromo-diphenyl ether.

Phenol derivatives

OH

04R

R

3 wherein R, is hydro, hydroxy, alkyl, chioro, nitro, phenyl, or benzyl; R, is hydro, hydroxy, C 1

-C

6 alkyl, or halo; R 3 is hydro, alkyl, hydroxy, chloro, nitro, or a sulfur in the form of an alkali metal salt or ammonium salt; R, is hydro or methyl, and R, is hydro or nitro. Halo is bromo or, preferably, chloro.

Specific examples of phenol derivatives include, but are not limited to, chlorophenols in-, 2, 4-dichlorophenol, p-nitrophenol, picric acid, xylenol, p-chloro-m-xylenol, cresols in-, p-chloro-m-cresol, pyrocatechol, resorcinol, 4n-hexylresorcinol, pyrogallol, phloroglucin, carvacrol, thyinol, p-chlorothymol, o-phenylphenol, o-benzylphenol, p-chloro-o-benzylphenol, phnl,4 ethylphenol, and 4-phenolsulfonic acid. other phenol derivatives are listed in WO 98/55096, incorporated herein by reference.

WO 00/78275 PCT/US00/15729 26 Diphenyl Compounds R'2 R'i RI R2

R'

3 X R 3 R'4 R' 5

R

5 R4 wherein X is sulfur or a methylene group, R, and R', are hydroxy, and R 3

R'

3 R4, R' 4 Rs, and R's, independent of one another, are hydro or halo.

Specific, nonlimiting examples of diphenyl compounds are hexachlorophene, tetrachlorophene, dichlorophene, 2,3-dihydroxy-5,5'-dichlorodiphenyl sulfide, 2,2'-dihydroxy-3,3',5,5'-tetrachlorodiphenyl sulfide, 2,2'-dihydroxy-3,5',5,5',6,6'-hexachlorodiphenyl sulfide, and 3,3'-dibromo-5,5'-dichloro-2,2'dihydroxydiphenylamine. Other diphenyl compounds are listed in WO 98/55096, incorporated herein by reference.

2. Surfactant In addition to the antibacterial agent, a present antimicrobial composition also contains a surfactant. The surfactant is present in an amount of about 0.1% to about 40%, and preferably about 0.3% to about 20%, by weight, of the composition.

To achieve the full advantage of the present invention, the antibacterial composition contains about to about 15%, by weiaht. nf the surfct nt.

WO 00/78275 PCT/US00/15729 27 Ready-to-use compositions typically contain about 0.1% to about 10%, preferably about 0.3% to about and most preferably, 0.5% to about 3%, by weight, of the composition. Concentrated compositions suitable for dilution typically contain greater than about by weight, of a surfactant.

The amount of surfactant present in the composition is related to the amount and identity of the antibacterial agent in the composition and to the identity of the surfactant. The amount of surfactant is determined such that the percent saturation of the antibacterial agent in the continuous aqueous phase of the composition is at least about preferably at least about 75%, and most preferably at least about In this embodiment, wherein the presence of a hydric solvent and a hydrotrope is optional, the identity of the surfactant is important with respect to providing a composition having a percent saturation of antibacterial agent in the continuous aqueous phase of at least about 50%. As illustrated hereafter, surfactants useful in this embodiment of the invention include anionic surfactants and selected cationic surfactants. Nonionic surfactants and anionic surfactants containing a relatively high amount of ethoxylation are not useful in this embodiment. Ethoxylated surfactants containing more than two moles of ethylene oxide have a strong affinity for the antibacterial agent, and in this embodiment substantially reduce the efficacy of the antibacterial agent.

Accordingly, in this embodiment the surfactant is selected from the following classes of WO 00/78275 PCT/US00/15729 28 surfactants: a C,-C, 1 alkyl sulfate, a C 8

-C,

8 fatty acid salt, a alkyl ether sulfate having one or two moles of ethoxylation, a alkamine oxide, a

C

8 alkoyl sarcosinate, a Cg-C, 1 sulfoacetate, a C 8

C,

1 sulfosuccinate, a alkyl diphenyl oxide disulfonate, a alkyl carbonate, a C-C, 8 alphaolefin sulfonate, a methyl ester sulfonate, and mixtures thereof. The C 8

-C,

1 alkyl group contains eight to sixteen carbon atoms, and can be straight chain lauryl) or branched 2-ethylhexyl). The cation of the anionic surfactant can be an alkali metal (preferably sodium or potassium), ammonium, alkylammonium (mono-, di-, tri), or C,-C alkanolammonium (mono-, di-, tri-). Lithium and alkaline earth cations magnesium) can be used, but antibacterial efficacy is reduced.

Specific surfactants that can be used in this embodiment include, but are not limited to, lauryl sulfates, octyl sulfates, 2-ethy.hexyl sulfates, lauramine oxide, decyl sulfates, tridecyl sulfates, cocoates, lauroyl sarcosinates, lauryl sulfosuccinates, linear diphenyl oxide disulfonates, lauryl sulfosuccinates, lauryl ether sulfates (1 and 2 moles ethylene oxide), myristyl sulfates, oleates, stearates, tallates, cocamine oxide, decylamine oxide, myristamine oxide, ricinoleates, cetyl sulfates, and similar surfactants. Additional examples of surfactants can be found in "CTFA Cosmetic Ingredient Handbook," J.M. Nikitakis, ed., The Cosmetic, Toiletry and Fragrance Association, Inc., Washington, D.C. (1988) (hereafter CTFA Handbook), paqes 10-13. 42-46. and R7- 94, inrprtd herrin by reference.

WO 00/78275 PCT/US00/15729 29 3. Carrier The carrier in this embodiment comprises water.

4. Optional InQredients An antibacterial composition of the present invention also can contain optional ingredients well known to persons skilled in the art. For example, the composition can contain a hydric solvent and/or a hydrotrope. These particular optional ingredients and the amount that can be present in the composition are discussed hereafter.

The compositions also can contain other optional ingredients, such as dyes and fragrances, that are present in a sufficient amount to perform their intended function and do not adversely affect the antibacterial efficacy of the composition. Such optional ingredients typically are present, individually, from 0% to about by weight, of the composition, and, collectively, from 0% to about 20%, by weight, of the composition.

Classes of optional ingredients include, but are not limited to, dyes, fragrances, pH adjusters, thickeners, viscosity modifiers, buffering agents, foam stabilizers, antioxidants, foam enhancers, chelating agents, opacifiers, and similar classes of optional ingredients known to persons skilled in the art.

Specific classes of optional ingredients include alkanolamidri fo'am bccctZcr and stab-iiizers; gums and polymers as thickening agents; inor- WO 00/78275 PCT/US00/15729 30 ganic phosphates, sulfates, and carbonates as buffering agents; EDTA and phosphates as chelating agents; and acids and bases as pH adjusters.

Examples of preferred classes of basic pH adjusters are ammonia; mono-, di-, and tri-alkyl amines; mono-, di-, and tri-alkanolamines; alkali metal and alkaline earth metal hydroxides; and mixtures thereof. However, the identity of the basic pH adjuster is not limited, and any basic pH adjuster known in the art can be used. Specific, nonlimiting examples of basic pH adjusters are ammonia; sodium, potassium, and lithium hydroxide; monoethanolamine; triethylamine; isopropanolamine; diethanolamine; and triethanolamine.

Examples of preferred classes of acidic pH adjusters are the mineral acids and polycarboxylic acids. Nonlimiting examples of mineral acids are hydrochloric acid, nitric acid, phosphoric acid, and sulfuric acid. Nonlimiting examples of polycarboxylic acids are citric acid, glycolic acid, and lactic acid. The identity of the acidic pH adjuster is not limited and any acidic pH adjuster known in the art, alone or in combination, can be used.

An alkanolamide to provide composition thickening, foam enhancement, and foam stability can be, but are not limited to, cocamide MEA, cocamide DEA, soyamide DEA, lauramide DEA, oleamide MIPA, stearamide MEA, myristamide MEA, lauramide MEA, capramide DEA, ricinoleamide DEA, myristamide DEA, stearamide DEA, oleylamide DEA, tallowamide DEA, lauramide MIPA, tallowamide MEA, isostearamide DEA, isostearamide MEA, and mixtiurp thereof.

WO 00/78275 PCT/US00/15729 31 B. Antibacterial Compositions Containing an Antibacterial Agent, a Surfactant, and a Hydric Solvent and/or a Hydrotrope In another embodiment, the antibacterial compositions comprise an active antibacterial agent, a surfactant, and a hydric solvent and/or a hydrotrope. The compositions of embodiment B exhibit a rapid bacteria kill, and are essentially unlimited in the identity of the surfactant in the composition. The solvent and/or hydrotrope assists in solubilizing the antibacterial agent, and reduces the affinity of the antibacterial agent to enter surfactant micelles. Accordingly, at least saturation of the antibacterial agent in the continuous aqueous phase can be achieved regardless of the identity of the surfactant.

1. Antibacterial Acent The amount and identity of the antibacterial agent present in this embodiment of the invention is discussed above in A.1.

In addition, to achieve the desired bacteria kill in a short contact time, like 15 to seconds, the continuous aqueous phase of the composition contains an amount of antibacterial agent that is at least about 25%, and preferably at least about 50, and more preferably at least about 75%, of the saturation concentration of the antibacterial agent in water, when measured at room temperature.

To achieve the full advantage of the present inven- WO 00/78275 PCT/US00/15729 32 tion, the continuous aqueous phase is about 95% to 100% saturated with the antibacterial agent.

2. Surfactant The amount of surfactant present in this embodiment of the present invention is identical to the amount disclosed above in A.2. However, due to the presence of a hydric solvent and/or a hydrotrope, the identity of the surfactant is not limited as in A.2.

In particular, the presence of a hydric solvent and/or hydrotrope, as defined hereafter, reduces the affinity of the antibacterial agent to enter surfactant micelles. Accordingly, a sufficient amount of the antibacterial agent is present in the continuous aqueous phase to quickly and effectively kill a broad spectrum of bacteria regardless of the identity of the surfactant. In embodiments wherein a hydric solvent and hydrotrope are absent, various surfactants, like ethoxylated nonionic surfactants, have such a strong affinity for the antibacterial agent that the antibacterial agent is not available for a rapid bacteria kill.

Accordingly, in this embodiment the surfactant can be an anionic surfactant, a cationic surfactant, a nonionic surfactant, or a compatible mixture of surfactants. The surfactant also can be an ampholytic or amphoteric surfactant, which have anionic or cationic properties depending upon the pH of the composition.

The anti-hi -art-ril .t Lii.L.a can contain an anionic surfactant disclosed above in WO 00/78275 PCT/US00/15729 33 and more generally can contain any anionic surfactant having a hydrophobic moiety, such as a carbon chain including about 8 to about 30 carbon atoms, and particularly about 12 to about 20 carbon atoms, and further has a hydrophilic moiety, such as sulfate, sulfonate, carbonate, phosphate, or carboxylate. Often, the hydrophobic carbon chain is etherified, such as with ethylene oxide or propylene oxide, to impart a particular physical property, such as increased water solubility or reduced surface tension to the anionic surfactant.

Therefore, suitable anionic surfactants include, but are not limited to, compounds in the classes known as alkyl sulfates, alkyl ether sulfates, alkyl ether sulfonates, sulfate esters of an alkylphenoxy polyoxyethylene ethanol, alpha-olefin sulfonates, beta-alkoxy alkane sulfonates, alkylaryl sulfonates, alkyl monoglyceride sulfates, alkyl monoglyceride sulfonates, alkyl carbonates; alkyl ether carboxylates, fatty acids, sulfosuccinates, sarcosinates, oxtoxynol or nonoxynol phosphates, taurates, fatty taurides, fatty acid amide polyoxyethylene sulfates, isethionates, or mixtures thereof. Additional anionic surfactants are listed in McCutcheon's Emulsifiers and Detergents, 1993 Annuals, (hereafter McCutcheon's), McCutcheon Division, MC Publishing Co., Glen Rock, NJ, pp. 263-266, incorporated herein by reference. Numerous other anionic surfactants, and classes of anionic surfactants, are disclosed in Laughlin et al. U.S. Patent No. 3,929,678, incorporated herein by reference.

The antihac tcrial cT ccsit"r contain nonionic surfactants. Typically, a nonionic WO 00/78275 PCT/US00/15729 34 surfactant has a hydrophobic base, such as a long chain alkyl group or an alkylated aryl group, and a hydrophilic chain comprising a sufficient number 1 to about 30) of ethoxy and/or propoxy moieties. Examples of classes of nonionic surfactants include ethoxylated alkylphenols, ethoxylated and propoxylated fatty alcohols, polyethylene glycol ethers of methyl glucose, polyethylene glycol ethers of sorbitol, ethylene oxide-propylene oxide block copolymers, ethoxylated esters of fatty (C,-C 18 acids, condensation products of ethylene oxide with long chain amines or amides, and mixtures thereof.

Exemplary nonionic surfactants include, but are not limited to, methyl gluceth-10, methyl glucose distearate, PEG-20 methyl glucose sesquistearate, Cn.l 1 pareth-20, ceteth-8, ceteth-12, dodoxynol-12, laureth-15, PEG-20 castor oil, polysorbate 20, steareth-20, polyoxyethylene-10 cetyl ether, polyoxyethylene-10 stearyl ether, polyoxyethylene-20 cetyl ether, polyoxyethylene-10 oleyl ether, polyoxyethylene-20 oleyl ether, an ethoxylated nonylphenol, ethoxylated octylphenol, ethoxylated dodecylphenol, or ethoxylated fatty (C,-C 2 alcohol, including 3 to 20 ethylene oxide moieties, polyoxyethylene-20 isohexadecyl ether, polyoxyethylene-23 glycerol laurate, glyceryl stearate, PPG-10 methyl glucose ether, PPGmethyl glucose ether, polyoxyethylene-20 sorbitan monoesters, polyoxyethylene-80 castor oil, polyoxyethylene-15 tridecyl ether, polyoxy-ethylene-6 tridecyl ether, laureth-2, laureth-3, laureth-4, PEG-3 mixtures, dioeaiethereof. ai mixtures thereof.

WO 00/78275 PCT/US00/15729 35 Numerous other nonionic surfactants are disclosed in McCutcheon's Detergents and Emulsifiers, 1993 Annuals, published by McCutcheon Division, MC Publishing Co., Glen Rock, NJ, pp. 1-246 and 266- 272; in the CTFA International Cosmetic Ingredient Dictionary, Fourth Ed., Cosmetic, Toiletry and Fragrance Association, Washington, D.C. (1991) (hereinafter the CTFA Dictionary) at pages 1-651; and in the CTFA Handbook, at pages 86-94, each incorporated herein by reference.

In addition to anionic and nonionic surfactants, cationic, ampholytic, and amphoteric surfactants can be used in the antimicrobial compositions. Cationic surfactants include amine oxides, for example.

Ampholytic surfactants can be broadly described as derivatives of secondary and tertiary amines having aliphatic radicals that are straight chain or branched, and wherein one of the aliphatic substituents contains from about 8 to 18 carbon atoms and at least one of the aliphatic substituents contains an anionic water-solubilizing group, e.g., carboxy, sulfonate, or sulfate. Examples of compounds falling within this description are sodium 3- (dodecylamino)propionate, sodium 3-(dodecylamino)propane-l-sulfonate, sodium 2-(dodecylamino)ethyl sulfate, sodium 2-(dimethylamino)octadecanoate, disodium 3-(N-carboxymethyl-dodecylamino)propane-lsulfonate, disodium octadecyliminodiacetate, sodium l-carboxymethyl-2-undecylimidazole, and sodium N,Nbis(2-hydroxyethyl)-2-sulfato-3-dodecoxypropylamine.

WO 00/78275 WO 0078275PCTIUSOO/15 729 36 More particularly, one class of ampholytic surfactants include sarcosinates and taurates having the general structural formula wherein R' is C 1 1 through C 2 alkyl, R' is hydrogen or

C

1

-C

2 alkyl, Y is C0 2 M or SOM, M is an alkali metal, and n is a number 1 through 3.

Another class of ampholytic surfactants is the amide sulfosuccinates having the structural formula 0 S0 3 -Na+ 11 1

R:

1 -N1CCH 2 -CH-C0 2 -Na+ The following classes of ampholytic surfactants also can be used: 0 CH 2

CO

2 -Na+ 11 1 RCNI{CH2CH2

T

CH

2

CH

2

OH

alkoamphoglycinates, WO 00/78275 WO 0078275PCT/USOO/15 729 37 0 CH 2 C0 2 -Na"

R'CNHCH

2

CH

2 T CH 2 C0 2

H

CH

2

CH

2 0H al koamphocarboxyg lycinates 0CH 2 C11 2 C0 2 Na'

R

1

CN'HCH

2

CH

2

NJ

CH

2

CH

2

OH

alkoamphopropionates 0 CH 2

CH

2

CO

2 -Na' R CNHCl.,CH 2

NCH--

2

C

2

H

CH

2

CH

2 O0i al koamphocarboxypropionates WO 00/78275 WO 0078275PCT[USOO/15 729 38

OH

0 -CH 2 C HCH 2

SO

3 -Na*

CH

2

CH

2

OH

alkoamphopropyl sul fonates CH3 RlGNH (CH 2 3

N~-CH

2

CO

2

CH

3 alkamidopropyl betaines 0 CH 3

OH

R±-WNI (CH 2 3 N"-C1{ 2

CHCH

2

SO

3 201

CH

3 alkamidopropyl hydroxysultaine

R

1

NHCH

2

CH

2 C-0-Na* aikylaminopropionates WO 00/78275PCJSO/72 PCTIUSOO/15729 39

CH

2

CH

2 CO2f

RH

CH

2

CH

2

CO

2

H

alkyliminopropionates.

Additional classes of ampholytic surfactants include the phosphobetaines and the phosphitaines.

