CA2491670A1 - Compositions having enhanced deposition of a topically active compound on a surface - Google Patents

Abstract

Topically active compositions having enhanced effectiveness are disclosed. T he compositions contain a topically active compound, an an-ionic surfactant, a hydric solvent, a hydrotrope, an optional cosurfactant, and water, wherein a percent saturation of the topical active compound of the composition is at least 25 %. The compositions exhibit a rapid and effective topical effect, a nd effectively deposit the topically active compound for an effective residual effect.

Description

- 1 - ..
COMPOSITIONS HAVING ENHANCED DEPOSITION
OF A TOPICALhY ACTIVE COMPOUND ON A SURFACE
CROSS-REFERENCE TO RELATED APPLICATION
This application is a continuation-in-part of U.S. application Serial No. 09/578,020, filed May 24, 2000, allowed, which is a continuation of U.S.
application Serial No. 09/338,654, filed June 23, 2999, now U.S. Patent No. 6,107,261.
FIELD OF THE INVENTION
, The present invention is directed to com-positions, particularly personal care compositions, having an improved ability to deposit topically active compounds on a surface, such as skin or hair.
More particularly, the present invention is directed to compositions comprising a topically active com-pound, a-primary surfactant, a hydrotrope, a hydric solvent, an optional cosurfactant, and other option-al ingredients. The topically active compounds include antibacterial agents, sunscreens, vitamins, medicaments, fragrance materials,, antioxidants, conditioners, emollients, and the like. The topi-cally active compounds typically are insoluble in water, and the compositions,deposit the topically active compounds to surfaces more effectively than present-day commercial compositions.
SUBSTITUTE SHEET (RULE 26) For many personal care products, it is desirable not only to provide consumers the basic function of cleansing the skin or hair, but also to deposit a topically active compound that provides a predetermined benefit. The paradoxical problem of cleaning skin, or other surfaces, such as hair, cloth, or hard surfaces, while simultaneously de-positing a topically active compound has been in-vestigated for decades. Recent publications show 'that simultaneous cleaning and deposition of topi-cally active ingredients is still a challenge, for example, see U.S. Patent Nos. 5,885,948P 6,080,707:
and 6,080,708.
The need for cleansing compositions that efficiently deposit topically active compounds is magnified when the typically high cost of the topi-cally active compounds is considered, because a substantial portion of these expensive compounds is wasted in present-day compositions. In addition, particular topically active compounds, like antimi--crobial agents, can provide both quick-acting and residual benefits. The value of a quick-acting antimicrobial agent is evident, and the residual benefit of antimicrobial agents is discussed in WO 98/55095 and U.S. Patent No. 6,213,933, incorpo-rated herein by reference.
Topically active compounds encompass a wide range of materials, including antibacterial agents, sunscreens, vitamins, medicaments, fragrance materials, antioxidants, conditioners, emollients, SUBSTITUTE SHEET (RULE 26) and other hair-care and skin-care ingredients. Many of these compounds are relatively water insoluble.
Present-day compositions typically rely upon solu-bilization of active compounds in a surfactant system. Other systems rely upon a dispersion of emulsified active oil droplets.
A surfactant solubilized active compound is not effectively deposited unless the active com-pound is present at a very high level of saturation in the composition, or the active compound is chem-ically and/or physically modified to enhance deposi-tion. However, there is a practical limit to incor-porating a high level of saturation of active com-pound with traditional surfactant systems because of cost and/or regulatory constraints: For example, a composition containing 15o ammonium lauryl sulfate can require about 3% triclosan to form a saturated system. Because of the high cost of triclosan, such a composition would be too expensive to commercial-ize. Physical/chemical modifications of the active compounds, while possibly enhancing deposition, may not be desirable because of additional cost to an already expensive ingredient and/or the need for regulatory reapproval and additional testing re-quired for the modified active compound.
The dispersion-type of emulsion composi-Lion typically operates by dilution deposition, and has the potential to deposit active compounds rela-tively well. However, this type of composition has limitations. For example, typical compositions are thickened dispersions, and cannot be used in certain SUBSTITUTE SHEET (RULE 26) dispensers (e. g., a self-foaming pump). In addi-tion, some active compounds may not be biologically available on the skin, hair, or other surface when in the form of relatively large hydrophobic droplets or dissolved in a carrier oil.
Other strategies to enhance deposition include the addition of certain materials that en-hance substantivity of active compounds by "codepo-sition,"~i.e., a "deposition aid" which adheres to the skin or hair and purportedly enhances deposition of an active ingredient. This strategy also has a limitation of decreased bioavailability when the active compound/deposition aid complex contacts the skin or hair, because the active compound may be less prone to diffuse to the site of action and/or may not be uniformly dispersed over the treated surface.
While not being bound by theory, it is envisioned that a present composition combines two principles to enhance deposition of active com-pounds. The first principle is the use of high thermodynamic activity (i.e., high percent satura-tion) to enhance the tendency of the active compound to deposit on surfaces. Allawalla et al., J. Amen Pharmaceut., Assn., ~fLII, pp. 267-274 (1953) dis-close the importance of this factor of the activity of antimicrobial agents. In fact, as illustrated herein, thermodynamic activity is an important factor in enhancing deposition of other active com-pounds as well.
SUBSTITUTE SHEET (RULE 26) The second principle that contributes to' enhanced deposition is the surprising and unique property of a present composition to release the active compound upon dilution. While the novel com-S positions containing an active compound, an anionic surfactant, a hydrotrope, a hydric solvent, an op-tional cosurfactant, and other optional ingredients form clear, mobile, phase-stable compositions, the compositions become unstable upon dilution with water and deposit the active compound to~a surface in a highly effective manner. This type of behavior is in sharp contrast to typical solubiliaed active systems that generally remain stable upon dilution.
The mechanism of deposition also is different from the dilution deposition of compositions disclosed in prior art because the present compositions do not contain dispersed oil droplets typical in existing emulsion systems.
Persons skilled in the art have evaluated numerous, diverse strategies to enhance the deposi-tion of topically active compounds on the skin and hair. A review of these diverse strategies to solve the problem of cleaning a surface and depositing a topically active compound on the surface is summar-ized below. It can be seen that the present compo sitions are novel and nonobvious even over the art.
Compositions encompassed by the present invention include, but are not limited to, skin care, hair care, hard surface cleaning, and similar compositions used to cleanse and/or treat a surface.
The present disclosure is directed primarily to SUBSTITUTE SHEET (RULE 26) antibacterial compositions, but also applies to other compositions containing a topically active compound.
With respect to antibacterial personal care compositions, such 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.
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 indi-cates 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 spec-trum reduction in microorganism populations quickly and without problems associated with toxicity and skin irritation.
In particular, antibacterial cleansing compositions typically contain an active antibac-terial 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., SUBSTITUTE SHEET (RULE 26) chlorhexidine digluconate), diphenyl compounds, . benzyl alcohols, trihalocarbanilides, quaternary ammonium compounds, ethoxylated phenols, and pheno-lic 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-diphen-ylether). Present-day antimicrobial compositions based on such antibacterial agents exhibit a wide range of antibacterial activity, ranging from low to 10, high, depending on the microorganism to be con-trolled and the particular antibacterial composi-tion.
Most commercial antibacterial composi-tions, 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 pro-vided by the antibacterial composition correlates to antibacterial activity. A log reduction of 3-5 is most preferred, a 1-3 reduction is preferred, where-as a log reduction of less than 1 is least pre-ferred, 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 dis-closures illustrate attempts to provide such anti-bacterial compositions, which, to date, do not pro-SUBSTITUTE SHEET (RULE 26) - g -vide the rapid, broad range control of microorgan-isms desired by consumers.
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-sitions having such pH values can irritate the skin and other surfaces, and, therefore, typically are avoided. It has been difficult to impossible to achieve a high log reduction using an antibacterial composition having,a neutral pH of about 5 to about 8, and especially about 6 to about 8.
For example, W098/O1I10 discloses compo-sitions comprising triclosan, surfactants, solvents, chelating agents, thickeners, buffering agents, and water. W098/01110 is directed to reducing skin irritation by employing a reduced amount of surfac-tant.
Fendler et al. U.S. 5,635,462 discloses compositions comprising PCMX and selected surfac-tants. The compositions disclosed therein are devoid of anionic surfactants and nonionic surfac-tants.
W097/46218 and W096/06152 disclose com-positions based on triclosan, organic acids or salts, hydrotropes, and hydric solvents.
EP 0 505 935 discloses compositions con-taming PCMX in combination with nonionic and anionic surfactants, particularly nonionic block copolymer surfactants.
SUBSTITUTE SHEET (RULE 26) _ g _ W095/32705 discloses a mild surfactant combination that can be combined with antibacterial compounds, like triclosan.
W095/09605 discloses antibacterial com-positions containing anionic surfactants and alkyl-polyglycoside surfactants.
W098/55096 discloses antimicrobial wipes having a porous sheet impregnated with an antibac-terial composition containing an active antimicro-bial agent, an anionic surfactant, an acid, and water, wherein the composition has a pH of about 3.0 to about 6Ø
N.A. Allawala et al., J. Amen Pharm.
Assoc_--Sci. Ed., Vol. X.LII, no. 5, pp. 267-275 (1953) discusses the antibacterial activity of active antibacterial agents in combination with surfactants.
r A.G. Mitchell, J. Pharm. Pharmacol. , Vol.
16, pp. 533-537 (1964? discloses compositions con-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.
Prior disclosures have not addressed the issue of which composition ingredient in an anti-bacterial composition provides bacterial control.
Prior compositions also have not provided an effec-tive, fast, and broad spectrum control of bacteria at a neutral pH of about 5 to about 8, and especial-ly at about 6 to about 8.
SUBSTITUTE SHEET (RULE 26) An efficacious antibacterial composition has been difficult to achieve because of the prop-erties of the antibacterial agents and the effects of a surfactant on an antibacterial agent. For example, several active antibacterial agents, like phenols, have an exceedingly low solubility in water, e.g., triclosan solubility in water is about 5 to 10 ppm (parts per million). The solubility of the antibacterial agent is increased by adding sur-factants to the composition. However, an increase in solubility of the antimicrobial agent, and in turn, the amount of antibacterial agent in the composition, does not necessarily lead to an in-creased antibacterial efficacy.
Without being bound to any particular theory, it is theorized'that the addition of a surfactant increases antimicrobial agent solubility, but also typically reduces the availability of the antibacterial agent because a surfactant in water forms micelles above the critical micelle concentra-tion of the surfactant. The critical micelle con-centration varies from surfactant to surfactant.
The formation of micelles is important because micelles have a lipophilic region that attracts and solubilizes the antibacterial agent, and thereby renders the antibacterial agent unavailable to immediately contact bacteria, and thereby control bacteria in short time period (i.e., one minute or less).
The antibacterial agent solubilized in the surfactant micelles will control bacteria, but in SUBSTITUTE SHEET (RULE 26) relatively long time frames. The antibacterial 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 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, an antibacterial agent 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 residual antibacterial benefit. Rather, the anti-bacterial agent is washed away and wasted. The present invention is directed to enhancing the deposition of topically active compounds, like antibacterial agents.
As previously discussed, prior investi-gators have employed various strategies to improve deposition of a topically active compound on a surface. One strategy is to chemically modify the topically active compound, which is not a practical solution to compound deposition. Other investi-gators considered the nature of surface being treated. However, a commercially practicable com-position should be useful on a variety of surfaces.
Other investigators utilised water-soluble cationic polymers as deposition aids for the topi-cally active compound. See U.S. Patent Nos.
SUBSTITUTE SHEET (RULE 26) 3,489,686; 3,580,853; and 3,723,325, disclosing the use of polyethylenimine and the reaction product of polyethyleneimine and either ethylene oxide or propylene oxide, quaternary ammonium-substituted cellulose derivatives, and a polymer formed on tetraethylenepentamine and epichlorohydrin. Other patents and applications directed to the use of a deposition aid for a topically active compound include W099/66886; U.S. Patent Nos. 3,726,815;
3, 875, 071; 4, 894,220; 6, 057, 275; and 6, 126, 954;
W099/63965; W000/33807; W099/63953.
Still other investigators directed atten-tion to dilution deposition of a topically active compound. This is considered to be a primary dep-osition mechanism for many commercially available "two-in-one" conditioning shampoos. Dilution dep-osition involves the use of a topically active com-pound in a composition that is phase stable during storage and application to the hair, but becomes phase unstable and separates during rinsing. The additional water added to the composition during rinsing causes phase separation and deposition of the oil phase (which contains the topically active compound) onto the hair. Examples of patents re-lating to dilution deposition include EP 0 552 024;
W099/32079; W099/53889; U.S. Patent Nos. 5,981,465;
~, 051, 546; and 5, 928, 632; W001/01949; W099/26585;
W099/13854; W099/62477; WO00/43984; and W000/25739.
Other strategies used to enhance deposi-tion of topically active compounds include varying the amount and type of surfactant in the composi-SUBSTITUTE SHEET (RULE 26) tion, entrapping the topically active compound in a polymer matrix, utilizing separate cleansing and treatment compositions, using a wipe cloth to apply the topically acti:-e compound, and utilizing elec-trostatic sprays or liquid crystals. These strat-egies are disclosed in U.S. Patent Nos. 5,409,695 and 5,814,323; WO00/64406e EP 0 573 229; W000/00170;
W099/55303; W099/13861; W099/21532: W099/12519;
W001/12138; and W001/13871.
Accordingly, a need exists for a topically active composition that is highly efficacious in a short time period, and effectively deposits a topi-cally active compound on a surface to provide re-sidual benefits. The present invention is directed to such compositions, including antibacterial compositions and skin- and hair-care compositions.
SUMMARY OF THE INVENTION
The present invention relates to topically active compositions that provide (a) a rapid and substantial benefit attributed to a topically active compound, and (b) an efficacious deposition of the topically active compound on a surface to provide a residual benefit. In particular, the present inven-tion relates to topically active compositions con-taming a topically active compound, wherein (a) the topically active compound is present in the con, tinuous aqueous phase (in contrast to being present in micelles), in an amount of at least 250 of satur-ation, when measured at room temperature, (b) pro-vides a substantial beneficial result, e.g., a SUBSTITUTE SHEET (RULE 26) substantial reduction in Gram positive and Gram negative bacteria, within one minute, and (c) effec-tively deposits the topically active compound on the treated surface to provide a residual benefit.
Therefore, one aspect of the present in-vention is to provide a topically active composition having an enhanced deposition of a topically active compound to a surface during a cleansing and/or rinsing step. More particularly, the present inven-tion is directed to topically active compositions comprising a topically active compound, a primary surfactant, a hydrotrope, a hydric solvent, an optional cosurfactant, other optional ingredients, and water.
Accordingly, one aspect of the present invention is to provide a liquid topically active composition comprising:
(a) about O.OOlo to about 50, by weight, of a topically active compound;
(b) about O.lo to about 15%, by weight, of an anionic surfactant;
(c) about 0.5o to about 350, by weight, of a hydrotrope;
(d) about 0.5o to about 250, by weight, of a water-soluble hydric solvent;
(e) Oo to about 50~, by weight, of a co-surfactant selected from the group consisting of a nonionic surfactant, an ampholytic surfactant, and mixtures thereof; and (f) water.
SUBSTITUTE SHEET (RULE 26) The topically active compound is a water-insoluble compound that provides a benefit to a surface contacted by the composition. The topically active compound can be, for example, an antibac-terial agent, an antidandruff agent, a sunscreen, a medicament, a skin or hair conditioner, a vitamin, an emollient, an antioxidant, a fragrance, and other skin and hair care compounds.
Another aspect of the present invention is to provide a topically active composition comprising about 0.001% to about 50 of a water-insoluble topi-cally active compound, about 5% to about 15% di-propylene glycol, about 10% to about 20% sodium xylene sulfonate, about 0.5% to about 5o ammonium lauryl sulfate, and 0% to about 5% cocamidopropyl-betaine.
Yet another aspect of the present inven-tion is to provide consumer products based on a , topically active composition of the present inven-tion, for example, a skin cleanser, a conditioning shampoo, an antidandruff shampoo, a body splash, a topical medicament, a surgical scrub, a wound care agent, a hand sanitizes gel, a disinfectant, a mouth wash, a pet shampoo, a hard surface sanitizes, and other skin and hair-care compositions.
A further aspect of the present invention is to provide a method of rapidly reducing the Gram positive and/or Gram negative bacteria populations on animal tissue, including human tissue, by con-tacting the tissue, like the dermis, with an anti-bacterial composition of the present invention for a SUBSTITUTE SHEET (RULE 26) sufficient time, such as about 15 seconds to 5 minutes, to reduce the bacteria level to a desired level, and depositing a substantial amount of the antibacterial agent on the tissue to provide a residual bacterial action.
The above and other novel aspects and advantages of the present invention are illustrated in the following, nonlimiting detailed description of the preferred embodiments.
DETAILED DESCRIPTION OF THE PREFERRED EI~ODIMENTS
Personal care products incorporating a topically active compound have been used for many years. Since the introduction of such personal care products, many claims have been made that these products provide a benefit attributed to a topically active compound, like an antibacterial agent, pres-ent in the composition. With respect to antibac-terial compositions, to be most effective, an anti-bacterial composition should provide a high log reduction against a broad spectrum of organisms in as short a contact time as possible, and also deposit on the skin to provide a residual antibac-terial activity. This dual function of rapid and residual activity for antibacterial agents, and other topically active compounds, is difficult to achieve in a water-based composition that is-applied to the skin, then rinsed off the skin in a rela-tively short time.
As presently formulated, commercial liquid antibacterial soap compositions provide a poor to SUBSTITUTE SHEET (RULE 26) - l7 -marginal time kill efficacy, i.e., rate of killing bacteria. Table 1 summarizes the kill efficacy of commercial products, each of which contains about 0.2o to 0.30, by weight, triclosan (an antibacterial agent).
Table 1 Time Kill Efficacy of Commercial Liquid Hand Soaps Organism (Log Reductions after Product 1 Minute Contact Time) Gram PositiveGram negativeGram negative S, aureus E. coli K. pneum.

