AU5472000A - Antibacterial compositions - Google Patents

Description

WO 00/78275 PCT/USOO/15729 ANTIBACTERIAL COMPOSITIONS FIELD OF THE INVENTION 5 The present invention is directed to anti bacterial compositions, like personal care composi tions, including hand sanitizer gels, having im proved antibacterial effectiveness. More particu larly, the present invention is directed to antibac 10 terial compositions comprising an antibacterial agent and a surfactant or a relatively low amount of a disinfecting alcohol, and that provide a substan tial reduction, e.g., greater than 99%, in Gram positive and Gram negative bacterial populations 15 within one minute. BACKGROUND OF THE INVENTION Antibacterial personal care compositions 20 are known in the art. Especially useful are anti bacterial cleansing compositions, which typically are used to cleanse the skin and to destroy bacteria and other microorganisms present on the skin, espe cially the hands, arms, and face of the user. 25 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, 30 the hands and fingers, and the composition is al lowed to evaporate from the skin. Wiping of the composition from the skin is not necessary because the high alcohol content of present-day hand sani- WO 00/78275 PCT/USOO/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 5 service industry, meat processing industry, and in the private sector by individual consumers. The widespread use of antibacterial compositions indi cates the importance consumers place on controlling bacteria and other microorganism populations on 10 skin. It is important, however, that antibacterial compositions provide a substantial and broad spec trum reduction in microorganism populations quickly and without problems associated with toxicity and skin irritation. 15 In particular, antibacterial cleansing compositions typically contain an active antibacte rial agent, a surfactant, and various other ingredi ents, for example, dyes, fragrances, pH adjusters, thickeners, skin conditioners, and the like, in an 20 aqueous carrier. Several different classes of anti bacterial agents have been used in antibacterial cleansing compositions. Examples of antibacterial agents include a bisguanidine (e.g., chlorhexidine digluconate), diphenyl compounds, benzyl alcohols, 25 trihalocarbanilides, quaternary ammonium compounds, ethoxylated phenols, and phenolic compounds, such as halo-substituted phenolic compounds, like PCMX (i.e., p-chloro-m-xylenol) and triclosan (i.e., 2,4,4'-trichloro-2'hydroxy-diphenylether). Present 30 day antimicrobial compositions based on such anti bacterial agents exhibit a wide range of antibacte rial activity, ranging from low to high, depending WO 00/78275 PCT/USOO/15729 -3 on the microorganism to be controlled and the par ticular antibacterial composition. Hand sanitizer gels contain a high per centage of an alcohol, like ethanol. At the high 5 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 10 alcohol, i.e., about 40% or greater by weight of the composition, however, have a tendency to dry and irritate the skin. Most commercial antibacterial composi tions, however, generally offer a low to moderate 15 antibacterial activity. Antibacterial activity is assessed against a broad spectrum of microorganisms, including both Gram positive and Gram negative mi croorganisms. The log reduction, or alternatively the percent reduction, in bacterial populations 20 provided by the antibacterial composition correlates to antibacterial activity. A log reduction of 3-5 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 25 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 dis closures illustrate attempts to provide such anti 30 bacterial compositions, which, to date, do not pro vide the rapid, broad range control of microorgan isms desired by consumers.

WO 00/78275 PCT/USOO/15729 -4 It should be noted that high log reduc tions 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. Compo 5 sitions 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 10 difficult to impossible to achieve a high log reduc tion using an antibacterial composition having a neutral pH of about 5 to about 8, and especially about 6 to about 8, without simultaneously incorpo rating a high percentage of an alcohol. 15 For example, WO 98/01110 discloses compo sitions 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 20 surfactant. Fendler et al. U.S. 5,635,462 discloses compositions comprising PCMX and selected surfac tants. The compositions disclosed therein are de void of anionic surfactants and nonionic surfac 25 tants. WO 97/46218 and WO 96/06152 disclose com positions based on triclosan, organic acids or salts, hydrotropes, and hydric solvents. EP 0 505 935 discloses compositions con 30 taining PCMX in combination with nonionic and an ionic surfactants, particularly nonionic block co polymer surfactants.

WO 00/78275 PCT/USOO/15729 -5 WO 95/32705 discloses a mild surfactant combination that can be combined with antibacterial compounds, like triclosan. WO 95/09605 discloses antibacterial compo 5 sitions containing anionic surfactants and alkylpolyglycoside surfactants. WO 98/55096 discloses antimicrobial wipes having a porous sheet impregnated with an antibacte rial composition containing an active antimicrobial 10 agent, an anionic surfactant, an acid, and water, wherein the composition has a pH of about 3.0 to about 6.0. N.A. Allawala et al., J. Amer. Pharm. Assoc.--Sci. Ed., Vol. XLII, no. 5, pp. 267-275, 15 (1953) discusses the antibacterial activity of ac tive antibacterial agents in combination with sur factants. A.G. Mitchell, J. Pharm. Pharmacol., Vol. 16, pp. 533-537, (1964) discloses compositions con 20 taining 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. 25 With respect to hand sanitizer gels, Osborne et al. U.S. Patent No. 5,776,430 discloses a topical antimicrobial cleaner containing chlorhexi dine and an alcohol. The compositions contain about 50% to 60%, by weight, denatured alcohol and about 30 0.65 to 0.85%, by weight, chlorhexidine. The compo sition is applied to the skin, scrubbed into the skin, then rinsed from the skin.

WO 00/78275 PCT/USOO/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 5 combined weight of not more than 3% by weight. The gel is rubbed into the hands and allowed to evapor ate to provide disinfected hands. As illustrated in EP 0 604 848, the amount and identity of the anti bacterial agent is not considered important because 10 the hand sanitizer gels contain a high percentage of an alcohol to provide antibacterial activity. The disclosed compositions often do not provide immedi ate sanitization and do not provide residual anti bacterial efficacy. 15 Prior disclosures have not addressed the issue of which composition ingredient in an antibac terial composition provides bacterial control. Prior compositions also have not provided an effec tive, fast, and broad spectrum control of bacteria 20 at a neutral pH of about 5 to about 8, and espe cially at about 6 to about 8. An efficacious antibacterial composition has been difficult to achieve because of the proper ties of the antibacterial agents and the effects of 25 a surfactant on an antibacterial agent. For exam ple, several active antibacterial agents, like phe nols, have an exceedingly low solubility in water, e.g., triclosan solubility in water is about 5 to 10 ppm (parts per million). The solubility of the 30 antibacterial agent is increased by adding surfac tants to the composition. However, an increase in solubility of the antimicrobial agent, and in turn, the amount of antibacterial agent in the composi- WO 00/78275 PCT/USOO/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 5 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 concentra tion of the surfactant. The critical micelle con 10 centration varies from surfactant to surfactant. The formation of micelles is important because mi celles have a lipophilic region that attracts and solubilizes the antibacterial agent, and thereby renders the antibacterial agent unavailable to imme 15 diately contact bacteria, and thereby control bacte ria in short time period (i.e., one minute or less). The antibacterial agent solubilized in the surfactant micelles will control bacteria, but in relatively long time frames. The antibacterial 20 agent, if free in the aqueous solution and not tied up in the surfactant micelle (i.e., is activated), is attracted to the lipophilic membrane of the bac teria and performs its function quickly. If the antibacterial agent is tied up in the surfactant 25 micelle (i.e., 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 30 solubilized in the micelle is readily washed from the skin during the rinsing process, and is not available to deposit on the skin to provide a resid- WO 00/78275 PCT/USOO/15729 -8 ual antibacterial benefit. Rather, the antibacte rial agent is washed away and wasted. With respect to sanitizers, hand sanitizer gels typically contain: (a) at least 60% by weight 5 ethanol or a combination of lower alcohols, such as ethanol and isopropanol, (b) water, (c) a gelling polymer, such as a crosslinked polyacrylate mate rial, and (d) other ingredients, such as skin condi tioners, fragrances, and the like. Hand sanitizer 10 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 15 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 20 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 25 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 com 30 position ingredient in such an antibacterial compo sition provides bacterial control. Therefore, for formulations containing a reduced alcohol concentra tion, the selection of an antibacterial agent that WO 00/78275 PCT/USOO/15729 -9 provides both a rapid antibacterial effect and a persistent antibacterial benefit is difficult. Prior compositions also have not provided an effec tive, fast, and broad spectrum control of bacteria 5 at a neutral pH of about 5 to about 8, and espe cially at about 6 to about 8. Accordingly, a need exists for an antibac terial composition that is highly efficacious against a broad spectrum of Gram positive and Gram 10 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 composi 15 tions. SUMMARY OF THE INVENTION The present invention relates to antibac 20 terial compositions that provide a substantial re duction in Gram positive and Gram negative bacteria in less than about one minute. More particularly, in one embodiment, the present invention relates to antimicrobial compositions containing an active 25 antibacterial agent, a surfactant, and water, wherein the antibacterial agent is present in the continuous aqueous phase (in contrast to being pres ent in micelles), in an amount of at least 50% of saturation, when measured at room temperature. The 30 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 WO 00/78275 PCT/USOO/15729 - 10 is present in an amount of at least 25% of satura tion, when measured at room temperature. In another embodiment, the present inven tion relates to antimicrobial compositions contain 5 ing 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 tem perature. The present invention also relates to 10 antimicrobial compositions containing an active antibacterial agent, a disinfecting alcohol, a gel ling agent, a hydrotrope, and water, wherein the antibacterial agent is present in an amount of at least 25% of saturation, when measured at room tem 15 perature. Accordingly, one aspect of the present invention is to provide a liquid, antibacterial composition comprising: (a) about 0.001% to about 10%, by weight, of an antibacterial agent; (b) about 20 0.1% to about 40%, by weight, of a surfactant se lected from the group consisting of a C 8 -Ci 8 alkyl sulfate, a C 8 -Cl 8 fatty acid salt, a C -C 18 alkyl ether sulfate having one or two moles of ethoxylation, a

C

8

-C

18 alkamine oxide, a C 8

-C

18 alkyl sarcosinate, a 25 C.-Cis sulfoacetate, a C 8 -Ci 8 sulfosuccinate, a C.-C,, alkyl diphenyl oxide disulfonate, a C.-Ci 8 alkyl carbonate, a C 8

-C

8 alpha-olefin sulfonate, a methyl ester sulfonate, and mixtures thereof; and (c) wa ter, wherein the antibacterial agent is present in 30 the composition in an amount of at least 50% of saturation concentration, when measured at room temperature.

WO 00/78275 PCT/USOO/15729 - 11 Another aspect of the present invention is to provide an alternative embodiment of the antibac terial composition, wherein the composition com prises: 5 (a) about 0.001% to about 10%, by weight, of an antimicrobial agent; (b) about 0.1% to about 40%, by weight, of a surfactant selected from the group consisting of an anionic surfactant, a cationic surfactant, a 10 nonionic surfactant, an ampholytic surfactant, and mixtures thereof; (c) about 0% to about 30%, by weight, of a hydrotrope; (d) about 0% to about 25%, by weight, of 15 a water-soluble hydric solvent; and (e) water, wherein the composition contains at least one of the hydrotrope and hydric solvent, and wherein the antimicrobial agent is present in the 20 composition in an amount of at least 25% of satura tion concentration, when measured at room tempera ture. Still another aspect of the present inven tion is to provide another alternative embodiment of 25 the antibacterial composition, wherein the composi tion comprises: (a) 0.001% to about 10%, by weight, of an antimicrobial agent; (b) 0 to about 10%, by weight, of a 30 surfactant selected from the group consisting of an anionic surfactant, a cationic surfactant, a nonionic surfactant, an ampholytic surfactant, and mixtures thereof; WO 00/78275 PCT/USOO/15729 - 12 (c) 0% to about 40%, by weight, of a hydrotrope; (d) 0% to about 60%, by weight, of a water-soluble hydric solvent; and 5 (e) 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 pres 10 ent in the composition in an amount of at least 25% of the saturation concentration, when measured at room temperature. Another aspect of the present invention is to provide a liquid, antibacterial composition com 15 prising: (a) about 0.05% to about 5%, by weight, of an antibacterial agent; (b) about 1% to about 40%, by weight, of a disinfecting alcohol, like a C 1 6 alcohol; (c) about 0.01% to about 5% by weight of a gelling agent, like a colloidal or a polymeric gel 20 ling agent; and (d) water, wherein the antibacterial agent is present in the composition in an amount of at least 50% of saturation concentration, when mea sured at room temperature. Still another aspect of the present inven 25 tion is to provide an alternative embodiment of the antibacterial composition, wherein the composition comprises: (a) about 0.05% to about 5%, by weight, of an antimicrobial agent; 30 (b) about 1% to about 40%, by weight, of a disinfecting alcohol; (c) about 0.01% to about 5%, by weight, of a gelling agent; WO 00/78275 PCT/USOO/15729 - 13 (d) 0.1% to about 30%, by weight, of a hydrotrope; and (e) water, wherein the antimicrobial agent is present 5 in the composition in an amount of at least 25% of saturation concentration, when measured at room temperature. Still another aspect of the present inven tion is to provide another alternative embodiment of 10 the antibacterial composition, wherein the composi tion comprises: (a) 0.05% to about 5%, by weight, of an antimicrobial agent; (b) about 1% to about 40%, by weight, of 15 a disinfecting alcohol; and (c) water, wherein the composition contains the dis infecting alcohol and an optional polyhydric solvent in an amount sufficient to solubilize the antimi 20 crobial 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. Yet another aspect of the present inven 25 tion is to provide an antibacterial composition that exhibits a log reduction against Gram positive bac teria (i.e., S. aureus) of at least 2 after 30 sec onds of contact. Still another aspect of the present inven 30 tion is to provide an antibacterial composition that exhibits a log reduction against Gram negative bac teria (i.e., E. coli) of at least 2.5 after 30 sec onds of contact.

WO 00/78275 PCT/USOO/15729 - 14 Another aspect of the present invention is to provide an antibacterial composition that exhib its a substantial log reduction against Gram posi tive and Gram negative bacteria, and has a pH of 5 about 5 to about 8. Another aspect of the present invention is to provide consumer products based on an antibacte rial composition of the present invention, for exam ple, a skin cleanser, a body splash, a surgical 10 scrub, a wound care agent, a hand sanitizer gel, a disinfectant, a mouth wash, a pet shampoo, a hard surface sanitizer, and the like. A further aspect of the present invention is to provide a method of reducing the Gram positive 15 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 bacte 20 ria level to a desired level, and to provide a re sidual control of bacteria levels. The composition can be wiped or rinsed from the skin. In some em bodiments, the composition is allowed to remain on the skin until the volatile components of the 25 composition evaporate. The above and other novel aspects and advantages of the present invention are illustrated in the following, nonlimiting detailed description of the preferred embodiments. 30 WO 00/78275 PCT/USOO/15729 - 15 DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Personal care products incorporating an active antibacterial agent have been known for many 5 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 10 against a broad spectrum of organisms in as short a contact time as possible. It also would be benefi cial if the antibacterial compositions provided a residual bacterial control. As presently formulated, commercial liquid 15 antibacterial soap compositions provide a poor to marginal time kill efficacy, i.e., rate of killing bacteria. Table 1 summarizes the kill efficacy of commercial products, each of which contains about 0.2% to 0.3%, by weight, triclosan (an antibacterial 20 agent), and a surfactant. Table 1 Time Kill Efficacy of Commercial Liquid Hand Soaps Organism 25 (Log Reductions after Product 1 Minute Contact Time) Gram Positive Gram negative Gram negative S. aureus R. coli K. pneum. Commercial 1.39 0.00 0.04 Product A 30 Commercial 2.20 0.00 0.01 Product B Commercial 1.85 0.00 0.00 Product C 35 WO 00/78275 PCT/USOO/15729 - 16 Antibacterial hand sanitizer compositions typically do not contain a surfactant and rely upon a high concentration of an alcohol to control bacte ria. The alcohols evaporate and, therefore, cannot 5 provide residual bacterial control. The alcohols also can dry and irritate the skin. Present-day products especially lack effi cacy against Gram negative bacteria, such as E. coli, which are of particular concern to human 10 health. The present invention, therefore, is di rected to antibacterial compositions having an ex ceptionally high broad spectrum antibacterial effi cacy, as measured by a rapid kill of bacteria (i.e., time kill), which is to be distinguished from per 15 sistent kill. The present antibacterial compositions provide significantly improved time kill efficacy compared to prior compositions, for example, prior sanitizer compositions that incorporate a high per 20 centage of an alcohol, i.e., 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 mi 25 crobe. 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 30 an active agent is proportional to its thermodynamic activity in the external phase. Accordingly, ther modynamic activity, as opposed to concentration, is the more important variable with respect to WO 00/78275 PCT/USOO/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 5 of the composition. Many compounds have a solubility limit in aqueous solutions termed the "saturation concentra tion," which varies with temperature. Above the saturation concentration, the compound precipitates 10 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 satura tion concentration in water by the addition of com 15 pounds 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. 20 The % saturation of an active antibacte rial agent in any composition, including a surfactant-containing composition, ideally can be expressed as: % saturation = [C/C,]x100% 25 wherein C is the concentration of antibacterial agent in the composition and Cs 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 30 the continuous aqueous phase of a surfactant-con taining composition is in equilibrium with the micellar pseudophase of said composition, and fur ther 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 pseudo phase according to a partition law. Accordingly, the percent saturation, or alternatively the rela 5 tive thermodynamic activity or relative chemical potential, of an antibacterial active agent dis solved in a composition is the same everywhere within the composition. Thus, the terms percent saturation of the antibacterial agent "in a composi 10 tion," "in the aqueous continuous phase of a compo sition," and "in the micellar pseudophase of a com position" are interchangeable, and are used as such throughout this disclosure. Maximum antibacterial efficacy is achieved 15 when the difference in thermodynamic activities of the active antibacterial agent between the composi tion and the target organism is maximized (i.e., when the composition is more "saturated" with the active ingredient). A second factor affecting anti 20 bacterial 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 25 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: (1) its availability, 30 as dictated by its thermodynamic activity, i.e., percent saturation in the continuous aqueous phase of a composition, and (2) the total amount of avail able active agent in the solution.

