CA2371925A1

Antibacterial compositions

Abstract

Antibacterial compositions having enhanced antibacterial effectiveness are disclosed. The antibacterial compositions contain a phenolic antibacterial agent, a surfactant or a disinfecting alcohol, and water, wherein a percent saturation of the antibacterial agent in a continous aqueous phase of the composition is at least 25 %.

CA2371925A1, drawing sheet 1 — Sheet 1 of 5

Term

Term ended

Projected expiry passed 8 June 2020, 6.3 years ago.

79 claims: 25 independent, 54 dependent

1
CA 02371925 2001-12-19 WO 00/78275 PCT/US00/15729 - 140 WHAT IS CLAIMED IS:1. An antimicrobial composition comprising : (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 -C 18 alkyl sulfate, a C 8 -C 18 fatty acid salt, a C 8 -C 1B 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 C 8 -C 18 sulfoacetate, a C 8 -C ia sulfosuccinate, a C 8 -C 18 alkyl diphenyl oxide disulfonate, a C 8 -C 13 alkyl carbonate, a C 8 -C 18 alpha-olefin sulfonate, a methyl ester sulfonate, and mixtures thereof;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 .
10
An antimicrobial composition comprising :(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 -C 18 alkyl sulfate, a C a -C 18 fatty acid salt, a C a -C 18 alkyl ether sulfate having one or two moles of ethoxylation, a C 8 -C 18 alkamine oxide, a C a -C ia alkyl sarcosinate, a C e -C 18 sulfoacetate, a C 8 -C ia sulfosuccinate, a C 8 -C 18 alkyl diphenyl oxide disulfonate, a C g -C 18 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 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. CA 02371925 2001-12-19 WO 00/78275 PCT/US00/15729 - 145
11
An antibacterial composition comprismg :(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.
22
24. An antibacterial composition comprising :(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. CA 02371925 2001-12-19 WO 00/78275 PCT/US00/15729 - 149
23
25. An antibacterial composition comprising :(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
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. CA 02371925 2001-12-19 WO 00/78275 PCT/US00/15729 - 150
27
29. The composition of claims 11 and 25 wherein the antibacterial agent is present in an amount of at least 50% of saturation concentration.
28
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.
29
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.
30
32. An antibacterial composition comprising :(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 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 K. coli. CA 02371925 2001-12-19 WO 00/78275 PCT/US00/15729 - 151
36
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. CA 02371925 2001-12-19 WO 00/78275 PCT/US00/15729 - 152
37
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.
39
41. An antimicrobial composition comprising :(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 concentrâtion, when measured at room temperature.
54
56. An antimicrobial composition comprising :(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 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 negative bacteria of at least 2.5 after 30 seconds of contact, as measured against E. coli. CA 02371925 2001-12-19 WO 00/78275 PCT/US00/15729 - 157
55
57. An antibacterial composition comprising :(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.
64
66. An antibacterial composition comprising :(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 negative bacteria of at least 2.5 after 30 seconds of contact, as measured against E. coli. CA 02371925 2001-12-19 WO 00/78275 PCT/US00/15729 - 161
65
67. An antibacterial composition comprising :(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.
66
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.
67
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.
68
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. CA 02371925 2001-12-19 WO 00/78275 PCT/US00/15729 - 162
69
71. An antibacterial composition comprising :(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 negative bacteria of at least 2.5 after 30 seconds of contact, as measured against E. coli.
75
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.
76
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.
77
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. CA 02371925 2001-12-19 WOOO/78275 PCT/US00/15729 - 164
78
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.

Independent claims25

1,472 paragraphs in 394 sections, as filed

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- 1 ANTIBACTERIAL COMPOSITIONS

FIELD OF THE INVENTION

The present invention is directed to antibacterial compositions, like personal care compositions, including hand sanitizer gels, having improved antibacterial effectiveness. More particularly, the present invention is directed to antibacterial compositions comprising an antibacterial agent and a surfactant or a relatively low amount of a disinfecting alcohol, and that provide a substantial reduction, e.g., greater than 99%, in Gram positive and Gram negative bacterial populations within one minute.

BACKGROUND OF THE INVENTION

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

Another class of antibacterial personal care compositions is the hand sanitizer gels. This class of compositions is used primarily by medical personnel to disinfect the hands and fingers. The hand sanitizer gel is applied to, and rubbed into, the hands and fingers, and the composition is allowed to evaporate from the skin. Wiping of the composition from the skin is not necessary because the high alcohol content of present-day hand saniCA 02371925 2001-12-19

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- 2 tizer gels leads to a fast and essentially complete evaporation of the composition from the skin.

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

In particular, antibacterial cleansing compositions typically contain an active antibacterial agent, a surfactant, and various other ingredients, for example, dyes, fragrances, pH adjusters, thickeners, skin conditioners, and the like, in an aqueous carrier. Several different classes of antibacterial agents have been used in antibacterial cleansing compositions. Examples of antibacterial agents include a bisguanidine (e.g., chlorhexidine digluconate), diphenyl compounds, benzyl alcohols, 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). Presentday antimicrobial compositions based on such antibacterial agents exhibit a wide range of antibacterial activity, ranging from low to high, depending

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- 3 on the microorganism to be controlled and the particular antibacterial composition.

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

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

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- 9 provides both a rapid antibacterial effect and a persistent antibacterial benefit is difficult.

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

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

SUMMARY OF THE INVENTION

The present invention relates to antibacterial compositions that provide a substantial reduction in Gram positive and Gram negative bacteria in less than about one minute. More particularly, in one embodiment, the present invention relates to antimicrobial compositions containing an active antibacterial agent, a surfactant, and water, wherein the antibacterial agent is present in the continuous aqueous phase (in contrast to being present in micelles), in an amount of at least 50% of saturation, when measured at room temperature. The present invention also relates to antimicrobial compositions containing an active antibacterial agent, a surfactant, water, and a hydric solvent and/or a hydrotrope, wherein the antibacterial agent

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-10is present in an amount of at least 25% of saturation, when measured at room temperature.

In another embodiment, the present invention relates to antimicrobial compositions containing an active antibacterial agent, a disinfecting alcohol, a gelling agent, and water, wherein the antibacterial agent is present in an amount of at least 50% of saturation, when measured at room temperature. The present invention also relates to antimicrobial compositions containing an active antibacterial agent, a disinfecting alcohol, a gelling agent, a hydrotrope, and water, wherein the antibacterial agent is present in an amount of at least 25% of saturation, when measured at room temperature .

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 0.1% to about 40%, by weight, of a surfactant selected from the group consisting of a C8-C18 alkyl sulfate, a C8-C18 fatty acid salt, a C8-C18 alkyl ether sulfate having one or two moles of ethoxylation, a C8-C18 alkamine oxide, a Ce-C18 alkyl sarcosinate, a Cs-C18 sulfoacetate, a C8-C18 sulfosuccinate, a C8-C18 alkyl diphenyl oxide disulfonate, a C8-C18 alkyl carbonate, a Ca-C18 alpha-olefin sulfonate, a methyl ester sulfonate, and mixtures thereof; 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.

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- 11 Another aspect of the present invention is to provide an alternative embodiment of the antibacterial composition, wherein the composition comprises :

(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 nonionic surfactant, an ampholytic surfactant, and mixtures thereof;

(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 antimicrobial agent is present in the composition in an amount of at least 25% of saturation concentration, when measured at room temperature .

Still another aspect of the present invention is to provide another alternative embodiment of the antibacterial composition, wherein the composition comprises:

(a) 0.001% to about 10%, by weight, of an antimicrobial agent;

(h) 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 ;

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- 12 (c) 0% to about 40%, by weight, of a hydrotrope;

Personal care products incorporating an active antibacterial agent have been known for many years. Since the introduction of antibacterial personal care products, many claims have been made that such products provide antibacterial properties. However, to be most effective, an antibacterial composition should provide a high log reduction against a broad spectrum of organisms in as short a contact time as possible. It also would be beneficial if the antibacterial compositions provided a residual bacterial control.

As presently formulated, commercial liquid antibacterial soap compositions provide a poor to marginal time kill efficacy, 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 agent), and a surfactant.