Specific, nonlimiting examples of ampholytic surfactants useful in the present invention are sodium coconut N-methyl taurate, sodium oleyl Nmethyl. taurate, sodium tall oil acid N-methyl taurate, sodium palmitoyl N-methyl taurate, cocodimethylcarboxymethylbetaine, lauryldimethylcarboxymethylbetaine, lauryldimethylcarboxyethylbetaine, cetyldimethylcarboxymethylbetaine, lauryl-bis- (2hydroxyethyl) carboxymethylbetaine, oleyldimethylgammacarboxypropylbetaine, lauryl-bis- (2-hydroxypropyl) -carboxyethylbetaine, cocoamidodimethylpropylsultaine, stearylamidodimethylpropylsultaine, laurylamido-bis- (2-hydroxyethyl) propylsultaine, disodium oleamide PEG-2 sulfosuccinate, TEA oleamido PEG-2 sulfosuccinate, disodium oleamide MEA sulfosuccinate, disodium oleamide MIPA sulfosuccinate, disodium, ricinoleamide MEA sulfosuccinate, disodium undecylenamide MEA sulfosuccinate, disodium wheat germamido MEA sulfosuccinate, disodium wheat germamido PEG-2 sulfosuccinate, disodium isostearamideo MEA sulfosuccinate, cocoamphoglycinate, cocoamphocarboxyglycinate, lauroamuhoolveinMtA -"ro-hcarboxyglycinate, capryloamphocarboxyglycinate, WO 00/78275 PCT/USOO/15729 40 cocoamphopropionate, cocoamphocarboxypropionate, lauroamphocarboxypropionate, capryloamphocarboxypropionate, dihydroxyethyl tallow glycinate, cocamido disodium 3-hydroxypropyl phosphobetaine, lauric myristic amido disodium 3-hydroxypropyl phosphobetaine, lauric myristic amido glyceryl phosphobetaine, lauric myristic amido carboxy disodium 3hydroxypropyl phosphobetaine, cocoamido propyl monosodium phosphitaine, lauric myristic amido propyl monosodium phosphitaine, and mixtures thereof.

3. Carrier The carrier in this embodiment comprises water.

4. Optional Ingredients The optional ingredients discussed in above, also can be utilized in this embodiment of the invention, in the same amounts and for the same purposes.

Hydric Solvent and Hydrotrope This embodiment of the present invention contains 0% to about 25%, by weight, of a hydric solvent, and 0% to about 30%, by weight, of a hydrotrope, wherein the antibacterial composition contains at least one of the hydric solvent and hydrotrope. Preferred embodiments contain both a hvdrir- ml-.ent -rd hydr.trpe.

WO 00/78275 PCT/US00/15729 41 Preferred embodiments contain about 2% to about 20%, by weight, of a hydric solvent and/or about 2% to about 25%, by weight, of a hydrotrope.

Most preferred embodiments contain about 5% to about 15%, by weight, of a hydric solvent and/or about to about 20%, by weight, of a hydrotrope.

As defined herein, the term "hydric solvent" is a water-soluble organic compound containing one to six, and typically one to three, hydroxyl groups. The term "hydric solvent" therefore encompasses water-soluble alcohols, diols, triols, and polyols. Specific examples of hydric solvents include, but are not limited to, methanol, ethanol, isopropyl alcohol, n-butanol, n-propyl alcohol, ethylene glycol, propylene glycol, glycerol, diethylene glycol, dipropylene glycol, tripropylene glycol, hexylene glycol, butylene glycol, 1,2,6hexanetriol, sorbitol, PEG-4, and similar hydroxylcontaining compounds.

A hydrotrope is a compound that has the ability to enhance the water solubility of other compounds. A hydrotrope utilized in the present invention lacks surfactant properties, and typically is a short-chain alkyl aryl sulfonate. Specific examples of hydrotropes includes, but are not limited to, sodium cumene sulfonate, ammonium cumene sulfonate, ammonium xylene sulfonate, potassium toluene sulfonate, sodium toluene sulfonate, sodium xylene sulfonate, toluene sulfonic acid, and xylene sulfonic acid. Other useful hydrotropes include sodium polynaphthalene sulfonate, sodium polystyrene sulfonate, sodium methyl napht-hAloneP lfnatc, and disodium succinate.

WO 00/78275 PCT/US00/15729 42 C. Antibacterial Compositions Containing an Antibacterial Agent and a Hydric Solvent and/or a Hydrotrope In still another embodiment, the antibacterial compositions comprise an active antibacterial agent, and a hydric solvent and/or a hydrotrope.

The compositions of embodiment C exhibit a rapid bacteria kill, and also are essentially unlimited in the identity of the surfactant in the composition.

The solvent and/or hydrotrope assists in solubilizing the antibacterial agent. Accordingly, at least 25% saturation of the antibacterial agent in the continuous aqueous phase can be achieved even in the absence of a surfactant.

1. Antibacterial Agent The amount and identity of the antibacterial agent present in this embodiment of the invention is discussed above in A.1.

In addition, similar to embodiment B, in order to achieve the desired bacteria kill in a short contact time, like 15 to 60 seconds, the continuous aqueous phase of the composition contains an amount of antibacterial agent that is at least about and preferably at least about 50%, and more preferably at least about 75%, of the saturation concentration of the antibacterial agent in water, when measured at room temperature. To achieve the full advantage of the present invention, the continuous aqueous phase is about 95% to 100% saturated with the antibacterial agent.

WO 00/78275 PCT/US00/15729 43 2. Surfactant The surfactant is an optional ingredient in this embodiment. However, if present, the amount of surfactant present in this embodiment of the present invention is 0% to about 10% by weight, preferably 0% to about by weight. To achieve the full advantage of the present invention, the surfactant is present in an amount of 0% to about by weight. Due to the presence of a hydric solvent and/or a hydrotrope, the identity of the surfactant in this embodiment is identical to the surfactants disclosed in B.2.

3. Carrier The carrier in this embodiment comprises water.

Hydric Solvent and Hydrotrope The hydric solvent and hydrotrope discussed in above, also can be utilized in this embodiment of the invention, for the same purpose.

the arICouiL u£ ihyric solvent and/or hydrotrope present in this embodiment can be greater than WO 00/78275 PCT/US00/15729 44 the amount disclosed in above, because an additional amount of solvent and/or hydrotrope may be necessary to solubilize the antibacterial agent in the absence of a surfactant.

Therefore, in embodiment C, the compositions can contain 0% to about 60%, by weight, of a hydric solvent, and 0% to about 40%, by weight, of a hydrotrope. However, the composition contains at least one of the hydrotrope and hydric solvent.

Preferred embodiments contain about 2% to about by weight, of a hydric solvent and/or about 2% to about 25%, by weight, of a hydrotrope. Highly preferred embodiments contain about 5% to about 15%, by weight, of a hydric solvent and/or about 5% to about 20%, by weight, of a hydrotrope. Most preferred embodiments contain both a hydric solvent and a hydrotrope.

D. Antibacterial Compositions Containing Antibacterial Agent, a Disinfecting Alcohol, a Gelling Agent In another embodiment, the antibacterial compositions comprise an active antibacterial agent, a disinfecting alcohol, and a gelling agent. The compositions of embodiment D exhibit a rapid bacteria kill. The compositions of embodiment D are excellent hand sanitizers.

1. Antibacterial Agent The identity of the antibacterial agent in thi ~embodiment or the invention is discussed above WO 00/78275 PCT/US00/15729 45 in A.1. In this embodiment, the antibacterial agent is present in an amount of about 0.05% to about and preferably about 0.1% to about by weight of the composition. To achieve the full advantage of the present invention, the antibacterial agent is present in an amount of about 0.25% to about by weight, of the composition.

2. Carrier The carrier in the present composition comprises water.

3. Disinfecting Alcohol Antibacterial compositions of the present invention contain about 1% to about 40%, by weight, of a disinfecting alcohol. Preferred embodiments contain about 2% to about 38%, by weight, of a disinfecting alcohol. Most preferred embodiments contain about 5% to about 30%, by weight, of a disinfecting alcohol.

As defined herein, the term "disinfecting alcohol" is a water-soluble alcohol containing one to six carbon atoms. Disinfecting alcohols include, but are not limited to, methanol, ethanol, propanol, and isopropyl alcohol.

WO 00/78275 PCT/US00/15729 46 4. Gelling Agent The present antibacterial compositions also contain about 0.01% to about by weight, and preferably 0.10% to about by weight, of a gelling agent. To achieve the full advantage of the present invention, the antibacterial compositions contain about 0.25% to about by weight, of a gelling agent. The antibacterial compositions typically contain a sufficient amount of gelling agent such that the composition is a viscous liquid, gel, or semisolid that can be easily applied to, and rubbed on, the skin. Persons skilled in the art are aware of the type and amount of gelling agent to include in the composition to provide the desired composition viscosity or consistency.

The term "gelling agent" as used here and hereafter refers to a compound capable of increasing the viscosity of a water-based composition, or capable of converting a water-based composition to a gel or semisolid. The gelling agent, therefore, can be organic in nature, for example, a natural gum or a synthetic polymer, or can be inorganic in nature.

As previously stated, the present compositions are free of a surfactant. A surfactant is not intentionally added to a present antibacterial composition, but may be present in an amount of 0% to about by weight, because a surfactant may be present in a commercial form of a gelling agent to help dispense the gelling agent in water. A surfactant also may be present as an additive or byproduct in nthpr -nmr itien iv4-ngrcdi WO 00/78275 PCT/US00/15729 47 Surfactants are omitted from the present compositions to help avoid micelle formation, which in turn solubilize the active antibacterial compound and reduce its effectiveness. Similarly, preferred gelling agents are those that do not form micelles in particular, and do not complex or bind with the active antibacterial agents, or otherwise adversely effect the antibacterial properties of the antibacterial agent. Regardless of the identity of the gelling agent, the amount of gelling agents and other composition ingredients is selected such that the antibacterial agent is present in an amount of at least 25% of saturation, when measured at room temperature.

The following are nonlimiting examples of gelling agents that can be used in the present invention. In particular, the following compounds, both organic and inorganic, act primarily by thickening or gelling the aqueous portion of the composition: acacia, acrylates/steareth-20 methacrylate copolymer, agar, algin, alginic acid, ammonium acrylate copolymers, ammonium alginate, ammonium chloride, ammonium sulfate, amylopectin, attapulgite, bentonite, C9-15 alcohols, calcium acetate, calcium alginate, calcium carrageenan, calcium chloride, caprylic alcohol, carbomer 910, carbomer 934, carbomer 934P, carbomer 940, carbomer 941, carboxymethyl hydroxyethylcellulose, carboxymethyl hydroxypropyl guar, carrageenan, cellulose, cellulose gum, cetearyl alcohol, cetyl alcohol, corn starch, damar, dextrin, dibenzylirlinP dorbitl, ethylznC dihydrogenated tallowamide, ethylene dioleamide, ethylene WO 00/78275 PCT/US00/15729 48 distearamide, gelatin, guar gum, guar hydroxypropyltrimonium chloride, hectorite, hyaluronic acid, hydrated silica, hydroxybutyl methylcellulose, hydroxyethylcellulose, hydroxyethyl ethylcellulose, hydroxyethyl stearamide-MIPA, hydroxypropylcellulose, hydroxypropyl guar, hydroxypropyl methylcellulose, isocetyl alcohol, isostearyl alcohol, karaya gum, kelp, lauryl alcohol, locust bean gum, magnesium aluminum silicate, magnesium silicate, magnesium trisilicate, methoxy PEG-22/dodecyl glycol copolymer, methylcellulose, microcrystallinc cellulose, montmorillonite, myristyl alcohol, oat flour, oleyl alcohol, palm kernel alcohol, pectin, PEG-2M, polyacrylic acid, polyvinyl alcohol, potassium alginate, potassium aluminum polyacrylate, potassium carrageenan, potassium chloride, potassium sulfate, potato starch, propylene glycol alginate, sodium acrylate/vinyl alcohol copolymer, sodium carboxymethyl dextran, sodium carrageenan, sodium cellulose sulfate, sodium chloride, sodium polymethacrylate, sodium silicoaluminate, sodium sulfate, stearalkonium bentonite, stearalkonium hectorite, stearyl alcohol, tallow alcohol, TEA-hydrochloride, tragacanth gum, tridecyl alcohol, tromethamine magnesium aluminum silicate, wheat flour, wheat starch, xanthan gum, and mixtures thereof.

The following additional nonlimiting examples of gelling agents act primarily by thickening the nonaqueous portion of the composition: abietyl alcohol, acrylinoleic acid, aluminum behenate, aluminum caprylate, aluminum dilinoleate. aluminulm ri tet-earate, alinum icct at laurates/palmitates or stearates, aluminum isostear- WO 00/78275 PCT/US00/15729 49 ates/myristates, aluminum isostearates/palmitates, aluminum isostearates/stearates, aluminum lanolate, aluminum myristates/palmitates, aluminum stearate, aluminum stearates, aluminum tristearate, beeswax, behenamide, behenyl alcohol, butadiene/acrylonitrile copolymer, C29-70 acid, calcium behenate, calcium stearate, candelilla wax, carnauba, ceresin, cholesterol, cholesteryl hydroxystearate, coconut alcohol, copal, diglyceryl stearate malate, dihydroabietyl alcohol, dimethyl lauramine oleate, dodecanedioic acid/cetearyl alcohol/glycol copolymer, erucamide, ethylcellulose, glyceryl triacetyl hydroxystearate, glyceryl triacetyl ricinoleate, glycol dibehenate, glycol dioctanoate, glycol distearate, hexanediol distearate, hydrogenated C6-14 olefin polymers, hydrogenated castor oil, hydrogenated cottonseed oil, hydrogenated lard, hydrogenated menhaden oil, hydrogenated palm kernel glycerides, hydrogenated palm kernel oil, hydrogenated palm oil, hydrogenated polyisobutene, hydrogenated soybean oil, hydrogenated tallow amide, hydrogenated tallow glyceride, hydrogenated vegetable glyceride, hydrogenated vegetable glycerides, hydrogenated vegetable oil, hydroxypropylcellulose, isobutylene/isoprene copolymer, isocetyl stearoyl stearate, Japan wax, jojoba wax, lanolin alcohol, lauramide, methyl dehydroabietate, methyl hydrogenated rosinate, methyl rosinate, methylstyrene/vinyltoluene copolymer, microcrystalline wax, montan acid wax, montan wax, myristyleicosanol, myristyloctadecanol, octadecene/maleic anhydride copolymer, octyldodecyl stearoyl stearate.d ol mi yeylterien, ne, curtecuryl ax, oxidized polyethylene, ozokerite, palm kernel alco- WO 00/78275 WO 0078275PCTUSOO/15 729 s0 hol, paraffin, pentaerythrityl hydrogenated rosinate, pentaerythrityl rosinate, pentaerythrityl tetraabietate, pentaerythrityl tetrabehenate,- pentaerythrityl tetraoctanoate, pentaerythrityl tetraoleate, pentaerythrityl tetrastearate, phthalic anhydride/glycerin/glycidyl decanoate copolymer, phthalic/trimellitic/glycols copolymer, polybutene, polybutylene terephthalate, polydipentene, polyethylene, polyisobutene, polyisoprene, polyvinyl butyral, polyvinyl laurate, propylene glycol dicaprylate, propylene glycol dicocoate, propylene glycol diisononanoate, propylene glycol dilaurate, propylene glycol dipelargonate, propylene glycol distearate, propylene glycol diundecanoate, PVP/eicosene copolymer, PVP/hexadecene copolymer, rice bran wax, stearalkonium bentonite, stearalkonium hectorite, stearamide, stearamide DEA-distearate, stearamide DIBA-stearate, stearamide MEA-stearate, stearone, stearyl alcohol, stearyl erucamide, stearyl stearate, stearyl stearoyl stearate, synthetic beeswax, synthetic wax, trihydroxystearin, triisononanoin, triisostearin, triisononanoin, triisostearin, triisostearyl trilinoleate, trilaurin, trilinoleic acid, trilinolein, trimyristin, triolein, tripalmitin, tristearin, zinc laurate, zinc myristate, zinc neodecanoate, zinc rosinate, zinc stearate, and mixtures thereof.

Optional Ingiredients a. Polyhydric Solvent ydr-.c .A.L c L all, is present in an amount of about 0.1% to about WO 00/78275 PCT/US00/15729 51 and preferably about 5% to about 50%, by weight of the composition. To achieve the full advantage of the present invention, the polyhydric solvent is present in an amount of about 10% to about 50% by weight of the composition. In contrast to a disinfecting alcohol, a polyhydric solvent contributes little, if at all, to the antibacterial efficacy of the present composition.

As defined herein, the term "polyhydric solvent" is a water-soluble organic compound containing two to six, and typically two or three, hydroxyl groups. The term "water-soluble" means that the polyhydric solvent has a water solubility of at least 0.1 g of polyhydric solvent per 100 g of water at 25 0 C. There is no upper limit to the water solubility of the polyhydric solvent, the polyhydric solvent and water can be soluble in all proportions.

The term "polyhydric solvent" therefore encompasses water-soluble diols, triols, and polyols. Specific examples of hydric solvents include, but are not limited to, ethylene glycol, propylene glycol, glycerol, diethylene glycol, dipropylene glycol, tripropylene glycol, hexylene glycol, butylene glycol, 1,2,6-hexanetriol, sorbitol, PEG-4, and similar polyhydroxy compounds.

b. Hydrotrope A hydrotrope, if present at all, is present in an amount of about 0.1% to about 30%, and preferably abhoit n.5% t 2bcut 25, by weilL .JL L1he composition. To achieve the full advantage of the WO 00/78275 PCT/US00/15729 52 present invention, the hydrotrope is present in an amount of about 1% to about 20%, by weight of the composition. The identity of the hydrotropes is discussed in above, and is used in this embodiment of the invention for the same purpose.

c. Other Optional Ingredients Other optional ingredients discussed in above, also can be utilized in this embodiment of the invention, in the same amounts and for the same purposes.