WO 00/78275 PCT/USOO/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 5 antibacterial agent in solution, or more impor tantly, affect the percent saturation of the active agent in the continuous aqueous phase of the compo sition. This effect can be explained in the case of a sparingly water-soluble antibacterial agent in an 10 aqueous surfactant solution, where the active agent is distributed between the aqueous (i.e., continu ous) phase and the micellar pseudophase. For anti bacterial agents of exceedingly low solubility in water, such as triclosan, the distribution is 15 shifted strongly toward the micelles (i.e., a vast majority of the triclosan molecules are present in surfactant micelles, as opposed to the aqueous phase). The ratio of surfactant to antibacterial 20 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, 25 the number of micelles relative to active molecules also increases, with the micelles being proportion ately 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 30 micellar pseudophase, as the saturation of antibac terial agent in the micellar phase decreases, so does the saturation of the antibacterial agent in the continuous phase. The converse is also true.

WO 00/78275 PCT/USOO/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 5 determines the antibacterial activity of the compo sition. The active agent present in the surfactant micelles, however, can serve as a reservoir of ac tive agent to replenish the continuous aqueous phase as the active agent is depleted. 10 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 15 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 20 active agent in the composition, or alternatively the percent saturation of the active agent in the continuous aqueous phase of the composition, deter mines antibacterial efficacy. The present compositions are, antibacterial 25 compositions having an improved effectiveness against both Gram negative and Gram positive bacte ria, and that exhibit a rapid bacteria kill. In one embodiment, as illustrated below, an antibacterial composition of the present invention comprises: (a) 30 about 0.001% to about 10%, by weight, of an antibac terial agent; (b) about 0.1% to about 40%, by weight, of a surfactant; (c) an optional hydric solvent; (d) an optional hydrotrope; and (e) water.

WO 00/78275 PCT/USOO/15729 - 21 In another embodiment, an antibacterial composition of the present invention comprises: (a) about 0.05% to about 5%, by weight, of an antibacte rial agent; (b) about 1% to about 40%, by weight, of 5 a disinfecting alcohol; (c) about 0.01% to about 5%, by weight, of a gelling agent; (d) an optional hydrotrope; and (e) water. The present compositions also can contain an optional polyhydric solvent. The compositions can further include a hydrotrope 10 and additional optional ingredients disclosed here after, like polyhydric solvents, pH adjusters, dyes, skin conditioners, vitamins, and perfumes. The present compositions are free of surfactants, i.e., contain 0% to about 0.5%, by weight, of compounds 15 that exhibit surface activity. The compositions also are mild, and provide a persistent kill because it is not necessary to rinse or wipe the composi tions from the skin. The compositions of these embodiments, and 20 all other embodiments, have a percent saturation of antibacterial agent in the continuous aqueous phase of at least about 25%, when measured at room temper ature. The compositions exhibit a log reduction against Gram positive bacteria of about 2 after 30 25 seconds contact. The compositions exhibit a log reduction against Gram negative bacteria of about 2.5 after 30 seconds contact. The following illustrates important, non limiting embodiments of the present invention. 30 WO 00/78275 PCT/USOO/15729 - 22 A. Antibacterial Compositions Containing an Antibacterial Agent and a Surfactant 5 In one embodiment of the present inven tion, 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 sol 10 vent and a hydrotrope. The presence of a hydric solvent and/or a hydrotrope does not adversely af fect the antimicrobial properties of the composi tion, but such optional ingredients are not neces sary ingredients. The compositions can further 15 include additional optional ingredients disclosed hereafter, like pH adjusters, dyes, and perfumes. 1. Antibacterial Agent 20 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 5%, by weight of the composition. To achieve the full advantage of the present invention, 25 the antibacterial agent is present in an amount of about 0.05% to about 2%, by weight, of the composi tion. The antibacterial compositions can be ready to use compositions, which typically contain 30 0.001% to about 2%, preferably 0.01% to about 1.5%, and most preferably about 0.05% to about 1%, of an antibacterial agent, by weight of the composition. The antibacterial compositions also can be formu lated as concentrates that are diluted before use WO 00/78275 PCT/USOO/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. 5 Applications also are envisioned wherein the end use composition contains greater than 2%, by weight, of the antibacterial agent. As discussed above, the absolute amount of antibacterial agent present in the composition is 10 not as important as the amount of available antibac terial 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 compo 15 sition, 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 con tinuous aqueous phase of the composition contains an 20 amount of antibacterial agent that is at least about 50%, and preferably at least about 75%, of the satu ration concentration of the antibacterial agent in water, when measured at room temperature. To achieve the full advantage of the present invention, 25 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 30 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/USOO/15729 - 24 The antimicrobial agents useful in the present invention are phenolic compounds exemplified by the following classes of compounds: 5 (a) 2-Hydroxydiphenyl compounds Yo ZP 10 (OH)Z H)n OH 15 wherein Y is chlorine or bromine, Z is SO 2 H, NO 2 , or Cl-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. 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 20 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 25 compound has the structure: Cl 0 (Q Cl OH Cl 30 having the adopted name, triclosan, and available commercially under the tradename IRGASAN DP300, from WO 00/78275 PCT/USOO/15729 - 25 Ciba Specialty Chemicals Corp., Greensboro, NC. Another useful 2-hydroxydiphenyl compound is 2,2' dihydroxy-5,5'-dibromo-diphenyl ether. 5 (b) Phenol derivatives OH Rs R1 10 10 ~ R4 * R2

R

3 wherein R 1 is hydro, hydroxy, C 1

-C

4 alkyl, chloro, 15 nitro, phenyl, or benzyl; R 2 is hydro, hydroxy, C 1 -C. 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; R 4 is hydro or methyl, and R. is hydro or nitro. Halo is bromo or, prefera 20 bly, chloro. Specific examples of phenol derivatives include, but are not limited to, chlorophenols (o-, m-, p-), 2,4-dichlorophenol, p-nitrophenol, picric acid, xylenol, p-chloro-m-xylenol, cresols (o-, m-, 25 p-), p-chloro-m-cresol, pyrocatechol, resorcinol, 4 n-hexylresorcinol, pyrogallol, phloroglucin, carvacrol, thymol, p-chlorothymol, o-phenylphenol, o-benzylphenol, p-chloro-o-benzylphenol, phenol, 4 ethylphenol, and 4-phenolsulfonic acid. Other phe 30 nol derivatives are listed in WO 98/55096, incorpo rated herein by reference.

WO 00/78275 PCT/USOO/15729 - 26 (c) Diphenyl Compounds R'2 R'i R 1 R2 5

R'

3

X*R

3 R'4 R' 5

R

5 R4 10 wherein X is sulfur or a methylene group, R 1 and R' 1 are hydroxy, and R 2 , R' 2 , R 3 , R' 3, R 4 , R' 4, R 5 , and

R'

5 , independent of one another, are hydro or halo. Specific, nonlimiting examples of diphenyl compounds are hexachlorophene, tetrachlorophene, dichloro 15 phene, 2,3-dihydroxy-5,5'-dichlorodiphenyl sulfide, 2,2'-dihydroxy-3,3',5,5'-tetrachlorodiphenyl sul fide, 2,2'-dihydroxy-3,5',5,5',6,6'-hexachlorodi phenyl sulfide, and 3,3'-dibromo-5,5'-dichloro-2,2' dihydroxydiphenylamine. Other diphenyl compounds 20 are listed in WO 98/55096, incorporated herein by reference. 2. Surfactant 25 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. 30 To achieve the full advantage of the present inven tion, the antibacterial composition contains about 0.5% to about 15%, by weight, of the surfactant.

WO 00/78275 PCT/USOO/15729 - 27 Ready-to-use compositions typically con tain about 0.1% to about 10%, preferably about 0.3% to about 5%, and most preferably, 0.5% to about 3%, by weight, of the composition. Concentrated compo 5 sitions suitable for dilution typically contain greater than about 5%, 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 10 the identity of the surfactant. The amount of surfactant is determined such that the percent satu ration of the antibacterial agent in the continuous aqueous phase of the composition is at least about 50%, preferably at least about 75%, and most prefer 15 ably at least about 95%. 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 20 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 se lected cationic surfactants. Nonionic surfactants 25 and anionic surfactants containing a relatively high amount of ethoxylation are not useful in this em bodiment. Ethoxylated surfactants containing more than two moles of ethylene oxide have a strong af finity for the antibacterial agent, and in this 30 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/USOO/15729 - 28 surfactants: a C 8

-C

18 alkyl sulfate, a C 8

-C

8 fatty acid salt, a C 8

-C

18 alkyl ether sulfate having one or two moles of ethoxylation, a C 8

-C

8 alkamine oxide, a

C

8

-C,

8 alkoyl sarcosinate, a C 8

-C

1 , sulfoacetate, a C 8 5 C,, sulfosuccinate, a C 8

-C

18 alkyl diphenyl oxide disulfonate, a C 8 -Ci 8 alkyl carbonate, a C 8 -C,, alpha olefin sulfonate, a methyl ester sulfonate, and mixtures thereof. The C 8

-C

18 alkyl group contains eight to sixteen carbon atoms, and can be straight 10 chain (e.g., lauryl) or branched (e.g., 2-ethyl hexyl). The cation of the anionic surfactant can be an alkali metal (preferably sodium or potassium), ammonium, C 1

-C

4 alkylammonium (mono-, di-, tri), or

C

1

-C

3 alkanolammonium (mono-, di-, tri-). Lithium 15 and alkaline earth cations (e.g., 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-ethylhexyl sul 20 fates, lauramine oxide, decyl sulfates, tridecyl sulfates, cocoates, lauroyl sarcosinates, lauryl sulfosuccinates, linear C 10 diphenyl oxide disulfo nates, lauryl sulfosuccinates, lauryl ether sulfates (1 and 2 moles ethylene oxide), myristyl sulfates, 25 oleates, stearates, tallates, cocamine oxide, decylamine oxide, myristamine oxide, ricinoleates, cetyl sulfates, and similar surfactants. Additional examples of surfactants can be found in "CTFA Cos metic Ingredient Handbook," J.M. Nikitakis, ed., The 30 Cosmetic, Toiletry and Fragrance Association, Inc., Washington, D.C. (1988) (hereafter CTFA Handbook), pages 10-13, 42-46, and 87-94, incorporated herein by reference.

WO 00/78275 PCT/USOO/15729 - 29 3. Carrier The carrier in this embodiment comprises water. 5 4. Optional Ingredients An antibacterial composition of the pres ent invention also can contain optional ingredients 10 well known to persons skilled in the art. For exam ple, 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. 15 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 20 optional ingredients typically are present, individ ually, from 0% to about 5%, by weight, of the compo sition, and, collectively, from 0% to about 20%, by weight, of the composition. Classes of optional ingredients include, 25 but are not limited to, dyes, fragrances, pH adjust ers, thickeners, viscosity modifiers, buffering agents, foam stabilizers, antioxidants, foam enhancers, chelating agents, opacifiers, and similar classes of optional ingredients known to persons 30 skilled in the art. Specific classes of optional ingredients include alkanolamides as foam boosters and stabiliz ers; gums and polymers as thickening agents; inor- WO 00/78275 PCT/USOO/15729 - 30 ganic phosphates, sulfates, and carbonates as buff ering agents; EDTA and phosphates as chelating agents; and acids and bases as pH adjusters. Examples of preferred classes of basic pH 5 adjusters are ammonia; mono-, di-, and tri-alkyl amines; mono-, di-, and tri-alkanolamines; alkali metal and alkaline earth metal hydroxides; and mix tures thereof. However, the identity of the basic pH adjuster is not limited, and any basic pH ad 10 juster known in the art can be used. Specific, nonlimiting examples of basic pH adjusters are ammo nia; sodium, potassium, and lithium hydroxide; monoethanolamine; triethylamine; isopropanolamine; diethanolamine; and triethanolamine. 15 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 polycar 20 boxylic 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 25 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, 30 stearamide DEA, oleylamide DEA, tallowamide DEA, lauramide MIPA, tallowamide MEA, isostearamide DEA, isostearamide MEA, and mixtures thereof.

WO 00/78275 PCT/USOO/15729 - 31 B. Antibacterial Compositions Containing an Antibacterial Agent, a Surfactant, and a Hydric Solvent and/or a Hydrotrope 5 In another embodiment, the antibacterial compositions comprise an active antibacterial agent, a surfactant, and a hydric solvent and/or a hydro trope. The compositions of embodiment B exhibit a 10 rapid bacteria kill, and are essentially unlimited in the identity of the surfactant in the composi tion. The solvent and/or hydrotrope assists in solubilizing the antibacterial agent, and reduces the affinity of the antibacterial agent to enter 15 surfactant micelles. Accordingly, at least 25% saturation of the antibacterial agent in the contin uous aqueous phase can be achieved regardless of the identity of the surfactant. 20 1. Antibacterial Agent The amount and identity of the antibacte rial agent present in this embodiment of the inven tion is discussed above in A.1. 25 In addition, to achieve the desired bacte ria kill in a short contact time, like 15 to 60 seconds, the continuous aqueous phase of the compo sition contains an amount of antibacterial agent that is at least about 25%, and preferably at least 30 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/USOO/15729 - 32 tion, the continuous aqueous phase is about 95% to 100% saturated with the antibacterial agent. 2. Surfactant 5 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 hydro 10 trope, 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 15 enter surfactant micelles. Accordingly, a suffi cient amount of the antibacterial agent is present in the continuous aqueous phase to quickly and ef fectively kill a broad spectrum of bacteria regard less of the identity of the surfactant. In embodi 20 ments 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. 25 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 30 anionic or cationic properties depending upon the pH of the composition. The antibacterial compositions, therefore, can contain an anionic surfactant disclosed above in WO 00/78275 PCT/USOO/15729 - 33 A.2., 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 5 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, 10 such as increased water solubility or reduced sur face 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 sul 15 fates, 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 20 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 25 in McCutcheon's Emulsifiers and Detergents, 1993 Annuals, (hereafter McCutcheon's), McCutcheon Divi sion, MC Publishing Co., Glen Rock, NJ, pp. 263-266, incorporated herein by reference. Numerous other anionic surfactants, and classes of anionic surfac 30 tants, are disclosed in Laughlin et al. U.S. Patent No. 3,929,678, incorporated herein by reference. The antibacterial compositions also can contain nonionic surfactants. Typically, a nonionic WO 00/78275 PCT/USOO/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 (i.e., 1 to about 30) of ethoxy and/or propoxy moi 5 eties. 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 10 copolymers, ethoxylated esters of fatty (C 8

-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, PEG-20 15 methyl glucose distearate, PEG-20 methyl glucose sesquistearate, C 11

-

1 pareth-20, ceteth-8, ceteth-12, dodoxynol-12, laureth-15, PEG-20 castor oil, poly sorbate 20, steareth-20, polyoxyethylene-10 cetyl ether, polyoxyethylene-10 stearyl ether, polyoxy 20 ethylene-20 cetyl ether, polyoxyethylene-10 oleyl ether, polyoxyethylene-20 oleyl ether, an ethoxyl ated nonylphenol, ethoxylated octylphenol, ethoxyl ated dodecylphenol, or ethoxylated fatty (C 6

-C

22 ) alcohol, including 3 to 20 ethylene oxide moieties, 25 polyoxyethylene-20 isohexadecyl ether, polyoxy ethylene-23 glycerol laurate, polyoxy-ethylene-20 glyceryl stearate, PPG-10 methyl glucose ether, PPG 20 methyl glucose ether, polyoxyethylene-20 sorbitan monoesters, polyoxyethylene-80 castor oil, polyoxy 30 ethylene-15 tridecyl ether, polyoxy-ethylene-6 tri decyl ether, laureth-2, laureth-3, laureth-4, PEG-3 castor oil, PEG 600 dioleate, PEG 400 dioleate, and mixtures thereof.

WO 00/78275 PCT/USOO/15729 - 35 Numerous other nonionic surfactants are disclosed in McCutcheon's Detergents and Emulsifi ers, 1993 Annuals, published by McCutcheon Division, MC Publishing Co., Glen Rock, NJ, pp. 1-246 and 266 5 272; in the CTFA International Cosmetic Ingredient Dictionary, Fourth Ed., Cosmetic, Toiletry and Fra grance Association, Washington, D.C. (1991) (herein after the CTFA Dictionary) at pages 1-651; and in the CTFA Handbook, at pages 86-94, each incorporated 10 herein by reference. In addition to anionic and nonionic sur factants, cationic, ampholytic, and amphoteric sur factants can be used in the antimicrobial composi tions. Cationic surfactants include amine oxides, 15 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 20 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 com pounds falling within this description are sodium 3 25 (dodecylamino)propionate, sodium 3-(dodecylamino) propane-l-sulfonate, sodium 2-(dodecylamino)ethyl sulfate, sodium 2-(dimethylamino)octadecanoate, disodium 3-(N-carboxymethyl-dodecylamino)propane-l sulfonate, disodium octadecyliminodiacetate, sodium 30 1-carboxymethyl-2-undecylimidazole, and sodium N,N bis(2-hydroxyethyl)-2-sulfato-3-dodecoxypropylamine.