<td colspan="4"> Table 1 Time Kill Efficacy of Commercial Liquid Hand Soaps</td>

<td> Product</td><td colspan="3"> Organism (Log Reductions after 1 Minute Contact Time)</td>

<td></td><td> Gram Positive S. aureus</td><td> Gram negative E. coll</td><td> Gram negative K. pneum.</td>

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- 21 In another embodiment, an antibacterial composition of the present invention comprises: (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; (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 and additional optional ingredients disclosed hereafter, like polyhydric solvents, pH adjusters, dyes, skin conditioners, vitamins, and perfumes. The present compositions are free of surfactants, i.e., contain 0% to about 0.5%, by weight, of compounds that exhibit surface activity. The compositions also are mild, and provide a persistent kill because it is not necessary to rinse or wipe the compositions from the skin.

The compositions of these embodiments, and all other embodiments, have a percent saturation of antibacterial agent in the continuous aqueous phase of at least about 25%, when measured at room temperature. The compositions exhibit a log reduction against Gram positive bacteria of about 2 after 30 seconds contact. The compositions exhibit a log reduction against Gram negative bacteria of about 2.5 after 30 seconds contact.

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

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- 22 A. Antibacterial Compositions Containing an Antibacterial Agent and a Surfactant

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

1. Antibacterial Agent

An antibacterial agent is present in a composition of the present invention in an amount of about 0.001% to about 10%, and preferably about 0.01% to about 5%, by weight of the composition. To achieve the full advantage of the present invention, the antibacterial agent is present in an amount of about 0.05% to about 2%, by weight, of the composition .

The antibacterial compositions can be ready to use compositions, which typically contain 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 formulated as concentrates that are diluted before use

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- 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. 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 not as important as the amount of available antibacterial agent in the composition. The amount of available antibacterial agent in the composition is related to the identity of the surfactant in the composition, the amount of surfactant in the composition, and the presence of optional ingredients in the composition.

To achieve the desired bacteria kill in a short contact time, like 15 to 60 seconds, the continuous aqueous phase of the composition contains an amount of antibacterial agent that is at least about 50%, and preferably at least about 75%, of the saturation concentration of the antibacterial agent in water, when measured at room temperature. To achieve the full advantage of the present invention, the continuous aqueous phase is about 95% to 100% saturated with the antibacterial agent. The amount of antibacterial agent present in the continuous aqueous phase can be defined as the total amount of antibacterial agent in the composition, less any antibacterial agent present in surfactant micelles. The method of determining percent saturation of antibacterial agent in the composition is disclosed hereafter.

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- 24 The antimicrobial agents useful in the present invention are phenolic compounds exemplified by the following classes of compounds:

(a) 2-Hydroxydiphenyl compounds

- 29 3. Carrier

The carrier in this embodiment comprises water.

4. Optional Ingredients

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

The compositions also can contain other optional ingredients, such as dyes and fragrances, that are present in a sufficient amount to perform their intended function and do not adversely affect the antibacterial efficacy of the composition. Such optional ingredients typically are present, individually, from 0% to about 5%, by weight, of the composition, and, collectively, from 0% to about 20%, by weight, of the composition.

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

Specific classes of optional ingredients include alkanolamides as foam boosters and stabilizers; gums and polymers as thickening agents; inorCA 02371925 2001-12-19

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- 30 ganic phosphates, sulfates, and carbonates as buffering agents; EDTA and phosphates as chelating agents; and acids and bases as pH adjusters.

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

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

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

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- 31 B. Antibacterial Compositions Containing an Antibacterial Agent, a Surfactant, and a Hydric Solvent and/or a Hydrotrope

In another embodiment, the antibacterial compositions comprise an active antibacterial agent, a surfactant, and a hydric solvent and/or a hydrotrope. The compositions of embodiment B exhibit a rapid bacteria kill, and are essentially unlimited in the identity of the surfactant in the composition. The solvent and/or hydrotrope assists in solubilizing the antibacterial agent, and reduces the affinity of the antibacterial agent to enter surfactant micelles. Accordingly, at least 25% saturation of the antibacterial agent in the continuous aqueous phase can be achieved regardless of the identity of the surfactant.

1. Antibacterial Agent

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

In addition, to achieve the desired bacteria kill in a short contact time, like 15 to 60 seconds, the continuous aqueous phase of the composition contains an amount of antibacterial agent that is at least about 25%, and preferably at least about 50, and more preferably at least about 75%, of the saturation concentration of the antibacterial agent in water, when measured at room temperature.

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- 32 tion, the continuous aqueous phase is about 95% to 100% saturated with the antibacterial agent.

2. Surfactant

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

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

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

The antibacterial compositions, therefore, can contain an anionic surfactant disclosed above in

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- 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 atoms, and further has a hydrophilic moiety, such as sulfate, sulfonate, carbonate, phosphate, or carboxylate. Often, the hydrophobic carbon chain is etherified, such as with ethylene oxide or propylene oxide, to impart a particular physical property, such as increased water solubility or reduced surface tension to the anionic surfactant.

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

The antibacterial compositions also can contain nonionic surfactants. Typically, a nonionic

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- 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 moieties. Examples of classes of nonionic surfactants include ethoxylated alkylphenols, ethoxylated and propoxylated fatty alcohols, polyethylene glycol ethers of methyl glucose, polyethylene glycol ethers of sorbitol, ethylene oxide-propylene oxide block copolymers, ethoxylated esters of fatty (C8-C18) 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 methyl glucose distearate, PEG-20 methyl glucose sesquistearate, Cu.15 pareth-20, ceteth-8, ceteth-12, dodoxynol-12, laureth-15, PEG-20 castor oil, polysorbate 20, steareth-20, polyoxyethylene-10 cetyl ether, polyoxyethylene-10 stearyl ether, polyoxyethylene-20 cetyl ether, polyoxyethylene-10 oleyl ether, polyoxyethylene-20 oleyl ether, an ethoxylated nonylphenol, ethoxylated octylphenol, ethoxylated dodecylphenol, or ethoxylated fatty (C6-C22) alcohol, including 3 to 20 ethylene oxide moieties, polyoxyethylene-20 isohexadecyl ether, polyoxyethylene-23 glycerol laurate, polyoxy-ethylene-20 glyceryl stearate, PPG-10 methyl glucose ether, PPG20 methyl glucose ether, polyoxyethylene-20 sorbitan monoesters, polyoxyethylene-80 castor oil, polyoxyethylene-15 tridecyl ether, polyoxy-ethylene-6 tridecyl ether, laureth-2, laureth-3, laureth-4, PEG-3 castor oil, PEG 600 dioleate, PEG 400 dioleate, and mixtures thereof .

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J1 , I r1cnh(ch2)3n+-ch2chch2so3_ ch3 alkamidopropyl hydroxysultaine x ii

R1NHCH2CH2C-O_Na+ a1ky1ami noprop i onates

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- 39 CH2CH2CO2”

I

RNH

CH2CH2CO2H alkyliminopropionates.

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

Specific, nonlimiting examples of ampholytic surfactants useful in the present invention are sodium coconut N-methyl taurate, sodium oleyl Nmethyl taurate, sodium tall oil acid N-methyl taurate, sodium palmitoyl N-methyl taurate, cocodimethyl carboxymethylbetaine, 1auryldimethylcarboxymethylbetaine, lauryldimethylcarboxyethylbetaine, cetyldimethylcarboxymethylbetaine, lauryl-bis-(2hydroxyethyl)carboxymethylbetaine, oleyldimethylgammacarboxypropylbetaine, lauryl-bis-(2-hydroxypropyl)-carboxyethylbetaine, cocoamidodimethylpropylsultaine, stearylamidodimethylpropylsuitaine, laurylamido-bis-(2-hydroxyethyl) propylsuitaine, disodium oleamide PEG-2 sulfosuccinate, TEA oleamido PEG-2 sulfosuccinate, disodium oleamide MEA sulfosuccinate, disodium oleamide MIPA sulfosuccinate, disodium ricinoleamide MEA sulfosuccinate, disodium undecylenamide MEA sulfosuccinate, disodium wheat germamido MEA sulfosuccinate, disodium wheat germamido PEG-2 sulfosuccinate, disodium isostearamideo MEA sulfosuccinate, cocoamphoglycinate, cocoamphocarboxyglycinate, lauroamphoglycinate, lauroamphocarboxyglycinate, capryloamphocarboxyglycinate,

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- 40 cocoamphopropionate, cocoamphocarboxypropionate, lauroamphocarboxypropionate, capryloamphocarboxypropionate, dihydroxyethyl tallow glycinate, cocamido disodium 3-hydroxypropyl phosphobetaine, lauric myristic amido disodium 3-hydroxypropyl phosphobetaine, lauric myristic amido glyceryl phosphobetaine, lauric myristic amido carboxy disodium 3hydroxypropyl phosphobetaine, cocoamido propyl monosodium phosphitaine, lauric myristic amido propyl monosodium phosphitaine, and mixtures thereof.