Additional optional ingredients useful in this embodiment include skin conditioners. Examples of skin conditioners, include emollients, such as, cetyl myristate, glyceryl dioleate, isopropyl myristate, lanolin, methyl laurate, PPG-9 laurate, soy stearyl, octyl palmitate, and PPG-5 lanoate, for example. The skin conditioner also can be a humectant, for example, glucamine and pyridoxine glycol, for example. Occlusive skin conditioners, for example, aluminum lanolate, corn oil, methicone, coconut oil, stearyl stearate, phenyl trimethicone, trimyristin, olive oil, and synthetic wax, also can be used. Combinations of the classes of skin conditioners, in addition to miscellaneous skin conditioners known to persons skilled in the art, alone or in combination can be used. Nonlimiting examples of miscellaneous skin conditioners include aloe, cholesterol, cystine, keratin, lecithin, egg yolk, glycine, PPG-12, retinol, salicylic acid, orotic acid. vgincole n ilers and be use animal Uor in ci.

The skin conditioners can be used alone, or in com- WO 00/78275 PCT/US00/15729 53 bination with a skin protectant, like petroleum, cocoa butter, calamine, and kaolin, for example. A skin protectant also can be used alone. Additional examples of skin conditioners and protectants can be found in "CTFA Cosmetic Ingredient Handbook," J.M.

Nikitakis, ed., The Cosmetic, Toiletry and Fragrance Association, Inc., Washington, D.C. (1988) (hereafter CTFA Handbook), pages 79-85, incorporated herein by reference.

Antibacterial compositions of the present invention comprising an active antibacterial agent, a disinfecting alcohol, and a hydrotrope exhibit a rapid bacteria kill. The alcohol and hydrotrope assist in solubilizing the antibacterial agent.

Accordingly, at least 25% saturation of the antibacterial agent in the composition can be achieved even in the absence of a surfactant.

The antibacterial compositions of the present invention do not rely upon a low pH or a high pH to provide a rapid reduction in bacterial populations. Antibacterial compositions of the present invention can have a pH of about 4 to about 9, but at the two extremes of this pH range, the compositions can be irritating to the skin or damaging to other surfaces contacted by the composition.

Accordingly, antibacterial compositions of the present invention preferably have a pH of about 5 to about 8, and more preferably about 6 to about 8. To achieve the full advantage of the present invention, the antibacterial compositions have a pH of about to about 7.

C n additn, the antibacte compositions of the present invention also do not WO 00/78275 PCT/US00/15729 54 rely upon a high concentration of disinfecting alcohol.

To demonstrate the new and unexpected results provided by the antibacterial compositions of the present invention, the following Examples and Comparative Examples were prepared, and the ability of the compositions to control Gram positive and Gram negative bacteria was determined. The weight percentage listed in each of the following examples represents the actual, or active, weight amount of each ingredient present in the composition. The compositions were prepared by blending the ingredients, as understood by those skilled in the art and as described below.

The following materials were used as ingredients in the examples. The source of each ingredient, and its abbreviation, are summarized below: a) Alkyl (linear) diphenyl oxide disulfonate, Pilot Chemical Co., Santa Fe Springs, CA, CALFAX 10L-45 (active=45.4%), b) Alkyl polyglucoside (APG), Henkel Corp., Hoboken, NJ, PLANTAREN 2000N UP (active=55.53%), c) Alpha-olefin sulfonate (AOS), Stepan Chemical Co., Northfield, IL, BIOTERGE AS-40 (active=38.80%), d) Ammonium lauryl sulfate (ALS), Henkel Corp., STANDAPOL A (active level=28.3%), e) Ammonium xylene sulfonate (AXS), Stepan Corp., STEPANATE AXS WO 00/78275 WO 0078275PCT/USOO/15729 55 f) Cocamidopropyl betaine (CAPB), McIntyre Group, Ltd., Chicago, IL, MACKAM (est. 30% active betaine), g) Dipropylene glycol (DPG), Dow Chemical Co., Midland, MI, h) Disodium laureth sulfosuccinate (DSLScct), McIntyre Group, Ltd., MACKANATE EL (active=33.8%), i) Disodium lauryl sulfosuccinate (DSLrylScct), McIntyre Group, Ltd., MACKANATE LO (active j) DMDM Hydantoin (DMDM), Maclntyre Group, Ltd., MACKSTAT DM (approx. 55% active), k) DowFax Hydrotrope Solution (DFX), Dow 1s Chemical Co., DowFax Hydrotrope Solution (Benzene, 1,1' -oxybis-, sec-hexyl derivatives, sulfonated sodium salt) (active=45.7%), 1) Glycerin (GLY), Henikel/Emery, Cincinnati, OH, Emery 916 Glycerine CP/USP), m) Isopropanol (IPA), Fisher Scientific, Pittsburgh, PA, 2-Propanol, HPLC Grade A 451-4, n) Lauramine oxide (LAO), McIntyre Group, Ltd., MACKAMINE LO (active=30.55%), o) Liquid Perfume (PF), p) Lithium lauryl sulfate (LLS), Henkel, TEXAPON LLS (active=28.8%), q) Magnesium lauryl sulfate (MLS), Stepan Chemical Co., STEPANOL MG (active=28.3%), r) Methyl ester sulfonate (MES), Stepan Chemical Co., ALPHA-STEP ML-40 (Sodium methyl-2 sulfo laurate and disodium 2-sulfo lauric acid) (active=36.47%).

WO 00/78275 WO 0078275PCTUSOO/15729 56 s) Monoethanolamine (MEA), Dow Chemical Co., t) Monoethanolamine lauryl sulfate (MEALS), Albright Wilson, Cumnbria, England, EMPICOL LO 33/F (active=33%),u) Octylphenol ethoxylate, 9-10 moles EQ (TX100), Union Carbide, TRITON-X 100, v) PEG-6ME, polyethylene glycol 300 methyl ether, available from Dow Chemical Co., Midland, MI, as MPEG 350 (active=est. 100%), w) Poloxymer 338 (F1O8), BASF, Wyandotte, MI, PLURONIC F108 (active=est. 100%), X) Potassium cocoate (KCO), McIntyre Group, Ltd., MACKADET 40-K (active=38.4%), y) Potassium laurate prepared from lauric acid (Sigma, #L-4250, active=99.8%) and potassium hydroxide, Z) Potassium oleate Norman, Fox Co., Vernon, CA, NORFOX KO (active=aoprox. aa) Propylene glycol Dow Chemical Co., LISP Grade (active level=99.96%), bb) Sodium 2-ethylhexyl sulfate (S2EHS), Henkel, SULFOTEX OA (active=39.68%), cc) Sodium sulfate (SC12-18S) Henkel., TEXAPON ZHC needles (active=90.95%), dd) Sodium cocoamphoacetate (SCA), McIntyre Group, Ltd., MACKAN IC-90 (active=approx.

32%), ee) Sodium cumene sulfonate (SCS), Stepan Chemical Co., STEPANATE SCS (active=44.6%), ff) Sodium decyl sulfate (SDecS), Henkel, SULFOTEX 110 (activp=inl.Rn!l) WO 00/78275 WO 008275PUS0/15729 57 gg) Sodium lauroyl sarcosinate CSLSarc), Hampshire Chemical Co., Lexington, MA, HAIMPOSYL Type 724 (active=29.9%), hh) Sodium lauryl ether sulfate, 1 mole EQ (SLES-l), Henkel, STANDAPOL ES-i (active=25.40%), ii) Sodium lauryl ether sulfate, 2 mole EQ (SLES-2), Henkel, STANDAPOL ES-2 (active level=25.71%), jj) Sodium lauryl sulfate/sodium dodecyl sulfate (SL.S/SDS), BDH Biochemical, BDH Ltd., Poole, England, (active=99.0%), kk) Sodium lauryl sulfoacetate (SLSA), Stepan Chemical Co., LANTHANOL LAL (active=72.65%), 11) Sodium octyl sulfate (SOS), Henkel, STANDAPOL LF (active=32.90%), mm) Sodium salt of NEODOX 23-4 (NDX23-4), Shell Chemical Co., derived from NEODOX 23-4, a compound having a 194 molecular weight chain, 4 moles of EQ and a carboxylate group (activ.e=94 nfl) Sodium tridecyl sulfate (SC13S), Rhodia, Parsippany, NJ, RHODAPON TDS (active=24.65%), oo) Sodium xylene sulfonate (SXS), Stepan Chemical Co., STEPANATE SXS (active level=40-42%), pp) Triclosan (TCS), IRGASAN DP-300, Ciba Specialty Chemicals Corp., Greensboro, NC (GC assay on lots used=99.8-99.9% active TCS; mp=56.O-58.O qq) Triethanolamine lauryl sulfate (TEALS), Henkel, STANDAPOL T rr) Tripropylene Glycol (TPG), Dow Chemical Co.: Tr-21c1rCC!,t WO 00/78275 PCT/US00/15729 58 ss) p-Chloro-m-xylenol (PCMX), NIPACIDE PX-R, Nipa Inc., Wilmington, Delaware (about 100% active), tt) Glyceryl polymethacrylate and propylene glycol (LUBRAGEL DV), International Speciality Products, Wayne, New Jersey (about 46% active), uu) CARBOPOL ULTREZ 10 (ULTREZ crosslinked polyacrylic acid, BF Goodrich Specialty Chemicals, Cleveland, Ohio (about 98% active), vv) Diisopropylamine, Air Products and Chemicals, Allentown, Pennsylvania (about 100% active), ww) LAPONITE XLG (lithium magnesium silicate, synthetic smectite clay), Southern Clay Products, Gonzales, Texas (about 99% active), xx) CELQUAT CS230M (Polyquaternium National Starch and Chemical Company, Bridgewater, New Jersey (about 92% active), yy) Polypropylene glycol-9 (PPG-9), Polyglycol P425, Dow Chemical Company, Midland, Michigan (about 100% active), zz) Ethanol (Denatured Ethyl Alcohol Gold Shield, Hayward, California (about 100% active), aaa) Water--Unless otherwise indicated, the water was prepared as follows: deionized (DI) water was distilled once through a Corning AG-3 water still.

The following methods were used in the preparation and testing of the examples: a) Determination of Rapid Germicidal (Time Kill A-+irity -f _Antibacteral The activity of antibacterial compositions was measured WO 00/78275 PCT/USOO/15729 59 by the time kill method, whereby the survival of challenged organisms exposed to an antibacterial test composition is determined as a function of time. In this test, a diluted aliquot of the composition is brought into contact with a known population of test bacteria for a specified time period at a specified temperature. The test composition is neutralized at the end of the time period, which arrests the antibacterial activity of the composition. The percent or, alternatively, log reduction from the original bacteria population is calculated.

In general, the time kill method is known to those skilled in the art.

The composition can be tested at any concentration from 0-100%. The choice of which concentration to use is at the discretion of the investigator, and suitable concentrations are readily determined by those skilled in the art. For example, viscous samples usually are tested at 50% dilution, whereas nonviscous samples are not diluted. The test sample is placed in a sterile 250 ml beaker equipped with a magnetic stirring bar and the sample volume is brought to 100 ml, if needed, with sterile deionized water. All testing is performed in triplicate, the results are combined, and the average log reduction is reported.

The choice of contact time period also is at the discretion of the investigator. Any contact time period can be chosen. Typical contact times range from 15 seconds to 5 minutes, with 30 seconds and 1 minute being typical contact times. The contact tmnpT-Atinre =l czn b y temeLi, Lypically room temperature, or about 25 degrees Celsius.

WO 00/78275 PCT/US0O/15729 60 The bacterial suspension, or test inoculum, is prepared by growing a bacterial culture on any appropriate solid media agar). The bacterial population then is washed from the agar with sterile physiological saline and the population of the bacterial suspension is adjusted to about 108 colony forming units per ml (cfu/ml).

The table below lists the test bacterial cultures used in the following tests and includes the name of the bacteria, the ATCC (American Type Culture Collection) identification number, and the abbreviation for the name of the organism used hereafter.

Organism Name ATCC Abbreviation Staphylococcus aureus 6538 S. aureus Escherichia coli 11229 E. coli Klebsiella pneumoniae 10031 K. pneum.

Salmonella choleraesuis 10708 S. choler.

S. aureus is a Gram positive bacteria, whereas E.

coli, K. pner, and S. choler. are Gram negative bacteria.

The beaker containing the test composition is placed in a water bath (if constant temperature is desired), or placed on a magnetic stirrer (if ambient laboratory temperature is desired). The sample then is inoculated with 1.0 ml of the test bacteria suspension. The inoculum is stirred with the test composition for the predetermined contact time. When the contact time expires, 1.0 ml of the test composition/bacteria mixture is transferred WO 00/78275 PCT/USOO/15729 61 into 9.0 ml of Tryptone-Histidine-Tween Neutralizer Solution (THT). Decimal dilutions to a countable range then are made. The dilutions can differ for different organisms. Plate selected dilutions in triplicate on TSA+ plates (TSA+ is Trypticase Soy Agar with Lecithin and Polysorbate 80). The plates then are incubated for 25+2 hours, and the colonies are counted for the number of survivors and the calculation of percent or log reduction. The control count (numbers control) is determined by conducting the procedure as described above with the exception that THT is used in place of the test composition. The plate counts are converted to cfu/ml for the numbers control and samples, respectively, by standard microbiological methods.

The log reduction is calculated using the formula Log reduction=logi (numbers control)-log,,(test sample survivors).

The following table correlates percent reduction in bacteria population to log reduction: Reduction Log Reduction 1 99 2 99.9 3 99.99 4 99.999 WO 00/78275 PCT/US00/15729 62 b) Preparation of saturated solutions of TCS in water: A four liter flask was equipped with a 3-inch magnetic stir bar and charged with approximately 7.5 grams TCS and 3 liters of water.

The flask then was placed in a water bath, stirred, and heated (40-45 0 C) for at least 8 hours. The flask containing the resulting TCS/water suspension was removed from the water bath, and the warm suspension filtered through a Coors #32-H porcelain Bfchner funnel equipped with Whatman #40 filter paper. The filtering assembly was attached to a two liter vacuum filter flask, and filtration was conducted in batches. The filtrate then was transferred to another four liter flask and allowed to cool. Typically, fine needles of TCS crystals formed after the filtrate was stored at room temperature for a few days.

For some time kill studies, the TCS solution was refiltered at room temperature before use in the study. For other time kill studies, a small amount of crystalline TCS was allowed to remain in the test container to ensure saturation in the event of a temperature change. It was assumed that TCS crystals present in the time kill test vessel would not affect test results because crystalline TCS is unavailable to act on the bacteria is not solubilized).

To determine the concentration of TCS in the water solutions, filtered samples (in triplicate) were analyzed by HPLC. The apparatus used to filter the solutions was a Whatman AUTOVIAL®, with 0.45pm PTFE membrane and glass microfiber prefilter.

cat. No. AV125UORG. TCS concentrations were calcu- WO 00/78275 PCT/US00/15729 63 lated using a linear regression line fit (Microsoft EXCEL® software) to TCS/IPA standards included on the same HPLC run.

c) Preparation of aqueous TCS/surfactant compositions: A French square bottle was charged with a solution containing a variable concentration of a surfactant and by weight, TCS. The mixture was stirred and heated (35-40 0 C) for several hours until the TCS was solubilized. Variable transformer-controlled heat lamps were used for warming and the temperature of the solution was monitored with a digital thermometer. Stirring then was stopped, TCS seed crystals (about 1 mg) were added to the solution, and the mixture was allowed to stand at about 20 0 C. In a few days, crystals were observed on the bottom of solution containers in which the maximum solubility of TCS was exceeded.

The approximate concentration of surfactant necessary to almost completely solubilize the 0.3% TCS was determined by use of an experimental design in which the concentration of surfactant was serially reduced by a factor of two over a series of test samples until the approximate saturation point of TCS in the surfactant was observed.

Then the difference in concentration (saturated vs.

just solubilized) was halved until a close endpoint for TCS saturation could be determined. The saturation point of TCS/surfactant compositions could be effectively estimated with small-scale (15 to 100 mL) samples, but about 600-800 g samples were required to obtain reliable final results. The initial ranges: hifre, .r tabl'ihed WiLi WO 00/78275 PCT/US0O/15729 64 small-scale samples, and the final concentrations were determined using larger-scale samples.

d) Preparation of compositions containing TCS and a solvent or solvent/hydrotrope combination: TCS first was dissolved in the solvent used in the composition. Water then was added to the TCS/solvent composition, followed by the addition of about 1 mg of TCS seed crystals, and the resulting mixture was allowed to stand at about 20 0 C to crystallize. In compositions containing a solvent, hydrotrope, and surfactant, the TCS was dissolved in the solvent as above, and then the hydrotrope and surfactant were added to the TCS/solvent solution.

The resulting mixture then was diluted to the batch total with water. Adjustment of pH also was performed, if required. The mixture was stirred at room temperature for about an hour, seed TCS was added, and the mixture allowed to stand and crystallize as above. The determination of the TCS saturation point described above also was used halving surfactant concentrations). Methods similar to the above for determination of maximum additive concentration have been described in the literature.

For example, P.H. Elworthy et al., "Solubilization by surface-active agents and its application in chemistry and biological sciences," Chapman and Hall, Ltd., London, pp. 62-65 (1968), describes determination of concentrations near saturation by observing turbidity of the mixture. A similar technique was used by observing the sample at right angles with a high-intensity light from a small flashlight equipped with a beam focusing attachment MINI MAGLITE® AA, MAG Instruments, Califor- WO 00/78275 PCT/US00/15729 65 nia, USA). This method also was used with solutions very near to saturation to enhance observation of small amounts of crystals formed on the bottom of containers.

Table 2 summarizes the results of time kill tests performed on TCS/water compositions. Two series of results, I and II, demonstrate the effect of saturation in TCS/water compositions, i.e., that within a given test series, reduction in saturation produces a concomitant reduction in time kill efficacy.

Table 2--Time Kill Results for Saturated TCS/Water Compositions LOG REDUCTION TCS S. aureus S. coi X. Pneun. S. chol.