Commercial 1.39 0.00 0.04 Product A

Commercial ~-~0 0.00 0.01 Product B

Commercial 1.85 ,0.00 0.00 Product C

Present-day products especially lack efficacy against Gram negative bacteria, such as E.
coli, which are of particular concern to human health. In one aspect, the present invention, therefore, is directed to antibacterial compositions having an exceptionally high broad spectrum antibac-terial efficacy, as measured by a rapid kill of bac-teria (i.e., time kill), which is to be distin-guished from persistent, or residual, kill.
In addition, as presently formulated, commercial cleansing compositions provide a poor to marginal deposition of topically active compounds.
Typically, 980 or more of the applied topically active compound is wasted during application.
Accordingly, there is a need to improve the deposi-tion of such expensive active compounds in these SUBSTITUTE SHEET (RULE 26) compositions. Therefore, the present invention also is directed to providing a residual benefit attributed to the topically active compound, while incorporating a relatively low amount of the active comound in the composition.
The present antibacterial compositions provide significantly improved time kill efficacy compared to prior compositions. The basis of this improved time kill is the discovery that the anti-microbial efficacy of an active agent can be correlated to the rate at which the agent has access to an active site on the microbe. The driving force that determines the rate of agent transport to the site of action is the difference in chemical poten-25 tial between the site at which the agent acts and the external aqueous phase. Alternatively stated, the microbicidal activity of an active agent is proportional to its thermodynamic activity in the external phase. Accordingly, thermodynamic activity, as opposed to concentration, is the more important variable with respect to antimicrobial efficacy. As discussed more fully hereafter, thermodynamic activity is conveniently correlated to the percent saturation of the active antibacterial agent in the continuous aqueous phase of the compo-sition.
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 from solution: Percent saturation is the measured SUBSTITUTE SHEET (RULE 26) 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 compounds like surfactants. Surfactants not only increase the solubility of compounds in the contin-uous aqueous phase of the composition, but also form micelles, and can solubilize compounds in the micelles.
The o saturation of an active antibac-terial agent in any composition, including a surfac-tant-containing composition, ideally can be ex-pressed as:
o saturation = [C/Cs]x1000 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, it is contemplated that the continuous aqueous phase of a surfactant-con-taining composition is in equilibrium with the micellar pseudophase of said composition, and further that any dissolved species, such as an antibacterial active~agent, is distributed between the aqueous continuous phase and the micellar pseudophase according to a partition law. Accord-ingly, the percent saturation, or alternatively the relative thermodynamic activity or relative chemical potential, of an antibacterial active agent dis-solved in a surfactant-containing composition is the SUBSTITUTE SHEET (RULE 26) same everywhere within the composition. Thus, the terms percent saturation of the antibacterial agent "in a composition," "in the aqueous continuous phase of a composition," and "in the micellar pseudophase of a composition" are interchangeable, and are used as such throughout this disclosure.
Maximum antibacterial efficacy is achieved when the difference in thermodynamic activities of the active antibacterial agent between the cornposi-IO tion and the target organism is maximized (i.e., when the composition is more "saturated" with the active ingredient). A second factor affecting anti-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 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, 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.
An important ingredient in antibacterial cleansing compositions is a surfactant, which acts as a solubilizer, cleanser, and foaming agent. Sur-factants affect the percent saturation of an anti-bacterial agent in solution, or more importantly, SUBSTITUTE SHEET (RULE 26) - ~i -affect the percent saturation of the active agent in the continuous aqueous phase of the composition.
This effect can be explained in the case of a spar-ingly water-soluble antibacterial agent in an aqueous surfactant solution, where the active agent is distributed between the aqueous (i.e., contin-uous) phase and the micellar pseudophase. For antibacterial agents of exceedingly low solubility in water, such as triclosan, the distribution is shifted strongly toward the micelles (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 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, 20' 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 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 also is true.
Active agent solubilizeel in the micellar pseudophase is not immediately available to contact the micro organisms, and it is the percent saturation of SUBSTITUTE SHEET (RULE 26) active agent in the continuous aqueous phase that determines the antibacterial activity of the compo-sition. The active agent present in the surfactant micelles, however, can serve as a reservoir of active agent to replenish the continuous aqueous phase as the active agent is depleted.
To summarize, the thermodynamic activity, or percent saturation, of an antibacterial agent in the continuous aqueous phase of a composition drives antibacterial activity. Further, the total amount of available active agent determines the ultimate extent of efficacy. In compositions wherein the active agent is solubilized by a surfactant, the active agent present in surfactant micelles is not directly available for antibacterial activity. For such compositions, the percent saturation of the active agent in the composition, or alternatively the percent saturation of the active agent in the continuous aqueous phase of the composition, determines antibacterial efficacy.
The present compositions are topically active compositions having an improved effectiveness with respect to imparting a rapid benefit and a residual benefit. As illustrated in the following embodiments, a topically active composition of the present invention comprises: (a) about O.OOlo to about 5%, by weight, of a topically active compound;
(b) about 0.1o to about 150; by weight, of an anionic surfactant: (c) about 0.5o to about 35~, by weight, of a hydrotropej (d) about 0.5% to about 25o, by weight, of a water-soluble hydric solvent;
SUBSTITUTE SHEET (RULE 26) (e) 0% to about 50, by weight, of a cosurfactant selected from the group consisting of a nonionic surfactant, an ampholytic surfactant, and mixtures thereof; and (f) water. The compositions have a percent saturation of topically active compound in the continuous aqueous phase of at least about 250, when measured at room temperature. Antibacterial compositions of the present invention exhibit a log reduction against Gram positive bacteria of at least about 2 after 30 seconds contact. The compositions exhibit a log reduction against Gram negative bacteria of at least about 2.5 after 30 seconds contact.
In addition to providing a rapid and effi-cient benefit, a residual topical efficacy also is desired. To achieve a residual activity, the top-ically active compound must be deposited on the skin in the short time span between application of the composition to the skin and rinsing from the skin.
It also is important that a variety of topically active compounds, such as medicaments, antibacterial agents, conditioners, fragrances, and the like, are effectively deposited on the skin prior to rinsing of the composition from the skin.
The present invention, therefore, is di-rected to topically active compositions that effec-tively and rapidly deposit the topically active compound on a cleansed surface. The following Table summarizes results of deposition tests comparing commercial products to examples of the present com-positions. The compositions contain triclosan (TCS) SUBSTITUTE SHEET (RULE 26) as the water-insoluble topically active compound.
As seen from these test results, the present compositions have superior efficacy over commercial products in the deposition of the topically active compound.
Efficacy of Deposition of Triclosan (TCS) from Liquid Hand Soaps % TCS Remaining on Skin Sample % TCS vs.
Applied Dosel~

Test I

Commercial Product 0.2 7.39 C (LD) Example 15D 0.2 26.95 Relative Deposition (compared Sample % TCS to Commercial Product CD