WO 00/78275 PCT/USOO/15729 - 36 More particularly, one class of ampholytic surfactants include sarcosinates and taurates having the general structural formula 5 .RI-C-N- (CH 2) n-Y 10 wherein R 1 is C 11 through C 21 alkyl, R 2 is hydrogen or

C

1

-C

2 alkyl, Y is CO 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 15 formula O SO3Na+

R'-NHCCH

2

-CH-CO

2 -Na+ 20 The following classes of ampholytic sur factants also can be used: 0

CH

2

CO

2 Na+ 25 | R'CNHCH 2

CH

2 I

CH

2

CH

2 OH alkoamphoglycinates 30 WO 00/78275 PCT/USOO/15729 - 37 0 CH 2 CO2§Na+ 11

R'CNHCH

2

CH

2

NCH

2

CO

2 H 5 CH 2

CH

2 OH alkoamphocarboxyglycinates 100

CH

2

CH

2

CO

2 Na+ RlCNHiCH 2

CH

2 If

CH

2

CH

2 OH 15 alkoamphopropionates 0 ~CH 2

CH

2

CO

2 -Nal 20

R

1 NHCH 2

CH"

2

N.CH

2

CO

2 H

CH

2

CH

2 OH al koamphocarboxypropionates 25 WO 00/78275 PCT/USOO/15729 - 38 OH O CH 2

CHCH

2

SO

3 ~Na+ R 1 CNHCH 2

CH

2 N 5 CH 2

CH

2 OH alkoamphopropylsulfonates 10 0 CH 3 RICNH (CH 2 ) 3

N+-CH

2 CO2

CH

3 15 alkamidopropyl betaines 0 CH 3 OH RlCNH (CH 2 ) 3

N+-CH

2

CHCH

2

SO

3 20

CH

3 alkamidopropyl hydroxysultaine 25 O

R

1

NHCH

2

CH

2 C-0-Na+ 30 alkylaminopropionates WO 00/78275 PCT/USOO/15729 - 39 CH 2

CH

2 CO2 RNH

CH

2

CH

2 CO2H 5 alkyliminopropionates. Additional classes of ampholytic surfactants include 10 the phosphobetaines and the phosphitaines. Specific, nonlimiting examples of ampho lytic surfactants useful in the present invention are sodium coconut N-methyl taurate, sodium oleyl N methyl taurate, sodium tall oil acid N-methyl 15 taurate, sodium palmitoyl N-methyl taurate, cocodi methylcarboxymethylbetaine, lauryldimethylcarboxy methylbetaine, lauryldimethylcarboxyethylbetaine, cetyldimethylcarboxymethylbetaine, lauryl-bis-(2 hydroxyethyl)carboxymethylbetaine, oleyldimethyl 20 gammacarboxypropylbetaine, lauryl-bis-(2-hydroxy propyl)-carboxyethylbetaine, cocoamidodimethylpro pylsultaine, stearylamidodimethylpropylsultaine, laurylamido-bis-(2-hydroxyethyl)propylsultaine, disodium oleamide PEG-2 sulfosuccinate, TEA oleamido 25 PEG-2 sulfosuccinate, disodium oleamide MEA sulfo succinate, disodium oleamide MIPA sulfosuccinate, disodium ricinoleamide MEA sulfosuccinate, disodium undecylenamide MEA sulfosuccinate, disodium wheat germamido MEA sulfosuccinate, disodium wheat germ 30 amido PEG-2 sulfosuccinate, disodium isostearamideo MEA sulfosuccinate, cocoamphoglycinate, cocoampho carboxyglycinate, lauroamphoglycinate, lauroampho carboxyglycinate, capryloamphocarboxyglycinate, WO 00/78275 PCT/USOO/15729 - 40 cocoamphopropionate, cocoamphocarboxypropionate, lauroamphocarboxypropionate, capryloamphocarboxy propionate, dihydroxyethyl tallow glycinate, cocamido disodium 3-hydroxypropyl phosphobetaine, 5 lauric myristic amido disodium 3-hydroxypropyl phos phobetaine, lauric myristic amido glyceryl phospho betaine, lauric myristic amido carboxy disodium 3 hydroxypropyl phosphobetaine, cocoamido propyl mono sodium phosphitaine, lauric myristic amido propyl 10 monosodium phosphitaine, and mixtures thereof. 3. Carrier The carrier in this embodiment comprises 15 water. 4. Optional Ingredients The optional ingredients discussed in 20 A.4., above, also can be utilized in this embodiment of the invention, in the same amounts and for the same purposes. 5. Hydric Solvent and Hydrotrope 25 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 30 contains at least one of the hydric solvent and hydrotrope. Preferred embodiments contain both a hydric solvent and a hydrotrope.

WO 00/78275 PCT/USOO/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 5 15%, by weight, of a hydric solvent and/or about 5% to about 20%, by weight, of a hydrotrope. As defined herein, the term "hydric sol vent" is a water-soluble organic compound containing one to six, and typically one to three, hydroxyl 10 groups. The term "hydric solvent" therefore encom passes water-soluble alcohols, diols, triols, and polyols. Specific examples of hydric solvents in clude, but are not limited to, methanol, ethanol, isopropyl alcohol, n-butanol, n-propyl alcohol, 15 ethylene glycol, propylene glycol, glycerol, diethylene glycol, dipropylene glycol, tripropylene glycol, hexylene glycol, butylene glycol, 1,2,6 hexanetriol, sorbitol, PEG-4, and similar hydroxyl containing compounds. 20 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 25 examples of hydrotropes includes, but are not lim ited to, sodium cumene sulfonate, ammonium cumene sulfonate, ammonium xylene sulfonate, potassium toluene sulfonate, sodium toluene sulfonate, sodium xylene sulfonate, toluene sulfonic acid, and xylene 30 sulfonic acid. Other useful hydrotropes include sodium polynaphthalene sulfonate, sodium polystyrene sulfonate, sodium methyl naphthalene sulfonate, and disodium succinate.

WO 00/78275 PCT/USOO/15729 - 42 C. Antibacterial Compositions Containing an Antibacterial Agent and a Hydric Solvent and/or a Hydrotrope 5 In still another embodiment, the antibac terial compositions comprise an active antibacterial agent, and a hydric solvent and/or a hydrotrope. The compositions of embodiment C exhibit a rapid 10 bacteria kill, and also are essentially unlimited in the identity of the surfactant in the composition. The solvent and/or hydrotrope assists in solubil izing the antibacterial agent. Accordingly, at least 25% saturation of the antibacterial agent in 15 the continuous aqueous phase can be achieved even in the absence of a surfactant. 1. Antibacterial Agent 20 The amount and identity of the antibacte rial agent present in this embodiment of the inven tion is discussed above in A.1. In addition, similar to embodiment B, in order to achieve the desired bacteria kill in a 25 short contact time, like 15 to 60 seconds, the con tinuous 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 30 concentration of the antibacterial agent in water, when measured at room temperature. To achieve the full advantage of the present invention, the contin uous aqueous phase is about 95% to 100% saturated with the antibacterial agent.

WO 00/78275 PCT/USOO/15729 - 43 2. Surfactant The surfactant is an optional ingredient in this embodiment. However, if present, the amount 5 of surfactant present in this embodiment of the present invention is 0% to about 10% by weight, preferably 0% to about 5%, by weight. To achieve the full advantage of the present invention, the surfactant is present in an amount of 0% to about 10 2%, 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. 15 3. Carrier The carrier in this embodiment comprises water. 20 4. Optional Ingredients The optional ingredients discussed in A.4., above, also can be utilized in this embodiment of the invention, in the same amounts and for the 25 same purposes. 5. Hydric Solvent and Hydrotrope The hydric solvent and hydrotrope dis 30 cussed in B.5., above, also can be utilized in this embodiment of the invention, for the same purpose. However, the amount of hydric solvent and/or hydro trope present in this embodiment can be greater than WO 00/78275 PCT/USOO/15729 - 44 the amount disclosed in B.5., above, because an additional amount of solvent and/or hydrotrope may be necessary to solubilize the antibacterial agent in the absence of a surfactant. 5 Therefore, in embodiment C, the composi tions 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. 10 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. Highly pre ferred embodiments contain about 5% to about 15%, by weight, of a hydric solvent and/or about 5% to about 15 20%, by weight, of a hydrotrope. Most preferred embodiments contain both a hydric solvent and a hydrotrope. D. Antibacterial Compositions Containing 20 Antibacterial Agent, a Disinfecting Alcohol, a Gelling Agent In another embodiment, the antibacterial 25 compositions comprise an active antibacterial agent, a disinfecting alcohol, and a gelling agent. The compositions of embodiment D exhibit a rapid bacte ria kill. The compositions of embodiment D are excellent hand sanitizers. 30 1. Antibacterial Acrent The identity of the antibacterial agent in this embodiment of the invention is discussed above WO 00/78275 PCT/USOO/15729 - 45 in A.l. In this embodiment, the antibacterial agent is present in an amount of about 0.05% to about 5%, and preferably about 0.1% to about 4%, by weight of the composition. To achieve the full advantage of 5 the present invention, the antibacterial agent is present in an amount of about 0.25% to about 2%, by weight, of the composition. 2. Carrier 10 The carrier in the present composition comprises water. 3. Disinfecting Alcohol 15 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 dis 20 infecting alcohol. Most preferred embodiments con tain about 5% to about 30%, by weight, of a disin fecting alcohol. As defined herein, the term "disinfecting alcohol" is a water-soluble alcohol containing one 25 to six carbon atoms. Disinfecting alcohols include, but are not limited to, methanol, ethanol, propanol, and isopropyl alcohol.

WO 00/78275 PCT/USOO/15729 - 46 4. Gelling Agent The present antibacterial compositions also contain about 0.01% to about 5%, by weight, and 5 preferably 0.10% to about 3%, by weight, of a gel ling agent. To achieve the full advantage of the present invention, the antibacterial compositions contain about 0.25% to about 2.5%, by weight, of a gelling agent. The antibacterial compositions typi 10 cally 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 15 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 capa 20 ble 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 compo 25 sitions 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 0.5%, by weight, because a surfactant may be present in a commercial form of a gelling agent 30 to help dispense the gelling agent in water. A surfactant also may be present as an additive or by product in other composition ingredients.

WO 00/78275 PCT/USOO/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 5 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 antibac terial agent. Regardless of the identity of the 10 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. 15 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 thick ening or gelling the aqueous portion of the compo 20 sition: acacia, acrylates/steareth-20 methacrylate copolymer, agar, algin, alginic acid, ammonium acrylate copolymers, ammonium alginate, ammonium chloride, ammonium sulfate, amylopectin, attapul 25 gite, bentonite, C9-15 alcohols, calcium acetate, calcium alginate, calcium carrageenan, calcium chlo ride, caprylic alcohol, carbomer 910, carbomer 934, carbomer 934P, carbomer 940, carbomer 941, carboxy methyl hydroxyethylcellulose, carboxymethyl hydroxy 30 propyl guar, carrageenan, cellulose, cellulose gum, cetearyl alcohol, cetyl alcohol, corn starch, damar, dextrin, dibenzylidine sorbitol, ethylene dihydroge nated tallowamide, ethylene dioleamide, ethylene WO 00/78275 PCT/USOO/15729 - 48 distearamide, gelatin, guar gum, guar hydroxypropyl trimonium chloride, hectorite, hyaluronic acid, hydrated silica, hydroxybutyl methylcellulose, hydroxyethylcellulose, hydroxyethyl ethylcellulose, 5 hydroxyethyl stearamide-MIPA, hydroxypropylcellu lose, hydroxypropyl guar, hydroxypropyl methyl cellulose, isocetyl alcohol, isostearyl alcohol, karaya gum, kelp, lauryl alcohol, locust bean gum, magnesium aluminum silicate, magnesium silicate, 10 magnesium trisilicate, methoxy PEG-22/dodecyl glycol copolymer, methylcellulose, microcrystallinc cellu lose, montmorillonite, myristyl alcohol, oat flour, oleyl alcohol, palm kernel alcohol, pectin, PEG-2M, PEG-5M, polyacrylic acid, polyvinyl alcohol, potas 15 sium 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 20 cellulose sulfate, sodium chloride, sodium polymeth acrylate, sodium silicoaluminate, sodium sulfate, stearalkonium bentonite, stearalkonium hectorite, stearyl alcohol, tallow alcohol, TEA-hydrochloride, tragacanth gum, tridecyl alcohol, tromethamine mag 25 nesium aluminum silicate, wheat flour, wheat starch, xanthan gum, and mixtures thereof. The following additional nonlimiting exam ples of gelling agents act primarily by thickening the nonaqueous portion of the composition: 30 abietyl alcohol, acrylinoleic acid, alumi num behenate, aluminum caprylate, aluminum dilin oleate, aluminum distearate, aluminum isostearates/ laurates/palmitates or stearates, aluminum isostear- WO 00/78275 PCT/USOO/15729 - 49 ates/myristates, aluminum isostearates/palmitates, aluminum isostearates/stearates, aluminum lanolate, aluminum myristates/palmitates, aluminum stearate, aluminum stearates, aluminum tristearate, beeswax, 5 behenamide, behenyl alcohol, butadiene/acrylonitrile copolymer, C29-70 acid, calcium behenate, calcium stearate, candelilla wax, carnauba, ceresin, choles terol, cholesteryl hydroxystearate, coconut alcohol, copal, diglyceryl stearate malate, dihydroabietyl 10 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 15 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 20 polyisobutene, hydrogenated soybean oil, hydroge nated tallow amide, hydrogenated tallow glyceride, hydrogenated vegetable glyceride, hydrogenated vege table glycerides, hydrogenated vegetable oil, hy droxypropylcellulose, isobutylene/isoprene copoly 25 mer, isocetyl stearoyl stearate, Japan wax, jojoba wax, lanolin alcohol, lauramide, methyl dehydro abietate, methyl hydrogenated rosinate, methyl rosinate, methylstyrene/vinyltoluene copolymer, microcrystalline wax, montan acid wax, montan wax, 30 myristyleicosanol, myristyloctadecanol, octadecene/ maleic anhydride copolymer, octyldodecyl stearoyl stearate, oleamide, oleostearine, ouricury wax, oxidized polyethylene, ozokerite, palm kernel alco- WO 00/78275 PCT/USOO/15729 - 50 hol, paraffin, pentaerythrityl hydrogenated rosin ate, pentaerythrityl rosinate, pentaerythrityl tetraabietate, pentaerythrityl tetrabehenate, penta erythrityl tetraoctanoate, pentaerythrityl tetra 5 oleate, pentaerythrityl tetrastearate, phthalic anhydride/glycerin/glycidyl decanoate copolymer, phthalic/trimellitic/glycols copolymer, polybutene, polybutylene terephthalate, polydipentene, polyeth ylene, polyisobutene, polyisoprene, polyvinyl 10 butyral, polyvinyl laurate, propylene glycol dicap rylate, propylene glycol dicocoate, propylene glycol diisononanoate, propylene glycol dilaurate, propyl ene glycol dipelargonate, propylene glycol distear ate, propylene glycol diundecanoate, PVP/eicosene 15 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 stear 20 ate, stearyl stearoyl stearate, synthetic beeswax, synthetic wax, trihydroxystearin, triisononanoin, triisostearin, triisononanoin, triisostearin, tri isostearyl trilinoleate, trilaurin, trilinoleic acid, trilinolein, trimyristin, triolein, tripalmi 25 tin, tristearin, zinc laurate, zinc myristate, zinc neodecanoate, zinc rosinate, zinc stearate, and mixtures thereof. 5. Optional Ingredients 30 a. Polyhydric Solvent A polyhydric solvent, if present at all, is present in an amount of about 0.1% to about 50%, WO 00/78275 PCT/USOO/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 5 weight of the composition. In contrast to a dis infecting alcohol, a polyhydric solvent contributes little, if at all, to the antibacterial efficacy of the present composition. As defined herein, the term "polyhydric 10 solvent" is a water-soluble organic compound con taining 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 15 water at 25 0 C. There is no upper limit to the water solubility of the polyhydric solvent, e.g., the polyhydric solvent and water can be soluble in all proportions. The term "polyhydric solvent" therefore 20 encompasses water-soluble diols, triols, and polyols. Specific examples of hydric solvents in clude, but are not limited to, ethylene glycol, propylene glycol, glycerol, diethylene glycol, di propylene glycol, tripropylene glycol, hexylene 25 glycol, butylene glycol, 1,2,6-hexanetriol, sorbi tol, PEG-4, and similar polyhydroxy compounds. b. Hydrotrope 30 A hydrotrope, if present at all, is pres ent in an amount of about 0.1% to about 30%, and preferably about 0.5% to about 25%, by weight of the composition. To achieve the full advantage of the WO 00/78275 PCT/USOO/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 B.5., above, and is used in this em 5 bodiment of the invention for the same purpose. c. Other Optional Ingredients Other optional ingredients discussed in 10 A.4., 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 15 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 20 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 25 be used. Combinations of the classes of skin condi tioners, in addition to miscellaneous skin condi tioners known to persons skilled in the art, alone or in combination can be used. Nonlimiting examples of miscellaneous skin conditioners include aloe, 30 cholesterol, cystine, keratin, lecithin, egg yolk, glycine, PPG-12, retinol, salicylic acid, orotic acid, vegetable oil, and soluble animal collagen. The skin conditioners can be used alone, or in com- WO 00/78275 PCT/USOO/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 5 found in "CTFA Cosmetic Ingredient Handbook," J.M. Nikitakis, ed., The Cosmetic, Toiletry and Fragrance Association, Inc., Washington, D.C. (1988) (hereaf ter CTFA Handbook), pages 79-85, incorporated herein by reference. 10 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. 15 Accordingly, at least 25% saturation of the anti bacterial agent in the composition can be achieved even in the absence of a surfactant. The antibacterial compositions of the 20 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 25 compositions can be irritating to the skin or damag ing to other surfaces contacted by the composition. Accordingly, antibacterial compositions of the pres ent invention preferably have a pH of about 5 to about 8, and more preferably about 6 to about 8. To 30 achieve the full advantage of the present invention, the antibacterial compositions have a pH of about 6.5 to about 7.5. In addition, the antibacterial compositions of the present invention also do not WO 00/78275 PCT/USOO/15729 - 54 rely upon a high concentration of disinfecting alco hol. To demonstrate the new and unexpected results provided by the antibacterial compositions 5 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 10 represents the actual, or active, weight amount of each ingredient present in the composition. The compositions were prepared by blending the ingredi ents, as understood by those skilled in the art and as described below. 15 The following materials were used as in gredients in the examples. The source of each in gredient, and its abbreviation, are summarized be low: a) Alkyl (linear) diphenyl oxide 20 disulfonate, Pilot Chemical Co., Santa Fe Springs, CA, CALFAX 1OL-45 (active=45.4%), b) Alkyl polyglucoside (APG), Henkel Corp., Hoboken, NJ, PLANTAREN 2000N UP (ac tive=55.53%), 25 c) Alpha-olefin sulfonate (AOS), Stepan Chemical Co., Northfield, IL, BIOTERGE AS-40 (ac tive=38.80%), d) Ammonium lauryl sulfate (ALS), Henkel Corp., STANDAPOL A (active level=28.3%), 30 e) Ammonium xylene sulfonate (AXS), Stepan Corp., STEPANATE AXS (active=40%), WO 00/78275 PCT/USOO/15729 - 55 f) Cocamidopropyl betaine (CAPB), McIntyre Group, Ltd., Chicago, IL, MACKAM 35-HP (est. 30% active betaine), g) Dipropylene glycol (DPG), Dow Chemi 5 cal Co., Midland, MI, h) Disodium laureth sulfosuccinate (DSLScct), McIntyre Group, Ltd., MACKANATE EL (ac tive=33.8%), i) Disodium lauryl sulfosuccinate 10 (DSLrylScct), McIntyre Group, Ltd., MACKANATE LO (active est.=40%), j) DMDM Hydantoin (DMDM), MacIntyre Group, Ltd., MACKSTAT DM (approx. 55% active), k) DowFax Hydrotrope Solution (DFX), Dow 15 Chemical Co., DowFax Hydrotrope Solution (Benzene, 1,1'-oxybis-, sec-hexyl derivatives, sulfonated sodium salt) (active=45.7%), 1) Glycerin (GLY), Henkel/Emery, Cincinnati, OH, Emery 916 Glycerine (99.7% CP/USP), 20 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), 25 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 30 Chemical Co., ALPHA-STEP ML-40 (Sodium methyl-2 sulfo laurate and disodium 2-sulfo lauric acid) (active=36.47%), WO 00/78275 PCT/USOO/15729 - 56 s) Monoethanolamine (MEA), Dow Chemical Co., t) Monoethanolamine lauryl sulfate (MEALS), Albright & Wilson, Cumbria, England, 5 EMPICOL LQ 33/F (active=33%), u) Octylphenol ethoxylate, 9-10 moles EO (TX100), Union Carbide, TRITON-X 100, v) PEG-6ME, polyethylene glycol 300 methyl ether, available from Dow Chemical Co., Mid 10 land, MI, as MPEG 350 (active=est. 100%), w) Poloxymer 338 (F108), BASF, Wyandotte, MI, PLURONIC F108 (active=est. 100%), x) Potassium cocoate (KCO), McIntyre Group, Ltd., MACKADET 40-K (active=38.4%), 15 y) Potassium laurate (KL), prepared from lauric acid (Sigma, #L-4250, active=99.8%) and po tassium hydroxide, z) Potassium oleate (KO), Norman, Fox & Co., Vernon, CA, NORFOX KO (active=approx. 80%), 20 aa) Propylene glycol (PG), Dow Chemical Co., USP Grade (active level=99.96%), bb) Sodium 2-ethylhexyl sulfate (S2EHS), Henkel, SULFOTEX OA (active=39.68%), cc) Sodium C 12