3. Carrier

The carrier in this embodiment comprises water.

4. Optional Ingredients

The optional ingredients discussed in 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

This embodiment of the present invention contains 0% to about 25%, by weight, of a hydric solvent, and 0% to about 30%, by weight, of a hydrotrope, wherein the antibacterial composition contains at least one of the hydric solvent and hydrotrope. Preferred embodiments contain both a hydric solvent and a hydrotrope.

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Antibacterial Agent, a Disinfecting

Alcohol, a Gelling Agent

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

1. Antibacterial Agent

The identity of the antibacterial agent in this embodiment of the invention is discussed above

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- 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 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

The carrier in the present composition comprises water.

- Disinfecting Alcohol

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

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

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- 49 ates/myristates, aluminum isostearates/palmitates, aluminum isostearates/stearates, aluminum lanolate, aluminum myristates/palmitates, aluminum stearate, aluminum stearates, aluminum tristearate, beeswax, behenamide, behenyl alcohol, butadiene/acrylonitrile copolymer, C29-70 acid, calcium behenate, calcium stearate, candelilla wax, carnauba, ceresin, cholesterol, cholesteryl hydroxystearate, coconut alcohol, copal, diglyceryl stearate malate, dihydroabietyl alcohol, dimethyl lauramine oleate, dodecanedioic acid/cetearyl alcohol/glycol copolymer, erucamide, ethylcelluiose, glyceryl triacetyl hydroxystearate, glyceryl triacetyl ricinoleate, glycol dibehenate, glycol dioctanoate, glycol distearate, hexanediol distearate, hydrogenated C6-14 olefin polymers, hydrogenated castor oil, hydrogenated cottonseed oil, hydrogenated lard, hydrogenated menhaden oil, hydrogenated palm kernel glycerides, hydrogenated palm kernel oil, hydrogenated palm oil, hydrogenated polyisobutene, hydrogenated soybean oil, hydrogenated tallow amide, hydrogenated tallow glyceride, hydrogenated vegetable glyceride, hydrogenated vegetable glycerides, hydrogenated vegetable oil, hydroxypropylcellulose, isobutylene/isoprene copolymer, isocetyl stearoyl stearate, Japan wax, jojoba wax, lanolin alcohol, lauramide, methyl dehydroabietate, methyl hydrogenated rosinate, methyl rosinate, methylstyrene/vinyltoluene copolymer, microcrystalline wax, montan acid wax, montan wax, myristyleicosanol, myristyloctadecanol, octadecene/maleic anhydride copolymer, octyldodecyl stearoyl stearate, oleamide, oleostearine, ouricury wax, oxidized polyethylene, ozokerite, palm kernel alcoCA 02371925 2001-12-19

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- 54 rely upon a high concentration of disinfecting alcohol .

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

The following materials were used as ingredients in the examples. The source of each ingredient, and its abbreviation, are summarized below :

a) Alkyl (linear) diphenyl oxide disulfonate, Pilot Chemical Co., Santa Fe Springs, CA, CALFAX 10L-45 (active=45.4%) ,

b) Alkyl polyglucoside (APG), Henkel Corp., Hoboken, NJ, PLANTAREN 2000N UP (active=55.53 %),

c) Alpha-olefin sulfonate (AOS), Stepan Chemical Co., Northfield, IL, BIOTERGE AS-40 (active=38.80%),

d) Ammonium lauryl sulfate (ALS), Henkel Corp., STANDAPOL A (active level=28.3%),

e) Ammonium xylene sulfonate (AXS), Stepan Corp., STEPANATE AXS (active=40%),

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- 55 f) Cocamidopropyl betaine (CAPB), McIntyre Group, Ltd., Chicago, IL, MACKAM 35-HP (est. 30% active betaine),

g) Dipropylene glycol (DPG), Dow Chemical Co., Midland, MI,

h) Disodium laureth sulfosuccinate (DSLScct), McIntyre Group, Ltd., MACKANATE EL (active=33.8%),

i) Disodium lauryl sulfosuccinate (DSLrylScct), McIntyre Group, Ltd., MACKANATE LO (active est.=40%),

j) DMDM Hydantoin (DMDM), MacIntyre Group, Ltd., MACKSTAT DM (approx. 55% active),

DowFax Hydrotrope Solution (DFX), Dow DowFax Hydrotrope Solution (Benzene, sec-hexyl derivatives, sulfonated active=45.7%) ,

Glycerin (GLY), Henkel/Emery,

Cincinnati, OH, Emery 916 Glycerine (99.7% CP/USP), m) Isopropanol (IPA), Fisher Scientific, Pittsburgh, PA, 2-Propanol, HPLC Grade A 451-4,

Chemical Co. 1,1'-oxybissodium salt)

Lauramine oxide (LAO), McIntyre

Group, Ltd., MACKAMINE LO (active=30.55%),

o) Liquid Perfume (PF),

p) Lithium lauryl sulfate (LLS), Henkel, TEXAPON LLS (active=28.8%),

q) Magnesium lauryl sulfate (MLS),

Stepan Chemical Co., STEPANOL MG (active=28.3%),

r) Methyl ester sulfonate (MES), Stepan Chemical Co., ALPHA-STEP ML-40 (Sodium methyl-2 sulfo laurate and disodium 2-sulfo lauric acid) (active=36.47%),

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- 56 Monoethanolamine (MEA), Dow Chemical

Co . ,

t) Monoethanolamine lauryl sulfate (MEALS), Albright & Wilson, Cumbria, England,

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., Midland, MI, as MPEG 350 (active=est. 100%),

w) Poloxymer 338 (F108), BASF,

Wyandotte, MI, PLURONIC FI08 (active=est. 100%),

x) Potassium cocoate (KCO), McIntyre Group, Ltd., MACKADET 40-K (active=38.4%),

y) Potassium laurate (KL), prepared from lauric acid (Sigma, #L-4250, active=99.8%) and potassium hydroxide,

z) Potassium oleate (KO), Norman, Fox & Co., Vernon, CA, NORFOX KO (active=approx. 80%), 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

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 Chemical Co., STEPANATE SCS (active=44.6%), ff) Sodium decyl sulfate (SDecS), Henkel, SULFOTEX 110 (active=30.80%),

Sodium C12-C18 sulfate (SC12-18S

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<td> Staphylococcus aureus</td><td> 6538</td><td> S. aureus</td>

<td> Escherichia coli</td><td> 11229</td><td> E. coli</td>

<td> Klebsiella pneumoniae</td><td> 10031</td><td> K. pneum.</td>

<td> Salmonella choleraesuis</td><td> 10708</td><td> S. choler.</td>

S. aureus is a Gram positive bacteria, whereas E. coli, K. pneum, and S. choler. are Gram negative bacteria .

The beaker containing the test composition is placed in a water bath (if constant temperature is desired), or placed on a magnetic stirrer (if ambient laboratory temperature is desired). The sample then is inoculated with 1.0 ml of the test bacteria suspension. The inoculum is stirred with the test composition for the predetermined contact time. When the contact time expires, 1.0 ml of the test composition/bacteria mixture is transferred

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- 61 into 9.0 ml of Tryptone-Histidine-Tween Neutralizer Solution (THT). Decimal dilutions to a countable range then are made. The dilutions can differ for different organisms. Plate selected dilutions in triplicate on TSA+ plates (TSA+ is Trypticase Soy Agar with Lecithin and Polysorbate 80). The plates then are incubated for 25+2 hours, and the colonies are counted for the number of survivors and the calculation of percent or log reduction. The control count (numbers control) is determined by conducting the procedure as described above with the exception that THT is used in place of the test composition. The plate counts are converted to cfu/ml for the numbers control and samples, respectively, by standard microbiological methods.