Test II -Commercial Product 1 5.80 A iPC) Commercial Product 1 4.11 B (SX) Commercial Product 0.2 1.00 C (LD) Example 14A 1 10.49 ~ Example 15C I 0.3 ~ 11.37 1' As deteriained by a pigskin deposition test described below.
The following illustrates important, nonlimiting embodiments of the present invention.
In particular, compositions of the present invention comprise a topically active compound, a primary surfactant, a hydrotrope, a hydric solvent, an optional cosurfactant, and water. The compositions can further include additional optional ingredients disclosed hereafter, like pH adjusters, dyes, and preservatives.
The following is a nonlimiting description of ingredients that can be included in a present composition.
1. Topically Active Compound A topically active compound is present in a composition of the present invention in an amount SUBSTITUTE SHEET (RULE 26) of about 0.001% to about 50, and preferably about 0.010 to about 30, by weight of the composition. To achieve the full advantage of the present invention, the topically active compound is present in an amount of about 0.050 to about 20, by weight, of the composition.
The topically active compositions can be ready to use compositions, which typically contain 0.0010 to about 2%, preferably 0.01% to about 1.50, and most preferably about 0.050 to about 1%, of a topically active compound, by weight of the composi-tion. The topically active compositions also can be formulated as concentrates that are diluted before use with one to about 100 parts water to provide an end use composition. The concentrated compositions typically contain greater than about O.lo and up to about 50, by weight, of the topically active com-pound. Applications also are envisioned wherein the end use composition contains greater than 20, by weight, of the topically active compound.
As discussed above, the absolute amount of topically active compound present in the composition is not as important as the amount of available top-ically active compound in the composition, and the ability of the composition to rapidly and effective-ly deposit the topically active compound on a treated surface. The amount of available topically active compound in the composition, and the ability of the composition to deposit the topically active compound, is related to the identity of the surfac-tant in the comp~sition, the amount of surfactant in SUBSTITUTE SHEET (RULE 26) the composition, and the presence of optional in-gredients in the composition.
For antibacterial agents, 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 95o to 100% saturated with the antibac-terial agent. The amount of antibacterial agent present in the continuous aqueous phase~can be de-fined as the total amount of antibacterial agent in the composition, less any antibacterial agent pres-ent in surfactant micelles.. The method of deter-mining percent saturation of antibacterial agent in the composition is disclosed hereafter.
To achieve the desired residual activity, the topically active compound is rapidly and effec-tively deposited on the surface contacted by a com-position of the present invention.
Topically active compounds of the present invention include, but are not limited to, antibac-terial agents, skin and hair conditioning agents, fragrances, antidandruff agents, vitamins, sunscreen agents, antioxidants, antiacne agents, external analgesics, skin protectants, antiinflammatory agents, topical anesthetics, ultraviolet light ab-SUBSTITUTE SHEET (RULE 26) sorbers, and other cosmetic and medicinal topically active compounds.
The topically active compound is a water-insoluble compound. As used herein, the term "water-insoluble" is defined as a compound having a water solubility, at 25°C and 1 atmosphere pressure, of 2 grams or less per 100 ml of water, with water solubilities being as low as about 1 ppm (part per million).
One embodiment of topically active com-pounds useful in the present invention are water-insoluble phenolic compounds having as antimicrobial properties, and exemplified by the following classes of compounds:
25 2-Hydroxydiphenyl compounds Yo ZP Yr O
(OH)m ~ (OH)n OH
wherein Y is chlorine or bromine, Z is SO~H, NOZ, or C1-4alkyl, r is 0 to 3, o is 0 to 3, p is 0 or l, 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 l, o is 1 or 2, r is 1 or 2, and p is 0.
SUBSTITUTE SHEET (RULE 26) In especially preferred embodiments, Y is chlorine, m is 0, n is 0, o is 1, r is 2, and p is 0.
A particularly useful 2-hydroxydiphenyl compound has the structure:
C1 ~ O ~ C1 OH CI
having the adopted name, triclosan, and available commercially under the tradename IRGASAN DP300, from Ciba Specialty Chemicals Corp., Greensboro, NC.
Another useful 2-hydroxydiphenyl compound is 2,2'-dihydroxy-5,5'-dibromo-diphenyl ether.
Phenol derivatives OH
R5 Rx R9 ~ _Ra wherein Rz is hydro, hydroxy, C1_~alkyl, ehloro, vitro, phenyl, or benzyl; R~ is hydro, hydroxy, C1_6alkyl, or halo; R3 is hydro, Cl_6alkyl, hydroxy, chloro, vitro, or a sulfur in the form of an alkali metal salt or ammonium salt; R9 is hydro or methyl, and R5 is hydro or vitro. Halo is bromo or, preferably, chloro.
SUBSTITUTE SHEET (RULE 26) 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-, 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-nol derivatives are listed in WO 98/55096, incorpo-rated herein by reference. _ biphenyl Compounds R~2 Rr1 R1 R2 R~3 ~ X ~ R3 R.4 R.5 R5 R4 wherein X is sulfur or a methylene group, R1 and R' 1 are hydroxy, and R2, R' ~, R3, R' 3, Rq, R' 9 R5, and R'S, independent of one another, are hydro or halo. Specific, nonlimiting examples of Biphenyl compounds are hexachlorophene, tetrachlorophene, dichlorophene, 2,3-dihydroxy-5,5'-dichlorodiphenyl sulfide, 2,2'-dihydroxy-3,3',5,5'-tetrachlorodi-phenyl sulfide, 2,2'-dihydroxy-3,5',5,5',6,6'-hexa-chlorodiphenyl sulfide, and 3,3'-dibromo-5,5'-di-chloro-2,2'-dihydroxydiphenylamine. Other Biphenyl compounds are listed in WO 98/55096, incorporated herein by reference.
SUBSTITUTE SHEET (RULE 26) Similarly, topically active medicaments, like antifungal compounds; antibacterial compounds;
antiinflammatory compounds; topical anesthetics;
skin rash, skin disease, and dermatitis medications;
and antiitch and irritation-reducing compounds can be included in a composition of the present inven-tion. For example, analgesics, such as benzocaine, dyclonine, aloe vera, and the like; anesthetics, IO such as butamben picrate, lidocaine, xylocaine, and the like; antibacterials and antiseptics, such as polymyxin b sulfate-bacitracin, zinc-neomycin sulfate-hydrocortisone, chloramphenicol, erythro-mycin, and the like; antiparasitics, such as lin-lane; antiinflammatory agents, such as alclometasone dipropionate, betamethasone valerate, and the like;
burn relief ointments, such as o-amino-p-toluenesul-fonamide monoacetate and the like;l depigmenting agents, such as monobenzone; dermatitis relief agents, such as the active steroid amcinonide, di-florasone, hydrocortisone, and the like; fungicides, such as butocouazole, haloprogin, clotrimazole, and the like; psoriasis, seborrhea, and scabicide agents, such as anthralin, methoxsalen, coal tar, pyrithione zinc, salicyclic acid, sulfur, and the like; steroids, such as 2-(acetyloxy)-9-fluoro-1',2',3',4'-tetrahydro-11-hydroxypregna-1,4-dieno-[16,17-b]naphthalene-3, 20-dione and 21-chloro-9-fluoro-1',2',3',4'-tetrahydro-11b-hydroxypregna-1,4-dieno[16z,17-b]naphthalene-3,20-dione. tiny other medication capable of topical administration also SUBSTITUTE SHEET (RULE 26) can be incorporated in a composition of the present invention in an amount sufficient to perform its intended function. Other topically active compounds are listed in Remington's Pharmaceutical Sciences, 17th Ed., Merck Publishing Co., Easton PA (1985), pp. 773-791 and pp. 1054-1058 (hereinafter Remington's), incorporated herein by reference.
The topically active compound also can be an antiacne agent such as benzoyl peroxide, erythro-mycinbenzoyl peroxide, clindamycin, 5,7-dichloro-8-hydroxyquinoline, salicylic acid, sulfur, and the like.
In addition, the topically active compound can be a sunscreen, such as benzophenone-3, benzo-phenone-4, trihydroxycinnamic acid, tannic acid, uric acid, quinine, dihydroxy naphtholic acid, an anthranilate, methoxycinnamate, p-aminobenzoic acid, phenylbenzimidazole sulfonic acid, dioxybenzone, ethyl 4-[bis(hydroxypropyl)] aminobenzoate, glyceryl aminobenzoate, homosalate, menthyl anthranilate, octocrylene, octyl methoxycinnamate, octyl salicyl-ate, oxybenzone, padimate 0, red petrolatum, 4-menthylbenzylidene camphor, benzophenone-1, benzo-phenone-2, benzophenone-6, benzophenone-12, iso-propyl dibenzoyl methane, butyl methoxydibenzoyl-methane, zotocrylene, cinoxate, digalloyl trioleate, benzophenone-8, glyceryl PABA, ethyl dihydroxypropyl PABA, benzophenone-4, and the like. Other sunscreen compounds are listed in CTFA Handbook, pages 86 and 87, incorporated herein by reference.
SUBSTITUTE SHEET (RULE 26) Additional classes of topically active compounds include external analgesics, such as benzyl alcohol, camphor, juniper tar, menthol, methyl salicylate, phenol, and resorcinol;
fragrances, such as the compounds dis-closed in Appendix A;
hair conditioning agents, such as the compounds disclosed in Appendix B
humectants, such as hydroquinone, mercaptopropionic acid, thioglycolic acid, and thiosalicylic acid;
skin protectants, such as allantoin, cal-amine, cocoa butter, dimethicone, petrolatum, and shark liver oil;
ultraviolet light absorbers, such as the compounds disclosed in Appendix Co and skin care agents, such as the compounds disclosed in Appendix D. The identity of the skin care agent is not particularly limited, as long as the agent does not adversely affect the stability or efficacy of the composition. One important class of skin care agents is emollients. Emollients are cosmetic ingredients that help to maintain a soft, smooth, and pliable skin appearance. Emollients .function by remaining on the skin surface or in the stratum corneum to act as. lubricants, to reduce flaking, and to improve skin appearance.
In general, the skin care agent includes polymers, protein derivatives (e. g., derivatized hydrolyzed wheat protein), ethoxylated fatty ethers, and similar skin care agents. For example, suitable SUBSTITUTE SHEET (RULE 26) skin care agents include, but are not limited to, esters comprising an aliphatic alcohol having 2 to about 18 carbon atoms condensed with an aliphatic or aromatic carboxylic acid including 8 to about 20 carbon atoms, e.g., isopropyl myristate, decyl oleate, and cetearyl isononanate. The ester is either straight chained or branched. Preferably, the ester has a molecular weight of less than about 500 and provides emollient properties.
Nonlimiting examples of other skin care agents include, but are not limited to, a methyl , ether of a polyethylene glycol, stearyl methicone, dimethicone copolyol, sorbitan oleate, steareth-2, PEG-7 glyceryl cocoate, a C12-Cao alcohol, canola oil, glyceryl laurate, triglyceryl monostearate, glyceryl monostearate, PPG-2 hydroxyethyl cocamide, mineral oil, petrolatum, and aloe barbadensis. The above skin care agents can be used alone or in admixture.
2. AI110n1C Surfactant ~0 In addition to the topically active com pound, a present composition also contains an anionic surfactant as the primary surfactant. The anionic surfactant is present in an amount of about 0.1o to about 15%, and preferably abo~:t 0.3o to about 80, by weight, of the composition. To achieve the full advantage of the present invention, the composition contains about 0.5o to about 50, by weight, of the anionic surfactant.
Ready-to-use compositions typically con-taro about O.lo to about 20, preferably about 0.30 SUBSTITUTE SHEET (RULE 26) to about 1.5%, and most preferably about 0.5% to about 1%, of an anionic surfactant, by weight of the composition. Concentrated compositions suitable for dilution typically contain greater than about 2%, by weight, of an anionic surfactant.
The amount of anionic surfactant present in the composition is related to the amount and identity of the topically active compound in the composition and to the identity of the surfactant.
The amount of surfactant is determined such that the percent saturation of the topically active compound is at least about 25%, preferably at least about 50%, and most preferably at least about 75%.
The topically active compositions can con-tain 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 having a hydro-philic moiety, such as sulfate, sulfonate, car-bonate, phosphate, or carboxylate. Often, the hydrophobic carbon chain is etherified, such as with ethylene oxide or propylene oxide, to impart a par-ticular 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 sul-fates, alkyl ether sulfonates, sulfate esters of an alkylphenoxy polyoxyethylene ethanol, alpha-olefin sulfonates, beta-alkoxy alkane sulfonates, alkylaryl SUBSTITUTE SHEET (RULE 26) sulfonates, alkyl monoglyceride sulfates, alkyl monoglyceride sulfonates, alkyl carbonates, alkyl ether carboxylates, fatty acids, sulfosuccinates, sarcosinates, octoxynol or nonoxynol phosphates, taurates, fatty taurides, fatty acid amide polyoxy-ethylene 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 refer-ence.
Examples of anionic surfactants include a C8-C18 alkyl sulfate, a Ca-C18 fatty acid salt, a C8-C18 alkyl ether sulfate having one or two moles of ethoxylation, a C$-C18 alkamine oxide, a C8-C1$ alkyl sarcosinate, a C8-C18 sulfoacetate, a Cg-C18 sulfo-succinate, a Cs-C18 alkyl diphenyl oxide disulfonate, a Ce-Cla alkyl carboxylate, a Ca-Cie alpha-olefin sulfonate, a methyl ester sulfonate, and mixtures thereof. The C$-C1$ alkyl group contains eight to eighteen carbon atoms, and can be straight chain (e. g., lauryl) or branched (e. g., 2-ethylhexyl).
The cation of the anionic surfactant can be an alkali metal (preferably sodium or potassium), ammonium, C1-CQ alkylammonium (mono-, di-, tri) , or C1-C3 alkanolammonium (mono-, di-, tri-) . Lithium SUBSTITUTE SHEET (RULE 26) and alkaline earth cations (e.g., magnesium) can be used, but antibacterial efficacy is reduced.
Specific surfactants include, but are not limited to, lauryl sulfates, octyl sulfates, 2-ethylhexyl sulfates, lauramine oxide, decyl sul-fates, tridecyl sulfates, cocoates, lauroyl sar-cosinates, lauryl sulfosuccinates, linear C1o Bi-phenyl oxide disulfonates, lauryl sulfosuccinates, lauryl ether sulfates (1 and 2 moles ethylene oxide), myristyl sulfates, oleates, stearates, ' tallates, cocamine oxide, decylamine oxide, myrist-amine oxide, ricinoleates, cetyl sulfates, and similar anionic surfactants.

3. gydric Solvent and Iiydrotrope The present invention also contains about 0.5o to about 250, by weight, of a hydric solvent, and 0.5o to about 350, by weight, of a hydrotrope.
Preferred embodiments contain about 2o to about 200, by weight, of a hydric solvent and about 3o to about 300, by weight, of a hydrotrope. Most preferred embodiments contain about 5o to about 150, by weight, of a hydric solvent and about 5% to about 250, 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 groups. The term "hydric solvent," therefore, encompasses water-soluble alcohols and diols.
Specific examples of hydric solvents include, but are not limited to, methanol, ethanol, isopropyl SUBSTITUTE SHEET (RULE 26) alcohol, n-butanol, n-propyl alcohol, ethylene glycol, propylene glycol, diethylene glycol, di-propylene glycol, tripropylene glycol, hexylene glycol, butylene gl;~col, PEA 4, and similar hydroxyl-containing compounds.
A hydrotrope is a compound that has the ability to enhance the water solubility of othex compounds. A hydrotrope utilized in the present invention lacks surfactant properties, and typically is a short-chain alkyl aryl sulfonate. Specific examples of hydrotropes includes, but are not limited to, sodium cumene sulfonate, ammonium cumene sulfonate, ammonium xylene sulfonate, potassium toluene sulfonate, sodium toluene sulfonate, sodium xylene sulfonate, toluene sulfonic acid, and xylene sulfonic acid. Other useful hydrotropes include sodium polynaphthalene sulfonate, sodium polystyrene sulfonate, sodium methyl naphthalene sulfonate, and disadium succinate.