-C

8 sulfate (SC12-18S) 25 Henkel, TEXAPON ZHC needles (active=90.95%), dd) Sodium cocoamphoacetate (SCA), McIntyre Group, Ltd., MACKAM IC-90 (active=approx. 32%), ee) Sodium cumene sulfonate (SCS), Stepan 30 Chemical Co., STEPANATE SCS (active=44.6%), ff) Sodium decyl sulfate (SDecS), Henkel, SULFOTEX 110 (active=30.80%), WO 00/78275 PCT/USOO/15729 - 57 gg) Sodium lauroyl sarcosinate (SLSarc), Hampshire Chemical Co., Lexington, MA, HAMPOSYL L-30 Type 724 (active=29.9%), hh) Sodium lauryl ether sulfate, 1 mole 5 EO (SLES-1), Henkel, STANDAPOL ES-1 (active=25.40%), ii) Sodium lauryl ether sulfate, 2 mole EO (SLES-2), Henkel, STANDAPOL ES-2 (active level=25.71%), jj) Sodium lauryl sulfate/sodium dodecyl 10 sulfate (SLS/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, 15 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 EO and a carboxylate group (active=94.2%), 20 nn) Sodium tridecyl sulfate (SC13S), Rhodia, Parsippany, NJ, RHODAPON TDS (ac tive=24.65%), oo) Sodium xylene sulfonate (SXS), Stepan Chemical Co., STEPANATE SXS (active level=40-42%), 25 pp) Triclosan (TCS), IRGASAN DP-300, Ciba Specialty Chemicals Corp., Greensboro, NC (GC assay on lots used=99.8-99.9% active TCS; mp=56.0-58.0 C.), qq) Triethanolamine lauryl sulfate 30 (TEALS), Henkel, STANDAPOL T (active=40.1%), rr) Tripropylene Glycol (TPG), Dow Chemi cal Co., Tripropylene Glycol, WO 00/78275 PCT/USOO/15729 - 58 ss) p-Chloro-m-xylenol (PCMX), NIPACIDE PX-R, Nipa Inc., Wilmington, Delaware (about 100% active), tt) Glyceryl polymethacrylate and propyl 5 ene glycol (LUBRAGEL DV), International Speciality Products, Wayne, New Jersey (about 46% active), uu) CARBOPOL ULTREZ 10 (ULTREZ 10), crosslinked polyacrylic acid, BF Goodrich Specialty Chemicals, Cleveland, Ohio (about 98% active), 10 vv) Diisopropylamine, Air Products and Chemicals, Allentown, Pennsylvania (about 100% ac tive), ww) LAPONITE XLG (lithium magnesium sil icate, synthetic smectite clay), Southern Clay Prod 15 ucts, Gonzales, Texas (about 99% active), xx) CELQUAT CS230M (Polyquaternium 10), National Starch and Chemical Company, Bridgewater, New Jersey (about 92% active), yy) Polypropylene glycol-9 (PPG-9), Poly 20 glycol P425, Dow Chemical Company, Midland, Michigan (about 100% active), zz) Ethanol (Denatured Ethyl Alcohol 40B), Gold Shield, Hayward, California (about 100% active), 25 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 30 preparation and testing of the examples: a) Determination of Rapid Germicidal (Time Kill) Activity of Antibacterial Products. 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 compo 5 sition is brought into contact with a known popula tion 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 composi 10 tion. 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 con 15 centration from 0-100%. The choice of which concen tration to use is at the discretion of the investi gator, and suitable concentrations are readily de termined by those skilled in the art. For example, viscous samples usually are tested at 50% dilution, 20 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 trip 25 licate, 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 30 range from 15 seconds to 5 minutes, with 30 seconds and 1 minute being typical contact times. The con tact temperature also can be any temperature, typi cally room temperature, or about 25 degrees Celsius.

WO 00/78275 PCT/USOO/15729 - 60 The bacterial suspension, or test inoculum, is prepared by growing a bacterial culture on any appropriate solid media (e.g., agar). The bacterial population then is washed from the agar 5 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 10 the name of the bacteria, the ATCC (American Type Culture Collection) identification number, and the abbreviation for the name of the organism used here after. 15 Organism Name ATCC # Abbreviation Staphylococcus aureus 6538 S. aureus Escherichia coli 11229 E. coli Klebsiella pneumoniae 10031 K. pneum. Salmonella choleraesuis 10708 S. choler. 20 S. aureus is a Gram positive bacteria, whereas E. coli, K. pneum, and S. choler. are Gram negative 25 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 30 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 5 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 con 10 trol count (numbers control) is determined by con ducting 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, respec 15 tively, by standard microbiological methods. The log reduction is calculated using the formula Log reduction=loglo (numbers 20 control)-logio(test sample survivors). The following table correlates percent reduction in bacteria population to log reduction: 25 % Reduction Log Reduction 90 1 99 2 30 99.9 3 99.99 4 99.999 5 WO 00/78275 PCT/USOO/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 approxi mately 7.5 grams (g) TCS and 3 liters (L) of water. 5 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 sus pension filtered through a Coors #32-H porcelain 10 Bachner funnel equipped with Whatman #40 (5.5cm) 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 15 to cool. Typically, fine needles of TCS crystals formed after the filtrate was stored at room temper ature for a few days. For some time kill studies, the TCS solu tion was refiltered at room temperature before use 20 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 25 not affect test results because crystalline TCS is unavailable to act on the bacteria (i.e., is not solubilized). To determine the concentration of TCS in the water solutions, filtered samples (in tripli 30 cate) 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/USOO/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 5 compositions: A French square bottle was charged with a solution containing a variable concentration of a surfactant and 0.3%, by weight, TCS. The mix ture was stirred and heated (35-40 0 C) for several hours until the TCS was solubilized. Variable 10 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 15 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 20 the 0.3% TCS was determined by use of an experimen tal design in which the concentration of surfactant was serially reduced by a factor of two over a se ries of test samples until the approximate satura tion point of TCS in the surfactant was observed. 25 Then the difference in concentration (saturated vs. just solubilized) was halved until a close endpoint for TCS saturation could be determined. The satura tion point of TCS/surfactant compositions could be effectively estimated with small-scale (15 to 100 30 mL) samples, but about 600-800 g samples were re quired to obtain reliable final results. The ini tial ranges, therefore, were established with WO 00/78275 PCT/USOO/15729 - 64 small-scale samples, and the final concentrations were determined using larger-scale samples. d) Preparation of compositions contain ing TCS and a solvent or solvent/hydrotrope combina 5 tion: 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 crys 10 tallize. 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 15 total with water. Adjustment of pH also was per formed, if required. The mixture was stirred at room temperature for about an hour, seed TCS was added, and the mixture allowed to stand and crystal lize as above. The determination of the TCS satura 20 tion point described above also was used (i.e., 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 25 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 tech 30 nique was used by observing the sample at right angles with a high-intensity light from a small flashlight equipped with a beam focusing attachment (i.e., MINI MAGLITE* AA, MAG Instruments, Califor- WO 00/78275 PCT/USOO/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. 5 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 % 10 saturation produces a concomitant reduction in time kill efficacy.

WO 00/78275 PCT/USOO/15729 -66 "-H 0 0 H c'i 0 w 0. 0 W 0 14 H -4 U) A (N C; .) 0' U))U p4Ln Ln 0 H H Q L) 0 -1 4-3 (N H- LA LA Ln H 0 r N H OD c (1 ~ 4 0 Ln OD E- 0 0 LO -II 0) 0 4.) Ui 14 LA LA LA :j H- H H 0 -. 4 '- 0. r.' C'n H0 0 H) 0 H N 44~ m ~ HO 00H vf m H c 4) ..- A' H C) H a m 0a H f H 0 0) C) 0 0) C H 0 C C CD 0 00 O0 0 HO i H H 0 H~ E-4 ) 0)~~- -P - ) a. m (dl al m~ 'd 0) C CD 0~ 0D 0~ 0 CD C CD -4 H- WO 00/78275 PCT/USOO/15729 - 67 Comparing the data in Tables 2 and 3 shows that at the very lowest concentration of TCS (i.e., 5 to 10 ppm), the efficacy of time kill is reduced compared to samples containing higher levels of TCS. 5 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 10 at shorter-contact time periods. Another example, in more complex compositions is illustrated in sam ples in Table 3, i.e., 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 15 log improvement in bacterial reduction after 1 min ute. The data in Table 3 also show differences in efficacy when different solvents/hydrotropes are used with approximately the same TCS concentrations.

WO 00/78275 PCT/USOO/15729 - 68 w. It' N- 00 N- c - L w In %fD In Lfl N '.w n m '.0 w~ %D0 '.0 r- m rn N N C' ) A IA A A A A A A 0 001 H n 0T r In I - In I I 'l CD It Nn H ( Ie) n I 0 N C A1 A A A A A i A A 0 0 4IJ CN 01 ND '.) Nr '. 0n N L n ci Hi H 1-1 H- ry) H H >1 * * * * * * * H ci c H AA A A A A A A AA I ~ I~ 4.) ~ H i H H (Y) H) Hn HNa C > 0 00 00 0 U N CD H C' '. H U) Hm( EA InI ki r' In 0\ 0\H 0 a I-q -i m C rA Alq A41 An A A C ) n H I- -. . NW CD O r.) O\O oW ow O H\ 0J- ~ I-( 1-4 n H '.0 i 0 In o 0 0 WO 00/78275 PCT/USOO/15729 - 69 C)i H In Lr) OD In '.D W -1C 00N m H mn a)~ m C) In C I A H )~A Co CD C) C) 4.) to ci A An 0 ~ 4-) 0 4 0z InL n MN I ~ >1) C) 14, Co ci) C I o A~ U). U) x~ x. x___ O \ P4- U) U) U) C) ) CD C 0 p0 CD ci CnLI -) 4H En In > 0 H~ C)p Cl) ~ ~ ~ ~ C -(D - - - - 4-) 4-) U Cl)C Cl) CS CDl) E-4Cl 00 D ) 04- HI H ) oW o\O 0'd n InCl.. Cl.. ClA WO 00/78275 PCT/USOO/15729 - 70 0) H H N- 0) ~j (Ncl Ll m (N Ul L- m * (N In H A m q C N A A U)C) IO C) In In C) IO In In (Y) H my H H- m H H Hi In H In (N N- m4 w H1 m M (N3 H H ~ q H N C) H >4 0 p 0 H1 rz 1 W In ) m In m In In r4 A 0f A A A A A (D A 0 4.3 C) In 0 In In C) In In) In 0m H m H H Cn H H- H4 HUm Wo H ) wO 14 coa 0 m 04 D w l (N In) a) uCD It C 4 m N In m C) A E-1 4- J-0 4 04 04 04 a4 04 04 a4 a4 a4 a4 U) ) r-I 4 0a4 0\0 0\0 0\0 0\ 0 0\ 0 0\0O o 0\0 o o\Ox 0043 4J F H In H ko m C) In (N C) C) CD U) co to > 0 0\0 0\0 C) C) a) In (N ) In C) CD C) r-A 1-4 N N- r-- \ H 0 - H M C) H (N-n C) C) In, In In N 1 c4 -I4 .1 In In) N 0 ) a) (N 0 m m In 0 3 CD M C u 4 C) v a) H (N C) m4 m k E-4 (N MC) U) r- w 0 H H H H4 WO 00/78275 PCT/USOO/15729 - 71 0 CD CD (D C> cn1 0 4 0 -H Cl 0) ~ -IA A 1 00 Cl ClDC C) r12( cl H C 00 A A C/ U 13) Cl) Cl l l Cl) EnCl C D) Cl) 4J) Cl 0 0 On .1-1 0A \0 0\0 0\0 0\0 H Hi H U U4 0 LO Ln ILn In > ~ 0 m\ U) p- 0\0- 0\ 04 0 O .. I L ) 04 a >400 0 0D 0 0 0) U) Ln 4-) 4J-4 U) 4 E) U) C) S ! C Flf OD- ) 0 ) In In) (D WO 00/78275 PCT/USOO/15729 - 72 Many compositions of the present invention contain a surfactant, which potentially can reduce the efficacy of the antibacterial agent. The fol lowing examples show the unexpected benefits 5 achieved by compositions of the present invention. Example 1 In this example, a composition of the 10 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 15 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 (CS), a prod 20 uct of Benckiser; and Soft Soap (SSp), a product of Colgate Palmolive.

WO 00/78275 PCT/USOO/15729 - 73 oo 0 0 H 4HA 0 D C 0 0D 0 00 Cd P4 0 Cd 14 0 0 ., A 0 0) 0 0 0 o o 4 D 0 0 G D N) 4-4 0 0 0 4J (d 0 CD C4-) OPd (I) 134 d 0 E u ~U) ,a r-) Cr)d 00 w~ WO 00/78275 PCT/USOO/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 compo 5 sitions. Thus, an aqueous composition containing triclosan in SLS, at 100% saturation, offers signif icantly greater antibacterial efficacy than any of the three commercial products tested, against Gram positive and against Gram negative microorganisms, 10 both of which can present a significant health threat to consumers. Example 2 15 This example demonstrates that the anti bacterial activity of an inventive composition is attributable to the active antibacterial agent, as opposed to the surfactant. Test compositions A-1 and A-2 were prepared. Composition A-1 is a solu 20 tion containing 0.3% triclosan, 1.35% ammonium lauryl sulfate, with the balance being water. Com position A-1 is 100% saturated with triclosan. Composition A-2 is a "placebo," i.e., an aqueous 1.35% ammonium lauryl sulfate solution that is free 25 of the active antibacterial agent.

WO 00/78275 PCT/USOO/15729 - 75 0 m mn 0 0)) -4) Ln 'L 0 to~ -I H AA 0 4) ) 0 C -4 (v aEa H~ J 'U0 $4 WO 00/78275 PCT/USOO/15729 - 76 The inventive composition A-1 clearly provided an excellent, broad spectrum antibacterial activity, whereas the "placebo" composition A-2 exhibited an extremely limited spectrum of activity. 5 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 10 composition A-1 clearly shows that the antibacterial activity is unambiguously attributed to the presence of the antibacterial agent in the continuous aqueous phase. 15 Example 3 In this example, a solvent, (i.e., propyl ene glycol (PG)) was used to solubilize triclosan in an aqueous carrier. No hydrotrope or surfactant was 20 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" 25 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 com position. In particular, it was observed that the excellent broad spectrum activity illustrated in 30 earlier examples at contact times of 1 and 5 minutes can be achieved in the presence of the hydric sol vent at a contact time of 30 seconds. This example further demonstrates that the antibacterial activity WO 00/78275 PCT/USOO/15729 - 77 of a present composition is unambiguously attribut able to the presence of the antibacterial agent.

WO 00/78275 PCT/USOO/15729 -78

-

1 0 N' ccn 0 -1 rd LfO 0 A 0 (D 0 H 4.J 0 00 CD 0 (D U 0 W J 0 : p WO 00/78275 PCT/USOO/15729 - 79 Example 4 This example illustrates that composition 5 of the present invention provide an acceptable sani tization efficacy even though the compositions con tain a relatively low concentration of disinfecting alcohol. Examples B-1, B-3, and B-5 contain 0.15%, by weight, triclosan, at 100% saturation. Examples 10 B-2, B-4, and B-6 are comparative examples contain ing 0% triclosan.

WO 00/78275 PCT/USOO/15729 - 80 0 0 0 C;C ci) Lfl Ln Ln -V C I H 0 0~ 0 C>, N, C>r >1 e, 0 S LA 0 H co L H m * 0 CP H 0 0 ci) Cq 0 rA U2 (L) 0 04~ H ) H4 P4 ) LC) H E- I D *4 H3 WO 00/78275 PCT/USOO/15729 - 81 The following table summarizes the results of a time kill test at 15 seconds. Log Reductions at 15 seconds 5 Example S. aureus E. coli K. pneum. S. chol. B-1 >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 10 B-5 >4.39 3.29 1.37 1.30 B-6 0.10 0.0 0.35 0.34 15 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 inven tion provide a persistent antibacterial benefit 20 because of the nonvolatile nature of the active ingredient, triclosan, whereas presently marketed compositions do not provide a persistent antibacte rial activity. In particular, Examples B-3 through B-6 25 demonstrate that the rapid antibacterial activity of the present compositions is attributable mainly to the antibacterial agent, e.g., triclosan, as opposed to a disinfecting alcohol. This is in contrast to prior art disclosures. For example, composition B-3 30 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/USOO/15729 - 82 alcohol concentration (i.e., >40%) to achieve a fast, broad-spectrum antibacterial activity. Example 5 5 This example illustrates the effect of the identity of the surfactant on the antibacterial activity of the composition. The test results sum marized below were performed on a wide variety of 10 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 exam ple is at least about 90%.