Sample (g/mL) 1 min/ 5 min. 1 min/ 5 mini 1 min/ 5 mini I min/ 5 min (by HPLC) or t or t or t or t 100% sat'd. 9.3xl10' 1.07/1s >3.91 0.44/15s >4.06 0.32/15s >4.00 sat'd. 3. 9x10'1 0.03/1s 1.71 0.13/1s 1.15 0.21/15s 2.76 aat'd. 6.7x10-1 0.03/15s 0.02 0.06/159 0.08 0/5Sa 0.14 100% sat'd. 9.6x10'1 3.93 1.76 2.85 2.15 sat'd. 4. 9x10-1 0.24 0.26 0.35 1.28 WO 00/78275 PCT/US00/15729 67 Comparing the data in Tables 2 and 3 shows that at the very lowest concentration of TCS to 10 ppm), the efficacy of time kill is reduced compared to samples containing higher levels of TCS.

For example, a sample in Table 2 containing 0.93 ppm TCS has a log reduction of 0.44 after 15 seconds vs.

E. coli, whereas a sample in Table 3 containing 484 ppm TCS had a log reduction of 4.13 after 15 seconds vs. the same organism. This effect is more apparent at shorter-contact time periods. Another example, in more complex compositions is illustrated in samples in Table 3, 50 ppm TCS (est.)/10%PG/5%SXS vs. (448 ppm TCS (est.)/20%PG/10%SXS). The sample with the higher TCS concentration showed at least a log improvement in bacterial reduction after 1 minute. The data in Table 3 also show differences in efficacy when different solvents/hydrotropes are used with approximately the same TCS concentrations.

Table 3--TCS in Solvent and/or Hydrotrope Systems rcs S. aureus E. coi Solvent/ ippm) Hydrotrope sec. 1 min. Sec. 1 min.

112 (est) 17%IPA >4.42 >3.56 0 1796IPA 0.42 -0.24 110 (est) 23.85%PG >4.39 2.37 342 40.01%PG 4 .971) /3 021 >5.17 4.29/30 >4.67 484 41.B6%PG >3.46/15 >3.46 4.13/15 >4.38 510 42.53%PG >5.17/30 >5.17 4.47/30 >4.67 723 44.20%PG >3.46/15 >3.46 >4.38/15 >4.38 1503 45.05%PG >4.69/15 >4.69 4.21/15 >4.65 1395 47.52%PG >5.17/30 >5.17 4.42/30 A4.67 1385 50.00%PG >4.49/15 >4.49 4.45/15 >4.65 0 S0.00%PG 0.15/15 0.13 0.25/15 0.26 0 75.00%PG 1.20/15 2.35 0.35/15 1.73 5359SXS >4.43 0.96 0 5%SXS 0.33 -0.15 Table 3--TCS in Solvent and/or Hydrotrope Systems Frcs S. aureus H. Coill Solvent/ (ppm) Kydrotrope sec. 1 min. Sec. 1 min.

57 5%SCS 3.64 0.80 0 5%SCS -0.05 -0.11 448 (eat) 20%PG/lO%SXS >4.14/30 >4.14 >5.25/30 >5.25 0 20%PG/l0%SXS 0.05/30 0.05 1.16/30 1.35 (eat) l0%PG/5*SXS 3.42 3.18 0 10%PG/5%SXS 0.05 0.35 (est) 10%PG/5%SCS 0.59 4.96 0 10%PG/5%SCS -0.03 0.96 502 (eat) 14.S%DPG/10%SXS >3.63/30 >3.63 >4.44/30 >4.44 0 14.5%DPG/10%SXS 0.03.30 0.04 0.26/30 0.17 Table 3--TCS in Solvent and/or Hydrotrope Systems TCS K. pneum. S. chol.

Solvent/ Ippm) Hydrotrope sec. 1 min. sec. 1 min.

112 (est) 17%IPA >4.11 >3.79 0 17%IPA 0.89 1.23 110 (est) 23.85%PG 342 40.01%PG 4.33/30 5.29 2.52/30 3.51 484 41.86%PG 2.96/15 >3.44 1.14/15 2.31 510 42.53%PG 4.61/30 >5.64 1.56/30 2.27 723 44.20%PG >3.44/15 >3.44 1.29/15 2.59 503 45.05%PG 2.60/15 4.79 1.79/15 >4.50 395 47.52%PG 5.26/30 >5.64 2.92/30 4.33 1385 50.00%PG 3.26/15 >5.04 2.69/15 >4.59 0 50.00%PG 0.54/15 0.63 0.17/15 0.24 0 75.00%PG 1.98/15 >3.44 1.34/15 3.56 63 0 Table 3- -TCS in Solvent and/or Hydrotrope Systems 'rcs K. pneum. S. chol.

Solvent Ippm) Hydrotrope sec. 1 min. aec. 1 min.

57 0 448 (est) 20%PG/10%SXS A4.32/30 >4.32 3.17/30 >3.68 0 20%PG/10%SXS 0.22/30 0.37 0 .25/30 1.29 (est) 0 (est) 10%PG/5*SCS 0 502 (est) 14.5%DPG/1O%SXS >4.14/30 >4.14 >4.14/30 >4.14 0 )4.5%DPG/10%SXS 0.34/30 0.39 0.36/30 0.47 Icg reduction; and ~'seconds.

WO 00/78275 PCT/US00/15729 72 Many compositions of the present invention contain a surfactant, which potentially can reduce the efficacy of the antibacterial agent. The following examples show the unexpected benefits achieved by compositions of the present invention.

Example 1 f-- In this example, a composition of the present invention was compared to three commercially available antibacterial cleansing compositions in a time kill test using a contact time of 5 minutes. A composition of the present invention (Product A) was a saturated solution containing 0.3% triclosan in a 1.5% aqueous sodium lauryl sulfate (SLS). The three commercially available antibacterial compositions having unknown triclosan concentrations, were Jergens Antibacterial (JA) Hand Soap, a product of Andrew Jergens Inc.; Clean and Smooth a product of Benckiser; and Soft Soap (SSp), a product of Colgate Palmolive.

Log Reduction at 5 minutes (time kill) Product Triclosan M% Saturation 3 S. aureus Z. Coll K. pnoum. S. choi.

A 0.3 100 >4.47 >4.41 >4.36 4.67 JA Unk. Unk. 2.48 0.20 0.18 Cs Unk. Unk. 2.80 0.00 0.10 SSp Unk. Unk. 1.62 0.00 0.20 1)1-"means not tested; Unk.11 means Unknown; and 3) 11% saturation" means percent saturation of TCS in the continuous aqueous phase.

WO 00/78275 PCT/US00/15729 74 Example 1 demonstrates the surprising improvement in log reduction of bacteria populations provided by an inventive composition compared to currently available commercial antibacterial compositions. Thus, an aqueous composition containing triclosan in SLS, at 100% saturation, offers significantly greater antibacterial efficacy than any of the three commercial products tested, against Gram positive and against Gram negative microorganisms, both of which can present a significant health threat to consumers.

Example 2 This example demonstrates that the antibacterial activity of an inventive composition is attributable to the active antibacterial agent, as opposed to the surfactant. Test compositions A-i and A-2 were prepared. Composition A-i is a solution containing 0.3% triclosan, 1.35% ammonium lauryl sulfate, with the balance being water. Composition A-1 is 100% saturated with triclosan.

Composition A-2 is a "placebo," an aqueous 1.35% ammonium lauryl sulfate solution that is free of the active antibacterial agent.

I Log Reduction at 5 minutes (time kill) Product Triclosan %Saturation S. aureus E. co2i K. pneuz. S. chol.

A-1 0.30 100 >3.61 3.16 >4.39 3.73 E A-2 j 0 0 >3.61 0.25 0.15 0.04 WO 00/78275 PCT/US00/15729 76 The inventive composition A-i clearly provided an excellent, broad spectrum antibacterial activity, whereas the "placebo" composition A-2 exhibited an extremely limited spectrum of activity.

Composition A-2 has especially poor efficacy against Gram negative organisms. Control of Gram negative organisms is of particular concern to consumers because such organisms present a significant health threat. The excellent broad spectrum activity of composition A-i clearly shows that the antibacterial activity is unambiguously attributed to the presence of the antibacterial agent in the continuous aqueous phase.

Example 3 In this example, a solvent, propylene glycol was used to solubilize triclosan in an aqueous carrier. No hydrotrope or surfactant was present. Composition A-3 contained 0.0872% by weight triclosan, 47.5% aqueous PG, and the balance being water. Composition A-3 was 100% saturated with triclosan and is a composition of the present invention. Test composition A-4 was a "placebo" consisting of 47.5% PG, by weight, and the balance water. This example illustrates an added advantage of including an optional hydric solvent in the composition. In particular, it was observed that the excellent broad spectrum activity illustrated in earlier examples at contact times of 1 and 5 minutes can be achieved in the presence of the hydric solvent t a ccntact tis t a f 3 we iauiib Tiilit example further demonstrates that the antibacterial activity WO 00/78275 PCT/USOO/15729 77 of a present composition is unambiguously attributable to the presence of the antibacterial agent.

Log Reduction at 30 seconds (time kill) Prouct Triclosan %Saturation S. aureus H. Coli K. pneum. S. chol.

A30.0872 100 >5.17 4.42 5.26 2.92 E A4000 0.15 0.25 0.54 0.17 WO 00/78275 PCT/US00/15729 79 Example 4 This example illustrates that composition of the present invention provide an acceptable sanitization efficacy even though the compositions contain a relatively low concentration of disinfecting alcohol. Examples B-l, B-3, and B-5 contain 0.15%, by weight, triclosan, at 100% saturation. Examples B-2, B-4, and B-6 are comparative examples containing 0% triclosan.

Zigredient (by weight) B-I B-2 B-3 B-4 B-5 B-6 Triclosan 0.15 0.0 0.15 0.0 0.15 0.0 E-:hanol 38 38.0 28.0 28.0 D.Lpropylene Glycol 11.18 11.18 40.0 40.0 U],TREZ 10 "1 0.3 0.3 0.3 0.3 0.3 0.3 D:.isopropylarnine 0.05 0.05 0.05 0.05 0.05 0.05 Perfume 0.04 0.04 0.04 0.04 0.04 0.04 Witter Balance Balance Balance Balance Balance Balance 1) added "as is" WO 00/78275 PCT/US00/15729 81 The following table summarizes the results of a time kill test at 15 seconds.

Log Reductions at 15 seconds Example S. aureus B. coli K. pneum. S. chol.

B-l >4.61 >4.78 >4.51 >4.49 B-2 >4.61 >4.78 >4.51 >4.49 B-3 >4.00 >4.44 >4.20 >3.92 B-4 2.50 1.20 >4.20 >3.92 B-5 >4.39 3.29 1.37 1.30 B-6 0.10 0.0 0.35 0.34 These results show that acceptable sanitization efficacy is achieved, even with reduced levels of disinfecting alcohol and other polyhydric solvents.

Furthermore, the compositions of the present invention provide a persistent antibacterial benefit because of the nonvolatile nature of the active ingredient, triclosan, whereas presently marketed compositions do not provide a persistent antibacterial activity.

In particular, Examples B-3 through B-6 demonstrate that the rapid antibacterial activity of the present compositions is attributable mainly to the antibacterial agent, triclosan, as opposed to a disinfecting alcohol. This is in contrast to prior art disclosures. For example, composition B-3 contains only 28% ethanol, yet exhibits excellent broad-spectrum antibacterial activity at 15 seconds.

Composition B-5 contains no alcohol, yet exhibits excellent antibacterial activity against S. aureus and E. coli. Prior art teachings rely on a high WO 00/78275 PCT/US00/15729 82 alcohol concentration to achieve a fast, broad-spectrum antibacterial activity.

Example This example illustrates the effect of the identity of the surfactant on the antibacterial activity of the composition. The test results summarized below were performed on a wide variety of compositions containing either an anionic surfactant or representative cationic, anionic/nonionic, amphoteric, and nonionic surfactants. The percent saturation of TCS in the compositions of this example is at least about s. aureus H. Coli £urfactant Type Active Cone. Surfactant and Amnount (1 min) (I min) Lnionic O.3%TCS 1.6% Sodium Lauryl Sulfate.....

(SLS)

;nionic 0.3%TCS 1.35% Ammonium Lauryl Sulfate (AiLS) Pnionic O.3%TCS 1.5W Triethanolamine Lauryl Sulfate (TEALS) Anionic 0.3%TCS St Sodium Octyl Sulfate (SOS) Anionic 0.3%TCS 9.5W sodium 2-Ethyihexyl Sul- fate (S2EHS) Cationic 0.3%TCS 1.5% Lauramine Oxide Aaiionic 0.3%TCS 2.5% Sodium Decyl Sulfate (SdecS) kiionic 0.3%TCS 2.5W Sodium Tridecyl sulfate 0 (SC13S) Anionic 0.3%TCS 1.5% Lithium Lauryl sulfate 0

(LLS)

Anionic 0.3%TCS 1.5% Potassium Cocoate (KCO) Anionic 0.3%TCS 2.0W Methyl Ester Sulfonate 0

(MES)

Aitionic 0.3%TCS 1.25% Sodium Lauroyl 0 Sarcosinate (SLSarc) Surfactant Type Active Conc. Surfactant and Amount Anionic O.3%TCS 1% Sodium Lauryl Sulfoacetate

(SLSA)

Anionic 0.3%TCS 3% C10 (Linear) Sodium Diphenyl Oxide Disulfonate (L1O-45) Anionic 0.3%TCS 1.5% Disodium Lauryl Sulfosuccinate (DSLryIScet) Aaionic/Nonionic 0.3%TCS 1.25% Sodium Lauryl Ether Sulfate, 1-mole EO (SLES-1) Aiionic/Nonionic 0.3%TCS 1% Sodium Lauryl Ether Sulfate, 2-mole EO (SLES-2) Ainphoteric 0.3%TCS 1.25W Sodium Cocoamphoacetate

(SCA)

Ainphoteric 0.3%TCS 1.75% Cocamidopropyl Betaine

(CAPB)

kiionic 0.3%TCS 1.25% Aipha-Olef in Sulfonate

(AOS)

Anionic 0.3%TCS 1.5% Sodium Alkyl Sulfate, C12.

18 (SC12-18S) Aniionic 0.3%TCS 1.5% Magnesium Lauryl Sulfate

(MLS)

AiLionic/Noflionic 0.3%TCS 2.0% Sodium Myreth-4 I ________Carboxylate (NaNDX23-4)

-J

S. aureua R. coi Surfactant Type Active Conc. Surfactant and Amount (I min) (1 min) Arijonic/Norijonic 0.3%TCS 1.25W Disodium Laureth 0 Sulfosuccinate (DSLSect) Nonionic 0.3*TCS Alkyl Polyglucose (APG) 0 0 N~nionic 0.3%TCS 4% Octoxynol-9 (TX100) 0 0 Ke 1': 4.+ 0 log reduction in time kill test >3.99 >2 .99 >1.99 >0.99 <0.99 WO 00/78275 PCT/US00/15729 86 The results summarized above demonstrate, unexpectedly, that antibacterial agents and anionic surfactants form highly effective antibacterial compositions when the saturation of antibacterial agent in the composition is high, at least In addition, it was observed that, within a homologous series of surfactants, efficacy can vary in the sodium alkyl sulfate homologous series, sodium lauryl sulfate and sodium octyl sulfate yielded high efficacy formulas). The efficacy with respect to the cation also is unexpected sodium, ammonium, and triethanolammonium lauryl sulfates provided high efficacy formulas, whereas lithium and magnesium lauryl sulfates did not).

Example 6 The following table summarizes the effect of surfactant identity on the antibacterial activity of the composition. This example expands upon the data provided in Example 5. The table includes results of tests performed on a wide variety of compositions containing either anionic surfactants or representative examples containing cationic, anionic/nonionic, amphoteric, and nonionic surfactants.

The results demonstrate that various anionic surfactants form highly effective systems.

The surfactants associated with very high activity a high log reduction for both Gram positive aureus) and Gram negative coli) bacteria) iluclude sodium lauryi sulface, sodium occyi suifate, sodium 2-ethylhexyl sulfate and lauramine oxide.

WO 00/78275 PCT/US00/15729 87 However, it is possible that the high activity of the lauramine oxide containing composition was due primarily to the surfactant.

Series I (Lauryl Sulfates) demonstrates efficacy effects attributed to the cation. The sodium lauryl sulfate had the highest efficacy, wherein ammonium, monoethanolammonium and triethanolammonium exhibited intermediate efficacy.

Lithium and magnesium sulfates exhibited low efficacy. Potassium lauryl sulfate was not tested because of its low solubility at room temperature.

Comparing Series I (Lauryl Sulfates) and Series II (Other Alkyl Sulfates) shows that efficacy varies within a homologous series sodium n-alkyl sulfates). Sodium lauryl sulfate and sodium octyl sulfate yield high efficacy formulas, as does the branched chain surfactant, sodium 2-ethylhexyl sulfate.

The data in Series III (Alkyl Carboxylates) suggests that TCS/carboxylate compositions are not highly active against Gram negative bacteria, but are of acceptable activity against Gram positive bacteria.

The results for Series IV (EO-Containing Surfactants) confirm observations that ethylene oxide (EO) in surfactants tends to inactivate TCS.

The activity of SLES-1 and SLES-2 vs. S. aureus is attributed to the anionic ("lauryl sulfate-like" character) of these anionic/nonionic surfactants.

The results for Series V (Miscellaneous Surfactants) shows that these compositions exhibit ludutadiL Lu luw dCLiviLy, WiLl LiL e~A-cpLi.i uf lauramine oxide. The portion of high activity of WO 00/78275 PCT/US00/15729 88 LAO is attributed to the surfactant alone because of its quasi-cationic character. The remaining surfactant/TCS compositions in Series V showed varied activity vs. S. aureus (Gram positive) and very little activity vs. E. coli (Gram negative).