4. Carrier The carrier of the composition comprises water.

5. Optional Ingredients A topically active composition of the present invention also can contain optional in-gredients well known to persons skilled in the art.
For example, the composition can contain an optional nonionic or ampholytie surfactant as a cosurfactant.
SUBSTITUTE SHEET (RULE 26) - 3g _ The compositions also can contain other optional ingredients, such as dyes and preserva-tives, that are present in a sufficient amount to perform their intended function and do not adversely affect the efficacy of the composition. Such op-tional ingredients typically are present, individ-ually, from 0% to about 5%, by weight, of the.com-position, and, collectively, from 0% to about 200, by weight, of the composition.
Classes of optional ingredients include, but are not limited to, a nonionic and/or ampholytic cosurfactant, dyes, pH adjusters, ,thickeners, vis-cosity modifiers, buffering agents, foam stabil-izers, 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 stabil izers; gums and polymers as thickening agents; in organic 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;
SUBSTITUTE SHEET (RULE 26) 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 polycar-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 thickening, foam enhancement, and foam stability can be, but is 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.
The topically active compositions can con-tain an optional nonionic cosurfactant. Typically, a nonionic surfactant has a hydrophobic base, such as a long chain alkyl group or an alkylated aryl group, and a hydrophilic chain comprising a suffi-cient 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, poly-ethylene glycol ethers of methyl glucose, polyethyl-ene glycol ethers of sorbitol, ethylene oxidepropyl-SUBSTITUTE SHEET (RULE 26) ene oxide block copolymers, ethoxylated esters of fatty (C8-C1$) 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, C11-15 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-ethylene-20 cetyl ether, polyoxyethylene-10 oleyl ether, polyoxyethylene-20 oleyl ether, an ethoxyl-ated nonylphenol, ethoxylated octylphenol, ethoxyl-ated dodecylphenol, or ethoxylat.ed fatty (C6-C22) alcohol, including 3 to 20 ethylene oxide moieties, polyaxyethylene-20 isohexadecyl ether, polyoxyethyl-ene-23 glycerol laurate, polyoxyethylene-20 glyceryl stearate, PPG-10 methyl glucose ether, PPG-20 methyl glucose ether, polyoxyethylene-20 sorbitan mono-esters, polyoxyethylene-80 castor oil, polyoxy-ethylene-15 tridecyl ether, polyoxyethylene-6 tri-decyl ether, laureth-2, laureth-3, laureth-4, PEG-3 castor oil, PEG 600 dioleate, PEG 400 dioleate, and mixtures thereof.
Numerous other nonionic surfactants are disclosed in McCutcheon's Detergents and Emulsi-fiers, 1993 Annuals, published by McCutcheon Divi-sion, MC Publishing Co. , ,Glen Rock, NJ, pp. 1-246 and 266-272; in the CTFA Tnternational Cosmetic .Ingredient Dictionary, Fourth Ed., Cosmetic, SUBSTITUTE SHEET (RULE 26) _ 41 -Toiletry and Fragrance Association, Washington, D.C.
(1991) (hereinafter the CTFA Dictionary) at pages 1-651; and in the CTFA Flandbobk, at pages 86-94, each incorporated herein by reference.
5- In addition to an optional nonionic co-surfactant, ampholytic and amphoteric surfactants can be used in the topically active compositions as the optional cosurfactant.
Ampholytic surfactants can be broadly de-scribed as derivatives of secondary and tertiary amines having aliphatic radicals that are straight chain or branched, and wherein one of the aliphatic substituents contains from about 8 to 18 carbon atoms and at least one of the aliphatic substituents contains an anionic water-solubilizing group, e.g., carboxy, sulfonate, or sulfate. Examples of com-pounds falling within this description are sodium 3-(dodecylamino)propionate, sodium 3-(dodecylamino)-propane-1-sulfonate, sodium 2-(dodecylamino)ethyl sulfate, sodium 2-(dimethylamino)octadecanoate, disodium 3-(N-carboxymethyldodecylamino)propane-1-sulfonate, disodium octadecyliminodiacetate, sodium 1-carboxymethyl-2-undecylimidazole, and sodium N,N-bis(2-hydroxyethyl)-2-sulfato-3-dodecoxypropylamine.
More particularly, one class of ampholytic surfactants include sarcosinates and taurates having the general structural formula II
Rl-C- i - ( CH2 ) n-Y

SUBSTITUTE SHEET (RULE 26) wherein Rl is C1~ through C21 alkyl, R2 is hydrogen or C1-C2 alkyl, Y is C02M or S03M, M is an alkali metal, and n is a number 1 through 3.
Another class of ampholytic surfactants is the amide sulfosuccinates having the structural formula O S03-Na+
Rl-NHCICH2-CH-C02-Na+
The following classes of ampholytic surfactants also can be used:
iH2CH2'Na+

alkoamphoglycinates fH2CH2-Na+
R1CNHCH2CH~~CH2CO~H

0 alkoamphocarboxyglyciriates iH~CH2C0~-Na+
R1CNHCH~CH~~
CH2CH~OH
alkoamphopropionates SUBSTITUTE SHEET (RULE 26) CH2CH2C02-Na+

CH2CH2oH
alkoamphocarboxypropionates OH
O CH2CHCH2S03-Na+

alkoamphopropylsulfonates R1CINH (CH2) gN+-CH2C02-alkamidopropyl betaines !H3 off R1CNH (CH2) 3 ~+-CH2C'HCH2S03-CH~
alkamidopropyl hydroxysultaine R1NHCH~CH~C -0-Na+
alkylaminopropionates SUBSTITUTE SHEET (RULE 26) CH2CH2C02_ RNH

alkyliminopropionates.
Additional classes of ampholytic surfactants include the phosphobetaines and the phosphitaines.
Specific, nonlimiting examples of ampholytic surfactants useful in the present in-vention are sodium coconut N-methyl taurate, sodium oleyl N-methyl taurate, sodium tall oil acid N-methyl taurate, sodium palmitoyl N-methyl taurate, cocodimethylcarboxymethylbetaine, lauryldimethylcar-boxymethylbetaine, lauryldimethylcarboxyethyl-betaine, cetyldimethylcarboxymethylbetaine, lauryl-bis-(2-hydroxyethyl)-carboxymethylbetaine, oleyl-dimethylgammacarboxypropylbetaine, lauryl-bis-(2-hydroxypropyl)-carboxyethylbetaine, cocoamidodimeth-ylpropylsultaine, stearylamidodimethylpropylsul-taine, laurylamido-bis-(2-hydroxyethyl)-propylsul-taine, disodium oleamide PEG-2 sulfosuccinate, TEA
oleamido PEG-2 sulfosuccinate, disodium oleamide MEA
sulfosuccinate, disodium oleamide MIPA sulfosuc-cinate, disodium ricinoleamide MEA sulfosuccinate, disodium undecylenamide MEA sulfosuccinate, disodium wheat germamido MEA sulfosuccinate, disodium wheat germamido PEG-2 sulfosuccinate, disodium isostear-amideo MEA sulfosuccinate, cocoamphoglycinate, coco-amphocarboxyglycinate, lauroamphoglycinate, lauro-amphocarboxyglycinate, capryloamphocarboxyglycinate, SUBSTITUTE SHEET (RULE 26) cocoamphopropionate, cocoamphocarboxypropionate, lauroamphocarboxypropionate, capryloamphocarboxy-propionate, dihydroxyethyl tallow glycinate, cocamido disodium 3-izydroxypropyl phosphobetaine, 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 monosodium phosphitaine, and mixtures thereof.
In addition, the topically active com-positions of the present invention do not rely upon a low pH or a high pH to provide a rapid reduction in bacterial populations. The topically active com-positions of the present invention can have a pH of about 4 to about 9, but at the two extremes of this pH range, the compositions can be irritating to the skin or damaging to other surfaces contacted by the composition. Accordingly, topically active composi-tions of the present invention preferably have a pH
of about 5 to about 8, and more preferably about 6 to about 8. To achieve the full advantage of the present invention, the topically active compositions have a pH of about 6.5 to about 7.5.
To demonstrate the new and unexpected re-sults~provided by the topically active 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, and to deposit a topically active compound on a surface, were determined. The SUBSTITUTE SHEET (RULE 26) weight percentage listed in each of the following examples represents the actual, or active, weight amount of each ingredient present in the composi-tion. 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) Biphenyl oxide di-sulfonate, Pilot Chemical Co., Santa Fe Springs, CA, CALFAX 10L-45 (active=45.40), 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=38.800), d) Ammonium lauryl sulfate (ALS), Henkel Corp., STANDAPOL A (active level=28.30), e) Ammonium xylene sulfonate (AXS), Stepan Corp., STEPANATE AXS (active=40o), f) Cocamidoprapyl betaine (CAPB), McIntyre Group, Ltd., Chicago, IL, MACKAM 35-HP
(est. 30o active betaine), g) Dipropylene glycol (DPG), Dow Chemical Co., Midland, MI, h) Disodium laureth sulfosuccinate (DSLScct), McIntyre Group, Ltd., MACKANATE EL
(active=33.80) , SUBSTITUTE SHEET (RULE 26) - 47 _ i) Disodium lauryl sulfosuccinate (DSLrylScct), McIntyre Group, Ltd., MACKANATE LO

(active est.= 40s), j) DMDM Hydantoin (DMDM), MacIntyre Group, Ltd., MACKSTAT DM (approx. 55o active), -k) DowFax Hydrotrope Solution (DFX), Dow 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 (99.7a CP/USP), m) Isopropanol (IPA), Fisher Scientific, Pittsburgh, PA, 2-Propanol, HPLC Grade A 451-4, n) Lauramine oxide (LAO), McIntyre Group, Ltd., MACKAMINE LO (active=30.550), o) Liquid Perfume (PF), p) Lithium lauryl sulfate (LLS), Henkel, TEXAPON LLS active=28.80), ( q) Magnesium lauryl sulfate (MLS), Stepan Chemical Co., STEPANOL
MG (active=28.30), 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 0), s) Monoethanolamine (MEA), Dow Chemical Co., t) Monoethanolamine lauryl sulfate (MEALS), Albright & Wilson, Cumbria, England, -EMPICOL LQ 33/F (active=33o), ~ u) Octylphenol ethoxylate, 9-10 moles EO
(TX100), Union Carbide, TRITON-X 100, SUBSTITUTE SHEET (RULE 26) v) PEG-6ME, polyethylene glycol 300 methyl ether, available from Dow Chemical Co., Midland, MI, as MPEG 350 (active=est. 1000), w) Poloxymer 338'(F108), BASF, Wyandotte, MI, PLURONIC F108 (active=est. 1000), x) Potassium cocoate (KCO}, McIntyre Group, Ltd., MACKADET 40-K (active=38.40), 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. 800), aa) Propylene glycol (PG), Dow Chemical Co., USP Grade (active level=99.960), bb) Sodium 2-ethylhexyl sulfate (S2EHS), Henkel, SULFOTEX OA (active=39.680), cc) Sodium C1~-C1g sulfate ( SC12-18S ) , Henkel, TEXAPON zHC needles (active=90.95%), dd) Sodium cocoamphoacetate (SCA), McIntyre Group, Ltd., MACKAM IC-90 (active=approx.
320), ee) Sodium cumene sulfonate (SCS), Stepan Chemical Co., STEPANATE SCS (active=44.60), ff) Sodium decyl sulfate (SDecS}, Henkel, SULFOTEX 110 (active=30.800), 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 EO ISLES-1), Henkel, STANDAPOL ES-1 (active=25.40%), SUBSTITUTE SHEET (RULE 26) - 49 - .
ii) Sodium lauryl ether sulfate, 2 mole EO ISLES-2), Henkel, STANDAPOL ES-2 (active level=
25.71%), jj) Sodium lauryl sulfate/sodium dodecyl sulfate (SLS/SDS), BDH Biochemical, BDH Ltd., Poole, England, ( active=9 9. 0 % ) , kk) Sodium lauryl sulfoacetate (SLSA), Stepan Chemical Co., LANTHANOL LAL (active=72.65%}, 11) Sodium octyl sulfate (SOS), Henkel, STANDAPOL LF (active=32.90%), mm) Sodium salt of NEODOX 23-4 (NDX23-4), Shell Chemical Co., derived from NEODOX 23-4, a compound having a 194 molecular weight chain, 4 moles of EO and a carboxylate group (active=94.2%), nn) Sodium tridecyl sulfate ~(SC13S), Rhodia, Parsippany, NJ, RHODAPON TDS (active=
24.65%), oo) Sodium xylene sulfonate (SXS), Stepan Chemical Co., STEPANATE SXS (active level=40-42%), pp) Triclosan (TCS), IRGASAN DP-300, Ciba Specialty Chemicals Corp., Greensboro, NC (GC assay on lots used=99.8-99.9% active TCS; mp=56.0-58.0 C.), qq) Triethanolamine lauryl sulfate (TEALS), Henkel, STANDAPOL T (active=40.1%), rr) Tripropylene Glycol (TPG), Dow Chem-ical Co., Tripropylene Glycol, ss) Water--Unless otherwise indicated, the water was laboratory deionized (DI) water, tt) Lauramide TEA (LDEA), Mclntyre Group, Ltd., MACKERNIUM L-10 (active=100%), SUBSTITUTE SHEET (RULE 26) uu) 2-Hydroxy-4-methoxybenzophenone (Bph-3), BASF Corp., Olive, NJ, UVINUL M40 (active=100%), vv) dl-a Tocopheryl acetate (VitE-OAc), Roche Vitamins, Inc., Parsippany, NJ, (actives=
1000)o and ww) a-Hexylcinnamaldehyde (AHCALD), Aldrich Chemical Co., Milwaukee, WI (actives=100x).
The following methods were used in the preparation and testing of the examples:
a) Determination of Rapid Germicidal (Time Kill) Activity of Antibacterial Products. The activity of antibacterial compositions~was measured ' 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-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-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-centration from 0-100%. The choice of which con-centration to use is at the discretion of the in-vestigator, and suitable concentrations are readily determined by those skilled in the art. For example, viscous samples usually are tested at 50%
SUBSTITUTE SHEET (RULE 26) dilution, whereas nonviscous samples are not diluted. The test sample is placed in a sterile 250 ml beaker equipped with a magnetic stirring bar and the sample volume is brought to 100 ml, if needed, with sterile deionized water. All testing is per-formed in triplicate, the results are combined, and the average log reduction is reported.
The choice of contact time period also is at the discretion of the investigator. Any contact time period can be chosen. Typical contact times range from 15 seconds to 5 minutes, with 30 seconds and 1 minute being typical contact times. The con-tact temperature also can be any temperature, typically room temperature, or about 25 degrees Celsius.
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 with sterile physiological saline and the population of the bacterial suspension is adjusted to about 108 colony forming units per ml (cfu/ml).
The table below lists the test bacterial cultures used in the following tests and includes the name of the bacteria, the ATGC (American Type Culture Collection) identification~number, and the abbreviation for the name of the organism used hereafter.
SUBSTITUTE SHEET (RULE 26) _ 52 -Organism Name ATCC # Abbreviation Staphylococcus aureus 6538 S. aureus Escherichia coli 11229 E. coli Klebsiella pneumoniae 10031 K. pneum.~