WO 00/78275 PCT/USOO/15729 -83 ri E + + + + + + + + + + + L~'+ + + + + +I + 0: 0 + 0 0 M E + + + + + + + + + + + ++ + + + + + + + + + + .14I +- S co 0 4JI ) l (U 4-4 m ~ 4-) 4l .r ~ J U .J) 4-i H- - 40 4-4 m 0a Hl :j 4J H- 4-4 ri 44 ClQ ) m ~ i-1 0 - 0 -W x - 4-4 Ci) ; 0 ) 4-4 0o a) -i Cl 4J 4-4 Q ) 0 H 0 -d 0) m~ u- l 0 ~ 0 u uOmn 4 ~ ~ 41J 0 1Ni: u a 0 H) >, I) a) Q)-H m w r 0 EuC) E E E ;j 4)i0 a -H- a )- E -rO w i -H -H ro (71'd d ro -H 0 'dc' N '0 '0rc 4-) 0~ L 0 410 )-H 0 U) (a 0- 0 -H 0 a) uJ)-H E) Cl) p -W '0 ) - i-1 ) CI) CJl) U -) CL4 2: 0 - dP~- r 0 0 -n dP o0 44- o\.Ci) LA) dOP 4-4 Ml dp a) dP Ao0 Q) p - dP U) o'p Oo C) LAOu w~ q~- m L-I LAH Ln 4-) u) Lt L u) LA-I LAU ) 0 W Cq 4 . Cfl :j . (d .C *CO Cl *. *4 *rX U to r- H- H O))A ) O44 H rN- CN r-H- -1 N - H U) 0 U VlC) CV2 C/) ul U) Cl) Cl) C) Cl) co) Cf) 01 U u U U Ul U U U U u U u > E- E-4 E- p P P p p H H H- H -1 O'L o \o O o oP O dP dP dp d dp df' 04 o 0 0) 0 C0 CD 0 0 0 0 00 u -4 -H1 -H - - 0 -H -H1 - -H - IV 9 r. F_ 0 . 0 0 r. 00ir 441 0 0 0 0 0 -Hi0 0 0 0 4-) -HI H - H H r WO 00/78275 PCT/USOO/15729 - 84 '- C) C) 0) 0 0 0) 0) C 0 0 C) (d q + + + + + + + + cci .Y+ + + + + - + Us-+ + + + + 0 )~+ 0 ;I ci) 4- a rd) Mi ccW m- r. 4) M ~ 04- . -l .1. H- rdi 0 4)W -H) Ln 4.- :H (a) *H i a) .1) aH) 0 - w 1 cc 0 4.) Ic Ul) 40 cci (a ) L4-4 coi (n 0 E o H- 4-4 1 -c 0 m - H 4-4 14, 4. 4H- >-, w U) a1) .0 ;j '-1H Ho U) >-, .441 E'm1 0~~U 'C') l > f)M 0 0 0/ () ;J 0 4- CN- 0 0 riH 4 i) rd ; I-4ix I 0 4 4 cci M 4- ' J 0 0 7 (13 cIS ) )4-4 : ~ co Ez0) fu iU) ri rl. H-i '-H : -O 4 H cc . ) l~ V -rW 00 ' E Ei 00 Q) Ql -H)-) 93 1- WO 0' uU oE 0 0 0 4 'icfl r.) 'HM JJ -H -1 U L 1-Hl U) 0H Ui U0 01 OH c i 0>-i U '0- c) Q1(U) '0) -- U)' I U) x (U 0 ci H) 0 O 0 OH O- dPm dP- cN - 0 44I f)UIn U'0J o'P L- LflO U)O 0 A1 P U) 4 nu) olpHrI A Ou) CAP 14 H - LO H Cl J- 5 (N r-~ cj0 flU u~ C)I-c0 0 dP U) dP X *. cci dP I .U) *U . .U . Z m~ 0- cQ HU) H 4-4 HC'N H - - H-- H- H - C 0 U)l U) U) U) U/) U) U) C/) U)I U) Ul) ci) U U U) U U U U U U U > E-' p- p- F' F- F- F- F F-' F- F -1 dP O~P O OP O )P 0\P OP p OP CAP m. r'c m r~ m m C'v oci C) C 0 CD 0) C) C) C) C) C) Cl) L0 1 0 0 0 4O 0 u 0 -H -H 4.) 0 0 ) a) U U) 0 U -H- -H- - -H -H 41) 4- - H -H S0. 0. 0. 0r 0 0 0 0, 0r. 441 0 0 0 0 0 .0 0. 0 0 0 0 -4 -H- -i H - - 04 - -H _j e WO 00/78275 PCT/USOO/15729 -85 0 .-1 hi ' ) 0 ( .V4 + '- + C C0 f, u Q) .) 4JQ) UJ2 a) OcI) 0 0 0 : Q) -H r H 0W J 0-A r-A 0 a w 0 >1 >1 Id -,1 0 -4 x 4J Q ; -1 0 (U k.'0 0 44-I If44 ap 0 cq (Nr Ln 41 : .* j . ' w 4) rJ) mf Cl) o -H 0 :J 40) 0H r. z 0) c 0) O eU -- U U1 M 0) 0) m 0) m 4.) u H -H- 0 . ( U -H r. r r- (v) rq-HlC0 (U 0 0 0 AA AA V 4.4 0 -H *H 0 0 ~+ + ul z z w++ + WO 00/78275 PCT/USOO/15729 - 86 The results summarized above demonstrate, unexpectedly, that antibacterial agents and anionic surfactants form highly effective antibacterial compositions when the % saturation of antibacterial 5 agent in the composition is high, i.e., at least 50%. In addition, it was observed that, within a homologous series of surfactants, efficacy can vary (i.e., in the sodium alkyl sulfate homologous se ries, sodium lauryl sulfate and sodium octyl sulfate 10 yielded high efficacy formulas). The efficacy with respect to the cation also is unexpected (i.e., sodium, ammonium, and triethanolammonium lauryl sulfates provided high efficacy formulas, whereas lithium and magnesium lauryl sulfates did not). 15 Example 6 The following table summarizes the effect of surfactant identity on the antibacterial activity 20 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, 25 anionic/nonionic, amphoteric, and nonionic surfac tants. The results demonstrate that various an ionic surfactants form highly effective systems. The surfactants associated with very high activity 30 (i.e., a high log reduction for both Gram positive (S. aureus) and Gram negative (E. coli) bacteria) include sodium lauryl sulfate, sodium octyl sulfate, sodium 2-ethylhexyl sulfate and lauramine oxide.

WO 00/78275 PCT/USOO/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 5 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 effi 10 cacy. Potassium lauryl sulfate was not tested be cause 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 (i.e., sodium 15 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 Carboxyl 20 ates) 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 25 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. 30 The results for Series V (Miscellaneous Surfactants) shows that these compositions exhibit moderate to low activity, with the exception of lauramine oxide. The portion of high activity of WO 00/78275 PCT/USOO/15729 - 88 LAO is attributed to the surfactant alone because of its quasi-cationic character. The remaining surfactant/TCS compositions in Series V showed var ied activity vs. S. aureus (Gram positive) and very 5 little activity vs. E. coli (Gram negative).

WO 00/78275 PCT/USOO/15729 -89 C) co LA -. 4 Co Co L(N en mn e H 0n m) 0) 00C) LA) *cq~ ' C) I en Hf A A A IT I ) 0-- -1 -- N- -- r, e LA . wo H 0) C) Co-0 LA 0C) 0 ) 0 wo o en LA en) LA m H LA (D *C) . LA C PA H - H C) I H A A A A ) C 0 * ~ N ~aN (J% 0) m) 0) 0) m 00 m en 0) 01 m en en H enm LA en en en m C) N- v 00 C IV j CC) U)A A A A A A A A en ~~ N- N N. - ) -. ~ a ) cd ) m) 0) a) m) 'r) %D m en Co e e n 0 ) .cl) en en e n 4 " M e A A A A (N (N I A H A A A en (N Ca a) 4.) H ul C/) U rn U) M 4- f - ~ 4-4 (d -o CoC Cd ~4 4r - .

- OD0 '4-A r- 4- 0 i Co U $4 Co) U) -$ - I 1 4--) '$ Co 1 l Co) CoEn C Q) 4)- 4.4 4-4 '0 H4 4-3 4-1 H1 4-) Co Co H H- Co 0 U (a rd >, i H a) (d 0 0 j 0 - (1) 4-4 4-4 4 >, 4-) 4-4 En Co) CO m (d 4-) 4-) H- H- :1 - rd H4 ) 4-4 a) (a M~ 0 j m~ ; 4-4 0 H- H- 4-) H- 41) 4-4 4-4 CU) Cn Hi (a H- U) 0 0 >1 wd l it Cl) H H- HJ X ~ 5- X 4-4 C) 4-4 j H- H- 0n CO 4 H C d 0) 0) H H ED ED )-, >, ~ 0 0 4-4 44 40 4 H l -d 4 -4 -Hi 4 H - H 1 H - H U >)C Ca >a M. Cd Cd En M r d O CO ,0 H 0) H4 U 4J 4 H- Hi H- -1 0 4-) 41) >1 0 >1 E-1 0 Hj Cd H H- 0d 0 ) -H 44 0) fa (d E 0 0 H- S I 0) S-i H -Hi H: H r. ld 4-) 4-) (N N 0 41) (d r. 4 ;J w - 0~ 0 0 5 55 Ej 14 0 0 0 a) 4- -H 0 1 -H H 5i 0 0U 0 r. a E 5 H - - H r 1 0 5 0 -H- 4-) 0) 0) $ j rd '0 ro '$ ' H0 0 md m 0 S-i -Hi Md 4.) -H - 0 0 0 0 0 C) Co e I-) H- r= id '0 ' m CO CO CO CO m1 A '44 0 0 4) op do~ LA Ln dp 'p *p o'p H a CO l )P oYp d(' dNP o' ,a r o C n en LA LA LA LA LA LA LA LA LA 41~ u) *~ Cl) o 43 H H H H H H LA LA 0) m) (N ( (d H 1 W4 - >1. . . . . . 0 u u u u C) v H u u UUU ;> p Co) H Co H p p E- p Co) p Co) p p H .40 d' A U o'e U do' di' di' d~ d U di' Ul di' 60' \i H1 er- n E- en H- en en en en 14 en p en E en en en u 0 60di . di' a) 0 i i C; ~ ~ ~ ~ ~ C C D0C CA ,Cc) 0CP)C) 0* C 4.) cd----------------------------------- 0 H H H C)~ ~~~~ u)C ) C )C )C ) C ma - -H -H -H *H -1 H a - -H -H - -H 0)-r 0 0 0 0 0 000 0 0 0 0 04-fO H 0 0-dO H 000i w- WO 00/78275 PCT/USOO/15729 - 90 0 V (N Nv W H r- 0 i~- ) m A 0 cl 00 cx l) C)~ . - .~ H (A IL) C0 Nq Cl C0 N H H C -4 00 1- 0 0 I C) 0 0 0 0) I 0 C IT C) 0) Ln 0) Cl Nr m Hq w H c; Ln CiA *IA A I~4 -. 0 0) M. Cl H 0 . -. mU C LA) ix H co ix) 00 ml N 'I wx oLO CN . 0 0) H H * 0 4 ~ 0 A 0) 0 nl H 0 A A I 0 1I ) N 4J 0 0S o 0 mu 41 H M 4J 44- (aJ -D - -U) 4-4 x -4 c - -1 H 0 P4 - 0 04 ;j _ 0 -4 a) to U) 4 -.4q - J., - C Cl C C 0 0 4Ji 14 u) 4 4) ai ) Q) 4~J 41 4J (V a) C 4- 4) .1-- (a CO mO v CD 0 Ci C rd S-i S-- S- -1 41 1 H CC0 H -1 -I Ci C O di4~ U 4.) C 0 0 0 H- H- ,-i ~ H C 93 >-. S- -') F= EIEEr- 4 - H H- -Hi - r-H ri E3 r= d U)U) m) U2 I U) CIn Ulr) (d 0 H 14U) U) U) U) En U) U) H3 r CC 44 - ) 4.) -W 4- 4-) CI 0 l ' H ) 0 0 0 0 0 0 0 44 U) -H 0 0 .4. 04 04 0 4 4 P 1-4 '0 u) 4Ji 1-i :3 0 1) .) Hn dE' C10 80 80 80 80 80 U)0 0 C o 0 H H N N N1 C1 Cl H'rN H Ci Cl l) ) Cl) cn '- m CMI) C) Ul) u) U ui ci ci) ci ciCi ui c >- P - FA P C) P- E-1 Ul) 4J H- P H P *-C H 810 6\0 810 Ui 810 810 ui V. 80 o1 80 * 43 ~ C V. ml m Cl) pl H) 0 M l Cl Cl uo 0 p . *p - u 0 0 C, 0 0 0 0 0 0 C) 0 0 _ 0 H CC -H- - *H -H -H CC -HO -HO -Hj V0 V.0 0 r. 0 00 r.0 0 U) -4 0 0 0 0 0 ri 0H 0- 0-H H-H4 -H-HH

.,

WO 00/78275 PCT/USOO/15729 -91 el ) LO 0oC H (N m C0 k0 co . N mf Cfl H 0 0- H-I N H r 0 CN Cl) N1 0 W -HA . 0 I -. r 0 0 C; 0 0; 0 - l - Ln -.- 0) - . -. C OW'9 00 0 (N w. 0 H 00 OD H H- Hl oH 0 Cl .r- H N 0 .. 0 - 0 0 A C)' I 0 ; 0 0 ) 0 I 0) 0 Nq Noc 0 Hi 0) -C) m 0w 1.0 m) IV 0 0 0)A A lz A LA A. -. - 11 m. - t - - A C LN LA CAI LA00 C . j odm LA 0 n to N H o Cl N- rI H '0 0: 0 A ml H' N H Cl) A H N I 4 J jC) 4JC u C) 0 >1 - 4 U) Cl) to 4 Q -Hi -i Cl) C)~ 4JU) Q) 0)6 wl 0 d Cf) Cd -H- 2I - Cw 0 U m) '44 Q) 0 u Cl) Wl U) C)4 $4 41 - u - H 4 :j d u 0 - U .H :: 0 Ji) 4)J -- * a U) w- (d a) 4)i ,4 Co C) C H 0 0 H1 i- 4i (a 04 4i 0 P U ) ( Cd ~-H 4) -H iCC d lm 0 44 (d 4Li U) wl .4 0 L4-1 H- f= 0 0) 0 4i I4-4 H- ;: Ea~£ ~ U 0) 0 H H 0) H 1 U -H0 .11 0 4 ;j El 0 0 Cd )-, x) Co 0 coi j 4 -Hi C) 0 0 H 4-)J 0 0 l Cd H- H- 0) 441 u C4 w E-4 aCd H4 >, 4i a) - 0 P4 > 0 (U 0) H E C- U) H- C-C u 0 H -4 0 = ) 0 Cd '0 0 -H - J~~ - -H Cd I- 0d r. -H 0o rdE - H 10 0 H , H -1 r- 0 0)4 3 ' 4 Cd Cd - '0 0n S 04 -H -H U H S3 0 u 0 U) -H -) H ---- 0 0 9 H (d EDCd U -H- '0 -H ) (a L U) U H '44 Ho HO '0 '0lzp' w. 14op dp 0 oY' H I o'p * 0 O dP o LA *~ LA U) *~ LA u 0 LA LA *p ALA LA Nq LA N 0) N H Nq N LA 4.) .P . - 6\ 0 0 M H H H- H H H4 N H Ml H H- CN 0 0) C/ U) U) U)l U) U) U) Ul) m) U) 0 u U U u U u U u U Uu >* (d P U) p p H H H H H H H -HO H r- p ) 0\ *p 'p oIP dp *P de o'o o'p dl' HJ Cl H- Cl E-4 Cl r) ml m U Cl) ml Clm 00 0 )6 - U - - UL 0C0 0 0 0 0 00 0) oH 0- 0 0 m> r. -rC) C-i C A ri H - -) C. 0) 0 r. r. r0 r r. 0 r. 0 0 0 -10 0 0- 0 0 0 0 4 4 -H 04 04 SE0 WO 00/78275 PCT/USOO/15729 - 92 Example 7 This example illustrates the effect of % saturation of TCS in surfactant compositions (i.e., 5 compositions free of a hydric solvent and hydro trope). The data summarized in the following table illustrate the effect of % saturation of TCS on the efficacy of TCS in TCS/surfactant/water composi tions. Two sections of the table (i.e., TCS/ALS 10 compositions vs. E. coli and TCS/SOS compositions vs. S. aureus) show a substantial decrease in anti bacterial 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 15 approaching that of 100% saturated samples contain ing 0.3% TCS. In these two examples, the effects are seen clearly for organisms wherein the sur factant does not show a strong placebo kill effect.

WO 00/78275 PCT/USOO/15729 -93 U AA A A A r.. A A A A A S 0 -CN 'D ' D C -A ii -'0)- M~ C. %n HD kn k 10 4J -1~ 0) 0 n r- or .4 M 0 A N H- H4 mA A A A A 44 m- ~-- 1-mC -k H ml- ko m ~ C) 0 0 m. L LA M n rn HW LA C:, LA c0 H 4 A n0 U -.4 I. A4 14 v 4 I o) m 6 ) m a a , a , o 0 ) 0 0)0mU m m mm) L4 A LA A LA A LA A LA A LA LA LAM m 0) mn 0) (n ) mn 0) 0) 0, ch mn mn L Ln ul mn (A .- 1 rC~ A en A MA mA MA MA L MA mn mn Mn m N H 0 N 41 A A A A A A A A A A A A to $4 4J

E-

dp 4J 4) Uq *- dP de o P 80 8 . . 80 8.0 8. 80 80 0P 0W 0 ui () LA LA LA LA N- LA 0D 0 0 0D 0) 0 LA LA LA LA 0) U) 414 en mn Mn MA W. L ' w. w. w. OD w. N- N- N - 0D 44 ~ H3 H- H H 0 H H H 1 H -H4 H LA' LA LA, LA * 4J 0 0 0 0 0 0) 0 0 C> 0 0) 0 0 CP 0 N H LA) N r H LA LA 0 N H LA L CN CN H LA 0 0) N CN H Ln0 0 N N H L LA H mL H LA H 02 0 0) 0 0) 0 0C0 0 0) 0 : 0 ; 0 0 0 WO 00/78275 PCT/USOO/15729 -94 0) A 0 44 0 (U -1 04 00 0N 0 C* 4J 0 (U 0 44J U d. o (a LO 4) 44' r 4.) (d 02l 0 02

U

WO 00/78275 PCT/USOO/15729 - 95 Example 8 This example illustrates a composition of the present invention that can be used as a hand 5 cleanser. This example further illustrates an em bodiment of the invention wherein the antibacterial agent is present in combination with a surfactant, hydric solvent, and hydrotrope. Composition A-5 contains, by weight, 0.3% triclosan, 0.5% ammonium 10 lauryl sulfate, 20% propylene glycol, and 10% sodium xylene sulfonate, with the balance water. Composi tion A-6, by weight, contains 0.1% triclosan, 0.125% ammonium xylene sulfonate, 20% propylene glycol, and 10% sodium xylene sulfonate the balance being water. 15 Compositions A-5 and A-6 were 100% saturated with triclosan. Composition A-7 was a "placebo" contain ing, by weight, 0.5% ammonium lauryl sulfate, 20% propylene glycol, 10% sodium xylene sulfate, and the balance being water.