TCS in Simple Surfactant Systems Active 1S. aureus 1R. coi Type JConc. I Other Ingredients _(30s/1 min.) (30s/1 min.) Series 1--Lauryl Sulfates Anionic 0.3%TCS 1.6% sodium lauryl sulfate (SLS) >3.94/>3.94 4.36/4.36 O%TCS 1.6t sodium lauryl sulfate (SLS) >3.94/>3.94 1.51/2.96 Anionic 0.3%TCS 1.35% ammonium lauryl sulfate (ALS) >3.97/>3.97 1.39/3.95 0%TCS 1.35% ammonium lauryl sulfate (ALS) >3.97/>3.97 -0.07/-0.02 Anionic 0.3%TCS 1.5W monoethanolamine lauryl sulfate (MEALS) 2.29/4.03 0.58/2.04 Anionic 0.3%TCS 1.5% triethanolamine laury). sulfate (TEALS) 2.74/3.73 1.3/4.38 Anionic 0.3%TCS 1.5% lithium lauryl sulfate (LLS) /4.1 .51/.81 Anionic: 0.3%TCS 1.5W magnesium lauryl sulfate (MLS) -I 0.45/0.52 Series 11- -Other Alkyl Sulfates Anionic 0.3%TCS 5% sodium octyl sulfate (SC'S) >4.39/>4.39 >4.83/>4.83 09%TCS 5% sodium octyl sulfate (SOS) 1.76/1.81 >4 .47/>4.47 Anionic 0.3%TCS 9.5% sodium 2-etnyihexyl sulfate (S2EHS) >4.34/>4.84 >4.47/>4.47 0%TCS 9.5% sodium 2-ethyihexyl sulfate (S2EHS) >3.39/>3.39 >4 .45/4 Anionic 0.3*TCS 2.5% sodium decyl. sulfate (SdedS) >4.39/>4.39 0.59/1.23 Anionic 0.3%TCS 2.5% sodium tridecyl sulfate (SC13S) 3. 24/>3 .39 -0.04/0.31 Anionic 0.3%TCS 11.5% sodium alkyl1 sulfate, C12-18 (SCl2-l8S) 2.09/2.85 0.06/0.01 TCS in Simple Surfactant Systems Type___ Coc __JOther Ingredients (30s/1 min.)_ (30s/1 mi.) Anionic 0.3%TCS 1.5% potassium cocoate (KCO) >4.34/>4.34 0.35/1.73 Anionic 0.3%TCS 1.0% potassium oleate (KO) 0.55/0.83 -0.08/-0.07 Anionic 0.3%TCS 2.5% potassium oleate (KO) 0.26/0.52 -0.23/-0.23 0%TCS 2.5% potassium oleate (KO) -0.15/-0.10 -0.30/0.026 Anionic 0.3%TCS 2.0% potassium laurate (KL) 3.08/3.61 0.10/-0.27 Anionic 0.3%TCS 3.0% potassium laurate (1(14 1.06/1.86 0.82/3.02 0%TCS 3.0% potassium laurate 0.18/0.21 1.74/>4.40 Series [V--O-Containing Surfactants Anionic/ 0.3%TCS 1.25% sodium lauryl ether sulfate, 1-mole EQ (SLES-l) >4.39/>4.39 0.41/0.46 Nonioni.: Anionic! 1 0.3%TCS 1% sodium lauryl ether sulfate, 2-mole EQ (SLES-2) >4.24/>4.25 0/0.12 Nonionil; Anionic!' 0.3%TCS 2.0% sodium myreth-4 carboxylate (NaNDX23-4) -0.49/-0.49 -0.19/-0.19 [Nonioni:1I [Nonionil: 0. CS 14% octoxynol-9 (TXlOO) 10.16/0.15 0.43/0.46 TCS in Simple Surfactant Systems Active Is. aureus B. col Type Conc. IOther Ingredients (30s/1 min.) (30s/l min.) Series V--Miscellaneous Surfactants Cationj.c 0.3%TCS 1.5% lauramine oxide (LAO) >4.25/>4.25 >4.63/>4.63 0%TCS 1.5% lauramine oxide (LAO) 3.55/3.86 4.18/4.73 Anionic: 0.3%TCS 1.25% sodium lauroyl sarcosinate (SLSarc) 4.04/>4.34 -0.05/0.04 Anionic 0.3%TCS 1.5% disodium lauryl sulfosuccinate (DSLrylScct) 2.95/4.06 0.02/0.16 Anionic/ 0.3%TCS 1.25% disodium laureth sulfosuccinate (DSLScct) 1.76/2.68 0.36/0.38 Nonionic Anionic 0.3%TCS 1% sodium lauryl sulfoacetate (SLSA) 3.19/3.83 -0.09/-0.03 Anionic 0.3%TCS 2.0% methyl eater aulfonate (MES) >4.64/>4.64 0.11/0.22 Anionic 0.3%TCS 1.25% aipha-olefin sulfonate (AOS) 0.28/0.33 Anionic 0.3% 3% C10 (linear) sodium diphenyl oxide disulfonate 2.77/4.04 0.18/0.23 TCS (L1O-45) Amphoteric 0.3%TCS 1.25% sodium cocoamphoacetate (SCA) -0.15/-0.20 -0.17/-0.15 Amphoteric 0.3%TCS 1.75% cocamidoproyl betaine (CAPB) -0.09/-0.03 0.21/0.61 Nonionic 0.3%TCS 2.5% alkyl polyglucose (APG) -0.10/-0.17 0.01/-0.02 WO 00/78275 PCT/US0O/15729 92 Example 7 This example illustrates the effect of saturation of TCS in surfactant compositions compositions free of a hydric solvent and hydrotrope). The data summarized in the following table illustrate the effect of saturation of TCS on the efficacy of TCS in TCS/surfactant/water compositions. Two sections of the table TCS/ALS compositions vs. E. coli and TCS/SOS compositions vs. S. aureus) show a substantial decrease in antibacterial activity with decreasing saturation.

Also, 100% saturated samples (0.15%TCS/0.67%ALS) and (0.15%TCS/4.0%SOS) have an antibacterial activity approaching that of 100% saturated samples containing 0.3% TCS. In these two examples, the effects are seen clearly for organisms wherein the surfactant does not show a strong placebo kill effect.

Effect og TCS Saturation on Antibacterial Efficacy Log Reduction S. aureus B. coi K. pneui.

TCS%/%Bat'n Surfactant (30./1 min) (30s/1 min) (30a/i min) 0.30/100 1.3596ALS >3.97/>3.97 1.39/3.95 0.27/90 1. 35%9ALS >3.97/>3.97 0.61/2.89 0.21/70 1.35%ALS >3.97/>3.97 0.37/1.54 0.15/50 1.35%ALS >3.97/>3.97 0.09/1.17 0.15/100 0.67%6ALS >3.97/>3.97 1.10/3.63 0/0 1.35WALS >3.97/>3.97 -0.07/-0.02 0.30/100 l.60%SLS >3.94/>3.94 4.36/4.36 0.27/90 1.60%SLS >3.94/>3.94 4.36/>4.46 0.21/70 l.60*SLS >3.94/>3.94 4.04/>4.46 0.15/50 1.60%SLS >3.94/>3.94 4.13/>4.46 0.15/100 0.80%SLS >3.94/>3.94 3.17/>4.46 0/0 1.60%SE.S >3.94/>3.94 1.51/2.96 0.30/100 5.75%SOS 3.3913.04 >4.44/3.98 0.27/90 5.75%SOS 2.59/3.04 >4.44/>4.44 0.21/70 5.75%SOS 1.59/1.82 >4.44/>4.44 0.15/SO 5.75%SOS 0.96/1.43 >4.44/>4.44 0.15/100 4.00%SOS 2.90/3.20 >4.44/>4.44 Effect of TCS Saturation on Antibacterial Efficacy Log Reduction S. aureus R. coi K. pneum.

TCS%/%Sat'n Surfactant (30s/1 min) (30s/i min) (30./i min) 0/0 5.75%SOS 0.23/0.30 >4.44/>4.44 WO 00/78275 PCT/US00/15729 95 Example 8 This example illustrates a composition of the present invention that can be used as a hand cleanser. This example further illustrates an embodiment of the invention wherein the antibacterial agent is present in combination with a surfactant, hydric solvent, and hydrotrope. Composition contains, by weight, 0.3% triclosan, 0.5% ammonium lauryl sulfate, 20% propylene glycol, and 10% sodium xylene sulfonate, with the balance water. Composition A-6, by weight, contains 0.1% triclosan, 0.125% ammonium xylene sulfonate, 20% propylene glycol, and sodium xylene sulfonate the balance being water.

Compositions A-5 and A-6 were 100% saturated with triclosan. Composition A-7 was a "placebo" containing, by weight, 0.5% ammonium lauryl sulfate, propylene glycol, 10% sodium xylene sulfate, and the balance being water.

Log Reduction at 30 seconds (time kill) Product Triclosan Saturation S. aureus E. Coil K. pneum. S. chol.

0.3 100 >3.84 A4.41 3.56 3.26 *6d 0.1 100 >3.84 >4.41 3.82 3.95 A-7 0.0 0 3.22 3.36 0.74 1.77 WO 00/78275 PCT/US00/15729 97 This example illustrates two important features of the present invention. First, the absolute amount of triclosan, or other antibacterial agent, is less important than the percent saturation of antibacterial agent in the composition. For example, composition A-6 (containing 0.10% triclosan) was at least as effective as composition (containing 0.3% triclosan). The important feature is that both compositions were 100% saturated with triclosan. Second, Example 5 also clearly showed that the active antibacterial agent is responsible for the excellent broad spectrum antibacterial activity. Compositions A-5 and A-6 of the invention clearly outperformed the "placebo" composition A-7, which did not contain an active antibacterial agent.

Example 9 This example demonstrates that a hydric solvent and hydrotrope can impart activity to an otherwise inactive surfactant and antibacterial agent composition. In the following table, all percentages are by weight, and the balance of all compositions is water. Composition B contains 1.35% ammonium lauryl sulfate (ALS) and 0.3% triclosan (TCS). Composition C contains 1.35% ALS and 0.0% TCS. Composition D contains 0.25% ALS, 14.4% DPG, 10.0% SXS, and 0.3% TCS, and Composition E contains 0.25% ALS, 14.4% DPG, 10.0% SXS with 0.0% TCS.

Compound F contains 2.5% alkyl polyglucoside (APG") with 0.3% TCS. Compound G contains 0.3% APG, 14.4% diprupyilee ylycuul (DPG), 0% usodium xyleiif: uiluIlate (SXS), and 0.3% TCS. Compound H contains 0.3% WO 00/78275 PCT/US00/15729 98 APG with 14.4% DPG, 10% SXS, and 0.0% TCS. Composition I contains 1.25% sodium cocoamphoacetate (SCA) and 0.3% TCS. Composition J contains 0.25% SCA, 14.4% DPG, 10.0% SXS, and 0.3% TCS. Composition K contains 0.25% SCA, 14.4% DPG, 10.0% SXS, and 0.0% TCS. Composition L contains 1.75% cocamidopropyl betaine (CAPB) and 0.3% TCS. Composition M contains 0.25% CAPB, 14.4% DPG, 10% SXS, and 0.3% TCS. Composition N contains 0.25% CAPB, 14.4% DPG, 10% SXS, and 0.0% TCS. Composition 0 contains 4% octoxynol-9 (TRITON X-100'

T

TX100). Composition P contains 0.75% TX100, 14.4% DPG, 10.0% SXS, and 0.3% TCS.

Composition Q contains 1.25% sodium lauryl ether sulfate (1 EO, SLES-1) and 0.3% TCS. Composition R contains 0.25% SLES-1, 14.4% DPG, 10.0% SXS, and 0.3% TCS.

Log Reduction (Time Kill) Trici osan B. aureuB Z. Coll Com~oaition %Other Ingredients Saturation (30s/60s) (30s/60s) B 0.3 l.35tALS -100 >3.97/>3.97 1.39/3.95 C 0.0 l.35tALS 0 >3.97/>3.97 -0.07/-0.02 D 0.3 0.25WALS, 14.4%DPG, 10.O%SXS -100 >3.80/>3.80 >4.38/>4.38 E 0.0 0.25%ALS, 14.4%DPS, 10.0%SXS -100 1.31/1.54 >2.49/>4.18 F 0.3 2.5%APG -100 1.19/1.21 >4.69/>4.69 G 0.3 0.3%APG, 14.4%DPG, lO.0%SXS -100 >4.69/>4.69 4.50/4.58 H 0.0 0.3%APG, 14.4%DPG, 10.O%SXS 0 1.19/1.21 >4.69/>4.69 I0.3 1.25%SCA -100 -0.15/-0.20 -0.17/-0.15 J0.3 0.25%SCA, 14.4%DPG, 10.0%SXS -100 >4.39/>4.39 >4.73/>4.73 K 0.0 0.25%SCA, 14.4%DPG, 10.0%SXS 0 0.86/0.88 2.90/4.05 Log Reduction (Time Kill) Triclosan aureus R. Coill Conmoaition Other Ingredients Saturation (30o/60s) (30s/60s) L 0.3 l.75%CAPB -100 -0.09/-0.03 0.21/0.61 M 0.3 0.25%CAP3, 14.4%DPO, 10.0%SXS -100 >4.39/>4.39 >4.73/>4.73 N 0.0 0.25%CAP3, 14.4%DPG3, 10.O%SXS 0 0.76/0.85 3.26/4.69 0 0.3 4%TX100 -100 0.16/0.15 0.43/0.46 p 0.3 0.75%TX100, 14.4WDP3, 10.09iSXS -100 0.53/0.58 3.59/>4.73 Q 0.3 l.25%SLES-1 -100 >4.39/>4.39 0.41/0.46 R 0.3 0.25WSLES--1, 14.496DPG, l0.0%SXS -100 >4.34/>4.84 >4.47/>4.47 WO 00/78275 PCT/US00/15729 101 The results of the time kill tests summarized in the above table very surprisingly show that the use of a hydric solvent and hydrotrope can impart a high antibacterial activity to surfactant/TCS combinations which alone exhibit only low to moderate efficacy compare efficacy of composition F vs. G; I vs. J; L vs. M; and Q vs. The hydric solvent and hydrotrope also can render active compositions more active in shorter contact times compare composition B vs. Especially surprising is the observation that a hydric solvent and hydrotrope can impart antibacterial efficacy against E.

coli even in a composition containing a nonionic surfactant, octoxynol-9 (compare compositions 0 vs. This result is unexpected because polyethoxylated surfactants are known to inactivate phenolic antibacterial agents.

Example This example demonstrates the importance of saturation in compositions containing a hydric solvent and hydrotrope. As observed in surfactant/- TCS compositions, the relative saturation of the antibacterial agent in the continuous aqueous phase of the composition also greatly influences the antibacterial activity of compositions containing a hydric solvent and hydrotrope. As the results summarized below illustrate, this influence on antibacterial activity is especially apparent with respect to the Gram negative bacterium, K. pneum.

Composition Triclosan Other Ingredients Saturation S 0.3 0.25WALS, 14.4%DPG, 10.0*SXS -100 T 0.3 0.50%ALS, 14.4%DPG, 10.OSXS <S U 0.3 1.O0%ALS, 14.4%DPG, 10.0%SXS T V 0.0 1.O0%ALS;, 14.4%DPG, 1O.096SXS 0 w 0.3 1.20%ALS, 2.5%DPG, 10.0%SXS -100 X 0.3 2.5WALS, 2.5%DPG, 10.0%SXS Y 0.3 5.0%ALS, 2.5%DPG, 10.0%SXS .cW, X Z 0.0 5.0%ALS, 2.5%DPG, 10.0%SXS 0 Reduction (time kill) Composition S. aureus E. Coil K. pneum. S. chol.

(309/ 60s) (30s/60s) (30s/60s) (30s60s) S >3.62/>3.62 >4.59/>4.59 2.64/>3.84 >3.85/>3.85 T >3.62/>3.62 >4.59/>4.59 2.43/3.69 >3.85/>3.85 U 1.67/2.31 >4.59/>4.59 0.89/1.93 3.501>3.85 V 1.10/1.29 3.42/4.59 0.28/0.67 2.17/>3.85 W 4.19/4.39 X 2.83/3.99 y 2.39/3.22 Z 1.80/2.52 WO 00/78275 PCT/US00/15729 104 From the above data, it is clear that an increase in antibacterial efficacy, as measured by a time kill test, is associated with an increasing saturation of the antibacterial agent in the aqueous phase of a given composition. This example further shows that compositions containing an antibacterial agent, surfactant, hydric solvent, and hydrotrope are effective when a high saturation of active antibacterial agent is maintained.

Example 11 This example, in conjunction with Example illustrates the effect of saturation of TCS in compositions containing a hydric solvent, hydrotrope, and surfactant. As previously observed with simple surfactant/TCS compositions, the relative saturation of the antibacterial agent in the composition also influences the antibacterial activity of a composition containing a hydric solvent and/or a hydrotrope. From the data summarized in the table of Example 10 and the following table, it is clear that a substantial gain in antibacterial efficacy (as measured by a time kill test) is associated with an increasing saturation of the antibacterial agent in a given type of composition. The tables demonstrate this effect from two different perspectives. The table in Example 10 shows the effect of changing the concentration of surfactant while maintaining the amount of other composition components constant. The following table shows the effect of h cctration of all other c nents is kept cnstant.

tration of all other components is kept constant.

WO 00/78275 PCT/US00/15729 105 In the table of Example 10, the information relating to saturation is relative because saturation is difficult to directly calculate. Even using this qualitative data, the effect of saturation of TCS is clear from both tables for all organisms tested.

Activity Dependence on Saturation of TCS in Hydric Solvent/Hydrotrope/Surfactant Compositions Log Reduction (Time Kill) S. aureus K. pneum.