Salmonella choleraesuis 10708 S. cholera S. aureus is a Gram positive bacteria, whereas E.
eolio 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 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 SUBSTITUTE SHEET (RULE 26) cfu/ml for the numbers control and samples, re-spectively, by standard microbiological methods.
The log reduction is calculated using the formula Log reduction=loglo(numbers control)-loglo(test sample survivors).
The following table correlates percent reduction in bacteria population to log reduction:
Reduction Log Reduction ' 99. 9 3 99.99 99. 999 5 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 approx-imately 7.5 grams (g) TCS and 3 liters (L) of water.
The flask then was placed in a water bath, stirred, and heated (40-45°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 Buchner 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 to cool. Typically, fine needles of TCS crystals SUBSTITUTE SHEET (RULE 26) 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 in the study. For other time kill studies, a small amount of crystalline TCS was allowed to remain in the test container to ensure saturation in the event of a temperature change. It was assumed that TCS
crystals present in the time kill test vessel would not affect test results because crystalline TCS is unavailable to act on the bacteria (i.e., is not solubilized).
To determine the concentration of TCS in the water solutions, filtered samples (in tripli-I5 sate) were analyzed by HPLC. The apparatus used to filter the solutions was a Whatman AUTOVIAL~, with 0.45*m PTFE membrane and glass microfiber prefilter, cat. No. AV125UORG. TCS concentrations were calcu-lated.using a linear regression line fit (Microsoft EXCEL~ software) to TCS/IPA standards included on the same HPLC run.
c) Preparation of aqueous TCS/surfactant compositions: A French square bottle was charged with a solution containing a variable concentration of a surfactant and 0.30, by weight, TCS. The mix-ture was stirred and heated (35-40°C) for several hours until the TCS was solubilized. Variable transformer-controlled heat lamps were used for warming and the temperature of the solution was monitored with a digital thermometer. Stirring then was stopped, TCS seed crystals (about 1 mg) were SUBSTITUTE SHEET (RULE 26) added to the solution, and the mixture was allowed to stand at about 20°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 surfac-tant necessary to almost completely solubilize the 0.3o TCS was determined by use of an experimental design in which the concentration of surfactant was serially reduced by a factor of two over a series of test samples until the approximate saturation point of TCS in the surfactant was observed. Then the difference in concentration (saturated vs. just sol-ubilized) was halved until a close endpoint for TCS
saturation could be determined. The saturation point of TCS/surfactant compositions could be effec-tively estimated with small-scale (15 to 100 mL) samples, but about 600-800 g samples were required to obtain reliable final results. The initial ranges, therefore, were established with small-scale samples, and the final concentrations were deter-mined using larger-scale samples.
d} Preparation of compositions contain-ing TCS and a solvent or solvent/hydrotrope combina-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°C to crystallize. In compositions containing a solvent, hydrotrope, and surfactant, the TCS was dissolved in the solvent as above, and then the hydrotrope and SUBSTITUTE SHEET (RULE 26) surfactant were added to the TCS/solvent solution.
The resulting mixture then was diluted to the batch total with water. Adjustment of pH also was 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-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 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-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, California, USA). This method also was used with solutions very near to saturation to enhance ob-servation of small'amounts of crystals formed on the bottom of containers.
e) Preparation~of samples: The prepa-ration of all samples involved equipment arid pro-cedures normally employed in formula development laboratories. All percents were by weight based on the active level of each ingredient.
SUBSTITUTE SHEET (RULE 26) - 57 - . _ f) Summary formula descriptions in example tables: A typical table entry for a test composition is "0.3TCS/SDPG/15SXS/0.75ALS." This entry is defined as 0.3% triclosan (TCS), 5% di-propylene glycol (DPG), 15% sodium xylene sulfonate (SXS), 0.75% ammonium lauryl sulfate (ALS), and the remainder of the formula is water (typically with 0.2%, by total weight, of a citrate/phosphate buffer designed to provide a pH of about 6).
g) Pigskin deposition test: The follow-ing protocol is a general description of how the relative deposition efficiencies of various text compositions were determined. The substrate was pigskin, which is similar to human skin in color and texture, and in having a layer of subcutaneous fat.
Pigskin is well known in the art as a model sub-strate for deposition assays. The test samples (0.03 to 3 grams) first are weighed into 16 mL
vials. The sample size varied depending upon the nature of the test, i.e., different test protocols were used to simulate different rise situations from high dilution to neat application. Next, the pig-skin samples (Brennen Medical, Inc., Mediskin I-Zenoderm, S-10~) were cut into 3/8 inch diameter disks with a punch. If the protocol ~equired addition of water to the sample, a controlled amount of water was added to the sample in the vial just prior to exposure of the pigskin disks to the sample. Typically, the water/sample mix was dis-persed for 15 seconds by agitating the sample with a laboratory vortexer attached to a timer. Four SUBSTITUTE SHEET (RULE 26) _ 58 -pigskin disks then were added, and the vial was agitated for another 30 seconds. The sample/water mixture then was drained with a pipette, and the pigskin was rinsed with 30 second vortexing in like fashion with 3x3 rnL aliquots of distilled water. On the last rinse, any remaining foam was carefully removed with a pipette. The pigskins then were extracted overnight with isopropyl alcohol, and the extracts were analyzed by high pressure liquid chromatography (HPLC) for the amount of active in-gredient extracted. Control/recovery experiments were performed prior to testing to ensure that the isopropyl alcohol extraction procedure could ade-quately dissolve a known amount of active compound from the pigskin disks.
h) Dilution phase stability test: This test provides an indication of the ability of various test compositions to deposit topically act~.ve compounds on the test substrate. It also demonstrated the fundamental difference between the dilution behavior of a present composition and tra-ditional compositions having solubilized actives.
The test was conducted by diluting a given composi-tion with a known amount of water (typically 25:50, 50:50, 75:25; all composition: water proportions weight/weight), then observing the formulation over an extended period of time. The diluted samples were maintained ~at about 22°C to 25°C. The appear-ance of a separate phase (e. g., turbidity, crystals, and/or precipitate) was considered an indication of active compound deposition. As demonstrated by the SUBSTITUTE SHEET (RULE 26) 5g -examples, the compositions typically exhibited a sign of phase separation within about 0.25 to 1 hour after dilution.
i) Volar forearm deposition test: An in vivo deposition test was performed using a small number of volunteer panelists and three sites on the volar forearms. The sites were designated L1, L2, L3, and R1, R2, R3, for left and right arms, respec-tively. Site 1 was closest to the wrist, site 2 was in the middle of the forearm, and site 3 was near the inner elbow.
Sites L3 and R3 were chosen as blank con-trol sites to give baseline values on untreated skin. These sites were treated as follows. A glass sampling device was held over the test site. One ml of isopropyl alcohol was placed on the skin area confined by a glass cylinder, and the area (about ~.5 cma) was scrubbed gently with a smooth glass rod for 60 seconds. When scrubbing was complete, the .isopropyl alcohol extract was transferred to a pre-weighed i6 mL vial using a fine-tipped 1 mL pipette.
Treated sites (L1, L2, R1, and R2) were processed as follows. The skin site was wet by placing the site under running, warm water for about 15 seconds. Test product was applied to the design-nated wet skin site, and the site was scrubbed gently for 30 seconds with the first and second fingers of the panelist's hand, followed by 15 seconds of rinsing with a gentle flow of warm tap water. The site then was gently pat dried with a paper towel, and extracted as above for L3 and R3, SUBSTITUTE SHEET (RULE 26) except three 1 mL extractions were made at each site.
The isopropyl alcohol extracts then were processed as described above in the "Pigskin I7eposi-tion Test" (HPLC analysis). The use of preweighed vials allowed for adjustments to be calculated for small solvent losses encountered in the extraction procedure.
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 o saturation produces a concomitant reduction in time kill efficacy.
SUBSTITUTE SHEET (RULE 26) a s N

O W

~

. y n o0 i.

~-iN

~t1~i N .-1 O

O

H O lD

1~ri Q.
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D

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~

A

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r-1O O O -1p O

r w dl 1~ O

I~O

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u7 /W-1O

r~ (~

O ~ N N

\ ,-iw-1.--i IIIri t~M ~ n'T~r -V O O O Q~N

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CV

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U M ~ ~'t iT o .4 H a~W o rnv~
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Q! m rordrnro ro~n m p, ~ w~
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SUBSTITUTE SHEET (RULE 26) 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.
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. coZi, whereas a sample in Table 3 containing 484 ppm TCS had a log reduction of 4.13 after 15 seconds vs. the same organism. This effect is more apparent at shorter-contact time periods. Another example, in more complex compositions is illustrated in samples in Table 3, 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 log improvement in bacterial reduction after 1 minute. The data in Table 3 also show differences in efficacy when different solvents/hydrotropes are used with approximately the same TCS concentrations.
SUBSTITUTE SHEET (RULE 26) Table 3--TCS
in Solvent and/or Hydrotrope Systems TCS Solvent/ S. aureus E. coli (PPm) Hydrotrope sec. 1 min. sec. !.min.

112 (est) 17$IPA >4.92 >3.56 0 17$IPA 0.42 -0.24 110 (est) 23.85$PG >4.39 2.37 392 40.01$PG 4.971~/30z~>5.17 4.29/30 >9.67 984 41.86$PG >3.96115 >3.46 4.13/15 >4.38 510 42.53~PG >5.17/30 >5.17 9.47/30 >4.67 723 44.20$PG >3.46/15 >3.46 >4.38/15 >4.38 603 45.05$PG >4.69/15 >4.69 4.21/15 >9.65 895 47.52$PG >5.17130 >5.17 4.42130 >4.67 1385 50.00$PG >4.49/15 >9.49 4.45/15 >4.65 0 50.00$PG 0.15/15 0.13 0.25/15 0.26 0 75.00$PG 1.20!15 2.35 0.35/15 1.73 63 5$SXS >4.43 0.96 0 5$SXS 0.33 -0.15 57 5$SCS 3.64 0.80 0 5$SCS -0.05 ~ -0.11 448 test) 20$PG/10$SXS >4.14/30 >4.14 >5.25/30 >5.25 0 20$PG/10$SXS 0.05/30 0.05 1.16/30 1.35 50 (est) 10$PG/5~SXS 3.42 3.18 0 10$PG/5$SXS 0.05 0.35 50 lest) 10$PG/5~SXS 0.59 9.96 0 10$PG/5~SCS -0.03 0.96 502 (est) 14.5$DPG/lO~SXS>3.63/30 >3.63 >4.44/30 >4.44 0 14.5$DPG/lO~SXS0.03/30 0.04 0.26/30 0.17 SUBSTITUTE SHEET (RULE 26) Table 3--TCS
in Solvent and/or Hydrotrope'Systems TCS Solvent/ K. pnetmm. S. chol.

(ppm) Hydrotrope sec. 1 min. sec. l.min.

112 (est) 17%IPA >4.11 >3.79 0 17%IPA 0.89 1.23 110 (est) 23.85%PG

342 40.01%PG 4.33/30 5.29 2.52/30 3.51 984 41.86%PG 2.96/15 >3.44 1.14/15 2.31 510 42.53%PG 4.61/30 >5.64 1.56/30 2.27 723 44.20%PG >3.44/15 >3.44 1.29/15 2.59 603 45.05%PG 2.60/15 4.79 1.79/15 >4.5U

895 47.52%PG 5.26/30 >5.64 2.92/30 4.33 1385 50.00%PG 3.26/15 >5.04 2.69/15 >4.59 0 50.OO~PG 0.54/15 0.63 0.17/15 0.24 0 75,.00%PG 1.98/15 >3.44 1.39/15 3.56 63 S%SXS

0 5%SXS

57 -5% SCS

0 5%SCS ' 448 (est) 20%PG/10%SXS >4.32/30 >9.32 3.17/30 >3.68 0 20%PG/10%SXS 0.22/30 0.37 0.25/30 1.29 50 (est) 10%PG/5%SXS

0 10%PG/5%SXS

50 (est) 10%PG/5%SXS

0 10%PG/5%SCS

502 (est) 14.5%DPG/10%SXS>4.14/30 >4.14 >4.14/30>4_14 0 14.5%DPG/lOoSXS0.34/30 0.39 0.36/30 0.47 log reduction; and seconds SUBSTITUTE SHEET (RULE 26) The 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 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 compositicns having unknown triclosan concentrations, were Jergens Antibacterial (JA) Hand Soap, a product of Andrew Jergens Inc.; Clean and Smooth (CS), a product of Benckiser; and Soft Soap (SSp), a product of Colgate Palmolive.
hog Reduction at 5 minutes (time killj Triclosan S. E. K. S.
Product (~) ~ Saturation3~aureus coli pneum. chol.

A 0.3 100 >4.47 >4.41 >4.36 4.67 JA Unk.z~ Unk. 2.48 0.~~ 0_18 CS Unk. Unk. 2.80 0.00 0.10 --SSp Unk. Unk. 1.62 0.00 0.20 --1) "--" means not tested;
2) "Unk." means Unknown; and 3) "o saturation" means percent saturation of TCS in the 2 5 continuous aqueous phase.
SUBSTITUTE SHEET (RULE 26) Example 1 demonstrates the surprising improvement in log reduction of bacteria populations provided by an inventive composition compared to currently available commercial antibacterial compo-sitions. Thus, an aqueous composition containing triclosan in SLS, at 1000 saturation, offers sig-nificantly greater antibacterial efficacy than any of the three commercial products tested, against Grain positive and against Gram negative microorgan-isms, both of which can present a significant health threat to consumers.
Ex~aple 2 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-tion containing 0.3o triclosan, 1.350 ammonium lauryl sulfate, with the balance being water.
Composition A-1 is 1000 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.
Log Reduction at 5 minutes (time kill) Triclosan S.' E. K. S.
Product (qs) ~ Saturation3'aureus cola pneum. chol.