The log reduction is calculated using the formula

Log reduction=log10 (numbers control)-log10 (test sample survivors).

The following table correlates percent reduction in bacteria population to log reduction:

<td> % Reduction</td><td> Log Reduction</td>

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- 62 b) Preparation of saturated solutions of TCS in water: A four liter flask was equipped with a 3-inch magnetic stir bar and charged with approximately 7.5 grams (g) TCS and 3 liters (L) of water.

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- 67 Comparing the data in Tables 2 and 3 shows that at the very lowest concentration of TCS (i.e., to 10 ppm), the efficacy of time kill is reduced compared to samples containing higher levels of TCS.

PCT/US00/15729

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<td rowspan="6"> Table 3--TCS in Solvent and/or Hydrotrope Systems</td><td rowspan="2"> r-l 0 s 03</td><td> β •ri i—1</td><td></td><td></td><td> 00 ID CO Λ</td><td> σ> CN 1-)</td><td></td><td></td><td></td><td></td><td> i—1 Λ</td><td> 0.47</td>

<td colspan="2"> Solvent/ Hydrotrope</td><td> 03 O 03 o\P LO</td><td> 03 U 03 cAP Lfl</td><td> 20%PG/10%SXS</td><td> ω « ω AP Ο r-1 Ο CM Α° Ο CN</td><td> 03 X ω ο\Ρ L0 Ü (X Λ® ο γΗ</td><td> 03 X 03 ο\ο L0 \ Ο CM ο*> ο</td><td> 03 υ 03 Α° ιη Ο cm ο¥> Ο rri</td><td> 03 U 03 oY> m O CM o\o O |—)</td><td> 03 X 03 o\o O i—l O CM Û oV» LD rd</td><td> 14.5%DPG/10%SXS</td>

a nJ a

-H

4-) u

T5 CQ

a) Ό m a o cn u ο Φ

I—I co

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- 72 Many compositions of the present invention contain a surfactant, which potentially can reduce the efficacy of the antibacterial agent. The following examples show the unexpected benefits achieved by compositions of the present invention.

Example 1

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

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 prod20 uct of Benckiser; and Soft Soap (SSp), a product of

Colgate Palmolive.

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<td> minute</td><td> & i4</td><td> Λ</td><td> ©</td><td> ο</td><td> Ο</td>

<td> iuction at</td><td> Ή 0 O cq</td><td> >4.41</td><td> © CN ©</td><td> ο ο ο</td><td> Ο ο ο</td>

<td></td><td> Triclosan</td><td> m ©</td><td> Ai β ro</td><td> 2«: β t)</td><td> Αί β £></td>

<td colspan="2"> Product</td><td></td><td> s</td><td> co U</td><td> a co CO</td>

d) co nJ

Λ a

O

1) nJ co β

c •H

-U c

QJ

4-) β

•H co

U

H

M-l •H

4J

Π3 β

4J nJ co

4-)

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

Example 2

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

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<td rowspan="4"> Log Reduction at 5 minutes (time kill)</td><td> 0 8</td><td> 3.73</td><td> O o</td>

<td colspan="2"> % Saturation</td><td> o o rH</td><td> O</td>

<td rowspan="4"> Log Reduction at 30 seconds (time kill)</td><td> Ή 0 XÎ 0 co</td><td> 2.92</td><td> r- cd O</td>

<td colspan="2"> % Saturation</td><td> o o «—1</td><td> o</td>

<td colspan="2"> Triclosan %</td><td> CN Γ- ΟΟ o o</td><td> o o</td>

<td colspan="2"> Product</td><td> m 1</td><td> 1</td>

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- 79 Example 4

This example illustrates that composition of the present invention provide an acceptable sanitization efficacy even though the compositions contain a relatively low concentration of disinfecting alcohol. Examples B-l, B-3, and B-5 contain 0.15%, by weight, triclosan, at 100% saturation. Examples B-2, B-4, and B-6 are comparative examples containing 0% triclosan.

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<td></td><td> m</td><td> o o</td><td> 1</td><td> 40.0</td><td> m ο</td><td> ιη ο ο</td><td> Ο Ο</td><td> j Balance</td>

<td></td><td> B-5</td><td> Lf) 1—1 o</td><td> ;</td><td> ο ο</td><td> 0.3</td><td> m ο ο</td><td> •3* ο ο</td><td> alanc</td>

<td></td><td> M1</td><td> o</td><td> o</td><td> σο r—1</td><td> rc</td><td> 05</td><td> ο</td><td rowspan="2"> Balanc</td>

<td rowspan="3"> weight)</td><td rowspan="2"> m</td><td rowspan="2"> ©</td><td rowspan="2"> 00 OJ</td><td rowspan="2"> Η ι-l</td><td rowspan="2"> ο</td><td rowspan="2"> ο</td><td rowspan="2"> ο</td>

<td> dP</td><td> B-3</td><td> 0.15</td><td> 28.0</td><td> 11.18</td><td> η ο</td><td> 0.05</td><td> ο ο</td><td> alanc</td>

<td></td><td> CN 1 CQ</td><td> 0.0</td><td> 38.0</td><td> ;</td><td> m ο</td><td> L0 Ο ο</td><td> 0.04</td><td> alanc</td>

co •H

CQ

TJ

-ΰ nJ

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- 81 The following table summarizes the results of a time kill test at 15 seconds.

<td colspan="5"> Log Reductions at 15 seconds</td>

<td> Example</td><td> S. aureus</td><td> E. coli</td><td> K. pneum.</td><td> S. chol.</td>

These results show that acceptable sanitization efficacy is achieved, even with reduced levels of disinfecting alcohol and other polyhydric solvents. Furthermore, the compositions of the present invention provide a persistent antibacterial benefit because of the nonvolatile nature of the active ingredient, triclosan, whereas presently marketed compositions do not provide a persistent antibacterial activity.

In particular, Examples B-3 through B-6 demonstrate that the rapid antibacterial activity of the present compositions is attributable mainly to the antibacterial agent, e.g., triclosan, as opposed to a disinfecting alcohol. This is in contrast to prior art disclosures. For example, composition B-3 contains only 28% ethanol, yet exhibits excellent broad-spectrum antibacterial activity at 15 seconds. Composition B-5 contains no alcohol, yet exhibits excellent antibacterial activity against S. aureus and E. coli. Prior art teachings rely on a high

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- 82 alcohol concentration (i.e., >40%) to achieve a fast, broad-spectrum antibacterial activity.

Example 5

This example illustrates the effect of the identity of the surfactant on the antibacterial activity of the composition. The test results summarized below were performed on a wide variety of compositions containing either an anionic surfactant or representative cationic, anionic/nonionic, amphoteric, and nonionic surfactants. The percent saturation of TCS in the compositions of this example is at least about 90%.

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<td> ant Type</td><td> /Nonionic</td><td> □</td><td> □</td>

4J cn

0) jj •H

0) £

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- 88 LAO is attributed to the surfactant alone because of its quasi-cationic character. The remaining surfactant/TCS compositions in Series V showed varied activity vs. S. aureus (Gram positive) and very little activity vs. E. coli (Gram negative).