Tric1~san %Other Ingredients Saturation (30s/60s) (30s/60s) 0.413 5%DPG, 15%SXS, 0.75%ALS 100 >4.55/>4.55 >3.811>3.81 0.372 5%DPG, 15*SXS, 0.75%ALS 90 >4.55/>4.55 3.81/>3.81 0.330 5%DPG, 15%SXS, 0.75%ALS 80 >4.55/>4.55 3.46/>3.81 0.300 5%DPG, 15%SXS, 0.75%ALS 73 >4.55/>4.55 3.40/>3.81 0.248 5%DPG, 15%SXS, 0.75WALS 60 3.02/4.05 2.73/>3.81 0. 207 5%DPG, 15%SXS, 0.75WALS 50 1.96/3.05 2.45/>3.81 0.166 MPG, 15%SXS, 0.75%ALS 40 1.94/2.15 2.30/>3.81.

0. 103 5IDPG, 15%SXS, 0.75%ALS 25 1.72/1.93 1.34/2.78 WO 00/78275 PCT/US00/15729 107 Example 12 This example illustrates the effect of different levels of hydric solvent and hydrotrope on antibacterial efficacy. In particular, the data summarized below demonstrates the effect of varying the relative amounts of hydric solvent and hydrotrope. It should further be noted that the addition of a perfume (PF) and/or a preservative (DMDM) to the composition has only a modest effect, if any, on the antibacterial efficacy of the compositions.

Log Reduction (Time Kill) Triclosan S. aureus B. coll K. pneum. S. choler.

Compoai:ion Other Ingredients (30s/60s) (30s/609) (309/60) (30s/60s) CCC Calc 14.5%DPG, l0.0%SXS >3.631>3.63 >4.44/>4.44 >4.14/>4.14 >4.14/>4.14 0.0502 DDD 0.0 14.5%DPG, 10.0%SXS 0.03/0.04 0.26/0.17 0.34/0.39 0.36/0.47 E 0.0 0.25%ALS, 14.4%DPG, 10.0%SXS 1.31/1.54 2.49/4.18 0.41/0.78 2.62/>4.04 S 0.3 0.25%ALS, 14.4%DPG, 10.0%SXS >3.62/>3.62 >4.59/>4.59 2.64/>3.84 >3.85/>3.85 T 0.3 0.50%ALS, 14.4%DPG, 10.0%SXS >3.62/>3.62 >4.59/>4.59 2.43/3.69 >3.851>3.85 U 0.3 1.00%ALS, 14.4%DPG, 10.0%SXS 1.67/2.31 >4.59/>4.59 0.89/1.93 3.50/>3.85 V 0.0 1.00%ALS, 14.4%DPG, 10.0%SXS 1.10/1.29 3.4214.59 0.28/0.67 2.17/>3.85 AA 0.3 0.75ALS, S.ODPG, 10.0%SXS 0.95/2.00 BB 0.3 0.75%ALS, 5.0%DFG, 12.5%SXS 1.77/3.36 CC 0.3 0.75%ALS, 5.0%DPG, 15.0%SXS 3.49/>3.69 DD 0.3 0.75%ALS, 5.0%DPG, 17.5%SXS >3.691>3.69 EE 0.3 0.75ALS; S.ODPG, 20.0%SXS >3.69/>3.69 FF 0.3 0.75%ALS, 7.5%DPG, 10.0%SXS 0.81/2.87 GG 0.3 0.75ALS, 7.5%DPG, 12.5%SXS 1.72/4.21 HH 0.3 0.75%ALS, 7.SDPG, 15.0%SXS 3.04/4.31 II 0.3 0.75TALS, 7.SDPG, 17.5%SXS >4.41/>4.41 Log Reduction (Time Kill) Triclosan B. aureus B. coi K. pneum. S. choler.

Composi'-ion %Other Ingredients (309/60s) (30s/60s) (30o/60s) jj 0.3 0.75%ALS, 7.5%DPG, 20.096SXS >4.41/>4.41 KK 0.3 l.O%ALS, 5.0%DPG, l0.0tSXS 0.08/1.49 LL 0.3 l.0%ALS, 5.0%DPG, 12.SWSXS 0.97/3.32 mm 0.3 l.0%ALS, 5.0%DPG, 15.0%SXS 2.57/>4.41 NN0.3 1.0%ALS, 5.0%DPG, l7.54sSXS >4.41/>4.41 00 0.3 1.0%ALS, 5.0%DPG, 20.0%SXS >4.41/>4.41 PP 0.3 1.0%ALS, 7.5%DPG, 10 05MS 0.17/0.920 00 0.3 1.0%ALS, 7.59&DPG, 12.54SXS 0.92/2.94 RR 0.3 1.0%ALS, 7.5%DPG, l5.04SXS 2.92/>3.69 SS 0.3 1.0%ALS, 7.5%DPG, 17 -554SXS >3.691>3.69 TT 0.3 1.0*ALS, 7.5%DPG, 20.0%SXS >3.69/>3.69 tJU 0.3 0.75%ALS, 5.0%DPG, 15.0%SXS 3. 79/>4.64 >4.57/>4.57 4.07/>4.69 >3.97/>3.97 vv 0.3 0.75%ALS, 5.C)%DPG, 15.0%SXS 3.07/3.76 4.01/>4.34 3.40/>4.46 >4.04/>4.04 WW 0.0 0.75%ALS, 5.O%DPG, 15.0%SXS 0.79/0.90 >4.34/>4.34 0.41/1.53 >4.04/>4.04 XX 0.3 0.75tALS, 10.0%DPG, 10.0%SXS >4.78/>4.78 0.67/1.46 YY 0.3 0.75%ALS, 10.0*DPG, 20.0%SXS >4.78/>4.78 >4.17/>4.17 ZZ 0.0 0.75%ALS, 10.0%DPG, 20.0tSXS >4.78/>4.78 1>4.17/>4.17 Log Reduction (Time Kill) Triclosan S. auraus B. Coil X. pneum. S. choler.

Composition %Other Ingredients (30o/60s) (30s/60s) (30s/60s) (30s/60s) AAA 0.3 10.75WALS, 14.4%DPG, l0%SXS >4.95/>4.95 BBB 0.0 0.75%ALS, 14.4%DPG 0.28/0.28 WO 00/78275 PCT/US00/15729 111 It was observed that for compositions S, T, and U, the antibacterial activity against S.

aureus and K. pneum. increases, especially, with a decreasing wt% of ALS surfactant an increase in saturation of TCS). Compositions CC, HH, MM, and RR demonstrate that about 15% SXS, or more, is preferred to exhibit high activity against K. pneum.

in compositions containing a hydric solvent and a hydrotrope. This observation suggests that the hydrotrope may be acting as an adjuvant for the TCS because the time required for a substantial antibacterial kill, log reduction of at least 2, is reduced.

Example 13 The data summarized in the following table support a theory that the two primary factors for improved antibacterial efficacy are the relative amounts of surfactant and hydrotrope to the amount of antibacterial agent in compositions containing a surfactant, hydric solvent, and antibacterial agent.

A higher percentage of surfactant can reduce the saturation, and thereby decrease the antimicrobial activity of the composition. On the other hand, a higher percentage of hydrotrope appears to provide a higher activity against certain organisms, like K.

pneum. and S. choler. It is theorized that the higher percentage of hydrotrope in the composition provides a greater amount of active antibacterial compound in the aqueous nonmicellar) phase of the cctpcityn, thei solvent.by th e, mayhiger ime kill activity. The solvent,, therefore, may be act- WO 00/78275 PCT/US00/15729 112 ing as both an additive to enhance antimicrobial activity and to provide better physical stability in these compositions.

Log Reduction (Time Kill) S. aureua B. Coll K. pneum. S. choler.

Composition Triclosan Other Ingredients (30o/60s) (30a/60s) (30o/60s) (30o/60s) CCC Caic. 14.5%DPG, 10.0%SXS >3.63/>3.63 >4.44/>4.44 >4.14/>4.14 >4.14/>4.14 0.0502 DDD 0.0 14.5%DPG, l0.0%SXS 0.03/0.04 0.26/0.17 0.34/0.39 0.36/0.47 EEE 0.3%TCS 0.25%ALS, 14.4%DPG, >3.80/>3.80 >4.38/>4.38 3.54/>4.07 >4.04/>4.04 0%SXS F'FF 0%TCS 0.25WALS, 14.4WDPG, 1.31/1.54 2.49/4.18 0.41/0.78 2.62/>4.04 0%SXS GGG 0.3%TCS 0.25%ALS, 14.4%DPG, >3.62/>3.62 >4.59/>4.59 2.64/>3.84 >3.85/>3.85 0%SXS HHH 0.3%TCS 0.5%ALS, 14.4%DPG, >3.62/>3.62 >4.59/>4.S9 2.43/3.69 >3.85/>3.85 0%SXS III 0.3%TCS 1%ALS, 14.4%DPG, 1.67/2.31 >4.59/>4.59 0.89/1.93 3.50/>3.85 0VSXS iii 0%TCS 196ALS, 14.4%DPG, 1.10/1.29 3.42/4.59 0.28/0.6? 2.17/>3.85 0%SxS KKK 0.4%TCS 0.25%ALS, 14.4%DPG, >4.59/>4.59 >4.70/>4.70 4.11/>4.41 >4.04/>4.04 10.0%SXS, 0.05%PF LLL 0.3%TCS 0.25%ALS, 14.4%DPG, >4.59/>4.59 >4.70/>4.70 4.06/>4.41 >4.04/>4.04 10.0%SXS, 0.05%PF MMM 0%TCS 0.25%ALS, 14.4%DPG, 1.70/2.19 3.97/>4.70 0.50/1.43 3.04/>4.04 I 10.0%SXS, 0.05%PP Log Reduction (Time Kill) S. aursus H. Coil K. pneum. S. choler.

Composit~ion Triclosan Other Ingredients (30s/60s) (30o/60s) (30a/609) (30a/60s) NNN 0.3%TCS 0.25%ALS, 14.4%DPG, >4.77/4.57 >4.71/>4.71 3 .90/>4 .55 >4.20/>4.20 10.0%SXS, 0.05%PF 000 0.3%TCS 1%ALS, 14.4%DPG, 3.18/4.09 >4.71/>4.71 1.11/3.62 3.90/>4.20 10.0%SXS, PPP 0.3%TCS 0.5%ALS, ]4.4%DPG, 4.39/>4.77 >4.71/>4.71 3.00/>4.55 >4.20/>4.20 l0.0%SXS, 0.05%PF QQQ 0%TCS l%ALS, 14.4%DPG, 2.42/3.07 3.03/>4.71 0.65/0.98 2.29/4.10 l0.0%SXS, 0.05%PF RRR 0.3%TCS 0.5%ALS, 14.4tDPG, >4.71/>4.71 >4.61/>4.61 2.10/3.97 >3.87/>3.87 10.0%SXS, 0.05%PF SSS 0.3%TCS 0.6%ALS, 14.4%DPG, >4.71/>4.71 4.61/>4.61 1.46/3.62 >3.87/>3.87 10.0%SXS, 0.05%PF TTT 0.3%TCS 0.75WALS, 14.4%DPG, 4.28/>4.71 >4.61/>4.61 1.42/3.34 >3.87/>3.87 10.0%SXS, 0.05%PF UUU 0.3%TCS 0.35%ALS, 10.0%DPG, >4.23/>4.23 >4.62/>4.62 3.30/4.63 >3.87/>3.87 10.0%sxs, 0.05%PF VVV 0.3%TCS 0.5%ALS, 10.0%DPG, >4.23/>4.23 >4.62/>4.62 2.86/4.18 >3.87/>3.87 10.0%SXS, 0.OS%PF WW0.3%TCS 0.5%ALS, 7.5%DPG, >4.23/>4.23 >4.62/>4.62 2.63/3.77 >3.87/>3.87 1 1 10.0%SXS, 0.05%PF Log Reduction (Time Kill) S. aureus E. Coll K. pneum. S. choler.

Compooil:ion Triclosan Other Ingredients (30u/60s) (30s/60s) (30o/60s) (30s/60s) xxx 0.3WTCS 0.6%ALS, 7.5%DPG, >4.23/>4.23 >4.62/>4.62 2.45/3.15 >3.87/>3.87 10.0%SXS, 0.05*PF YYY 0.3%TCS 0.SWALS, )4.4%DPG, >3.83/>3.83 >4.41/>4.41 2.89/>3.76 >3.59/>3.59 10.0%SXS, 0.05%PF, o ZZZ 0%TCS 0.5WALS, 14.4%DPG, 1.48/2.10 3.84/>4.41 0.38/1.12 2.09/3.45 10.0*SXS, 0.05*PF, 0.25 %DMDM AAAA 0.3%TCS 0.75%ALS, 5.0%DPG, >4.07/>4.07 3.90/4.03 1.97/3.66 3.24/3.24 10.0%SXS, 0.0S%PF BBBB 0.3%TCS 0.75WALS, 5.O%DPG, >4.07/>4.07 3.10/4.28 0.25/2.23 0.91/2.80 0.05%PF CCCC 0.3%TCS 0.75WALS, 7.5%DPG, >4.07/>4.07 3.82/>4.53 1.49/3.56 2.93/>3.34 10.0%SXS, DDDr 0.3%TCS 0.75%ALS, 7.5*DPG, >4.07/>4.07 3.47/4.18 0.19/2.00 0.99/2.76 7.5%SXS, 0.05%PF WO 00/78275 PCTIUSOO/15729 116 Exam~1e 14 This example shows that other hydric solvents can be used in a composition of the present invention.

Log Reduction (Time Kill) Triclosan S. aureus H. coi K. pneum. S. choler.

Conzp~sition %Other Ingredients (30o/60a) (30s/60s) (30s/60s) (30e160s) E:EEE 0.3 0.75%ALS, 5.0% tripropylene 4.24.3.91 >4.73/>4.73 (TPG), 10.0WSXS FFFF 0.3 0.75%ALS, l0.0%'TPG, 2.59/3.65 >4.73/>4.73- 0%SXS CGGG 0.0 0.75%ALS, 10.0%TPO, 0.77/1.11 3.60/4.40 0wSXS FHH0.3 0.75%ALS, 14.41s propylene >4.44/>4.44 4.58/>4.78- 10.0%SXS 1110.3 1.0%ALS, 10.0%PG, l0.0%SXS >4.44/>4.44 4.481>4.78 JJJ0.3 0.StALS, 20.0%PG, 10.0%SXS >3.99/>3.99 >4.45/>4.55 3.66/>4.04 3.23/>3.68 FKKK 0.1 0.5%ALS, 20.0%PG, 10.0%SXS >3.99/>3.99 3.75/>4.55 1.08/3.13 1.51/2.84 LLLL 0.0 0.S%ALS, 20.0%PG, 10.0%SXS >3.99/>3.99 2.58/4.14 0.25/.072 1.28/2.36 MMMM 0.1 0.12%ALS, 20.0%PG, 10.0%SXS >3.84/>3.84 >4.41/>4.41 3 .82/>3 .92 3.95/>3.95 NNNN 0.3 0.5%ALS, 20.0tPG, 10.0%SXS >3.841>3.84 >4.41/>4.41 3 .56/>3 .92 3.26/>3.95 0000 0.0 0.5%ALS, 20.0%PG, 10.0%SXS 3.22/3.84 3.36/>4.41 0.74/1.49 1.77/2.93 PPPP 0.3 0.8%SLS, 10.0%PG, 5.0%SXS >4.11/>4.11 2.50/>3.61- CQQQ 0.0 0.8%SLS, 1.0.0%PG, 5.0%SXS 2.67/3.91 1.19/2.40 RRRR 0.3 0.8%ALS, 10.0%PG, 5.0%SXS >4.11/>4.11 11.66/3.25 Log Reduction (Time Kill) Triclosan S. auraus B. coi K. pneum. S. choler.

Composition %Other Ingredienta (30o/60s) (30o/60s) (30o160s) (30s160s) SSSS 0.0 O.BALS, 3i0.0%PG, 5.09%SXS 2.28/3.03 0.79/1.63 ITTT 0.26 O.9%5ALS, 10.O%PG, 5.O%SXS >4.24/>4.25 0.16/0.93 -0.02/0.07 0.53/0.33 UUUU 0.0 O.9%ALS, 10.0*PG, 5.0%SXS 2.53/>4.25 0. 06/0.21 0.10/0.00 0.17/0.13 WO 00/78275 PCT/US0O/15729 119 In addition to the observation that other solvents PG and TPG) can be used in compositions of the present invention, products JJJJ through 0000 illustrate another effect of relative saturation of antibacterial agent in the system.

The relative saturation (highest to lowest) of the first three compositions is JJJJ>KKKK>LLLL. Composition KKKK has one-third the amount of TCS as composition JJJJ solubilized in the same level of ALS and compositions LLLL contains 0% TCS.

Significant reductions in activity were observed with respect to K. pneum. and S. choler. when the relative saturation of TCS in the composition decreases. It also was observed that when the relative saturation is essentially equal about 100%), the activity remains essentially constant even though the absolute amount of TCS in the composition is decreased compare Compositions MMMM to NNNN). These data further support the observations with respect to the importance of saturation set forth in Example 7.

In addition, a comparison of composition IIII to composition TTTT shows that composition TTTT contains slightly less ALS vs. 1.0% for IIII), the same amount of PG and one-half the amount of SXS vs. 10.0% for IIII). Experimental observations indicated that compositions IIII and TTTT were at or near 100% saturation. However, the log reductions of E. coli were considerably lower (about 4 log) for Composition TTTT. This observation further supports the data set forth in xam pl whijjiL LLiii IIILU itLVtei UL iiyULLLUP- Itldy u) WO 00/78275 PCT/US00/15729 120 needed for a high antibacterial efficacy against at least some Gram negative bacteria.

Example The following compositions 15-A through were prepared to demonstrate the superior germ kill provided by compositions of the present invention compared to control compositions compositions free of an antibacterial agent), even when very low amounts of disinfecting alcohol are present. Compositions 15A-15D were prepared using standard mixing techniques known in the art. Table 4 below lists the composition ingredients. Table below summarizes the antibacterial efficacy of compositions 15-A through 15-D, as measured in a time kill test.