A-1 0.30 100 >3.61 3.16 >4.39 3.73 A-2 0 0 >3.61 0.25 0.15 0.09 ~5 SUBSTITUTE SHEET (RULE 26) 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.
Composition A-2 has especially poor efficacy against Gram negative organisms. Control of Gram negative organisms is of particular concern to consumers because such organisms present a significant health threat. The excellent broad spectrum activity of composition A-1 clearly shows that the antibacterial activity is unambiguously attributed to the presence of the antibacterial agent in the continuous aqueous phase.
Example 3 In this example, a solvent, (i.e., propyl-ene glycol (PG)) was used to solubilize triclosan in an aqueous carrier. No hydrotrope or surfactant was present. Composition A-3 contained 0.08720 by weight triclosan, 47.5% aqueous PG, and the balance being water. Composition A-3 was 1000 saturated with triclosan and is a composition of the present invention. Test composition A-4 was a "placebo"
consisting of 47.50 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 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 SUBSTITUTE SHEET (RULE 26) further demonstrates that the antibacterial activity of a present composition is unambiguously attribut-able to the presence of the antibacterial agent.
Log Reduction at seconds (time kill) Triclosan S. E. K. S.
Product ('k) $ Saturationsureus coli pneum. chol.

A-3 0.0872 100 >5.17 4.42 5.26 2.92 A-4 0.0 0 ~ 0.15 0.25 0.59 0.17 ~ I I

Example 4 This example illustrates the effect of the 20 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, ampho-I5 te.ric, and nonionic surfactants. The percent satur-ation of TCS in the compositions of this example is at least about 900.
SUBSTITUTE SHEET (RULE 26) _ ~g _ ~
a o ..I

U + + + + +
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+ + + + + +

+ +

W + + + t + o o -1-o 0 o o o 0 o o o O o ~-dl m + + + + + + + + + + + + + +

+ + + + + + + t + +-+ + + + + + + ro t + + + + + + + + + + + + + + + + w +

cn + + + + + + + -1-+ + + + + + + + + o o ~ +

N

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n f-07 p I

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n n ~ ~

v .1.-1 cn.-I cntV + N ~ O ~ ~ N N U
-~

ro.-iO ~ v +~N O N m ro .W n cn W W y~..N

O W ~ ~ ~ ro.I~U +~O .t~LL O .~-Iro-.-1ro .7~.-I7-W- O N 4-db ',.1,roU N -.-iW 1.a~ +~ro 1~v ro~ ~ .-r a~.-14-W--p S.1U L1 .-IN v1N a O -i~

4.Jv1roN ?~ ro~ .-I O b ro ~ .a~ U N 4-,ro .-a a +~x w cn~ u,w cno ~ In-1.~s~rom ,-rw , ~ ~, rov rl cn+~~i w W

cn~,N W .~N ~ ri ro~ ri.-i.rirt ~ ~ .-it~

a G .j..~T5cn>,~-Io cn>,W a >,m .~a.>, m .-i~ ..-1~ > .i U ~ U O tn , , O S-a>, W ~ C1 I~
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~c ~ca z z x + + + + o SUBSTITUTE SHEET (RULE 26) The results summarized above demonstrate, unexpectedly, that antibacterial agents and anionic surfactants form highly effective antibacterial com-positions when the % saturation of antibacterial 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 series, sodium lauryl sulfate and sodium octyl sul-fate yielded high efficacy formulas). The efficacy with respect to the cation also is unexpected (i.e., sodium, ammonium, and triethanolammonium lauryl sul-fates provided high efficacy formulas, whereas lithium and magnesium lauryl sulfates did not).
Exam»le 5 The following table summarizes the effect of surfactant identity on the antibacterial activity of the composition. This example expands upon the data provided in Example 4. The table includes re-suits of tests performed on a wide variety of com-positions containing either anionic surfactants or representative examples containing cationic, anionic/nonionic, amphoteric, and nonionic surfac-tams .
The results demonstrate that various anionic surfactants form highly effective systems.
The surfactants associated with very high activity (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, SUBSTITUTE SHEET (RULE 26) _ 72 _ sodium 2-ethylhexyl sulfate, and lauramine oxide.
However, it is possible that the high activity of ' the lauramine oxide containing composition was due primarily to the surfactant.
Series I (Lauryl Sulfates) demonstrates efficacy effects attributed to the cation. The sodium lauryl sulfate had the highest efficacy, wherein ammonium, monoethanolammonium and tri-ethanolammonium exhibited intermediate efficacy.
Lithium and magnesium sulfates exhibited low efficacy. Potassium lauryl sulfate was not tested because of its low solubility at room temperature.
Comparing Series I (Lauryl Sulfates) and Series II (Other Alkyl Sulfates) shows that efficacy varies within a homologous series (i.e., sodium n-alkyl sulfates). Sodium lauryl sulfate and sodium octyl sulfate yield high efficacy formulas, as does the branched chain surfactant, sodium 2-ethylhexyl sulfate.
The data in Series III (Alkyl Carboxyl-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 Surfactants) confirm observations that ethylene oxide (E0) 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.
SUBSTITUTE SHEET (RULE 26) 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 LAO is attributed to the surfactant alone because of its quasi-cationic character. The remaining surfac-tant/TCS compositions in Series V showed varied activity vs. S. aureus (Gram positive) and very little activity vs. E. coli (Gram negative).
TCS
in Simple Surfactant Systems Active S. aureus E. coli Type Conc. Other Ingredients (30s/1 min.) (30s/1 min.) Series I--Lsuryl Sulfates 1.6~ sodium lauryl Anionic0.3~TCS >3.94/>3.94 4.36/4.36 sulfate (SLS) O~TCS 1.6~ sodium lauryl >3.94/>3.94 1.51/2.96 sulfate (SLS) 1.35 ammonium lauryl Anionic0.3~STCS >3.97/>3.97 1.39/3.95 sulfate (ALS) 0$TCS 1-35~ ammonium lauryl>3.g7/>3.97 -0.07/-0.02 sulfate (ALS) Anionic0.3$TCS 15~ monoethanolamine2.2g/4.03 0.58/2.04 lauryl sulfate (MEALS) Anionic0.3~TCS 1-5~ triethanolamine2.74/3.73 1.3/9.38 lauryl sulfate (TEALS) 1.5g lithium lauryl Anionic0.3~TCS --/4.1 .51/.81 sulfate (LLS) 1.5~ magnesium lauryl Anionic0.~3$TCS --/-- 0.45/0.52 sulfate (MLS) Series II--Other Alkyl Sulfates Anionic0.3sTC5 5~ sodium octyl >4,39/>4.39 >4.B3/>4 sulfate 83 (SOS) .

O~TCS 5~ sodium octyl 1_76/1.81 >4.47/>9 sulfate 47 (SOS) .

Anionic0.3sTCS g.5~ sodium 2-ethylhexyl>4_34/>4.84 >4.47/>4 sulfate (S2EHS~) .

O~TCS 9~5~ sodium 2-ethylhexyl>3_39/>3.39 >4.45/4.35 sulfate (S2EHS) 2.5g sodium decyl Anionic0.3~TCS >4.39/>4.39 0.59/1 sulfate (SdedS) .

2.5~ sodium tridecyl Anionic0.3~TCS 3.24/>3.39 -0.04/0.31 sulfate (SC13S) 1.5~ sodium alkyl Anionic0.3sTCS sulfate, C12-18 2.09/2.85 0.06/0.01 (SC12-18S) SUBSTITUTE SHEET (RULE 26) Ser3.es V--Miscellaneous Suxaotants Cationic 0.3$TCS 1~5~ lauramine oxide>q,25/>4 >4 25 63/>9 (LAO) . .
.

0$TCS 1.5~ lauramine oxide3.55/3 9 (LAO) . .
.

Anionic 0.3$TCS 125$ sodium lauroylq.09/>4.34 -0 sarcosinate (SLSarc) .
.

1.5~ disodium lauryl Anionic 0.3$TCS sulfosuccinate 2.95/4.06 0.02/0.16 (DSLrylScct) Anionic/ 1.25$ disodium laureth Nonionic 0.3$TCS sulfo succinate 1.76/2.68 0.36/0.38 (DSLScct) 1$ sodium lauryl 3.19!3.83 -0 Anionic 0.3$TCS 09/-0 sulfoacetate (SLSA) .
.

2.0~ methyl ester q_6q/>q 0 Anionic 0.3$TCS 54 11/0 sulfonate (MES) . .
.

1.25$ alpha-olefin 1.34/-- 0 Anionic 0.3$TCS 28/0 sulfonate (AOS) .
.

3$ C10 (Linear) sodium Anionic 0.3&TCS diphenyl oxide 2.77/4.04 0.1810.23 disulfonate (L10-45) 1.25$ sodium coco- _0,15/-0.20 -0 Amphoteric0.3$TCS 17/-0 - ~phoacetate (SCA) .
.

Am hoteric0.3gTCS 175$ cocamidopropyl p -0.091-0.03 0 &1 betaine (CAPB) .
.

Nonionic 0.3$TCS 2-5$ alkyl polyflucose -0.10/-0.17 0 (APG) .
.

Example 6 This example illustrates the effect of o saturation of TCS in surfactant compositions (i.e., compositions free of a hydric solvent and hydro-trope). The data summarized in the following table illustrate the effect of o saturation of TCS on the efficacy of TCS in TCS/surfactant/water composi-tions. Two sections of the table (i.e., TCS/ALS
compositions vs. E. coli and TCS/S0S compositions vs. S. aureus) show a substantial decrease in anti-bacterial activity with,decreasing % saturation.
Also, 1000 saturated samples (0.15oTCS/0.67oALS) and (0.15oTCS/4.OoS~S) have an antibacterial activity approaching that of 1000 saturated samples contain-SUBSTITUTE SHEET (RULE 26) ing 0.3o TCS. In these two examples, the effects are seen clearly for organisms wherein the surfac-tant does not show a strong placebo kill effect.
Effect of Rs TCS
Saturation on Antibacterial Efficacy Log Reduction TCS'b/

S. aureus E. Golf K. pnenm.
$Sat n. Surfactant (gOs/lmin) (30s/lm:in)(30s/lmin) 0.30/100 1.35%AL5 >3.97/>3.971.39/3.95 0.27190 1.35%ALS >3.97/>3.970.61/2.89'' 0.21/70 1.35%ALS >3.97/>3.970.37/1.54 0.15/50 1.35%ALS >3.97/>3.970.09/1.17 0.15/100 0.67%ALS >3.97/>3.971.10/3.63 0/0 1.35%ALS >3.97/>3.97-0.07/-0.02 0.30/100 1.60%ALS >3.94/>3.944.36/4.36 0.27/90 1.60%SLS >3.99/>3.944.36/>4.96 0.21/70 1.60%SLS >3.94/>3.944.04/>4.46 0.15/50 1.60%SLS 3.94/>3.94 9.13/>4.46 >

0.15/100 0.80%SLS >3.94/>3.943.17/>4.46 0/0 1.60%SLS >3.94/>3~.941.51/2.96 0.30/100 5.75%SOS 3.39/3.04 >4.44/3.98 0.27/90 5.75%SOS 2.59/3.04 >4.44/>4.44 0.21/70 5.75%SOS 1.59/1.82 >4.44/>4.49 0.15/50 5.75%SOS 0.96/1.43 >4.44/>4.44 0.15/100 4.00%SOS 2.90/3.20 >4.44/>4.44 0/0 5.75%SOS 0.23/0.30 >4.44/>4.44 This example illustrates a composition of the present invention that can be used as a hand cleanser. This example further illt.strates an embodiment of the invention wherein the antibac-terial agent is present in combination with a sur-factant, hydric solvent, and hydrotrope. Composi-tion A-5 contains, by weight, 0.3o triclosan, 0.50 ammonium lauryl sulfate, 20o propylene glycol, and 10o sodium xylene sulfonate, with the balance water.
SUBSTITUTE SHEET (RULE 26) - ~6 - _ Composition A-6, by weight, contains 0.10 triclosan, 0.1250 ammonium xylene sulfonate, 200 propylene glycol, and IOo sodium xylene sulfonate the balance being water. Compositions A-5 and A-6 were 100%
saturated with triclosan. Composition A-7 was a "placebo" containing, by weight, 0.50 ammonium lauryl sulfate, 200 propylene glycol, 100 sodium xylene sulfate, and the balance being water.
Example 7 Log Reduction at seconds (time kill) Triclosan S. E. K, g.
Product(~) ~ Saturation3~aureus coli pneum. chol.