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<td rowspan="5"> TCS in Simple Surfactant Systems</td><td> ΰ •rl •H Μ H 0 u to O . f*> hq —</td><td rowspan="4"> scellaneous Surfactants</td><td> kD Λ m VD Λ</td><td> 4.18/4.73</td><td> -0.05/0.04</td><td> 0.02/0.16</td><td> 0.36/0.38</td><td> -0.09/-0.03</td><td> 0.11/0.22</td><td> 0.28/0.33</td><td> 0.18/0.23</td><td> in r-1 O 1 Γ' H O 1</td><td> H kD O H CN O</td><td> 0.01/-0.02</td>

<td> Other Ingredients</td><td> ! flj T3 •H « 0 o Sh •d £ ti h 3 ti r—1 dP m |—1</td><td> 1.5% lauramine oxide (LAO)</td><td> 1.25% sodium lauroyl sarcosinate (SLSarc)</td><td> 1.5% disodium lauryl sulfosuccinate (DSLrylScct)</td><td> 1.25% disodium laureth sulfosuccinate (DSLScct)</td><td> 1% sodium lauryl sulfoacetate (SLSA)</td><td> 2.0% methyl ester sulfonate (MES)</td><td> 1.25% alpha-olefin sulfonate (AOS)</td><td> 3% CIO (linear) sodium diphenyl oxide disulfonate (L10-45)</td><td> 1.25% sodium cocoamphoacetate (SCA)</td><td> 1.75% cocamidoproyl betaine (CAPB)</td><td> 2.5% alkyl polyglucose (APG)</td>

<td> Active Cone .</td><td> U) u H dP m o</td><td> CQ o H dP O</td><td> CQ u H dP m o</td><td> CQ o H dP m o</td><td> CQ u dP (O o</td><td> 0.3%TCS</td><td> CQ o H dP m o</td><td> CQ U H dp m o</td><td> 0.3% TCS</td><td> CQ u H dP m o</td><td> CQ CJ H dP CO ©</td><td> CQ CJ E-» dP Γ0 o</td>

<td> Type</td><td> Series V--Mi</td><td> Cationic</td><td></td><td> Anionic</td><td> Anionic</td><td> Anionic/ Nonionic</td><td> Anionic</td><td> Anionic</td><td> Anionic</td><td> Anionic</td><td> Amphoteric</td><td> Amphoteric</td><td> Nonionic</td>

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<td colspan="2"> % Saturation</td><td> o o rd 1</td><td> Ο</td><td> Ο Ο rd</td><td> O O rd 1</td><td> © O rd r</td><td> o o rd î</td><td> O</td><td> o o rd J</td><td> O O rd ί</td><td> O</td>

<td colspan="2"> Other Ingredients</td><td> CQ J dP Lfl m H</td><td> CQ J dP LO ΓΩ Η</td><td> cq X ω dP ο ο Η Ο CU Q dp Η ω $ dP m (N ©</td><td> cq X cq dP o o H CQ & Q dP rd en 3 dP in CN o</td><td> O a «< dp m (N</td><td> CQ X CQ dP O O rd Ü eu o dP rd O CU dP ΓΩ O</td><td> CÛ X CQ dP O © H U eu Q dp rd Ü eu < dP m o</td><td> (J CQ dp lfl (N rd</td><td> CQ X CQ dP O o rd U CU Q dP rd U CQ dP Lfl CN O</td><td> CQ X CQ dP O O rd O eu Q dP rd U CQ dp un CN O</td>

<td colspan="2"> Triclosan %</td><td> m o</td><td> Ο Ο</td><td> cn ο</td><td> o o</td><td> ΓΩ o</td><td> n o</td><td> o o</td><td> ΓΩ O</td><td> rn o</td><td> O o</td>

<td colspan="2"> Composition</td><td> m</td><td> υ</td><td> Q</td><td> M</td><td> X</td><td> Ü</td><td></td><td> Hd</td><td> b</td><td> X</td>

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- 100 -

<td rowspan="2"> Log Reduction (Time Kill)</td><td> •r| u Μ O 0 υ \ W ♦ o Cq co</td><td> 0.21/0.61</td><td> ΓΊ Γ- Λ ΓΟ Λ</td><td> th KO KO <N m</td><td> 0.43/0.46</td><td> m > Λ σ\ in m</td><td> 0.41/0.46</td><td> > Λ M1 TF Λ</td>

<td colspan="2"> % Saturation</td><td> O O i—l ?</td><td> O o rd I</td><td> o</td><td> O O rd l</td><td> ο ο rd ί</td><td> o o rd i</td><td> Ο ο rd f</td>

<td colspan="2"> Other Ingredients</td><td> CQ eu o cP LT) > rd</td><td> co X co dP Ο Ο rd Ο eu ο dP rd (θ' eu nJ u dP Lfi (N O</td><td> CO X CO dP O O rd G eu Q dp rd CQ eu u dP Lfi (N O</td><td> O O rd g dP</td><td> ω X Μ dP Ο Ο rd Ο eu Q dp d1 rd O O rd X H dP m r- o</td><td> rd 1 CO ω J ω dP in cd rd</td><td> ω X ω dP Ο Ο rd Ο CU Q οΡ Tf rd rd I co ω j co dP LA CM O</td>

<td colspan="2"> Triclosan %</td><td> ΡΊ O</td><td> m o</td><td> O o</td><td> m o</td><td> m o</td><td> ΡΊ O</td><td> m o</td>

<td colspan="2"> Composition</td><td> J</td><td> S</td><td> S</td><td> O</td><td> eu</td><td> σ</td><td></td>

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- 101 The results of the time kill tests summarized in the above table very surprisingly show that the use of a hydric solvent and hydrotrope can impart a high antibacterial activity to surfactant/TCS combinations which alone exhibit only low to moderate efficacy (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 compositions more active in shorter contact times (i.e., compare composition B vs. D) . Especially surprising is the observation that a hydric solvent and hydrotrope can impart antibacterial efficacy against E. coli even in a composition containing a nonionic surfactant, i.e., octoxynol-9 (compare compositions O vs. P) . This result is unexpected because polyethoxylated surfactants are known to inactivate phenolic antibacterial agents.

Example 10

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

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- 102 -

<td> % Saturation</td><td> -100</td><td> co V</td><td> CO V</td><td> o</td><td> o o rH }</td><td> £ V</td><td> X ÎS V</td><td> O</td>

<td> Other Ingredients</td><td> co X co AP o o I—1 θ' CM Q t—1 co μ-Ί JP m CN o</td><td> co X ω JP o o ί—1 o' CM Q JP -+ -+ rH CO A° O in o</td><td> ω X co d\P o o i—1 0 CM Q o¥> + ·+ rH CO ι-Ί o\o O O r-1</td><td> co X co oV O o 1—1 o' CM Q JP -+ + rH co J < oY> O O rH</td><td> CO X co oV> o o rH o' CM Q oV in CN CO oV O CN rH</td><td> co X co JP o o rH o' CM Q JP n CN co' JP n CN</td><td> CO X co A° o o rH o' CM Û A° in CN co n A° O n</td><td> CO X co JP o o rH d CM Q oV> n CN co n oAP O n</td>

<td> Triclosan %</td><td> co o</td><td> CO o</td><td> CO O</td><td> O O</td><td> CO o</td><td> co o</td><td> co o</td><td> o o</td>

<td> Composition</td><td> ω</td><td> H</td><td></td><td> ></td><td> £</td><td> X</td><td> >H</td><td> N</td>

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- 103 -

- 108 -

<td rowspan="4"> 1 Log Reduction (Time Kill)</td><td> S. choler. (30s/60s)</td><td> >4.14/>4.14</td><td> 0.36/0.47</td><td> d1 © d* A CN kD CN</td><td> in co m A in co fA A</td><td> in co CA Λ in CD CA A</td><td> in co CA A \ O in ΓΑ</td><td> 2.17/>3.85</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td colspan="2"> Other Ingredients</td><td> CO X CQ dP o o t—1 ci CM Ω dp LQ d< h</td><td> CQ X CQ dP o © rd d CM Ω dP in d* H</td><td> CQ X CQ dP © o i—1 ci CM A dP d1 d< rd CQ 3 dp in CN o</td><td> CQ X CQ dp O O rd d CM Q dP d1 V rd CQ A dP in CN O</td><td> CQ X CQ dp O o rd d CM Ω dP d d1 rd CQ J dP o in o</td><td> CQ X CQ dp © O rd ci CM Û dP d rd CQ â dp o o rd</td><td> CQ X CQ dP © O rd d CM Ω dP d< d< rd CQ J dP O O rd</td><td> CQ X CQ dp O o rd d CM Q dP © in CQ â dP in r- o</td><td> CQ X CQ dP in CN rd d CM Q dP © in CQ 3 dP in r- o</td><td> CQ X CQ dP © m rd d CM o dP O m CQ ί dP in > o</td><td> CQ X CQ dP in r- rd d CM Q dP O in d J < dP in r- ©</td><td> CQ X CQ dP O O CN d CM Û dP O in CQ 3 dp in r· o</td><td> CQ X CQ dP © O rd d CM Û dP in r* co % dp in r- o</td><td> CQ X CQ dP in CN H d CM Q dP in r- CQ ί dP in Γ- o</td><td> CQ X CQ dP © in rd ci CM Û dP in e'- en â dP in o ©</td><td> CQ X CQ dP in r- rd d CM Ω dP in Γ- ιο dp in r- o</td>