WO 00/78275 PCT/USOO/15729 - 96 -H) 0 M

IV

0 0 A.~ m m o A A 43J a, a w d(N i ~ ~r1 0 0 -1 4J 0 HC C Z 0 WO 00/78275 PCT/USOO/15729 - 97 This example illustrates two important features of the present invention. First, the abso lute amount of triclosan, or other antibacterial agent, is less important than the percent saturation 5 of antibacterial agent in the composition. For example, composition A-6 (containing 0.10% tri closan) was at least as effective as composition A-5 (containing 0.3% triclosan). The important feature is that both compositions were 100% saturated with 10 triclosan. Second, Example 5 also clearly showed that the active antibacterial agent is responsible for the excellent broad spectrum antibacterial ac tivity. Compositions A-5 and A-6 of the invention clearly outperformed the "placebo" composition A-7, 15 which did not contain an active antibacterial agent. Example 9 This example demonstrates that a hydric 20 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% 25 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. 30 Compound F contains 2.5% alkyl polyglucoside (APG") with 0.3% TCS. Compound G contains 0.3% APG, 14.4% dipropylene glycol (DPG), 10% sodium xylene sulfon ate (SXS), and 0.3% TCS. Compound H contains 0.3% WO 00/78275 PCT/USOO/15729 - 98 APG with 14.4% DPG, 10% SXS, and 0.0% TCS. Composi tion 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 5 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. Com position N contains 0.25% CAPB, 14.4% DPG, 10% SXS, 10 and 0.0% TCS. Composition 0 contains 4% octoxynol-9 (TRITON X-100

TM

, 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 15 contains 0.25% SLES-1, 14.4% DPG, 10.0% SXS, and 0.3% TCS.

WO 00/78275 PCT/USOO/15729 -99 (N co 0 ) 0) Ln m -Ln 0 mH ko 03o~ H Cr- Ln 0,. Ow m1 A A A A I A 1 a) r3C- 00 0 0) 0) 0) r- mI 0 Mj.0 ' 0 rn IT W LA %D H L- M3 Hq 0T I~r Cq ~ E- A A A A I A 0 -.4l 43 o r r- 0 o) 0) :3 to~- 0) 0) 00 ~ H W0 H- (N m~ 00 04 00 ton . A A A H H A H- I A 0 to) tU2 - r, 0) H 0) a% m3 LI) m3 w o 0 0) m3 00 m Hq wA H4 H r OD m~ m m H H 0 1. 0 A A A A I A 0 .4 4J 0 0 0) 0 0(0 d d 0 0 0) 0 0) 0D 0 14 H H~ H H 0 4.) 0 0 10~~~~ 0q4P 4uP I 1) 0 0 04 01 03 0n Q M LA LA 44J LAdp dp N HIH H C3 0 m 0n 0 0 0 0 0 WO 00/78275 PCT/USOO/15729 - 100 ~IW .. 0. OW C A C, A A CO H en) 'kD mnH 0) .0 N N, N IT L A enA 0 -1 -I1 to . C' m LA LA OD en) 00 OD U H MIn %DW A C C' C; A A lOWM 0) 01% kL W mn Ol 0 0 m' rn H LA n e Cl)'- C' ~ C' C' ' I A A A 0 4.) C' 0 C) C' C' d 1 C' 0 ' C0 C' 0 o 14 H H- C' H H H 4.)) U)) V) 4.) H H H H 4 4 04 C) U) Q IM dP o'1 dP H N- It 'I oV LA H -14 H W 01 -H H C' U U~ ()

F

N N LN N CON 0 0 o en en C' en en en en U 0' C ' C' ' C' C' 14 E-4 0 "4 .4 0 0 ri WO 00/78275 PCT/USOO/15729 - 101 The results of the time kill tests summa rized in the above table very surprisingly show that the use of a hydric solvent and hydrotrope can im part a high antibacterial activity to surfactant/TCS 5 combinations which alone exhibit only low to moder ate efficacy (i.e., compare efficacy of composition F vs. G; I vs. J; L vs. M; and Q vs. R). The hydric solvent and hydrotrope also can render active compo sitions more active in shorter contact times (i.e., 10 compare composition B vs. D). Especially surprising is the observation that a hydric solvent and hydro trope can impart antibacterial efficacy against E. coli even in a composition containing a nonionic surfactant, i.e., octoxynol-9 (compare compositions 15 0 vs. P). This result is unexpected because poly ethoxylated surfactants are known to inactivate phenolic antibacterial agents. Example 10 20 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 25 antibacterial agent in the continuous aqueous phase of the composition also greatly influences the anti bacterial activity of compositions containing a hydric solvent and hydrotrope. As the results sum marized below illustrate, this influence on antibac 30 terial activity is especially apparent with respect to the Gram negative bacterium, K. pneum.

WO 00/78275 PCT/USOO/15729 - 102 0 od C l) E H1 V (nU Cl) co n)c In) C) f) m) x x' x C\O C\O C\O CDO 0\0C) o) 0\ 0\ 0\ HJ H H H 0 0 0 H H H) H)CD a2 4 04 04 00 Q. Q Q 40 40 lzi 00 O\ 0\- 0\O (D I) In U') CD C) CU) UO ) U) (N In 0 0 C 0 r4 rl In) Lflnm (V 0 0) 0 0 0 0 00 E'-4 0 m U) P D > >-' 0 0

U.

WO 00/78275 PCT/USOO/15729 - 103 CO CO 0) m CCC N (N 0 go m c) Cl W A A A A ( to l n Lr 0) r) ) C o) m w 0 - H 00 Ci) OD Lfl H A A ~ ~ 4 N ( OD w a') w %D Uj*o ci H 0l 1- A o -- Cy ) ON c (N 0 0 (N JI 0 4J3 (D rig r ~ U 0O A A A o CN aCoN ( .0 n Ll I) cq A AA 0 N ( . WW 0 ci ( 0D ic U~. A ( WO 00/78275 PCT/USOO/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 5 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. 10 Example 11 This example, in conjunction with Example 10, illustrates the effect of % saturation of TCS in 15 compositions containing a hydric solvent, hydro trope, and surfactant. As previously observed with simple surfactant/TCS compositions, the relative % saturation of the antibacterial agent in the compo sition also influences the antibacterial activity of 20 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 25 an increasing % saturation of the antibacterial agent in a given type of composition. The tables demonstrate this effect from two different perspec tives. The table in Example 10 shows the effect of changing the concentration of surfactant while main 30 taining the amount of other composition components constant. The following table shows the effect of varying the concentration of TCS while the concen tration of all other components is kept constant.

WO 00/78275 PCT/USOO/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 5 is clear from both tables for all organisms tested.

WO 00/78275 PCT/USOO/15729 -106 H 00 02 00 0 c o OW A m m c' m 0)IL A A A A A A A N (I 0 00 H wA 0 Cm LA 0D E-4 A~ cq m M~ C'N Cq N H 0 4.) U) LA LA LA) U U-' LA LA LA LA LA LA LA m~ :3 0 0 H 0) %0 .4 A A A A m rf N H rd CO LA LA LA LA (N kD 41 (N b) 0 LA LA LA LA 0) 0) m, N It 14 mi H H CO A A A A .4.) Eo E-4 0 0 004. C) C) 0 i00 a 0 () 0 0 0V LA 0 4 0 CdP U4 00 Q4 . w ) 0 4 LA LA LA LA LA LA) LA LA .l CA C) CA C; CA A CA CA Ha ul In co (n U -1~f W A U) U CA) U) CA VA CA V) >H do- 00 dP k* 0\' d* *p - ULA) LA LA LA LA LA LA LA) 4J4 -1H H H H H- H H- H .) ((sCD C D D C 0 P4 04~ 04 04 Q4 P4 P4 dP dPo dP * d V' dh p LA LA LA LA LA LA LA LA eU rn (Nl 0 0 0, N- W m CO H4 N m 0) 111 0 LA 0D 0 ' m' (fl mf (N (N4 H- H H u 0) 0 0 0 0 0 0 0 WO 00/78275 PCT/USOO/15729 - 107 Example 12 This example illustrates the effect of different levels of hydric solvent and hydrotrope on 5 antibacterial efficacy. In particular, the data summarized below demonstrates the effect of varying the relative amounts of hydric solvent and hydro trope. It should further be noted that the addition of a perfume (PF) and/or a preservative (DMDM) to 10 the composition has only a modest effect, if any, on the antibacterial efficacy of the compositions.

WO 00/78275 PCT/USOO/15729 - 108 in in H IV OD 00CL OW0 OD 00 %D A A) r N A A A A A U j uin in n 0 0i -1i q 0 1 n H A A A H 3 %DH O CO m w 0 in in in N N H toW A 0 0 A H 0 q M, A A A C'N -11 A c4) ;v a) i O n - mO 0) C) H- (N It H ra 0 H Y) Nr IV OD N (3) N in wn O r 0 CN 0q 0 D 0 0 H- Cl C 0 H ml A A A A t-~ O U-I in in mO ., torf H H . n H-l0 d4 V %D O A 0) -4 A A A P4 m 1 'IV W O M O C) C) (3 .0 It N L n in in 0 11 Clrn A A A A -d' lz %. Wn i H Ol * 0 u-I ml CN to A 0 Hi A A ' H OW l re) Hi cq N Nl 0 0 %D 0 ml Wn Wn i H rI l 0 Hi M, M, H A A A U) ) i) ) l) U) U) Ea U) ED Uf) Lo C/) f U) m U U) U) Ef U'< ><) a)< U) U)'<) U dE' dE dE' o'e o'P dp d,) A) Uo ) U) d) U 0 03 0 0 0) dE' 0E dE d' U) C/ 0 ILO C) n 0 0 i 4J x ) H H H) H H 0 C N iq n N- 0 0 (N in En U) r- rI H H H H- H- H (N H H H H 00 0C = C;~~~ ~ 040 0P 4P 0 12 0 0 02 00 dP 0 0 00 UI i in in in i UI N *p o dE' F: p PlPE'dP dP 6p U~l 0n 0 n U) in in in in in E c'n C'n 0 0 0 N N N N N N 0 0 0 H 0, 0 0 ) 0C0 0 0 0 w Hi 0m l l C 0 Cl) C) Cl l ml ml MI C m SM0 0 0 0 0 0 0 0) 0 0 0 0: 0 0 0 0 14 0 0 4 0 WO 00/78275 PCT/USOO/15729 - 109 _0)i 0 0 0- A A A 02 A A A H H- H 0 %D H H- - - A A A A A 0 A A A A A 04 M H0 L i H r N N N - ,t 'di o a'. N- CN H a 0 v '0 H H 0 0 EM h o o o o o A NA A A A A A .0 m N o 010 A A A A A A .0L H It0 No o tpo m 00 A A A A A .0. . 'o0o0 ~N H H H N 110 to~ On o od o- o o . . . o 0.0. . . N 0'. m) 0 0i ) 0) 0) U) ) U) 01) U) l) 0) 0i) 0) 0) 0) 0) 0 ) 0 0) o M ao EE 3Uo oX oP 0 d o o o o o' d\ 0 Od O 0 0 0 02 0 LA 0 LA 0 0) LA 0) LA 0 p. . L. . . . . . . . 0 N~ H1 H H H N H HH H N H4 H- H -'-4 M -> M -E - O- E- C D |>) N O d o dP o'E o' * * 0- O' 0 0 0 0 0 0 O0 0 0 0 LA LA LA LA L N- LA U. LA LA LA) N- N N N N LA LA LA H H H 0 g F: -:4 - - Ln ~LA) LA LA L) n L )0 0 0 0 0 0 N C> C.' 0H-H H IH HHH000000 00 C o M m (V m mi m ' m l Cl ml C m 0 ml e) 0 o 0 0 0 0 0 0; 0 0 0 , 0 0 0 0 0 0 0 -. i '-4 I I 0 Ur WO 00/78275 PCT/USOO/15729 -110 H0 0) m 0 0. - ) Cq 0 -'1W (N d Ow tn 0 ,0 j) HH D 0 0 -n 0 HdPQ 0 0 0 0

U

WO 00/78275 PCT/USOO/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 (i.e., an increase 5 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 10 hydrotrope may be acting as an adjuvant for the TCS because the time required for a substantial antibac terial kill, i.e., log reduction of at least 2, is reduced. 15 Example 13 The data summarized in the following table support a theory that the two primary factors for improved antibacterial efficacy are the relative 20 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 25 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 30 provides a greater amount of active antibacterial compound in the aqueous (i.e., nonmicellar) phase of the composition, thereby providing a higher time kill activity. The solvent, therefore, may be act- WO 00/78275 PCT/USOO/15729 - 112 ing as both an additive to enhance antimicrobial activity and to provide better physical stability in these compositions.

WO 00/78275 PCT/USOO/15729 - 113 ;v zr Ln LA Jn LA T : H N- 0 a) co 0 ) 00 00 0 0 C. M m re) %0 A A A A A A0 A A A ~D2 ~ j w LA) LA 0

U

0 H rf 0 N C) r- H C) kD. 00 00 ) N A0 A A N A AA A 00 m o'i N n H -1 e en) N- 00 .0 0) w. %A A e 0 A4 A 11 --- eAA bC ~ rj. OD C9 N 0 ) An en .r4 N en 0) C)L A ' E-4 A 0 A A A A ' A A A 0 00' L ) (A ( A ( 0 0) .0j r- m 0n LA) LA LA) 0 N- N N o o A 0 A I4 A A A ;4 A A to wND 0 m 0 N C 0 C> N' m) LI) Ln H) 0.' LA LA 0 04 fn en N) 00 en Iten e 5W 0 A A A NA A A N mU Cnen 0 N N NN 0m. a' 0o k.0 W a) IV ko LA H 0 LA LA) N :j C) en Hn fn en H H q H ' A C) A A A rq rI A A LA LA A.. A A A m co CfC) rZ -4 4 ClA U) Q Q 04 P4) Q . 0 p Q ) o') do.' p d dp *LA dcN'LA *LA C)o. 0'c caA Lo'c U)L A.) rz Q .- C) C) Co 0p HO HO 1 ,, $4 Q- r-I H U) H ri) H V 1H ITH l U aH H H tn C) 0 0 H' CDC1) LA LA LA L - LA l a* .l) Na N N) XO N ) X H4 H 4 C) CDU o )C N) Ln L LA ) LA) LA LA LA ) LA ) 0~ -4 -1 LA U L U L H HL C0 H 0 H C~ C) en *i e en En o'P 1' n w U 0 C) u u . ) . -400 C) 0 0 0) E-4 0 .4 43 0 u 44 HA~ C)'~ 0.

WO 00/78275 PCT/USOO/15729 - 114 o 0 N N N ((N 0 Co co co 00 co 00 *l H m 0 r n n e) mn en en 0W A A A lz A A A A A A u W 0 o 0 m~N N N 0 q cq ( (N co OD O 00 00 00 - Cq mn en) e) en en mn A A A A A A A A LA H . Co Ni (N Ln co N - o k H, C) 0) W (N 0 00 Wn 0 H'. H ~ 4 n co '.q E-4 0n 0~ b(N H c H e1N ( oH H H H H H H ( N ( oW A A A A A A A P4 l H H1 H1 - H H (q (N (N . 0 N- N- N 0 W W w k 0 A A A en A A A A A Cfl en en 9) 00 to -) A A A A A AA A N I- (N H H Co N e oo Hq .j N N N ( en tv (N .. j z A A A A A A 04 a dp p 4 p o P 4 dp Q ddp Q AQ.\- P4d a) dp d~ LLA Q ~ L LLA dLA Q~L dpL LA c .H v0 co 0 dO O O 0 0 0 0 0 dp0 000 -1 H 1 - H 4 H H 4 H L~ o En Hcn Uo ECo (n -C Cn m 0 Co '.pC q-C C -o I1o ,Co UCo 0\-d ~dP ~dP ~dp o o4 d o ~ dp .0 0 Ln L. . aLAOdP 4) (NO HH *H H- m Co O 0 o H o H -1 gHi *- H *1 DH 0 OH 0 0 0 C U) Co Co C0 EnCo C C o Co Co () U U U Co U U u U U U 0 dp dP o'.

0 H- dP o\. Ao o\. dp' d H en en en d en en en en en e .4 0 0; 0 0 0 0) 0 0D 0 E-4 0 4 04 0.

WO 00/78275 PCT/USOO/15729 -115 14 o~ a, u- n 0 ow 0 n m q 0nn 0 A A CN en) C to a, 0) 0% ci men en 00a ,q C 3 e) en (N en) 0D C 0 A A H N H kD (N Ln 0 % en A en (N en (N 04 n 0r f A 0 a ~ m LA a, enz ( r H h-(N 0 H H 0 0* 0 N C) A AAA W -. -- - o 0 ig C %D H) (NI C 0 A A en en N - N N to* (N a, 0 0 0 0 0 %0W A A (N A A A A 0 (N 0 0 0 0 0 v en H 4 A A A A A A V4"O Qd PdP P dP Q d d 0 Q n L c 0 Ln A LI) *Oo o ~ LA LO N 0 o n 0) .~ 0 1 0 ~ Idl O LA)' LAW) LA r L r c 0 Nl) C>) U) D ) U) U) LO Ln ) .) en en en en en enr - ) r 0. 0; 0 00 00 0

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WO 00/78275 PCT/USOO/15729 - 116 Example 14 This example shows that other hydric sol vents can be used in a composition of the present 5 invention.