A-5 0.3 100 >3.84 >4.41 3.56 3.26 A-6 0.1 100 >3.84 >4.41 3.82 3.95 A 7 0.0 0 3.22 3.36 0.74 1 77 This example illustrates two important features of the present invention. First, the absolute amount of triclosan, or other antibacterial agent, is less important than the percent saturation of antibacterial agent in the composition. For example, composition A-6 (containing 0.100 tri-closan) was at least as effective as composition A-5 (containing 0.30 triclosan). The important feature is that both compositions were~100o saturated with triclosan. Second, Example 5 also clearly showed that the active antibacterial agent is responsible for the excellent broad spectrum antibacterial activity. Compositions A-5 and A-6 of the invention clearly outperformed the "placebo" composition A-7, which did not contain an active antibacterial agent.
SUBSTITUTE SHEET (RULE 26) _ 77 -Example 8 This example demonstrates that a hydric solvent and hydrotrope can impart activity to an otherwise inactive surfactant and antibacterial agent composition. In the following table, all percentages are by weight, and the balance of all compositions is water. Composition B contains 1.350 ammonium lauryl sulfate (ALS) and 0.3o triclosan (TCS). Composition C contains 1.350 ALS and O.Oo TCS. Composition D contains 0.250 ALS, 14.4a DPG, 10.0% SXS, and 0.3o TCS, and Composition E contains 0.250 ALS, 14.40 DPG, 10.00 SXS with O.Oo TCS.
Compound F contains 2.5o alkyl polyglucoside (APG~') with 0.3o TCS. Compound G contains 0.3s APG, 14.4%
diprcpylene glycol (DPG), 10o sodium xylene sul-fonate (SXS), and 0.3o TCS. Compound H contains 0.3o APG with 14.44 DPG, 10o SXS, and O.Oo TCS.
Composition I contains 1.250 sodium cocoamphoacetate (SCA) and 0.3o TCS. Composition J contains 0.250 SCA, 14.4% DPG, lO.Oo SXS, and 0.3o TCS. Composi-tion IC contains 0.250 SCA, 14.40 DPG, lO.Oo SXS, and 0.0% TCS. Composition L contains 1.75a cocamido-propyl betaine (CAPB) and 0.3o TCS. Composition M
contains 0.250 CAPB, 14.40 DPG, 10o SXS, and 0.30 TCS. Composition N contains 0.250 CAPB, 14.4m DPG, 10% SXS, and O.Oo TCS. Composition O contains 40 octoxynol-9 (TRITON X-100TM, TX100). Composition P
contains 0.750 TX100, 14.40 DPG, lO.Oo SXS, and 0.3%
TCS. Composition Q contains 1.25% sodium lauryl ether sulfate (1 E0, SLES-1) and 0.3o TCS. Composi-SUBSTITUTE SHEET (RULE 26) _ 78 _ tion R contains 0.250 SZES-1, 14.4% DPG, 10.00 SXS, and 0.3o TCS.
Log Reduction (Time Kill) Compo- Tri- Other Satura- S. aureusE. coli sition closan Ingredients tion (30s/60s)(30s/60s) $

>3.97/ 1.39 B 0.3 1.35$ALS 100 >3.g7 3.95 >3.97/ -0.07/
C 0.0 1.35$ALS 0 >3.97 -0.02 0.25%ALS

>3.80/ >4.38/
D 0.3 14.9%DPG 100 >3,80 >4.38 10_0$SXS

0.25$ALS

1.31/ >2.49/
E 0.0 14.4$DPG 100 1.59 >4.38 10.0%SXS

1.19/ >4.69/
F 0.3 2.5$APG 100 1,21 4.69 0.3$APG

>4.6g/ 4.50/
G 0.3 14.4$DPG -100 , >q.69 4.58 10.0$SXS

0.3$APG

1.19/ >4.69/
H 0.0 19.4$DPG 0 1.21 >4.69 I0.0$SXS

I 0. 3 1 .25%SCA --100 -0 15/ -0. 17/

-0.20 -0.15 0.25%SCA, >4.39/ >4.73/
J 0.3 19.4%DPG, 100 >q.39 >4.73 10.0$SXS

0.25aSCA.

0.86/ 2.90/
K 0.0 14.4$DPG, 0 0_8g 4,05 10.0%SXS

L 0.3 1.75$CAPB 100 '009/ 0.21/

-0.03 0.61 0.25~SCA, >q.3g/ >4.73/
M 0.3 14.9$DPG, 100 >q.39 >4.73 10.0%SXS

0.25%SCA, 0.76/ 3.26/
N 0.0 14.4~DPG, 0 0.85 4.69 10.0%SXS

O 0.3 4%TX100 100 0.16/ 0.43/

0.15 0.46 0.75%TX100, 0.53/ 3.59/
P 0.3 14.4~DPG, 100 0.58 >4.73 lO.OUSXS

>4.391 0.41/
Q 0.3 1.25%SLES-1 100 >q,39 0.46 0.25%SLES-1, >q_34/ >4.47/
0.3 14.4%DPG, 100 >q,8q >q_47 10.0~SXS

The results of the time kill tests summarized in the above table very surprisingly show SUBSTITUTE SHEET (RULE 26) - 79 _ 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 compo-sition 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. col.i 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 Jcnown to inactivate phenolic antibacterial agents.
Example 9 This example demonstrates the importance of o saturation in compositions containing a hydric solvent and hydrotrope. As observed in surfactant/-TCS compositions, the relative o 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 anti-bacterial activity is especially apparent with respect to the Gram negative bacterium, K. pneum.
SUBSTITUTE SHEET (RULE 26) - ~0 -CompositionTriclosan Other Ingredients Rs Saturation $

S 0.3 0.25$ALS, 14.4$DPG, 10.0$SXS100 T 0.3 0.50$ALS, 19.9$DPG, 10.0$SXS<S

U 0.3 1.00$ALS, 19.4$DPG, 10.0$SXS<S, T

V 0.0 1.00$ALS, 14.4$DPG, 10.0$SXS0 W 0.3 1.20$ALS, 2.5$DPG, 10.0$SXS100 X 0.3 2.5$ALS, 2.5$DPG, 10.0$SXS<W

Y 0.3 5.0$ALS, 2.5$DPG, 10.0$SXS<W, X

Z 0.0 5.0$ALS, 2.5$DPG, 10.0$SXS0 Log Reduction (Time Kill) S. aureus E. aoli K. pneum. S. chol.
Composition(3ps/60s) (30s/60s) (30s/60s) (30s/60s) S >3.62/>3.62>4.59/>4.592.64/>3.84 >3.85/>3.85 T >3.62/>3.62>4.59/>4.590.43/3.69 >3.85/>3.85 U 1.67/2.31 >4.59/>4.590.89/1.93 3.50/>3.85 , V 1.10/1.29 3.42/9.59 0.28/0.67 2.17/>3.85 W __ __ __ 4.19/4.39 X __ __ __ 2.83/3.99 -__ __ __ 2.39/3.22 __ __ __ 1.80/2.52 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 o saturation of the antibacterial agent in the aqueous phase of a given composition. This example further shows that compositions containing an antibacterial agent, surfactant, hydric solvent, and hydrotrope are effective when a high o saturation of active antibacterial agent is maintained.
Example 10 This example, in conjunction with Example 9, illustrates the effect of o saturation of TCS in SUBSTITUTE SHEET (RULE 26) _ g1 _ compositions containing a hydric solvent, hydro-trope, and surfactant. As previously observed with simple surfactant/TCS compositions, the relative o saturation of the antibacterial agent in the compo-sition also influences the antibacterial activity of a composition containing a hydric solvent and/or a hydrotrope. From the data summarized in the table of Example 9 and the following table, it is clear that a substantial gain in antibacterial efficacy (as measured by a time Jcill test) is associated with an increasing o 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 9 shows the effect of changing the concentration of surfactant while main-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.
In the table of Example 9, the information relating to o saturation is relative because o saturation is difficult to directly calculate. Even using this qualitative data, the effect of o saturation of TCS
is clear from both tables for all organisms tested.
Activity Dependent on $
Saturation of TCS
in Hydric Solvent/Hydrotrope/Surfactant Compositions Log Reduction (Time Kill) Triclosan ~ S. aureus E. coli Other IngredientsSaturation(30s/60s) (30s/60s) 0.413 5oDPG, 15~SXS, 100 >4.55/>4.55>3.81/>3.81 0.75oALS

0.372 S~DPG, 15$SXS, 90 >4.55/>4.553.81/>3.81 0.75$ALS

0.330 S~DPG, 15~SXS, 80 >4.55/>9.553.46/>3.81 0.75$AZS

SUBSTITUTE SHEET (RULE 26) _ 8~ _ Activity Dependent on Rs Saturation of TCS
in Hydric Solvent/Hydrotrope/Surfactant Compositions Log Reduction (Time ' Kill) Triclosan ~ S. sureus E. coli $ Other IngredientsSaturation(30s/60s) (30s/60s) 0.300 5~DPG, 15~SXS, 73 >4.55/>4.553.40/>3.81 0.75~ALS

0.298 S~DPG, 15$SXS, 60 3.02/4.05 2.73/>3.81 0.75$ALS

0.207 S~DPG, 15~SXS, 50 1.96/3.05 2.45/>3.81 0.75$ALS

0.166 5$DPG, 15~SXS, 40 1.94/2.15 2.30/>3.81.

0.75~ALS

0.103 S~DPG, 15~SXS, 25 1.72/1.93 1.34/2.78 ~ . ~

0.75~ALS

EXaIiIIJ~.e ~.
This example illustrates the effect of 5' different levels of hydric solvent and hydrotrope on antibacterial efficacy. In particular, the data summarized below demonstrates the effect of varying the relative amounts of hydric solvent and hydro-trope. It should further be noted that the addition 1Q of a perfume (PF) and/or a preservative (DMDM} to the composition had only a modest effect, if any, on the antibacterial efficacy of the compositions.
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- N N ~no o r r r r r r r r r r o 0 0 0 0 0 c ~r O ~ ~ 0 0 0 ,~~ 0 0 0 0 0 0 o c o o ,-a.-~~ ,-W--r t~' N

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r1 riO O M M M O (nM M M M M M M <''7M M M M M M M

N rti . .

N U o 0 o a o 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 %

O U Ca ~ W U o W C=,C~x H h ~ ~l~ Z O w U U PaW cnH O ~ (Y7U G1W W C7x H h '.~ra~ Z O w SUBSTITUTE SHEET (RULE 26) r ~rv' a~O O

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m '~i n v'n n /~n n O

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n n n n n o O

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.

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H M M M M M M O M M O M O

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o a x cnH ~ ~ 3 x ?aN

U C~ fxcnE-~D ~ g x J-~N f0 SUBSTITUTE SHEET (RULE 26) It was observed that for compositions S, T, and U, the antibacterial activity against S.
aureus and K. pneum. increases, especially, with a decreasing wto of ALS surfactant (i.e., an increase in o saturation of TCS). Compositions CC, HH, MM, and RR demonstrate that about 15o SXS, or more, is preferred to exhibit high activity against K. pneum.
in compositions containing a hydric solvent and a hydrotroee. This observation suggests that the 1Q hydrotroee 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.
Example 12 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 hydrotroee to the amount of antibacterial agent in compositions containing a surfactant, hydric solvent, and antibacterial agent.
A higher percentage of surfactant can reduce the o saturation, and thereby decrease the antimicrobial activity of the composition. On the other hand, a higher percentage of hydrotroee appears to provide a higher activity against certain organisms, like K.
pneum. and S. choler. It is theorized that the higher percentage of hydrotroee 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 SUBSTITUTE SHEET (RULE 26) kill activity. The solvent, therefore, may be acting as both an additive to enhance antimicrobial activity and to provide better physical stability in these compositions.
SUBSTITUTE SHEET (RULE 26) _ 87 _ o m tn v ~r o o r r r 'd O a W W tntnO O ~c N O N C9 OD 07 O , W m . O . N O , 07 v c~V~. M M V C' V V W f~!('~c'~1 H n n a~n n m c'~n n v' n v n O

o \ O \ n \ \ n n \ \ n \ n \ ~ \ \ \
~n .G v \ c~w n ~n\ \ v c' \ o \ o \ r r r \

U .-itDO N W W O r O O v~ N O N 01 ap W pp d!

O M . l0. . y -i . p 01 . n7 V? n O M , ~

n N n M N n n M n ~''7n N n n n C

.-i r ~ .-I,-i o w n 01O COW 01M I~v v M tn N !n Op r N <t' fl1 , C N r ~D01l0. . C . 10 . 01 01 1D M
O n v M v cr cr v m \ O n O n M e-iO n n -1 l0 . n f~ n O N (h crJ
C, c' \ \ \ \ \ \ \ \ \ \ \ \
\

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01 ~

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r . W . . . ~ . . r . . . ,~ . ~
m d c ~-1v~.-ia~~rcrtn~r ~r v ~r v . a . <r m .~ n n n n n n n o d n n n a n ~ n p4H \ o \ a \ \ \ v \ \ n \ \ \
~O

n \ n \
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,am c v a w e~. c,..c.. c~ c v . v , cr W n o n N n n n ~nn n r~ n n n c~ n ~--<r n ~ ~ ~ u r r r r 00 . .

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N

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~ ~n m n o o w A Q o a w w w A

w aso owarL1U t?as ~w ow ao q a o ~ ~' ~ ~r w cp ~ a c a w " ' Ti o o e a v~. asdad d ~ v o . w : :
t w .-~.-I,~ v~v .-~~ ,-~,-y v~ c <r v LT ~ . . v v -i rr ~ C~ Cacnv~cn ,-~.-icn vi cn vi ~ . ~ . . vi H w w a a a ui a a a a w u, ~.,~, ~, w w w w w w w a A r~r.~~Ca . . ~w r~Cwr~wr.Cw.w aw w aw aw a as asw opop~ m cnda dP an an cn otodP ew as da r.~vi r.~r-~
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dP . ~p O -I -1O O O . .

r . O .~rlO O O O .-IO r-IO O O
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cp rd d1 W CnCnV7 U) U7 v1 U1 U7 V7 U1 f~

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r r r r W o m rn u~ ~r o , ~1 a O M ~D N

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ri M N r ~ r N ~ M 10 O O M

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t0 ~,\ \ \ \ \ \ \ \ \ \ \ \ \

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II) O M OD l0 V~ OD M ~ N V .-i l0O

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oa ~ ~ ~ w ~ m dr da do 0 .