<td colspan="2"> Triclosan %</td><td> fN □ o rd IQ f0 © CJ · O</td><td> O O</td><td> o ©</td><td> fA ©</td><td> CA ©</td><td> CA o</td><td> O ©</td><td> CA ©</td><td> CA O</td><td> fA ©</td><td> ΓΑ o</td><td> fA O</td><td> fA o</td><td> CA o</td><td> CA ©</td><td> fA o</td>

<td colspan="2"> Composition</td><td> CJ U CJ</td><td> Q Q Ω</td><td> ω</td><td> CQ</td><td></td><td></td><td> ></td><td></td><td> CQ CO</td><td> CJ CJ</td><td> Q Q</td><td> ω w</td><td> Cm</td><td> 0 O</td><td> ffi ffi</td><td> w H</td>

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- 110 -

<td rowspan="4"> Log Reduction (Time Kill)</td><td> 5. choler. (30s/60s></td><td></td><td></td>

<td colspan="2"> Other Ingredients</td><td> en X en dp o rd d eu Q dp Tf Tf pH en â c*> LD > O</td><td> O eu O dp rri en J dP in r- o</td>

<td colspan="2"> Triclosan %</td><td> 0.3</td><td> o o</td>

<td colspan="2"> Composition</td><td></td><td> BBB</td>

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- Ill 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 in % saturation of TCS). Compositions CC, HH, MM, and RR demonstrate that about 15% SXS, or more, is preferred to exhibit high activity against K. pneum. in compositions containing a hydric solvent and a hydrotrope. This observation suggests that the hydrotrope may be acting as an adjuvant for the TCS because the time required for a substantial antibacterial kill, i.e., log reduction of at least 2, is reduced.

Example 13

The data summarized in the following table support a theory that the two primary factors for improved antibacterial efficacy are the relative amounts of surfactant and hydrotrope to the amount of antibacterial - agent in compositions containing a surfactant, hydric solvent, and antibacterial agent. A higher percentage of surfactant can reduce the % saturation, and thereby decrease the antimicrobial activity of the composition. On the other hand, a higher percentage of hydrotrope appears to provide a higher activity against certain organisms, like K. pneum. and S. choler. It is theorized that the higher percentage of hydrotrope in the composition provides a greater amount of active antibacterial compound in the aqueous (i.e., nonmicellar) phase of the composition, thereby providing a higher time kill activity. The solvent, therefore, may be actCA 02371925 2001-12-19

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- 112 ing as both an additive to enhance antimicrobial activity and to provide better physical stability in these compositions.

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<td rowspan="4"> Log Reduction (Time Kill)</td><td> « 5 o o . w</td><td> >4.14/>4.14</td><td> 0.36/0.47</td><td> >4.04/>4.04</td><td> 2.62/>4.04</td><td> in 00 CO Λ in co ro Λ</td><td> in co CO Λ \ in co co Λ</td><td> in co co Λ © in ro</td><td> 2.17/>3.85</td><td> Μ* O Μ4 Λ Mi © Mi Λ</td><td> >4.04/>4.04</td><td> Μ* © Μ* Λ \ Mi © ΓΟ</td>

<td colspan="2"> Other Ingredients</td><td> CQ X CQ © o i—1 Ü iX Q dP in mi rH</td><td> U) X co dP © © i—1 d (¾ Q dP m Ml H</td><td> o' Pi a dP * CQ x H W H dP O 3 ° a dP LT) CN ©</td><td> d di Q dP « ω dp © 3 θ à κ dP in CN Ο</td><td> d Pi o dp CQ _u X H W Μ dP O 3 ° à dP in CN o</td><td> d Pl Q dp Μ* CQ ‘ X M* CQ 1—! dP O CQ O t-P <—1 dP in ©</td><td> o' Pj Q dP CQ Mi X • CQ Μ* dP Η © - O CQ H â dP H</td><td> o' Pl Q dP CQ Μ* X • CQ M· dP i—1 © - O CQ i-l hP dP i—l</td><td> d Pi Pl Pi Q dP dp in Ml © Mi O H - CQ CQ X J CQ < dP dP O m · CN O • ί—1 ©</td><td> θ' Pi Pl Û dP dp in Ml © M« O H - CQ CQ X J CQ < dP dP O in · CN o • ί—1 o</td><td> d Pi Pi Pi Q dp dP in M* © Μ* O ί-1 - CQ CQ X fP CQ < dP dP O m · CN © • r—1 ©</td>

<td colspan="2"> Triclosan %</td><td> CN U ° H 1/1 ti ° U ©</td><td> o o</td><td> CO O E-i dp CO ©</td><td> CO υ Η dP Ο</td><td> CQ O E-1 dP co ©</td><td> CQ O F dP CO o</td><td> CQ U E-i dP CO ©</td><td> CQ O H dP ©</td><td> CQ O H dP Μ* O</td><td> CQ O dP CO O</td><td> CQ O E-i dP O</td>

<td colspan="2"> Composition</td><td> O o o</td><td> Q a Q</td><td> ω ω ω</td><td> ti ti ti</td><td> o o Ü</td><td> ffi</td><td> l-l l-l H</td><td> b b b</td><td> X X</td><td> fP J fP</td><td> S</td>

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- 114 -

<td rowspan="4"> Log Reduction (Time Kill)</td><td> S. choler. (30s/60s)</td><td> o CN Tt4 Λ © CN Tf Λ</td><td> o CN Tf Λ © Φ m</td><td> o CN Tf Λ O CN Tf Λ</td><td> o rd Tf σ» CN CN</td><td> r- CO CQ Λ t- co m Λ</td><td> r- 00 m A c- OÙ m A</td><td> r- CD CQ Λ i- CO CQ A</td><td> >3.87/>3.87</td><td> Γ- ΟΟ CQ A Γ- ΟΟ CQ A</td><td> Γ- ΟΟ CQ A •'-, Γ- ΟΟ CQ Λ</td>

- 117 -

<td rowspan="4"> Log Reduction (Time Kill)</td><td> S. choler. (30s/60s)</td><td> ;</td><td> ;</td><td> !</td><td> 1</td><td> !</td><td> 00 ko en Λ ΓΑ CM en</td><td> 1.51/2.84</td><td> KO m CM CD CM rH</td><td> Ifl <n m Λ x. in en m</td><td> un <n m Λ Χχ ko CM m</td><td> 1.77/2.93</td><td> !</td><td> ;</td><td> ;</td>

<td colspan="2"> Other Ingredients</td><td> 0.75%ALS, 5.0% tripropylene glycol (TPG), 10.0%SXS</td><td> ci ft Η dP ° ω ο X S 05Η dP ο 3 θ â - dP m χ ο</td><td> ci ft H dP ° w o X 3 w H dP o 3 ° à h dP in r- o</td><td> 0.75%ALS, 14.4% propylene glycol (PG), 10.0%SXS</td><td> en X en dp ο ο rH ci ft dp Ο ο rH en rfJ dP Ο rH</td><td> en X cn dP O O rH ci ft dP O O CM en â dP m o</td><td> cn X cn dP o o i—1 ci ft dp O O fM en a! dP in o</td><td> cn X en dP O o rH ci ft dP O O CM en J rfj dp in o</td><td> cn X cn dP o o rH 0 ft dP O O CM en J dP CM rH O</td><td> en X cn dP Ο Ο rH ci ft dP Ο Ο CM en j rtj dP in o</td><td> cn X en dP o o rH 0 ft dP O O CM en J rtj dp in o</td><td> en X en dP O in o' ft dP O O rH en cn dP CO o</td><td> en X cn dP O m o ft dP O O rH en J cn dP 00 o</td><td> en X en dP O in 0 ft dP O O rH en i dP 00 O</td>

<td colspan="2"> Triclosan %</td><td> ca o</td><td> CO Ο</td><td> o o</td><td> m o</td><td> <Ά ο</td><td> en o</td><td> H O</td><td> o o</td><td> rH O</td><td> m o</td><td> o o</td><td> ca o</td><td> o o</td><td> rA O</td>