Table 4 Composition by weight (as active substance) TCS Ethanol PPG-9 DPG Water 0 25.86 11.5 Balance (control) 0.10 25.86 11.5 Balance 15-C 0 23.0 11.18 Balance (control) 0.10 23.0 11.18 Balance WO 00/78275 PCT/US00/15729 121 Table Composition Log reduction 15 sec/30 sec S. aureus E. coll K. pneum. S. chol.

15-A 0.55/1.73 0.18/0.43 1.15/0.71 2.51/4.24 3.27/>4.43 3.75/>4.51 1.33/3.10 4.09/4.34 0.01/0.0 0.17/0.12 0.4/0.11 0.18/0.17 >4.43/>4.43 3.20/3.48 3.19/4.03 2.86/3.99 Example 15 illustrates the surprisingly high efficacy of compositions of the present invention (15-B and 15-D), wherein high log reductions are observed against both Gram positive and Gram negative bacteria, even for compositions containing less than 26% ethanol. The results are in contrast to compositions described in prior disclosures, wherein high alcohol concentrations greater than about 40%) are relied upon to achieve a high, broad spectrum antibacterial activity.

Example 16 Example 16 shows that compositions of the present invention provide excellent, broad spectrum antibacterial activity, even at further reduced alcohol concentrations. Accordingly, composition 16-A containing 0.15% TCS, 11.18% ethanol, 25.71% DPG, the balance being water (as weight percent of active compounds), was prepared. For comparison, an identical control composition 16-B was prepared, except composition 16-B was free of TCS. The following table summarizes the results of antibacterial WO 00/78275 PCT/US00/15729 122 efficacy of compositions 16-A and 16-B by time kill tests.

Composition Log reduction 0 15 sec/30 sec S. aureus B. coli K. pneum. S. chol.

16-A 4.54/>4.69 >4.78/>4.78 3.63/>4.11 1.12/1.31 16-B 0.88/0.97 0.36/0.37 0.0/0.0 0.0/0.0 Example 16 further demonstrates that the concentration of alcohol in the present compositions can be reduced to very low levels without sacrificing antibacterial activity. Accordingly, compositions that provide excellent antibacterial efficacy, and that do not dry the skin, can be prepared.

Prior compositions that relied on a high alcohol concentration for antibacterial activity dried the skin, and often caused skin irritation.

Example 17 Example 17 demonstrates that highly effective compositions of the present invention can incorporate p-chloro-m-xylenol (PCMX) as the antibacterial active agent. Composition 17-A was prepared by admixing 0.1% PCMX, 13.42% ethanol, and the balance water (as weight percent of active compounds).

The antibacterial efficacy of composition 17-A was evaluated by a time kill test and exhibited log reductions against S. aureus, E. coli, K. pneum., and S. chol., at 30 seconds contact time, of 4.16, >4.34. 3.99. and >4.04. rpnrCt lv ip-i Thuii cnmrn%sition 17-A is a highly effective antibacterial WO 00/78275 PCT/US00/15729 123 composition, even though the composition contained a very low concentration of ethanol.

Example 18 Example 18 illustrates a composition of the present invention containing a cationic gelling agent, CELQUAT CS-230M. Composition 18-A was prepared by admixing 0.15% TCS, 28% ethanol, 11.18% DPG, and 2% CELQUAT CS-230M, and the balance was water (as weight percent of active compounds, except CELQUAT, which is The antibacterial efficacy of composition 18-A was evaluated by a time kill test. Composition 18-A demonstrated the following log reductions against S. aureus, E. coli, K.

pneum., and S. chol., at 30 seconds contact time of >3.83, 4.33, >4.43, and >3.55, respectively. Thus, composition 18-A is a highly effective antibacterial composition, even though the composition contained a very low concentration of ethanol.

Example 19 Compositions of the present invention can contain a wide variety of gelling agents, hydric solvents, and antibacterial active agents, illustrated by the following examples. In Table 6 below, all weight percentages are as active material, except where indicated by a which indicates an "as-is" weight. The compositions were prepared by mixing and gel preparation techniques well known to persons skilled in tne art. The compositions exhibited acceptable clarity, stability, and performance.

Table 6 Composition A B C! D 9 P G H I J ingredient TCS 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.15 0.1 0.11 Deionized water q sqs qs qs qs qs qs qs qs LJBRAGEL DV* 15 15 10 1010 10 10 10 IPA 18.5 24.93 Propylene Glycol 14 14 14d E:hanol 23 23 23 23 34.25 23 P ?G -9 11.5 36 D ?G 11.18 35 11.18 Pi~rfume LAPONITE XLG* C1HLQUAT CS-230M* PC MX ULTREZ Df.isopropylamine Table 6 Composition K L m N 0 p QR S T Ingredient TCS 0.1 0. 1 0.1 0.1 0.1 0.1 0.1 D~donized water q qs q I qs qs qs qs qs LtrBRAGEL DV* IIIA 18.5 18.5 Propylene Glycol 44.2 14 14 Ethanol 23 35 28 28 23 28.07 4.1 PI'G-9 14.14 11.16 7.26 DIG 11.18 11.18 11.18 L PErfume 0.04 0.2 0.04 LLPONITE XLG* 1.5 1.5 2 CE:LQUAT CS-230M* 2.5 2 2 2 PCMX 0.1 0.15 0.1 UITREZ 10* 0.3 0.3 0.3 Di isopropylamine 0.05 0.05 0.05 WO 00/78275 PCT/US00/15729 126 The data presented in all the above tables and examples show that saturation of antibacterial agent in the aqueous phase of the composition can be directly correlated to a log reduction of bacteria.

For example, as shown in the prior tables, a composition having 50% saturation of TCS in the aqueous phase demonstrates a log reduction versus S. aureus of 1.96 (30 seconds) and 3.05 (60 seconds) and a log reduction versus E. coli of 2.45 (30 seconds) and greater than 3.81 (60 seconds). A 75% saturated and a 100% saturated composition exhibited a log reduction of greater than 4.55 (30 and 60 seconds) vs. S.

aureus a log reduction in excess of the detection limit of the assay). The 75% and 100% saturated compositions exhibited a log reduction of 3.40 seconds) and greater than 3.81 (60 seconds) and greater than 3.81 (30 and 60 seconds) vs. E. coli, respectively. Accordingly, the present antibacterial compositions can be characterized as exhibiting a log reduction of at least about 2 (after 30 seconds) or at least about 3 (after 60 seconds) vs. S.

aureus, or of at least about 2.5 (after 30 seconds) or at least about 3.5 (after 60 seconds) vs. E.

coli.

The antibacterial compositions of the present invention have several practical end uses, including hand cleansers, mouthwashes, surgical scrubs, body splashes, hand sanitizer gels, and similar personal care products. Additional types of compositions include foamed compositions, such as creams, mousses, and the like, and compositions containing organic and inorganic filler materials, such as emulsions, lotions, creams, pastes, and the WO 00/78275 PCTIUS00/15729 127 like. The compositions further can be used as an antibacterial cleanser for hard surfaces, for example, sinks and countertops in hospitals, food service areas, and meat processing plants. The present antibacterial compositions can be manufactured as dilute ready-to-use compositions, or as concentrates that are diluted prior to use.

The compositions also can be incorporated into a web material to provide an antibacterial wiping article. The wiping article can be used to clean and sanitize skin or inanimate surfaces.

The present antimicrobial compositions provide the advantages of a broad spectrum kill of Gram positive and Gram negative bacteria in short contact times. The short contact time for a substantial log reduction of bacteria is important in view of the typical 15 to 60 second time frame used to cleanse and sanitize the skin and inanimate surfaces.

The present compositions are effective in short contact time because the antibacterial agent is present in the aqueous continuous phase of the composition, as opposed to surfactant micelles. The antibacterial agent, therefore, is available to immediately begin reducing bacterial populations, and further is available to deposit on the skin to provide residual antibacterial efficacy. In addition, because the antibacterial agent is in solution as opposed to surfactant micelles, the absolute amount of antimicrobial agent in the composition can be reduced without adversely affecting efficacy, and with the surfactant prior to performing its antibacwith the surfactant prior to performing its antibac- WO 00/78275 PCTUS00/15729 128 terial function. In addition, the amount of surfactant in the present antibacterial compositions typically is low, thereby providing additional environmental benefits.

The following examples illustrate various compositions of the present invention.

Example Hand Wash Composition A composition in accordance with the instant invention, suitable for use as a hand wash, was prepared. The composition contained the following components in the indicated weight percentages: Ingredient Weight Percent Triclosan 0.3 Ammonium Lauryl Sulfate 0.75 Dipropylene Glycol Sodium Xylene Sulfonate 10.0 Fragrance 0.05 Water q.s.

The composition was prepared by admixing the dipropylene glycol, TCS, and fragrance until homogeneous (about 5 minutes). After the triclosan was completely dissolved, as evidenced by the absence of undissolved solid material, the sodium xylene sulfonate was added to the solution. The resulting mixture then was stirred to completely utes). Finally, the ammonium lauryl sulfate and utes). Finally, the ammonium lauryl sulfate and WO 00/78275 PCT/US00/15729 129 water were added to the resulting solution, and the composition was stirred until homogeneous (about minutes).

The composition had a weight ratio of surfactant:triclosan of 2.5:1, and was at least about 90% saturated with triclosan. The composition was evaluated for antibacterial efficacy against S.

aureus and E. coli using a time kill test. Against S. aureus, the composition exhibited a log reduction of >4.07 in 30 seconds, while against E. coli the composition exhibited a log reduction of 3.90 in seconds. Thus, the composition exhibited an excellent broad spectrum antibacterial activity. Also, the composition was an excellent hand wash composition in an actual use test, providing both good cleansing and a smooth feel to the hands.

Example 21 Body Splash Composition A composition in accordance with the present invention, suitable for use as a body splash, is prepared using the following ingredients in the following weight percentages: WO 00/78275 PCT/US00/15729 130 Ingredient Weight Percent Triclosan 0.3 Alkyl Polyglycoside 0.3 Propylene Glycol 14.4 Sodium Xylene Sulfonate 10.0 Ethanol 10.0 Fragrance 0.05 Water q.s.

The composition is prepared by combining the triclosan, propylene glycol, fragrance, and ethanol, and admixing the components until all the triclosan is dissolved, as evidenced by the absence of undissolved solid material. The sodium xylene sulfonate then is added, and the resulting mixture is stirred until the sodium xylene sulfonate is completely dissolved. Finally, the alkyl polyglycoside and water are added, and the mixture again is stirred until homogeneous. The resulting composition forms an excellent and refreshing body splash that provides a desirable level of bacterial reduction on the skin of the user.

Example 22 Mouthwash Composition A composition in accordance with the present invention, suitable for use as a mouthwash, is prepared using the following ingredients in the following weight percentages: WO 00/78275 PCT/USOO/15729 131 Ingredient Weight Percent Triclosan 0.3 Alkyl Polyglycoside 0.3 Propylene Glycol 14.4 Sodium Xylene Sulfonate 10.0 Denatured alcohol 10.0 Oil of Wintergreen (flavor) 0.05 Water q. s.

The composition is prepared by combining the triclosan, propylene glycol, flavor, and denatured alcohol, and admixing the components by any conventional means until all the triclosan is dissolved, as evidenced by the absence of undissolved solid material. Then, the sodium xylene sulfonate is added, and the resulting mixture is stirred until the sodium xylene sulfonate is completely dissolved.

Finally, the alkyl polyglycoside and water are added, and the mixture again is stirred until homogeneous. The resulting composition forms an excellent and refreshing mouthwash that provides a desirable level of bacterial reduction on the teeth, gums, and tongue of the user.

Example 23 Wet Wipe Composition A composition in accordance with the present invention, suitable for impregnating a nonwoven material for the preparation of a wet wipe article, wfol nrnarrlg weiinght percenta wing inries in hp following weight percentages: WO 00/78275 PCT/US00/15729 132 Ingredient Weight Percent Triclosan 0.3 Ammonium Lauryl Sulfate 0.75 Dipropylene Glycol Sodium Xylene Sulfonate 15.0 Water q.s.

The composition was prepared by combining the triclosan and dipropylene glycol, and admixing the components until all the triclosan was dissolved, as evidenced by the absence of undissolved solid material. The sodium xylene sulfonate then was added, and the resulting mixture was stirred until the sodium xylene sulfonate was completely dissolved. Finally, the ammonium lauryl sulfate and water were added, and the mixture was again stirred until homogeneous.

A piece of nonwoven cellulosic web material a commercial paper towel) then was dipped by hand into the composition to form a wet wipe article, suitable for wiping and cleaning surfaces, for example, hands. The article formed an excellent wet wipe and the impregnated antibacterial composition was freely expressed from the web to provide a broad spectrum antibacterial activity.

WO 00/78275 PCT/US00/15729 133 Example 24 Hand Wash Composition A composition in accordance with the present invention, suitable for use as a hand wash, was prepared. The composition comprised the following components at the indicated weight percentages: Ingredient Weight Percent Triclosan 0.3 Ammonium Lauryl Sulfate 0.75 Dipropylene Glycol Sodium Xylene Sulfonate 15.0 Water q.s.

The composition was prepared by first admixing the triclosan and dipropylene glycol until homogeneous (about 5 minutes). After the triclosan was completely dissolved, as evidenced by the absence of undissolved solid material, the sodium xylene sulfonate was added to the solution. The mixture then was stirred to completely dissolve the sodium xylene sulfonate (about 5 minutes). Finally, the ammonium lauryl sulfate and water were added to the resulting solution, and the composition was stirred until homogeneous (about 5 minutes).

The composition had a weight ratio of surfactant:triclosan of 2.5:1 and was at least about 90% saturated with triclosan. The composition was evaluated for its antibacterial efficacy against S.

daurus, E. coli, K. pneaIui., and choler. using a time kill test, and a contact time of 30 seconds.

WO 00/78275 PCT/US00/15729 134 The composition exhibited log reductions of >3.59, >4.49, >3.20, and >4.27 against the four test organisms, respectively.

Thus, the composition exhibited an excellent broad spectrum antibacterial activity. In addition, the composition was an excellent hand wash composition in an actual use test, providing both good cleansing and a smooth feel to the hands.

Example Comparison to a Previously Disclosed Composition This example compares the antibacterial efficacy of a composition of the present invention to a previously disclosed composition. Accordingly, the composition of Example 24 was compared to the sole example disclosed in WO 98/01110. In both compositions, the active antibacterial agent was triclosan (TCS). Both compositions were evaluated for antibacterial efficacy in a time kill test against S. aureus, E. coli, K. pneum., and S.

choler. The example of WO 98/01110 was tested at 50% dilution, in accordance with the test procedure for viscous compositions. The following data summarizes the percent of active antibacterial agent in each composition at the test dilution test dilution is 100% for the composition of Example 24 and 50% for the example of WO 98/01110), and the log reduction observed in the time kill test at a contact time of 30 seconds.

WO 00/78275 PCT/US00/15729 135 Composition TCS Log Reduction at 30 seconds S. B. K. S.

aureus coli pneum. choler Example 18 0.3 >4.60 >4.50 4.21 >4.68 WO 98/01110 0.5 3.29 0.29 1.00 0.45 This example demonstrates the superior time kill performance of a composition of the present invention compared to a prior composition, especially against Gram negative bacteria. This superiority is demonstrated even through the comparative composition contained substantially more active antibacterial agent compared to the inventive composition. Thus, an inventive composition utilizes the active agent more efficiently, as illustrated in a higher log reduction using a reduced concentration of antibacterial agent.

Example 26 Comparison to a Previously Disclosed Composition This example compares the antibacterial efficacy of a composition of the present invention to a previously disclosed composition. Accordingly, the composition of Example 24 was compared to a composition disclosed in WO 96/06152. WO 96/06152 discloses effective compositions comprising TCS, an anionic surfactant, a hydrotrope, a hydric solvent, and further comprising an organic acid, specifically citric acid. WO 96/06152 contains additional pH adjusting agents, such as monoethanolamine and so- WO 00/78275 PCT/US00/15729 136 dium hydroxide. Further, the examples disclosed in WO 96/06152 all have a pH of 4 or 9.1, with no examples having a desirable, neutral pH of about 7. A pH of about 7 is desired for compositions contacting skin or inanimate surfaces because compositions of pH substantially different from 7, such as 4 or 9.1, have a greater potential to damage the surfaces they contact. Accordingly, the composition of Example 1 of WO 96/06152 (hereafter referred to as composition 26-A) was prepared. For comparison, composition 26-A was prepared as above, except that the pH was adjusted to 7 by the addition of further monoethanolamine (this composition hereafter referred to as composition 26-B). To provide an additional comparison, the composition of Example 3 of WO 96/06152 was prepared, except that it was prepared at a pH of 7 by the addition of further monoethanolamine (this composition is hereafter referred to as composition 26-C The table below summarizes the results of a time kill test on the compositions of this example against the bacteria indicated at a contact time of seconds.

Composition pH TCS Log Reduction at 30 Seconds s. E. K. S.

aureus coli pneum. choler.

Example 24 7.1 0.3 >4.54 >4.25 3.67 >4.77 Comparative 4 0.075 >4.84 26-A Comparative 7 0.075 0.07 26-B Comparative 7 0.15 4.44 2.91 0.28 4.67 26-C WO 00/78275 PCT/US00/15729 137 This example demonstrates the superior time kill performance of a composition of the present invention compared to prior compositions, especially with respect to Gram negative bacteria at a pH of about 7. From the data presented in this example, it can be concluded that the compositions of WO 96/06152 rely substantially on a relatively extreme pH (either 4 or 9, as disclosed) to achieve a desirable, rapid and broad spectrum reduction of bacterial populations. This is in contrast to Example 18 of the present invention, which provides a rapid broad spectrum bacteria kill at the desirable pH of about 7.

Example 27 Antibacterial Composition Containing PCMX An antibacterial composition in accordance with the present invention containing p-chloro-mxylenol (PCMX) as the active antibacterial agent was prepared. The composition contained the following components in the indicated weight percentages: Ingredient Weight Percent PCMX 0.1 Ethanol 13.42 Water q.s.