WO 00/78275 PCT/USOO/15729 -117 14 %n a) m o i I I I AA A I I en H H m H C)O) 0 m m) b4 OWI I I A enA A -4I E-) b4 H Nm 9i m m Ur en en 03 H H H H o U o- -. N r- r- U,) 14j IL %00 A r" m ~ e : ZK K A A A A A A A A N e m1 en e C) OD coCOL) 0 H H- w K ON w .0 N- N- w tU4 Lf IV H 1.0 tJp A A zvA en A en m ~ 0 v m' 01. (h. q4 H H U). H U) H v~ 0'. a'. al. OD O)D H H H1 %04 en en H A A A A A A A en) A en A 010 aN 0'. N 0) aN a'. a'. COr N H 0 (N U, N- m mI (A. 00. 00. CO a H WD H A A A A A A A A A U) U] U] U] U] U] U] U]~ ~ m] U ] U] U ] U U] u] H> U ) C)) MCc Cf) V / ~~~'\ o 4 op d Hp~ , U V4 4 E-1 p- 0oC0H)> 4) 04 d P H H H H H H U) L f .r _1H 0 ) 0 U) 14C 0) HJ Lo C)X ri P4' '-"P 04 P4 P4 f4 P.4 P4 b) 4 dP de do O~ . d df' d 1 p dP AP dF tD d0 0 C)C C) C) C) . C) C)0 C H ~ U]) UC0 H 4 C ; C) C) C) C C) C r- q ~H H (N (N cN (N cq H H H a) C) ) L AH 0 )a U 0~ oY dP O' e dpO' C) U, H, U, U, Ud codP C) H C) C) C) 05 C) C) o en) enf n e n H C) H1 en C) en C) en o ) C ) CC) C) C) C) C) C)0) C) C) C) C) .1 $4 0 .4 S r-4 0) U H h3 0 4 CY P 0 i ) U H IF) 2 0 WO 00/78275 PCT/USOO/15729 -118 a 0 00 Ln Hi 00 o 0 C m 00 00 -1 10 0 %0 H- 0 0. .0 - H 0 M 0 0) 0 0 ~ ~ A LA A de )P dp W C0 0 0 4.) U) U) L 4) 04 0 0 Hl 0 0 0D H- H H .) -. 0 0) 0 4 0p O 0 C)0 E-4 0 P'4 0 WO 00/78275 PCT/USOO/15729 - 119 In addition to the observation that other solvents (e.g., PG and TPG) can be used in composi tions of the present invention, products JJJJ through 0000 illustrate another effect of relative 5 saturation of antibacterial agent in the system. The relative % saturation (highest to lowest) of the first three compositions is JJJJ>KKKK>LLLL. Compo sition KKKK has one-third the amount of TCS as com position JJJJ solubilized in the same level of ALS 10 (0.5%), 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 rela 15 tive % saturation is essentially equal (i.e., about 100%), the activity remains essentially constant even though the absolute amount of TCS in the compo sition is decreased (i.e., compare Compositions MMMM to NNNN). These data further support the observa 20 tions 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 (0.9% vs. 1.0% for IIII), 25 the same amount of PG (10.0%), and one-half the amount of SXS (5.0% vs. 10.0% for IIII). Experimen tal observations indicated that compositions IIII and TTTT were at or near 100% saturation. However, the log reductions of E. coli were considerably 30 lower (about 4 log) for Composition TTTT. This observation further supports the data set forth in Example 8 wherein minimum level of hydrotrope may be WO 00/78275 PCT/USOO/15729 - 120 needed for a high antibacterial efficacy against at least some Gram negative bacteria. Example 15 5 The following compositions 15-A through 15-D were prepared to demonstrate the superior germ kill provided by compositions of the present inven tion compared to control compositions (i.e., compo 10 sitions free of an antibacterial agent), even when very low amounts of disinfecting alcohol are pres ent. Compositions 15A-15D were prepared using stan dard mixing techniques known in the art. Table 4 below lists the composition ingredients. Table 5 15 below summarizes the antibacterial efficacy of com positions 15-A through 15-D, as measured in a time kill test. Table 4 20 Composition % by weight (as active substance) TCS Ethanol PPG-9 DPG Water 15-A 0 25.86 11.5 -- Balance (control) 15-B 0.10 25.86 11.5 -- Balance 25 15-C 0 23.0 -- 11.18 Balance (control) 15-D 0.10 23.0 -- 11.18 Balance WO 00/78275 PCT/USOO/15729 - 121 Table 5 Composition Log reduction @ 15 sec/30 sec S. aureus E. coli K. pneum. S. chol. 5 15-A 0.55/1.73 0.18/0.43 1.15/0.71 2.51/4.24 15-B 3.27/>4.43 3.75/>4.51 1.33/3.10 4.09/4.34 15-C 0.01/0.0 0.17/0.12 0.4/0.11 0.18/0.17 15-D >4.43/>4.43 3.20/3.48 3.19/4.03 2.86/3.99 10 Example 15 illustrates the surprisingly high efficacy of compositions of the present inven tion (15-B and 15-D), wherein high log reductions 15 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 (i.e., greater 20 than about 40%) are relied upon to achieve a high, broad spectrum antibacterial activity. Example 16 25 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% 30 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 fol lowing table summarizes the results of antibacterial WO 00/78275 PCT/USOO/15729 - 122 efficacy of compositions 16-A and 16-B by time kill tests. Composition Log reduction @ 15 sec/30 sec 5 S. aureus E. 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 10 Example 16 further demonstrates that the concentration of alcohol in the present compositions can be reduced to very low levels without sacrific ing antibacterial activity. Accordingly, composi 15 tions 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. 20 Example 17 Example 17 demonstrates that highly effec tive compositions of the present invention can in 25 corporate p-chloro-m-xylenol (PCMX) as the antibac terial active agent. Composition 17-A was prepared by admixing 0.1% PCMX, 13.42% ethanol, and the bal ance water (as weight percent of active compounds). The antibacterial efficacy of composition 17-A was 30 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, respectively. Thus, compo sition 17-A is a highly effective antibacterial WO 00/78275 PCT/USOO/15729 - 123 composition, even though the composition contained a very low concentration of ethanol. Example 18 5 Example 18 illustrates a composition of the present invention containing a cationic gelling agent, CELQUAT CS-230M. Composition 18-A was pre pared by admixing 0.15% TCS, 28% ethanol, 11.18% 10 DPG, and 2% CELQUAT CS-230M, and the balance was water (as weight percent of active compounds, except CELQUAT, which is "as-is"). The antibacterial effi cacy of composition 18-A was evaluated by a time kill test. Composition 18-A demonstrated the fol 15 lowing 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 20 very low concentration of ethanol. Example 19 Compositions of the present invention can 25 contain a wide variety of gelling agents, hydric solvents, and antibacterial active agents, illus trated by the following examples. In Table 6 below, all weight percentages are as active material, ex cept where indicated by a "*," which indicates an 30 "as-is" weight. The compositions were prepared by mixing and gel preparation techniques well known to persons skilled in the art. The compositions exhib ited acceptable clarity, stability, and performance.

WO 00/78275 PCT/USOO/15729 - 124 * CC) * U) C) rnH H 0 01 Hc') H 0 H * n Ci) 0 H m U 0 LA 0 01 0 tvaH HH 03 H H C') HH * U) 0 -II 0- 4. U) 0 ) 0~~ 01 H4' 0~- 01 HH0' m H 01 H ~ 1'4 14 01 H4 Hd H- f 4 b)) -r- 00 4 0 -H 01 r. mD f J) P a I ) u H - W 0 04 H 04I NU Q Q WO 00/78275 PCT/USOO/15729 - 125 Ln H- clq H mn C E*4 C. 0 0 0; o H Ln LA *H en 0 c1 I H 0 0 0; Hi Ln H 0~ 0 (12 CX; H H l P4 (f H C)N H 0D 0 0n 01 e 4 0m LA Hm C) 0 H H C LA H *LA H LA 0 V 1 -1 P: H 0 P4 ( 4J r21 0 H0 -i 0 0 P4 0 0) r 1 >1 H.Z Dp 0 *,. 0.. P4 MA 1) 44 0 Of x W. Ol C) -H 0 H O 54 N -H o 0 uA 0 4 0 f 0 ) g U~ ~~~~~ 0 1- 0 1 H Q C l 21 U Q WO 00/78275 PCT/USOO/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. 5 For example, as shown in the prior tables, a compo sition 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 10 greater than 3.81 (60 seconds). A 75% saturated and a 100% saturated composition exhibited a log reduc tion of greater than 4.55 (30 and 60 seconds) vs. S. aureus (i.e., a log reduction in excess of the de tection limit of the assay). The 75% and 100% satu 15 rated compositions exhibited a log reduction of 3.40 (30 seconds) and greater than 3.81 (60 seconds) and greater than 3.81 (30 and 60 seconds) vs. E. coli, respectively. Accordingly, the present antibacte rial compositions can be characterized as exhibiting 20 a log reduction of at least about 2 (after 30 sec onds) 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. 25 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 30 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 PCT/USOO/15729 - 127 like. The compositions further can be used as an antibacterial cleanser for hard surfaces, for exam ple, sinks and countertops in hospitals, food ser vice areas, and meat processing plants. The present 5 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 10 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 15 contact times. The short contact time for a sub stantial 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 sur faces. 20 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 25 immediately begin reducing bacterial populations, and further is available to deposit on the skin to provide residual antibacterial efficacy. In addi tion, because the antibacterial agent is in solution as opposed to surfactant micelles, the absolute 30 amount of antimicrobial agent in the composition can be reduced without adversely affecting efficacy, and the antibacterial agent is not rinsed from the skin with the surfactant prior to performing its antibac- WO 00/78275 PCT/USOO/15729 - 128 terial function. In addition, the amount of surfactant in the present antibacterial compositions typically is low, thereby providing additional envi ronmental benefits. 5 The following examples illustrate various compositions of the present invention. Example 20 Hand Wash Composition 10 A composition in accordance with the in stant invention, suitable for use as a hand wash, was prepared. The composition contained the follow ing components in the indicated weight percentages: 15 Ingredient Weight Percent Triclosan 0.3 Ammonium Lauryl Sulfate 0.75 Dipropylene Glycol 5.0 20 Sodium Xylene Sulfonate 10.0 Fragrance 0.05 Water q.s. 25 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 ab 30 sence of undissolved solid material, the sodium xylene sulfonate was added to the solution. The resulting mixture then was stirred to completely dissolve the sodium xylene sulfonate (about 5 min utes) . Finally, the ammonium lauryl sulfate and WO 00/78275 PCT/USOO/15729 - 129 water were added to the resulting solution, and the composition was stirred until homogeneous (about 5 minutes). The composition had a weight ratio of 5 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 10 of >4.07 in 30 seconds, while against E. coli the composition exhibited a log reduction of 3.90 in 30 seconds. Thus, the composition exhibited an excel lent broad spectrum antibacterial activity. Also, the composition was an excellent hand wash composi 15 tion in an actual use test, providing both good cleansing and a smooth feel to the hands. Example 21 Body Splash Composition 20 A composition in accordance with the pres ent invention, suitable for use as a body splash, is prepared using the following ingredients in the following weight percentages: 25 WO 00/78275 PCT/USOO/15729 - 130 Ingredient Weight Percent Triclosan 0.3 Alkyl Polyglycoside 0.3 Propylene Glycol 14.4 5 Sodium Xylene Sulfonate 10.0 Ethanol 10.0 Fragrance 0.05 Water q.s. 10 The composition is prepared by combining the triclosan, propylene glycol, fragrance, and ethanol, and admixing the components until all the 15 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 polyglyco 20 side and water are added, and the mixture again is stirred until homogeneous. The resulting composi tion forms an excellent and refreshing body splash that provides a desirable level of bacterial reduc tion on the skin of the user. 25 Example 22 Mouthwash Composition A composition in accordance with the pres 30 ent 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 5 Sodium Xylene Sulfonate 10.0 Denatured alcohol 10.0 Oil of Wintergreen (flavor) 0.05 Water q.s. 10 The composition is prepared by combining the triclosan, propylene glycol, flavor, and dena tured alcohol, and admixing the components by any 15 conventional means until all the triclosan is dis solved, 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. 20 Finally, the alkyl polyglycoside and water are added, and the mixture again is stirred until homo geneous. The resulting composition forms an excel lent and refreshing mouthwash that provides a desir able level of bacterial reduction on the teeth, 25 gums, and tongue of the user. Example 23 Wet Wipe Composition 30 A composition in accordance with the pres ent invention, suitable for impregnating a nonwoven material for the preparation of a wet wipe article, was prepared using the following ingredients in the following weight percentages: WO 00/78275 PCT/USOO/15729 - 132 Ingredient Weight Percent Triclosan 0.3 Ammonium Lauryl Sulfate 0.75 Dipropylene Glycol 5.0 5 Sodium Xylene Sulfonate 15.0 Water q.s. 10 The composition was prepared by combining the triclosan and dipropylene glycol, and admixing the components until all the triclosan was dis solved, as evidenced by the absence of undissolved solid material. The sodium xylene sulfonate then 15 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. 20 A piece of nonwoven cellulosic web mate rial (i.e., a commercial paper towel) then was dipped by hand into the composition to form a wet wipe article, suitable for wiping and cleaning sur faces, for example, hands. The article formed an 25 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/USOO/15729 - 133 Example 24 Hand Wash Composition A composition in accordance with the pres 5 ent invention, suitable for use as a hand wash, was prepared. The composition comprised the following components at the indicated weight percentages: Ingredient Weight Percent 10 Triclosan 0.3 Ammonium Lauryl Sulfate 0.75 Dipropylene Glycol 5.0 Sodium Xylene Sulfonate 15.0 Water q.s. 15 The composition was prepared by first admixing the triclosan and dipropylene glycol until homogeneous (about 5 minutes). After the triclosan 20 was completely dissolved, as evidenced by the ab sence 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, 25 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 30 90% saturated with triclosan. The composition was evaluated for its antibacterial efficacy against S. aureus, E. coli, K. pneum., and S. choler. using a time kill test, and a contact time of 30 seconds.

WO 00/78275 PCT/USOO/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 5 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. 10 Example 25 Comparison to a Previously Disclosed Composition 15 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 20 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 25 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 (i.e., test dilution is 100% for the composition of Example 24 30 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/USOO/15729 - 135 Composition % TCS Log Reduction at 30 seconds S. E. K. S. aureus coli pneum. choler Example 18 0.3 >4.60 >4.50 4.21 >4.68 5 WO 98/01110 0.5 3.29 0.29 1.00 0.45 10 This example demonstrates the superior time kill performance of a composition of the pres ent invention compared to a prior composition, espe cially against Gram negative bacteria. This superi ority is demonstrated even through the comparative 15 composition contained substantially more active antibacterial agent compared to the inventive compo sition. Thus, an inventive composition utilizes the active agent more efficiently, as illustrated in a higher log reduction using a reduced concentration 20 of antibacterial agent. Example 26 Comparison to a Previously Disclosed Composition 25 This example compares the antibacterial efficacy of a composition of the present invention to a previously disclosed composition. Accordingly, 30 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 35 citric acid. WO 96/06152 contains additional pH adjusting agents, such as monoethanolamine and so- WO 00/78275 PCT/USOO/15729 - 136 dium hydroxide. Further, the examples disclosed in WO 96/06152 all have a pH of 4 or 9.1, with no exam ples having a desirable, neutral pH of about 7. A pH of about 7 is desired for compositions contacting 5 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 10 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 monoeth anolamine (this composition hereafter referred to as composition 26-B). To provide an additional compar 15 ison, 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 20 time kill test on the compositions of this example against the bacteria indicated at a contact time of 30 seconds. composition pH % TCS Log Reduction at 30 Seconds 25 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 - 30 26-B Comparative 7 0.15 4.44 2.91 0.28 4.67 26-C 35 WO 00/78275 PCT/USOO/15729 - 137 This example demonstrates the superior time kill performance of a composition of the pres ent invention compared to prior compositions, espe cially with respect to Gram negative bacteria at a 5 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 10 bacterial populations. This is in contrast to Exam ple 18 of the present invention, which provides a rapid broad spectrum bacteria kill at the desirable pH of about 7. 15 Example 27 Antibacterial Composition Containing PCMX An antibacterial composition in accordance with the present invention containing p-chloro-m 20 xylenol (PCMX) as the active antibacterial agent was prepared. The composition contained the following components in the indicated weight percentages: Ingredient Weight Percent 25 PCMX 0.1 Ethanol 13.42 Water q.s. 30 The composition was prepared by first mixing the PCMX and ethanol to completely solubilize the PCMX (about 5 minutes). After the PCMX was completely dissolved, as evidenced by the absence of WO 00/78275 PCT/USOO/15729 - 138 undissolved solid material, the water was added, and the composition was stirred until homogeneous (about 5 minutes). The composition was at least about 90% 5 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. 10 coli the composition exhibited a log reduction of >4.34 in 30 seconds; against K. pneum. the composi tion exhibited a log reduction of 3.99 in 30 sec onds; and against S. choler. the composition exhib ited a log reduction of >4.04 in 30 seconds. Thus, 15 the composition exhibited an excellent broad spec trum antibacterial activity. Example 28 Antibacterial Composition Containing PCMX 20 A composition in accordance with the pres ent invention incorporating p-chloro-m-xylene as the active antibacterial ingredient was prepared. The composition contained the following components in 25 the indicated weight percentages: Ingredient Weight Percent PCMX 0.3 Ammonium Lauryl Sulfate 0.8 30 Water q.s.

WO 00/78275 PCT/USOO/15729 - 139 The composition was prepared by first combining the PCMX and water, then adding the ammo nium lauryl sulfate and mixing the components for such time as to completely admix the components and 5 dissolve the PCMX (about 2 hours). The composition was at least about 90% 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, 10 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. 15 Obviously, many modifications and varia tions 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 20 claims.

Claims (81)

1. An antimicrobial composition compris ing: (a) about 0.001% to about 5%, by weight, of a phenolic antibacterial agent; (b) about 0.1% to about 15%, by weight, of a surfactant selected from the group consisting of a C 8 -Cis alkyl sulfate, a C 8 -C 18 fatty acid salt, a C 8 -Ci, alkyl ether sulfate having one or two moles of ethoxylation, a C 8 -Cis alkamine oxide, a C 8 -C1 8 alkyl sarcosinate, a C 8 -Ci, sulfoacetate, a C.-C1. sulfo succinate, a C.-Ci 8 alkyl diphenyl oxide disulfonate, a C 8 -Ci 8 alkyl carbonate, a C.-C 18 alpha-olefin sulfo nate, a methyl ester sulfonate, and mixtures there of; and (c) 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.