<td colspan="2"> Composition</td><td> ω w ω ω</td><td> Cm Cm Cm Cm</td><td> Ü Ü Ü O</td><td> CC CC » CC</td><td> Ι-H H H 1—1</td><td> •o b b b</td><td> i</td><td> .-q J J J</td><td> 2 2 2 2</td><td> 1</td><td> o O O O</td><td> ft ft ft ft</td><td> o O σ σ</td><td> ft ft ft ft</td>

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- 118 -

<td rowspan="4"> Log Reduction (Time Kill)</td><td> » s 5 s . ω</td><td> I 1</td><td> 0.53/0.33</td><td> 0.17/0.13</td>

<td colspan="2"> Other Ingredients</td><td> ω X ω όΡ ο ιη Ü CM dp Ο Ο γΗ co' J < dp CD Ο</td><td> C0 X ω άΡ ο ιη θ' CM JP ο ο γΗ co < dP σ> ο</td><td> ω X ω dp Ο ιη Ο CM JP ο ο Η ω a dP en ο</td>

<td colspan="2"> Triclosan %</td><td> Ο ο</td><td> co <Ν ο</td><td> ο ο</td>

<td colspan="2"> Composition</td><td> ω co ω co</td><td> Η Η Η Εη</td><td> 1</td>

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- 119 In addition to the observation that other solvents (e.g., PG and TPG) can be used in compositions of the present invention, products JJJJ through 0000 illustrate another effect of relative saturation of antibacterial agent in the system.

The relative % saturation (highest to lowest) of the first three compositions is JJJJ>KKKK>LLLL. Composition KKKK has one-third the amount of TCS as composition JJJJ solubilized in the same level of ALS (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 relative % saturation is essentially equal (i.e., about 100%), the activity remains essentially constant even though the absolute amount of TCS in the composition is decreased (i.e., compare Compositions MMMM to NNNN). These data further support the observations with respect to the importance of % saturation set forth in Example 7.

In addition, a comparison of composition IIII to composition TTTT shows that composition TTTT contains slightly less ALS (0.9% vs. 1.0% for IIII), the same amount of PG (10.0%), and one-half the amount of SXS (5.0% vs. 10.0% for IIII). Experimental observations indicated that compositions IIII and TTTT were at or near 100% saturation. However, the log reductions of E. coli were considerably lower (about 4 log) for Composition TTTT. This observation further supports the data set forth in Example 8 wherein minimum level of hydrotrope may be

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- 120 needed for a high antibacterial efficacy against at least some Gram negative bacteria.

Example 15

The following compositions 15-A through 15-D were prepared to demonstrate the superior germ kill provided by compositions of the present invention compared to control compositions (i.e., compositions free of an antibacterial agent), even when very low amounts of disinfecting alcohol are present. Compositions 15A-15D were prepared using standard mixing techniques known in the art. Table 4 below lists the composition ingredients. Table 5 below summarizes the antibacterial efficacy of compositions 15-A through 15-D, as measured in a time kill test.

<td colspan="6"> Table 4</td>

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- 123 composition, even though the composition contained a very low concentration of ethanol.

Example 18

Example 18 illustrates a composition of the present invention containing a cationic gelling agent, CELQUAT CS-230M. Composition 18-A was prepared by admixing 0.15% TCS, 28% ethanol, 11.18%

DPG, and 2% CELQUAT CS-230M, and the balance was water (as weight percent of active compounds, except CELQUAT, which is as-is). The antibacterial efficacy of composition 18-A was evaluated by a time kill test. Composition 18-A demonstrated the following log reductions against S. aureus, E, coli, K. pneum., and S. chol., at 30 seconds contact time of >3.83, 4.33, >4.43, and >3.55, respectively. Thus, composition 18-A is a highly effective antibacterial composition, even though the composition contained a very low concentration of ethanol.

PCT/US00/15729

- 126 The data presented in all the above tables and examples show that % saturation of antibacterial agent in the aqueous phase of the composition can be directly correlated to a log reduction of bacteria. For example, as shown in the prior tables, a composition having 50% saturation of TCS in the aqueous phase demonstrates a log reduction versus S. aureus of 1.96 (30 seconds) and 3.05 (60 seconds) and a log reduction versus E. coli of 2.45 (30 seconds) and greater than 3.81 (60 seconds). A 75% saturated and a 100% saturated composition exhibited a log reduction of greater than 4.55 (30 and 60 seconds) vs. S. aureus (i.e., a log reduction in excess of the detection limit of the assay). The 75% and 100% saturated compositions exhibited a log reduction of 3.40 (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 antibacterial compositions can be characterized as exhibiting a log reduction of at least about 2 (after 30 seconds) or at least about 3 (after 60 seconds) vs. S. aureus, or of at least about 2.5 (after 30 seconds) or at least about 3.5 (after 60 seconds) vs. E. coli .

The antibacterial compositions of the present invention have several practical end uses, including hand cleansers, mouthwashes, surgical scrubs, body splashes, hand sanitizer gels, and similar personal care products. Additional types of compositions include foamed compositions, such as creams, mousses, and the like, and compositions containing organic and inorganic filler materials, such as emulsions, lotions, creams, pastes, and the

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- 127 like. The compositions further can be used as an antibacterial cleanser for hard surfaces, for example, sinks and countertops in hospitals, food service areas, and meat processing plants. The present antibacterial compositions can be manufactured as dilute ready-to-use compositions, or as concentrates that are diluted prior to use.

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

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

The present compositions are effective in short contact time because the antibacterial agent is present in the aqueous continuous phase of the composition, as opposed to surfactant micelles. The antibacterial agent, therefore, is available to immediately begin reducing bacterial populations, and further is available to deposit on the skin to provide residual antibacterial efficacy. In addition, because the antibacterial agent is in solution as opposed to surfactant micelles, the absolute amount of antimicrobial agent in the composition can be reduced without adversely affecting efficacy, and the antibacterial agent is not rinsed from the skin with the surfactant prior to performing its antibacCA 02371925 2001-12-19

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- 128 terial function. In addition, the amount of surfactant in the present antibacterial compositions typically is low, thereby providing additional environmental benefits .

The following examples illustrate various compositions of the present invention.

Example 20

Hand Wash Composition

A composition in accordance with the instant invention, suitable for use as a hand wash, was prepared. The composition contained the following components in the indicated weight percentages:

<td> Ingredient</td><td> Weight Percent</td>

<td> Triclosan</td><td> 0.3</td>

<td> Ammonium Lauryl Sulfate</td><td> 0.75</td>

<td> Dipropylene Glycol</td><td> 5.0</td>

<td> Sodium Xylene Sulfonate</td><td> 10.0</td>

<td> Fragrance</td><td> 0.05</td>

<td> Water</td><td> q.s.</td>

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

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- 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 surfactant :triclosan of 2.5:1, and was at least about 90% saturated with triclosan. The composition was evaluated for antibacterial efficacy against S. aureus and E. coli using a time kill test. Against S. aureus, the composition exhibited a log reduction of >4.07 in 30 seconds, while against E. coli the composition exhibited a log reduction of 3.90 in 30 seconds. Thus, the composition exhibited an excellent broad spectrum antibacterial activity. Also, the composition was an excellent hand wash composition in an actual use test, providing both good cleansing and a smooth feel to the hands.

Example 21

Body Splash Composition

A composition in accordance with the present invention, suitable for use as a body splash, is prepared using the following ingredients in the following weight percentages:

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<td> Ingredient</td><td> Weight Percent</td>

<td> Triclosan</td><td> 0.3</td>

<td> Alkyl Polyglycoside</td><td> 0.3</td>

<td> Propylene Glycol</td><td> 14.4</td>

<td> Sodium Xylene Sulfonate</td><td> 10.0</td>

<td> Ethanol</td><td> 10.0</td>

<td> Fragrance</td><td> 0.05</td>

<td> Water</td><td> q.s.</td>

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

Example 22

Mouthwash Composition

A composition in accordance with the present invention, suitable for use as a mouthwash, is prepared using the following ingredients in the following weight percentages:

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<td> Ingredient</td><td> Weight Percent</td>

<td> Triclosan</td><td> 0.3</td>

<td> Alkyl Polyglycoside</td><td> 0.3</td>

<td> Propylene Glycol</td><td> 14.4</td>

<td> Sodium Xylene Sulfonate</td><td> 10.0</td>

<td> Denatured alcohol</td><td> 10.0</td>

<td> Oil of Wintergreen (flavor)</td><td> 0.05</td>

<td> Water</td><td> q.s.</td>

The composition is prepared by combining the triclosan, propylene glycol, flavor, and denatured alcohol, and admixing the components by any conventional means until all the triclosan is dissolved, as evidenced by the absence of undissolved solid material. Then, the sodium xylene sulfonate is added, and the resulting mixture is stirred until the sodium xylene sulfonate is completely dissolved. Finally, the alkyl polyglycoside and water are added, and the mixture again is stirred until homogeneous. The resulting composition forms an excellent and refreshing mouthwash that provides a desirable level of bacterial reduction on the teeth, gums, and tongue of the user.