The composition was prepared by first mixing the PCMX and ethanol to completely solubilize completely dissolved, as evidenced by the absence of WO 00/78275 PCT/US00/15729 138 undissolved solid material, the water was added, and the composition was stirred until homogeneous (about minutes).

The composition was at least about saturated with PCMX. The composition was evaluated for antibacterial efficacy against S. aureus, E.

col, K. pneum., and S. choler. using a time kill test. Against S. aureus, the composition exhibited a log reduction of 4.16 in 30 seconds; against E.

coli the composition exhibited a log reduction of >4.34 in 30 seconds; against K. pneum. the composition exhibited a log reduction of 3.99 in 30 seconds; and against S. choler. the composition exhibited a log reduction of >4.04 in 30 seconds. Thus, the composition exhibited an excellent broad spectrum antibacterial activity.

Example 28 Antibacterial Composition Containing PCMX A composition in accordance with the present invention incorporating p-chloro-m-xylene as the active antibacterial ingredient was prepared. The composition contained the following components in the indicated weight percentages: Ingredient Weight Percent PCMX 0.3 Ammonium Lauryl Sulfate 0.8 Water q.s.

WO 00/78275 PCT/US00/15729 139 The composition was prepared by first combining the PCMX and water, then adding the ammonium lauryl sulfate and mixing the components for such time as to completely admix the components and dissolve the PCMX (about 2 hours).

The composition was at least about saturated with PCMX. The composition was evaluated for its antibacterial efficacy against S. aureus and E. coli using a time kill test. Against S. aureus, the composition exhibited a log reduction of >3.57 in 30 seconds; and against E. coli the composition exhibited a log reduction of >4.17 in 30 seconds.

Thus, the composition exhibited an excellent broad spectrum antibacterial activity.

Obviously, many modifications and variations of the invention as hereinbefore set forth can be made without departing from the spirit and scope thereof, and, therefore, only such limitations should be imposed as are indicated by the appended claims.

Claims

1. An antibacterial composition comprising: about 0.001% to about by weight, of a phenoiic antimicrobial agent; about 0.1% to about 15%, by weight, of an anionic surfactant and optionally a further surfactant selected from the group consisting of a cationic surfactant, a nonionic surfactant, an ampholytic surfactant, and mixtures thereof; 2% to about 30%, by weight, of a hydrotrope; 2% to about 25%, by weight, of a water-soluble hydric solvent; and water, 1o wherein the antimicrobial agent is present in an amount of at least 40% of saturation concentration, when measured at room temperature, and wherein said composition has a pH of about 6 to about 8.

2. The composition of claim 1 comprising about 0.05% to about 2% by weight, of the phenolic antibacterial agent. Is

3. The composition of claim 1 or 2, wherein the phenolic antibacterial agent is selected from the group consisting of: a 2-hydroxydiphenyl compound having the structure Yo (OH)m (OH)n OH wherein Y is chlorine or bromine, Z is SO 2 H, NO 2 or C 1 -C 4 alkyl, r is 0 to 3, o is 0 S 20 to 3, p is 0 or 1, m is 0 or 1, and n is 0 or 1; a phenol derivative having the structure OH OH R44 R2 R •R3 :wherein RI is hydro, hydroxy, Ci-C 4 alkyl, chloro, nitro, phenyl, or benzyl; R 2 is hydro, hydroxy, C 1 -C 6 alkyl, or halo; R 3 is hydro, C 1 -C 6 alkyl, hydroxy, chloro, nitro, or a sulfur in the form of an alkali metal salt or ammonium salt; R4 is hydro or methyl, and R SB: is hydro or nitro; a diphenyl compound having the structure R' 2 R' 1 R 1 R 2 R' s R 3 R' 4 R' 5 R 5 R 4 [R:\L1BH]581037.doc:aak 141 wherein X is sulfur or a methylene group, RI and R' 1 are hydroxy, and R 2 R'2, R 3 R' 3 R 4 R' 4 Rs, and R' 5 independent of one another, are hydro or halo; and mixtures thereof.

4. The composition of claim 3, wherein the antibacterial agent comprises triclosan, p-chloro-m-xylenol, or mixtures thereof.

The composition of any one of claims 1 to 4, wherein the surfactant has a cation selected from the group consisting of sodium, ammonium, potassium, alkyl(C 1 -4) ammonium, dialkyl (Ci4) ammonium, trialkyl (Cl-4)ammonium, alkanol(C 1 -4)ammonium, dialkanol (C 1 -4)ammonium, trialkanol(C 1 4)ammonium, and mixtures thereof.

6. The composition of any one of claims 1 to 4, wherein the surfactant is selected from the group consisting of a C 8 -CIs alkyl sulfate, a C 8 -C 8 alkamine oxide, and mixtures thereof.

7. The composition of any one of claims 1 to 4, wherein the surfactant comprises a lauryl sulfate, an octyl sulfate, a 2-ethylhexyl sulfate, lauramine oxide, and mixtures thereof.

8. The composition of any one of claims 1 to 7 having a log reduction against Gram positive bacteria of at least 2 after 30 seconds of contact, as measured against S. aureus, and a log reduction against Gram negative bacteria of at least 2.5 after 30 seconds of contact, as measured against E. coli. 20

9. The composition of any one of claims 1 to 8, wherein the antibacterial agent is °present in an amount of at least 50% of saturation concentration.

10. The composition of any one of claims 1 to 9, wherein the antibacterial agent is present in an amount of at least 75% of saturation concentration.

11. The composition of any one of claims 1 to 10, wherein the antibacterial agent 25 is present in an amount of at least 95% of saturation concentration.

12. The composition of any one of claims 1 to 5, wherein the surfactant comprises an anionic surfactant.

13. The composition of any one of claims 1 to 5, wherein the surfactant comprises an amnhnlvtic cnrf'atont 30

14. The composition of any one of claims 1 to 13, wherein the hydrotrope is present in an amount of about 5% to about 20% by weight.

The composition of any one of claims 1 to 14, wherein the hydric solvent present in an amount of about 5% to about 15% by weight.

16. The composition of any one of claims 1 to 15, wherein the hydric solvent comprises an alcohol, a diol, a triol, and mixtures thereof. [R:\LIBH]581037.doc:aak 142

17. The composition of any one of claims 1 to 16, wherein the hydric solvent comprises methanol, ethanol, isopropyl alcohol, n-butanol, n-propyl alcohol, ethylene glycol, propylene glycol, glycerol, diethylene glycol, dipropylene glycol, tripropylene glycol, hexylene glycol, butylene glycol, 1,2,6-hexanetriol, sorbitol, PEG-4, or mixtures thereof.

18. The composition of any one of claims 1 to 17, wherein the hydrotrope is selected from the group consisting of sodium cumene sulfonate, ammonium cumene sulfonate, ammonium xylene sulfonate, potassium toluene sulfonate, sodium toluene sulfonate, sodium xylene sulfonate, toluene sulfonic acid, xylene sulfonic acid, sodiyn polynaphthalene sulfonate, sodium polystyrene sulfonate, sodium methyl naphthalene sulfonate, disodium succinate, and mixtures thereof.

19. The composition of claim 1 comprising: about 0.01% to about by weight, of the antimicrobial agent; about 0.1% to about by weight, of the surfactant; is about 5% to about 20%, by weight, of the hydrotrope; and about 2% to about 15%, by weight, of the hydric solvent.

An antibacterial composition comprising: about 0-0.001% to about by weight, of a phenolic antimicrobial agent; about 0.1% to about 15%, by weight, of an anionic surfactant and optionally a 20 further surfactant selected from the group consisting of a cationic surfactant, a nonionic 'surfactant, an ampholytic surfactant, and mixtures thereof; about 2% to about 30%, by weight, of a hydrotrope; about 2% to about 25%, by weight, of a water-soluble hydric solvent; and water, wherein the composition has a log reduction against Gram positive bacteria of at least 2 after 30 seconds of contact, as measured against S. aureus, and has a log reduction against Gram negative bacteria of at least 2.5 after 30 seconds of contact, as measured against E. coli, and f JviiiJuvOuii n1a a pii uk 4tuuui V iu auuui 0. 30

21. The composition of claim 20, wherein the antibacterial agent is present in an amount of at least 50% of saturation concentration.

22. The composition of claim 20, wherein the antibacterial agent is present in an amount of at least 75% of saturation concentration.

23. The composition of claim 20, wherein the antibacterial agent is present in an amount of at least 95% of saturation concentration. [R\LIBH]581037.doc:aak 143

24. A method of reducing a bacteria population on a surface comprising contacting the surface with a composition of any one of claims 1 to 19 for 30 seconds to achieve a log reduction of at least 2 against S. aureus and a log reduction of at least against E. coli, then rinsing the composition from the surface.

25. The method of claim 24, wherein the composition contacts the surface for seconds to achieve a log reduction of at least 3 against S. aureus.

26. The method of claim 24, wherein the composition contacts the surface for seconds to achieve a log reduction of at least 3.75 against E. coli.

27. The method of claim 24, wherein the composition contacts the surface for 0o seconds to achieve a log reduction of at least 2 against K. pneum.

28. The method of any one of claims 24 to 27, wherein the surface is a skin of a mammal.

29. The method of any one of claims 24 to 27, wherein the surface is a hard, inanimate surface. Is

30. A method of reducing a bacteria population on a surface comprising contacting the surface with a composition of any one of claims 20 to 23 for 30 seconds to achieve a log reduction of at least 2 against S. aureus and a log reduction of at least against E. coli, then rinsing the composition from the surface.

31. The method of claim 30 wherein the composition contacts the surface for 20 seconds to achieve a log reduction of at least 3 against S. aureus.

32. The method of claim 30 wherein the composition contacts the surface for seconds to achieve a log reduction of at least 3.75 against E. coli.

33. The method of claim 30 wherein the composition contacts the surface for seconds to achieve a log reduction of at least 2 against K. pneum. 25

34. An antibacterial composition comprising: about 0.001% to about by weight, of a phenolic antimicrobial agent; about 0.1% to about 15%, by weight, of an anionic surfactant and optionally a further surfactant selected from the group consisting of a cationic surfactant, a nonionic r about 2% to about 30%, by weight, of a hydrotrope selected from the group consisting of sodium cumene sulfonate, ammonium cumene sulfonate, ammonium xylene sulfonate, potassium toluene sulfonate, sodium toluene sulfonate, sodium xylene sulfonate, toluene sulfonic acid, xylene sulfonic acid, sodium polynaphthalene sulfonate, sodium polystyrene sulfonate, sodium methyl naphthalene sulfonate, disodium succinate, and mixtures thereof; (RALIBH58 1037.doc:aak 144 0% to about 25%, by weight, of a water-soluble hydric solvent; and water, wherein the composition has a pH of about 6 to about 8, and wherein the antimicrobial agent is present in an amount of at least 25% of saturation concentration, when measured at room temperature.

The composition of claim 34 having a log reduction against Gram positive bacteria of at least 2 after 30 seconds of contact, as measured against S. aureus, and a log reduction against Gram negative bacteria of at least 2.5 after 30 seconds of contact, as measured against E. coli. 0o

36. The composition of claim 34 or 35, wherein the antibacterial agent is present in an amount of at least 50% of saturation concentration.

37. The composition of claim 36, wherein the antibacterial agent is present in an amount of at least 75% of saturation concentration.

38. The composition of claim 37, wherein the antibacterial agent is present in an amount of at least 95% of saturation concentration.

39. The composition of any one of claims 34 to 38, wherein the surfactant comprises an anionic surfactant.

40. The composition of any one of claims 34 to 39, wherein the hydrotrope is present in an amount of about 5% to about 20% by weight. 20

41. The composition of any one of claims 34 to 40, wherein the hydric solvent present in an amount of about 5% to about 15% by weight.

42. The composition of any one of claims 34 to 41, wherein the hydric solvent is selected from the group consisting of an alcohol, a diol, a triol, and mixtures thereof.

43. The composition of any one of claims 34 to 42, wherein the hydric solvent 25 comprises methanol, ethanol, isopropyl alcohol, n-butanol, n-propyl alcohol, ethylene glycol, propylene glycol, glycerol, diethylene glycol, dipropylene glycol, tripropylene glycol, hexylene glycol, butylene glycol, 1,2,6-hexanetriol, sorbitol, PEG-4, or mixtures thereof.

44 Th y C, aV ,laut 34 to 3t, VVcI I I l;lyuluirope is selected from the group consisting of sodium cumene sulfonate, ammonium cumene sulfonate, ammonium xylene sulfonate, potassium toluene sulfonate, sodium toluene sulfonate, sodium xylene sulfonate, toluene sulfonic acid, xylene sulfonic acid, sodium polynaphthalene sulfonate, sodium polystyrene sulfonate, sodium methyl naphthalene sulfonate, disodium succinate, and mixtures thereof.

45. An antibacterial composition comprising: (R:\LIBH581037.doc:aak 145 about 0.001% to about by weight, of a phenolic antimicrobial agent; about 0.1% to about 15%, by weight, of an anionic surfactant and optionally a further surfactant selected from the group consisting of a cationic surfactant, a nonionic surfactant, and mixtures thereof; about 2% to about 30%, by weight, of a hydrotrope selected from the group consisting of sodium cumene sulfonate, ammonium cumene sulfonate, ammonium xylene sulfonate, potassium toluene sulfonate, sodium toluene sulfonate, sodium xylene sulfonate, toluene sulfonic acid, xylene sulfonic acid, sodium polynaphthalene sulfonate, sodium polystyrene sulfonate, sodium methyl naphthalene sulfonate, disodium succinate, and mixtures thereof; about 0% to about 25%, by weight, of a water-soluble hydric solvent; and water, wherein the composition has a pH of about 6 to about 8, and wherein the composition has a log reduction against Gram positive bacteria of at least 2 after seconds of contact, as measured against S. aureus, and has a log reduction against Gram negative bacteria of at least 2.5 after 30 seconds of contact, as measured against E. coli.

46. A method of reducing a bacteria population on a surface comprising contacting the surface with a composition of any one of claims 34 to 45 for 30 seconds to achieve a log reduction of at least 2 against S. aureus and a log reduction of at least against E. coli, then rinsing the composition from the surface.

47. The method of claim 46, wherein the composition contacts the surface for seconds to achieve a log reduction of at least 3 against S. aureus.

48. The method of claim 46, wherein the composition contacts the surface for seconds to achieve a log reduction of at least 3.75 against E. coli. 25

49. The method of claim 46, wherein the composition contacts the surface for seconds to achieve a log reduction of at least 2 against K. pneum.

50. The composition of claim 34, having a log reduction against Gram positive S hhnrtpr2l nfant n last 2 f~pr 30A -f,-contact, againt S. t- l- reduction against Gram negative bacteria of at least 2.5 after 30 seconds of contact, as measured against E. coli.

51. The composition of claim 45, wherein the antibacterial agent is present in an amount of at least 75% of saturation concentration.

52. The composition of claim 51, wherein the antibacterial agent is present in an amount of at least 95% of saturation concentration. [R:\LIBH]581037.d(c:aak 146

53. The composition of any one of claims 34 to 45, comprising about 0.05% to about 2% by weight, of the phenolic antibacterial agent.

54. The composition of any one of claims 34 to 45 or 50 to 53, wherein the phenolic antibacterial agent is selected from the group consisting of: a 2-hydroxydiphenyl compound having the structure SYoY (OH) (OH), OH wherein Y is chlorine or bromine, Z is SO 2 H, NO 2 or CI-C 4 alkyl, r is 0 to 3, o is 0 to 3, p is 0 or 1 ,m is 0 or 1, and n is 0 or 1; a phenol derivative having the structure OH Rs 5 R, R4 R2 R3 wherein RI is hydro, hydroxy, CI-C 4 alkyl, chloro, nitro, phenyl, or benzyl; R 2 is hydro, hydroxy, Ci-C 6 alkyl, or halo; R 3 is hydro, CI-C 6 alkyl, hydroxy, chloro, nitro, or a sulfur in the form of an alkali metal salt or ammonium salt; R 4 is hydro or methyl, and R is hydro or nitro; Is a diphenyl compound having the structure R' 2 R' 1 Ri R 2 R* R-' 3 -R 3 R' 4 R's R 5 R 4 wherein X is sulfur or a methylene group, R 1 and R'i are hydroxy, and R 2 R' 2 R 3 R' 3 R 4 R' 4 Rs, and R' 5 independent of one another, are hydro or halo; and S(d) mixtures thereof. 20

55. The composition of claim 54, wherein the antibacterial agent comprises triclosan, p-chloro-m-xylenol, or mixtures thereof.

56. The composition of any one of claims 34 to 45 or 50 to 55, wherein the surtactant is present in an amount of about 0.5% to about by weight of the composition.

57. The composition of any one of claims 34 to 45 or 50 to 56, wherein the surfactant has a cation selected from the group consisting of sodium, ammonium, potassium, alkyl-(Ci-4) ammonium, dialkyl (C1-4) ammonium, trialkyl (Ci 1 4)-ammonium, [R:\LIBHJ581037.doc:aak 147 alkanol(Ci4)ammonium, dialkanol (Ci4)-ammonium, trialkanol(Cl4)ammonium, and mixtures thereof.

58. The composition of any one of claims 34 to 45 or 50 to 56, wherein the surfactant is selected from the group consisting of a C 8 -C 8 alkyl sulfate and mixtures thereof.

59. The composition of any one of claims 34 to 45 or 50 to 56, wherein the surfactant comprises a lauryl sulfate, an octyl sulfate, a 2-ethylhexyl sulfate, and mixtures thereof.

An antibacterial composition as defined in claim 1, substantially as hereinbefore described with reference to any one of the examples.

61. A method of reducing bacteria population on a surface comprising contacting the surface with an antibacterial composition as defined in claim 1, substantially as hereinbefore described with reference to any one of the examples. Dated 5 August, 2004 The Dial Corporation Patent Attorneys for the Applicant/Nominated Person SPRUSON FERGUSON e S a 9 0* [R:\LIBH]581 037.doc:aak