2. The composition of claim 1 further comprising: 0% to about 25%, by weight, of a water soluble hydric solvent, and 0% to about 30%, by weight, of a hydro trope.

3. The composition of claim 1 comprising about 0.05% to about 2% by weight, of the phenolic antibacterial agent. WO 00/78275 PCT/USOO/15729 - 141

4. The composition of claim 1 wherein the phenolic antibacterial agent is selected from the group consisting of: (a) a 2-hydroxydiphenyl compound having the structure Yo ZP Yr (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 to 3, p is 0 or 1, m is 0 or 1, and n is 0 or 1; (b) a phenol derivative having the struc ture OH R5 Ri R4 * R2 R3 wherein R 1 is hydro, hydroxy, C 1 -C 4 alkyl, chloro, nitro, phenyl, or benzyl; R 2 is hydro, hydroxy, C 1 -C 6 alkyl, or halo; R3 is hydro, C 1 -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 5 is hydro or nitro; WO 00/78275 PCT/USOO/15729 - 142 (c) a diphenyl compound having the struc ture R'2 R'i R 1 R2 R' 3 X Q R 3 R'4 R'S RS R4 wherein X is sulfur or a methylene group, R 1 and R', are hydroxy, and R2, R'2, R3, R'3, R4, R',, R,, and R' 5 , independent of one another, are hydro or halo; and (d) mixtures thereof.

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

6. The composition of claim 1 wherein the surfactant is present in an amount of about 0.5% to about 10%, by weight of the composition. WO 00/78275 PCT/USOO/15729 - 143

7. The composition of claim 1 wherein the surfactant is selected from the group consisting of a C 8 -C 18 alkyl sulfate, a CB-C 18 alkamine oxide, and mixtures thereof, and has a cation selected from the group consisting of sodium, ammonium, potassium, alkyl (C4) ammonium, dialkyl (C, 4 )ammonium, trialkyl (C 1 4 )ammonium, alkanol (C- 4 )ammonium, dialkanol(C 1 4 ) ammonium, trialkanol(C 1 4)ammonium, and mixtures thereof.

8. The composition of claim 1 wherein the surfactant comprises a lauryl sulfate, an octyl sulfate, a 2-ethylhexyl sulfate, lauramine oxide, and mixtures thereof.

9. The composition of claim 1 having a pH of about 5 to about 8. WO 00/78275 PCT/USOO/15729 - 144

10. An antimicrobial composition compris ing: (a) about 0.001% to about 5%, by weight, of a phenolic antibacterial agent; (b) about 0.1% to about 15%, by weight, of a surfactant selected from the group consisting of a C.-Cs alkyl sulfate, a C 8 -C 8 fatty acid salt, a C 8 -C 8 alkyl ether sulfate having one or two moles of ethoxylation, a C,-Ci, alkamine oxide, a C 8 -Cis alkyl sarcosinate, a C 8 -C1 sulfoacetate, a C.-Cis sulfo succinate, a C 8 -Cl. alkyl diphenyl oxide disulfonate, a C 8 -Cl. alkyl carbonate, a C 8 -C 18 alpha-olefin sulfonate, a methyl ester sulfonate, and mixtures thereof; and (c) water, wherein the composition has a log reduc tion 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 nega tive bacteria of at least 2.5 after 30 seconds of contact, as measured against E. coli. WO 00/78275 PCT/USOO/15729 - 145

11. An antibacterial composition compris ing: (a) about 0.001% to about 5%, by weight, of a phenolic antimicrobial agent; (b) about 0.1% to about 15%, 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; (c) 0% to about 30%, by weight, of a hydrotrope; (d) 0% to about 25%, by weight, of a water-soluble hydric solvent; and (e) water, wherein the composition contains at least one of the hydrotrope and hydric solvent and wherein the antimicrobial agent is present in an amount of at least 25% of saturation concentration, when measured at room temperature.

12. The composition of claim 11 wherein the antibacterial agent is present in an amount of at least 50% of saturation concentration.

13. The composition of claim 11 wherein the antibacterial agent is present in an amount of at least 75% of saturation concentration.

14. The composition of claim 11 wherein the antibacterial agent is present in an amount of at least 95% of saturation concentration. WO 00/78275 PCT/USOO/15729 - 146

15. The composition of claim 11 wherein the surfactant comprises an anionic surfactant, an ampholytic surfactant, or a mixture thereof.

16. The composition of claim 11 compris ing a hydrotrope and a hydric solvent.

17. The composition of claim 11 wherein the hydrotrope is present in an amount of about 5% to about 20% by weight.

18. The composition of claim 11 wherein the hydric solvent present in an amount of about 5% to about 15% by weight.

19. The composition of claim 11 wherein the hydric solvent comprises an alcohol, a diol, a triol, and mixtures thereof.

20. The composition of claim 11 wherein the hydric solvent comprises methanol, ethanol, isopropyl alcohol, n-butanol, n-propyl alcohol, ethylene glycol, propylene glycol, glycerol, di ethylene glycol, dipropylene glycol, tripropylene glycol, hexylene glycol, butylene glycol, 1,2,6 hexanetriol, sorbitol, PEG-4, or mixtures thereof. WO 00/78275 PCT/USOO/15729 - 147

21. The composition of claim 11 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, sodium polynaphthalene sulfonate, sodium polystyrene sulfonate, sodium methyl naphtha lene sulfonate, disodium succinate, and mixtures thereof.

22. The composition of claim 11 having a pH of about 5 to about 8.

23. The composition of claim 11 compris ing: (a) about 0.01% to about 0.5%, by weight, of the antimicrobial agent; (b) about 0.1% to about 5%, by weight, of the surfactant; (c) about 5% to about 20%, by weight, of the hydrotrope; and (d) about 2% to about 15%, by weight, of the hydric solvent. WO 00/78275 PCT/USOO/15729 - 148

24. An antibacterial composition compris ing: (a) about 0.001% to about 5%, by weight, of a phenolic antimicrobial agent; (b) about 0.1% to about 15%, 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; (c) about 0% to about 30%, by weight, of a hydrotrope; (d) about 0% to about 25%, by weight, of a water-soluble hydric solvent; and (e) water, wherein the composition contains at least one of the hydrotrope and hydric solvent, and 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. WO 00/78275 PCT/USOO/15729 - 149

25. An antibacterial composition compris ing: (a) about 0.001% to about 5%, by weight, of a phenolic antimicrobial agent; (b) 0% to about 40%, by weight, of a hydrotrope; (c) 0% to about 60%, by weight, of a water-soluble hydric solvent; and (d) water, wherein the composition contains at least one of the hydrotrope and hydric solvent, and wherein the antimicrobial agent is present in an amount of at least 25% of saturation concentration, when measured at room temperature.

26. The composition of claim 25 further comprising 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.

27. The composition of claim 25 compris ing a hydrotrope and a hydric solvent.

28. The composition of claims 1, 11, and 25 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. WO 00/78275 PCT/USOO/15729 - 150

29. The composition of claims 11 and 25 wherein the antibacterial agent is present in an amount of at least 50% of saturation concentration.

30. The composition of claims 1, 11, and 25 wherein the antibacterial agent is present in an amount of at least 75% of saturation concentration.

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

32. An antibacterial composition compris ing: (a) about 0.001% to about 5%, by weight, of a phenolic antimicrobial agent; (b) 0% to about 40%, by weight, of a hydrotrope; (c) 0% to about 60%, by weight, of a water-soluble hydric solvent; and (d) water, wherein the composition contains at least one of the hydrotrope and hydric solvent, and wherein the composition has a log re duction 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 nega tive bacteria of at least 2.5 after 30 seconds of contact, as measured against E. coli. WO 00/78275 PCT/USOO/15729 - 151

33. A method of reducing a bacteria popu lation on a surface comprising contacting the sur face with a composition of claim 1 for 30 seconds to achieve a log reduction of at least 2 against S. aureus and at least 2.5 against E. coli, then rins ing the composition from the surface.

34. The method of claim 33 wherein the surface is a skin of a mammal.

35. The method of claim 33 wherein the surface is a hard, inanimate surface.

36. A method of reducing a bacteria popu lation on a surface comprising contacting the sur face with a composition of claim 11 for 30 seconds to achieve a log reduction of at least 2 against S. aureus and at least 2.5 against E. coli, then rins ing the composition from the surface.

37. A method of reducing a bacteria popu lation on a surface comprising contacting the sur face with a composition of claim 25 for 30 seconds to achieve a log reduction of at least 2 against S. aureus and at least 2.5 against E. coli, then rins ing the composition from the surface.

38. The method of claims 35 through 37 wherein the composition contacts the surface for 60 seconds to achieve a log reduction of at least 3 against S. aureus. WO 00/78275 PCT/USOO/15729 - 152

39. The method of claims 35 through 37 wherein the composition contacts the surface for 60 seconds to achieve a log reduction of at least 3.75 against E. coli.

40. The method of claims 36 and 37 wherein the composition contacts the surface for 30 seconds to achieve a log reduction of at least 2 against K. pneum.

41. An antimicrobial composition compris ing: (a) about 0.05% to about 5%, by weight, of a phenolic antibacterial agent; (b) about 1% to about 40%, by weight, of a disinfecting alcohol; (c) about 0.1% to about 5%, by weight, of a gelling agent; and (d) water, wherein the composition is free of a surfactant, and wherein the antibacterial agent is present in the composition in an amount of at least 50% of saturation concentration, when measured at room temperature.

42. The composition of claim 41 compris ing about 0.1% to about 4% by weight, of the pheno lic antibacterial agent.

43. The composition of claim 41 compris ing about 0.25% to about 2% by weight, of the pheno lic antibacterial agent. WO 00/78275 PCT/USOO/15729 - 153

44. The composition of claim 41 wherein the phenolic antibacterial agent is selected from the group consisting of: (a) a 2-hydroxydiphenyl compound having the structure Yo Zp Yr (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 to 3, p is 0 or 1, m is 0 or 1, and n is 0 or 1; (b) a phenol derivative having the struc ture OH R5 R 1 R4 * R2 R3 wherein R 1 is hydro, hydroxy, C 1 -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 -C6 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 5 is hydro or nitro; WO 00/78275 PCT/USOO/15729 - 154 (c) a diphenyl compound having the struc ture R'2 R'i R 1 R2 R' 3 X Q R 3 R'4 R' 5 R 5 R4 wherein X is sulfur or a methylene group, R 1 and R' 1 are hydroxy, and R 2 , R' 2 , R 3 , R' 3 , R 4 , R' 4, R 5 , and R'5, independent of one another, are hydro or halo; and (d) mixtures thereof.

45. The composition of claim 44 wherein the antibacterial agent comprises triclosan, p chloro-m-xylenol, or mixtures thereof.

46. The composition of claim 41 wherein the disinfecting alcohol is present in an amount of about 2% to about 35%, by weight.

47. The composition of claim 41 wherein the disinfecting alcohol is present in an amount of about 5% to about 30%, by weight.

48. The composition of claim 41 wherein the disinfecting alcohol is a C1, alcohol or mix tures thereof. WO 00/78275 PCT/USOO/15729 - 155

49. The composition of claim 41 wherein the disinfecting alcohol is selected from the group consisting of methanol, ethanol, isopropyl alcohol, n-butanol, n-propyl alcohol, and mixtures thereof.

50. The composition of claim 41 wherein the gelling agent is present in an amount of about 0.1% to about 3%, by weight.

51. The composition of claim 41 wherein the gelling agent is present in an amount of about 0.25% to about 2.5%, by weight.

52. The composition of claim 41 wherein the gelling agent comprises a natural gum, a syn thetic polymer, a clay, an oil, a wax, and mixtures thereof.

53. The composition of claim 41 wherein the gelling agent is selected from the group con sisting of an acrylate homopolymer, an acrylate copolymer, a carbomer, a polyacrylic acid, cellu lose, a cellulose derivative, guar, a guar deriva tive, algin, an algin derivative, a water-insoluble C 8 -C 20 alcohol, carrageenan, and mixtures thereof.

54. The composition of claim 41 wherein the gelling agent comprises a polyacrylic acid, a polyacrylate, a smectite clay, or a polyquaternium compound.

55. The composition of claim 41 having a pH of about 5 to about 8. WO 00/78275 PCT/USOO/15729 - 156

56. An antimicrobial composition compris ing: (a) about 0.05% to about 5%, by weight, of a phenolic antibacterial agent; (b) about 1% to about 40%, by weight, of a disinfecting alcohol; (c) about 0.1% to about 5%, by weight, of a gelling agent; and (d) water, wherein the composition is free of a sur factant, and 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, or has a log reduction against Gram nega tive bacteria of at least 2.5 after 30 seconds of contact, as measured against E. coli. WO 00/78275 PCT/USOO/15729 - 157

57. An antibacterial composition compris ing: (a) about 0.05% to about 5%, by weight, of a phenolic antimicrobial agent; (b) about 1% to about 40%, by weight, of a disinfecting alcohol; (c) about 0.1% to about 5%, by weight, of a gelling agent; (d) 0.1% to about 30%, by weight, of a hydrotrope; (e) water, wherein the composition is free of a surfactant, and wherein the antimicrobial agent is present in an amount of at least 25% of saturation concentration, when measured at room temperature.

58. The composition of claim 57 wherein the antibacterial agent is present in an amount of at least 50% of saturation concentration.

59. The composition of claim 57 wherein the hydrotrope is present in an amount of about 0.5% to about 25% by weight.

60. The composition of claim 57 wherein the gelling agent comprises a natural gum, a syn thetic polymer, a clay, an oil, a wax, and mixtures thereof. WO 00/78275 PCT/USOO/15729 - 158

61. The composition of claim 57 further comprising about 0.1% to about 50%, by weight, of a polyhydric solvent selected from the group consist ing of a diol, a triol, and mixtures thereof.

62. The composition of claim 61 wherein the polyhydric solvent comprises ethylene glycol, propylene glycol, glycerol, diethylene glycol, di propylene glycol, tripropylene glycol, hexylene glycol, butylene glycol, 1,2,6-hexanetriol, sorbi tol, PEG-4, or mixtures thereof. WO 00/78275 PCT/USOO/15729 - 159

63. The composition of claim 57 wherein the hydrotrope is selected from the group consisting of sodium cumene sulfonate, ammonium cumene sulfon ate, ammonium xylene sulfonate, potassium toluene sulfonate, sodium toluene sulfonate, sodium xylene sulfonate, toluene sulfonic acid, xylene sulfonic acid, sodium polynaphthalene sulfonate, sodium poly styrene sulfonate, sodium methyl naphthalene sulfon ate, disodium succinate, and mixtures thereof.

64. The composition of claim 57 having a pH of about 5 to about 8.

65. The composition of claim 57 compris ing: (a) about 0.25% to about 2%, by weight, of the antimicrobial agent; (b) about 5% to about 30%, by weight, of a disinfecting alcohol; (c) about 0.25% to about 2.5%, by weight, of the gelling agent; and (d) about 1% to about 20%, by weight, of the hydrotrope. WO 00/78275 PCT/USOO/15729 - 160

66. An antibacterial composition compris ing: (a) about 0.05% to about 5%, by weight, of a phenolic antimicrobial agent; (b) about 1% to about 40%, by weight, of a disinfecting alcohol; (c) about 0.1% to about 5%, by weight, of a gelling agent; (d) 0.1% to about 30%, by weight, of a hydrotrope; (e) water, wherein the composition is free of a surfactant, and 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, or has a log reduction against Gram nega tive bacteria of at least 2.5 after 30 seconds of contact, as measured against E. coli. WO 00/78275 PCT/USOO/15729 - 161

67. An antibacterial composition compris ing: (a) about 0.05% to about 5%, by weight, of a phenolic antimicrobial agent; (b) about 1% to about 40%, by weight, of a disinfecting alcohol; (c) about 0.1% to about 30%, by weight, of a hydrotrope; and (d) water, wherein the composition is free of a surfactant, and wherein the antimicrobial agent is present in an amount of at least 25% of saturation concentration, when measured at room temperature.

68. The composition of claims 41, 57, and 67 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.

69. The composition of claims 41, 57, and 67 wherein the antibacterial agent is present in an amount of at least 75% of saturation concentration.

70. The composition of claims 41, 57, and 67 wherein the antibacterial agent is present in an amount of at least 95% of saturation concentration. WO 00/78275 PCT/USOO/15729 - 162

71. An antibacterial composition compris ing: (a) about 0.05% to about 5%, by weight, of a phenolic antimicrobial agent; (b) about 1% to about 40%, by weight, of a disinfecting alcohol; (c) about 0.1% to about 30%, by weight, of a hydrotrope; and (d) water, wherein the composition is free of a surfactant, and 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, or has a log reduction against Gram nega tive bacteria of at least 2.5 after 30 seconds of contact, as measured against E. coli.

72. A method of reducing a bacteria popu lation on a surface comprising contacting the sur face with a composition of claim 41 for a sufficient time to provide a log reduction of bacteria of at least 2 against S. aureus and at least 2.5 against E. coli, then rinsing the composition from the sur face.

73. The method of claim 72 wherein the surface is a skin of a mammal.

74. The method of claim 72 wherein the surface is a hard, inanimate surface. WO 00/78275 PCT/USOO/15729 - 163

75. A method of reducing a bacteria popu lation on a surface comprising contacting the sur face with a composition of claim 57 for a sufficient time to provide a log reduction of bacteria of at least 2 against S. aureus and at least 2.5 against E. coli, then rinsing the composition from the sur face.

76. A method of reducing a bacteria popu lation on a surface comprising contacting the sur face with a composition of claim 67 for a sufficient time to provide a log reduction of bacteria of at least 2 against S. aureus and at least 2.5 against E. coli, then rinsing the composition from the sur face.

77. The method of claims 72, 75, and 76 wherein the composition contacts the surface for 30 seconds to achieve a log reduction of at least 2 against S. aureus.

78. The method of claims 72, 75, and 76 wherein the composition contacts the surface for 60 seconds to achieve a log reduction of at least 3 against S. aureus.

79. The method of claims 72, 75, and 76 wherein the composition contacts the surface for 30 seconds to achieve a log reduction of at least 2.5 against E. coli. WO 00/78275 PCT/USOO/15729 - 164

80. The method of claims 72, 75, and 76 wherein the composition contacts the surface for 60 seconds to achieve a log reduction of at least 3.75 against E. coli.

81. The method of claims 75 and 76 wherein the composition contacts the surface for 30 seconds to achieve a log reduction of at least 2 against K. pneum.