Example 23

Wet Wipe Composition

A composition in accordance with the present invention, suitable for impregnating a nonwoven material for the preparation of a wet wipe article, was prepared using the following ingredients in the following weight percentages:

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<td> Ingredient</td><td> Weight Percent</td>

<td> Triclosan</td><td> 0.3</td>

<td> Ammonium Lauryl Sulfate</td><td> 0.75</td>

<td> Dipropylene Glycol</td><td> 5.0</td>

<td> Sodium Xylene Sulfonate</td><td> 15.0</td>

<td> Water</td><td> q.s.</td>

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

A piece of nonwoven cellulosic web material (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 surfaces, for example, hands. The article formed an excellent wet wipe and the impregnated antibacterial composition was freely expressed from the web to provide a broad spectrum antibacterial activity.

CA 02371925 2001-12-19

WO 00/78275

PCT/US00/15729

- 133 Example 24

Hand Wash Composition

A composition in accordance with the present invention, suitable for use as a hand wash, was prepared. The composition comprised the following components at the indicated weight percentages:

<td> Ingredient</td><td> Weight Percent</td>

<td> Triclosan</td><td> 0.3</td>

<td> Ammonium Lauryl Sulfate</td><td> 0.75</td>

<td> Dipropylene Glycol</td><td> 5.0</td>

<td> Sodium Xylene Sulfonate</td><td> 15.0</td>

<td> Water</td><td> q.s.</td>

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

The composition had a weight ratio of surfactant :triclosan of 2.5:1 and was at least about 90% saturated with triclosan. The composition was evaluated for its antibacterial efficacy against S. aureus, E. coli, K. pneum., and S. choler. using a time kill test, and a contact time of 30 seconds.

CA 02371925 2001-12-19

WO 00/78275 PCT/US00/15729

- 134 The composition exhibited log reductions of >3.59, >4.49, >3.20, and >4.27 against the four test organisms, respectively.

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

Example 25

Comparison to a Previously Disclosed Composition

This example compares the antibacterial efficacy of a composition of the present invention to a previously disclosed composition. Accordingly, the composition of Example 24 was compared to the sole example disclosed in WO 98/01110. In both compositions, the active antibacterial agent was triclosan (TCS). Both compositions were evaluated for antibacterial efficacy in a time kill test against S. aureus, E. coli, K. pneum., and S. choler. The example of WO 98/01110 was tested at 50% dilution, in accordance with the test procedure for viscous compositions. The following data summarizes the percent of active antibacterial agent in each composition at the test dilution (i.e., test dilution is 100% for the composition of Example 24 and 50% for the example of WO 98/01110), and the log reduction observed in the time kill test at a contact time of 30 seconds.

CA 02371925 2001-12-19

WO 00/78275

PCT/US00/15729

- 135 -

<td> Composition</td><td> % TCS</td><td colspan="4"> Log Reduction at 30 seconds</td>

<td></td><td></td><td> S. aureus</td><td> E. coli</td><td> K. pneum.</td><td> S. choler</td>

<td> Example 18</td><td> 0.3</td><td> >4.60</td><td> >4.50</td><td> 4.21</td><td> >4.68</td>

This example demonstrates the superior time kill performance of a composition of the present invention compared to a prior composition, especially against Gram negative bacteria. This superiority is demonstrated even through the comparative composition contained substantially more active antibacterial agent compared to the inventive composition. Thus, an inventive composition utilizes the active agent more efficiently, as illustrated in a higher log reduction using a reduced concentration of antibacterial agent.

Example 26

Comparison to a Previously

Disclosed Composition

This example compares the antibacterial efficacy of a composition of the present invention to a previously disclosed composition. Accordingly, the composition of Example 24 was compared to a composition disclosed in WO 96/06152. WO 96/06152 discloses effective compositions comprising TCS, an anionic surfactant, a hydrotrope, a hydric solvent, and further comprising an organic acid, specifically citric acid. WO 96/06152 contains additional pH adjusting agents, such as monoethanolamine and soCA 02371925 2001-12-19

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

The composition was at least about 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, the composition exhibited a log reduction of >3.57 in 30 seconds; and against E. coli the composition exhibited a log reduction of >4.17 in 30 seconds. Thus, the composition exhibited an excellent broad spectrum antibacterial activity.

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

Contents394

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Citations
Document	Relation	Office	Cited during
US10405544B2	Cited by	United States of America	Applicant
US10912294B2	Cited by	United States of America	Applicant
US8691292B2	Cited by	United States of America	Applicant
US9451763B2	Cited by	United States of America	Applicant
US10111425B2	Cited by	United States of America	Applicant
WO2009124392A1	Cited by	World Intellectual Property Organization (WIPO)	International search
WO2016131134A1	Cited by	World Intellectual Property Organization (WIPO)	International search
US9609864B2	Cited by	United States of America	Applicant

37 members in 14 offices

This recordMember, by publication datePriority claim4 more offices are in the list below

Priority claims9

Priority claims
Document	Office	Kind	Date
33865499	United States of America	A	1999-06-23
42552199	United States of America	A	1999-10-22
0015729	United States of America	W	2000-06-08
09338654	–	–	–
09425521	–	–	–
PCTUS0015729	–	–	–
US19990338654	–	–	–
US19990425521	–	–	–
WO2000US15729	–	–	–

Members37

Family members, oldest first
Document	Office	Kind
US6107261A	United States of America	A	2000-08-22
US6136771A	United States of America	A	2000-10-24
CA2371925A1This record	Canada	A1	2000-12-28
WO0078141A1	World Intellectual Property Organization (WIPO)	A1	2000-12-28
WO0078275A2	World Intellectual Property Organization (WIPO)	A2	2000-12-28
AU5471000A	Australia	A	2001-01-09
AU5472000A	Australia	A	2001-01-09
US6204230B1	United States of America	B1	2001-03-20
WO0078275A3	World Intellectual Property Organization (WIPO)	A3	2001-09-27
GT200000106A	Guatemala	A	2001-12-21
GT200000108A	Guatemala	A	2001-12-21
EP1191843A2	European Patent Office (EPO)	A2	2002-04-03
BR0011860A	Brazil	A	2002-04-30
US6451748B1	United States of America	B1	2002-09-17
AR024874A1	Argentina	A1	2002-10-30
JP2003502353A	Japan	A	2003-01-21
US2003125224A1	United States of America	A1	2003-07-03
TW546149B	Taiwan Province of China	B	2003-08-11
MXPA01013312A	Mexico	A	2003-09-04
CA2491670A1	Canada	A1	2004-01-15
WO2004004677A1	World Intellectual Property Organization (WIPO)	A1	2004-01-15
AU2003247720A1	Australia	A1	2004-01-23
AU777059B2	Australia	B2	2004-09-30
CN1553796A	China	A	2004-12-08
US6861397B2	United States of America	B2	2005-03-01
RU2004107901A	Russian Federation	A	2005-03-20
MXPA05000473A	Mexico	A	2005-03-23
EP1521569A1	European Patent Office (EPO)	A1	2005-04-13
AR044721A1	Argentina	A1	2005-10-05
JP2006502987A	Japan	A	2006-01-26
RU2272612C2	Russian Federation	C2	2006-03-27
MY122621A	Malaysia	A	2006-04-29
MY125333A	Malaysia	A	2006-07-31
CN1289051C	China	C	2006-12-13
TWI284020B	Taiwan Province of China	B	2007-07-21
CA2371925C	Canada	C	2009-02-17
AU2003247720B2	Australia	B2	2009-03-26

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	Event	Code
2011-06-08	LapsedLapsedMKLA	MKLA
2001-12-19	Examination requestEEER	EEER