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v a z o x SUBSTITUTE SHEET (RULE 26) 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 ,saturation of antibacterial agent in the system.
The relative o saturation (highest to lowest) of the first three~compositions is JJJJ>KKKK>LLLL. Compo-sition KKKK has one-third the amount of TCS as composition JJJJ solubilized in the same level of ALS (0.50), and compositions LLLL contains Oo TCS.
Significant reductions in activity were observed.
with respect to K. pneum. and S. choler. when the relative o saturation of TCS in the composition decreases. It also was observed that when the relative % saturation is essentially equal (i.e., about 1000), the activity remains essentially con-stant 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 o saturation set forth in Example 6.
In addition, a comparison of composition IIII to composition TTTT shows that composition TTTT
contains slightly less ALS (0.9o vs. 1.0% for IIII), the same amount of PG (lO.Oo), and one-half the amount of SXS (S.Oo vs. 10.0% for ITII). Experi-mental observations indicated that compositions IIII
and TTTT were at or near 1000 saturation. However, the log reductions of E. coli were considerably lower (about 4 log) for Composition TTTT. This ob-servation further supports the data set forth in SUBSTITUTE SHEET (RULE 26) Example 7 wherein minimum level of hydrotrope may be needed for a high antibacterial efficacy against at least some Gram negative bacteria.
Example 13 Dilution Tests As described above, this test provides an indication of the ability of various compositions of the present invention to deposit topically active compounds on a test substrate. It also demonstrates that there is a fundamental difference between the dilution behavior of the present compositions and traditional compositions having solubilized actives.
In the table below, Samples 13A through 13F are com-positions of the present invention. Samples 13A
through 13E show indications of phase separation very soon after dilution. Sample 13F phase sep-arated after about 2 weeks. This observation is attributed to Sample 13F having a lower percent saturation of active ingredient than Samples 13A-13E.
SUBSTITUTE SHEET (RULE 26) ~,~,~,~,o b ~

~s~ ~ v G ~ G G +1 UIN N fpt~tnN N tp 'r1'.i-rl-r1ri ? W,~,~ ','.,~t7, 5, .~3 rororordm ~ rt~o cu y 'Ov 'U'C5Ti'~'OTS T3 3 3 3 3 >,M f~N r7N ~ tn~ u1 ~ roN N N N N .--1.-ir-1v-I

v a~a~a~a~o a a a a a a a a a m n m m d m a~m m m m a a w a ~ +~+~+~+~~ +, o o o o +~ w w w w w w w w w ~ ~ ~ ~ rororororom ~om b a +~+~a o v ~ 'oTsw a TsTs v n.ra,a,a,. s~a~a~n~v a~v a~o~ u~

n.a o,a . rorncn~ a~cra,~ ~, tn a m ro~ ~ b a _ ~ U U U

U U U U U U

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w a a a a a a,~,a, a.

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N H H H H H H H H H H H H

M M M O M N M M M M M M

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SUBSTITUTE SHEET (RULE 26) Samples 13G through 13K are examples of active compound solubilized in surfactant alone (ALS). In those samples, the active compound does not phase separate from the composition upon dilution. These samples illustrate a fundamental difference in the present compositions versus surfactant-solubilized actives, i.e., although the TCS is nearly 1000 saturated in Samples 13G-13I
(0.3%TCS/1.35ALS), no phase separation is observed upon dilution. Therefore, percent saturation of topically active compound is one factor in the deposition performance of the present compositions, but not the only factor. The unique ability of the , present composition to phase separate upon dilution is also an important factor. Note also, Samples 13L-130 behave like solubilized active systems in that they do not phase separate on dilution.
Example 14 Deposition Test Using Triclosan (TCS) Examples of the present compositions were tested using the deposition test protocol described above. The mean deposition values were determined and subjected to, statistical analysis (analysis of variance, ANOVA). As indicated in the table below, means with different letters have statistically significant differences at the 95o confidence limit.
Note that four examples of the present composition (Samples 14A-14D) surprisingly have exceptional deposition enhancement over Commercial Product C, and substantial enhancements over Commercial Products A and B. Also note that although Sample SUBSTITUTE SHEET (RULE 26) 14B contains 0.3% TCS and Commercial Product C
contains 0.2% TCS, the improved deposition enhance-ment (12.6 times greater for Example 14B) cannot be expected from the TCS content difference alone (i.e., only 1.5 times more TCS).
Deposition Test Results (TCS) Deposition Relative Sample No. Ingredients loglo (gm/cm2)Deposition 14A 1.OTCS/2.5ALS/0.75CAPB/SDPG/-9.21390a 11.0 14B 0.3TCS/0.75ALS/SDPG/15SXS-9.15786a 12.6 14C 1.OTCS/2.5ALS/0.75CAPB/SDPG/-4.20673a 11.2 15SXS/0.3Fragrance 14D 0.6TCS/1.5ALS/0.75CAPB/SDPG/-4.37245b 7.7 Commercial 1~ TCS -4.45997b 6.3 Product .
A

(PC) Commercial 1$ TCS -4.62448c 4.3 Product B

(SX) Commercial 0.2~ TCS -5.25715d 1.0 Product C

(LD) Note: Means with different letters (3rd column) are significantly different at 95~.
Example 15 Deposition Test Using Triclosan (TCS) A second set of examples of the present compositions was tested using the deposition test protocol described above. The mean~deposition values were determined and are presented as above.
As in Example 14, samples based on the present compositions outperformed the traditional solubil-ized compositions. In this example, deposition enhancement was about fourteen times greater when compositions containing comparable amounts of TCS
were compared (i.e., Example 15C vs. Example 15E, SUBSTITUTE SHEET (RULE 26) and Example 15D vs. Commercial Product C). In addition, this example illustrates the effect of percent saturation on deposition efficacy. It was observed that relative deposition decreases with decreasing relative o saturation. Comparative Sample 15E was a traditional, solubilized active composition having a base formulation very similar to Commercial Product C.
Deposition Test Results (TCS) Mean Deposition RelatiireRelative ~

Sample No. Ingredients loglo SaturationDeposition (9m~~2>

15A 0.35TCS/0.75ALSl-3.98627a 100 30.6 15B 0.30TCS/0.75ALS/-4.07822b 86 24.7 , 2DPG/15SXS .

15C 0.30TCS/0.75ALS/-4.11729b -- 22.6 15D 0.20TCS/0.75ALS/-4.33085c 57 13.8 15E 0.3TCS/5.4ALS/-5,25315d -- 1.7 (Comparative)4.5SLES-2/4LDEA

Commercial 0.2TCS -5.47155e -- 1.0 Product C

(LD) Note: Means with different letters (3rd column) are sig-nificantly different at 95%
Example 26 Deposition Test Using the Sunscreen Benzophenone-3 (BPh-3) The present compositions also were tested for sunscreen deposition. The mean deposition values were determined and are presented as before.
As in earlier examples, samples which are based on the present compositions (i.e., Samples 16A, 16B, SUBSTITUTE SHEET (RULE 26) and 16D-16F) outperformed the traditional, solubil-ized composition (Samples 16C and 16G).
Deposition Test Results (BPh-3) Mean Deposition Relative Sample No. Ingredients loglo (gm/cm2)Deposition 16A 0.075BPh-3/0.75ALS/ -5.03626a 5.1 16B 0.05BPh-3/0.75ALS/ -5.17743b 3.7 ' 16C 0.075BPh-3/5.4ALS/ -5.79745c 1.0 (Comparative)9.5SLES-2/4LDEA

Note:. Means with different letters (3rd column) are sig-nificantly different at 95$
Example 16A Deposition Test Using the Sunscreen, Benzophenone-3 (BPh-3) Deposition Test Results (BPh-3) Mean Deposition Relative Sample No. Ingredients Iogla (gm/cm2)Deposition 16A 0.75BPh-3/0.75ALS/ -6.50234a 1.6 16C 0.075BPh-3/5.4ALS/ -6.71930b 1.0 (Comparative)4.55LES-2/4LDEA

16D 0.3BPh-3/4.5ALS/ -4.83944a 2.5 SDPG/15SXS ' 16E 0.3BPh-3/4.13ALS/ -4.88265a 2.2 16F 0.3BPh-3/6.OALS/ -4.88328a 2.2 16G 0.3BPh-3/5.4ALS/ -5.23377b 1.0 (Comparative)4.5SLE5-2/4LDEA

Note: Means with different letters (3rd column) are sig-nificantly different at 95~
Example 17 Deposition Test Using a Vitamin Derivative, Vitamin E Acetate (VitEOAe) The present compositions also were tested using a vitamin derivative. The mean deposition values were determined and are presented as before, SUBSTITUTE SHEET (RULE 26) except the ANOVA test was not performed in this test. The values are approximate because the HPLC
comparisons were estimated by hand analysis.
Notwithstanding the approximations, the indications are clear that samples are based on the present compositions outperformed the traditional, solubil-ized compositions, i.e., Compare Example 17A to Example 17B, and Example 17C to Commercial Product D.
Deposition Test Results (VitEOAc) Estimated Relative Sample No. Ingredient Deposition 17A 0.15VitE0Ac/12ALS/SDPG/15SXS24.5 17B 0.15 VitEOAc/5.4ALS/4.5SLES-1.0 (Comparative)2/4LDEA

17C 0.10 VitEOAc/12ALS/SDPG/15SXS7.5 Commercial 0.1~ VitEOAc 1.0 Product D

(UMD) Example 18 Deposition Test Using a Perfume Ingredient, alpha-Hexyl-cinnamaldehyde (AHCAhD) The present compositions were also tested using a fragrance ingredient. The mean deposition values were determined and are presented as before.
The sample based on the present compositions (Example 18A) outperformed a traditional, solubil-ized composition (Example 18B).
SUBSTITUTE SHEET (RULE 26) _ 98 _ Deposition Test Results (ACFiALD) ' Mean Deposition Relative Sample No. Ingredient loglo Deposition (gm/ cmz ) 18A 0.3ACHALD/1.35ALS/5DPG/15SXS-4.79393b 6.0 18B 0.3ACHALD/5.9ALS/9.SSLES--5.57978a 1.0 (Comparative)2/4LDEA

Note: Means with different letters (3rd column) are sig-nificantly different at 95~
Example 19 Deposition Test Using Triciosan (TCS) Solubilized,in Solutions of Ammonium I~au 1 Sulfate (AI,S) This examples shows the effect of percent saturation on the ability of the topically active ingredient to deposit on a surface. These results indicate, surprisingly, that for topically active compounds solubilized in surfactant solutions, the relative deposition increases with increasing per-cent saturation.
Deposition of TCS
from Solutions of ALS

EstimatedRelative Deposition of TCS

TCS ~ SaturationRte' Run Run Run Run Run ~S #1 #2 #3 #4 #5 #6 0.3 1.35 100 100 100 100 100 100 100 0.3 2.00 68 95 98.5 62 57 61 59 0.3 2.50 54 95 -- -- -- -- --0.3 5.00 27 88 82.3 47 38 43 40 0.3 10.0014 65 55.4 27 32 25 28 product 0.02/30.03/30.3/2.73/neat0.3/2.70.3/2.7 dose size, g/mL
Hz0 Example 20 Comparison of Pigskin vs.
Volar Forearm Deposition Test Results , This example includes tests showing a comparison of the Pigskin Deposition Test to a Volar SUBSTITUTE SHEET (RULE 26) Forearm Deposition Test, and contains additional examples illustrating improved deposition perfor-mance of compositions of the present invention over traditional compositions. The volar forearm test valielates the pigskin test. Further, the additional examples include a thickened composition that can be dispensed from ordinary packages as opposed to more expensive self-foaming pumps.
In particular, a composition of the pres-ent invention, i.e., Sample 20A, containing 0.975TCS/15SXS/SDPG/2.5AZS/0.75CAPB/0.20 Fragrance plus a pH buffer and colorants, was tested on human forearms. In a separate test, a commercially avail-able hand wash product containing 0.18% TCS was tested. The test results for these tests are illustrated in the table below.
volar Forearm Deposition Results Commercial Product Sample 20A
Site (0.18 TCS) TCS (0.975 TCS) Deposition (g/cm2) TCS Deposition (g/cm2) JLF-L1 4.12E-7 1.48E-5 JLF-R1 4.76E-7 1.29E-5 EPS-L1 3.93E-7 1.32E-5 EPS-R1 3.93E-7 1.26E-5 PSF-L1 1.19E-7 --PSF-R1 2.88E-7 --JLF-L2 4.68E-7 1.82E-5 JLF-R2 7.36E-7 1.94E-5 EPS-L2 7.36E-7 1.82E-5 PSF-L2 1.42E-7 --PSF-R2 2.29E-7 --Average 3.97E-7 1.55E-5 SUBSTITUTE SHEET (RULE 26) Y
For comparison, the samples used in the Volar Forearm Deposition Test were tested using the Pigskin Deposition Test, together with two addi-tional compositions of the present invention, i.e.:
Sample 20B (a thickened composition con-taining I.OTCS/15.OSXS/5.ODPG/2.5ALS/-0.75CAPB/0.8 Natrosol 250 HHR Cs (hydroxy-ethylcellulose polymer)/0.20 Fragrance (plus a pH buffer and colorants); and Sample No. 20C (a composition containing additional skin care ingredients, i.e., 0.46TCS/15.OSXS/5.0DPG/2.97 glycerin/1.0 sodium PCA/0.75ALS/0.75CAPB/0.25 Poly-quaternium-10/0.1 Cetyl Alcohol/0.1 Aloe Barbadensis/(plus fragrance, a pH buffer, preservatives and colorants).
Pigskin TCS
Deposition Results TCS

Relative Deposition Deposition TCS from Volar Relative Adjusted DepositionForearm for Test Sample No. DepositionTCS Content(g/cm2) (g/cmZ) 20A (0.97$ 17.0 3.06 1.99E-5 1.55E-5 TCS/invention) 20C (0:46$ 9.7 3.80 1.15E-5 --TCS/invention) 20B (1.0$ 18.6 3.35 2.18E-5 -- I

TCS/invention) Commercial 1.0 1.0 1.17E-6 3.97E-7 product (0.18$ TCS) 2f' The deposition results for Sample 20A in the pigskin test compared favorably with the data from the in vivo test. However, the pigskin results showed a somewhat higher deposition of the commer-cial product than the in vivo test. This has been attributed to an extraction technique for the pigskin test that may be more aggressive than in the SUBSTITUTE SHEET (RULE 26) in vivo test. Further, lower amounts of topically active compound may be more difficult to extract completely from a surface (i.e., binding "sites" are overwhelmed where more active compound is on the surface). As such, retrieval of most of the sample from a high deposition formula like Sample 20A is expected, whereas complete recovery of the active compound from a low depositing formula, like the commercial product, is not expected, especially if the extraction technique for the in vivo test is less aggressive. The pigskin'deposition test, therefore, has been demonstrated as an effective screening model for deposition performance on human skin.
I5 In addition, it should be noted that all of the three examples of the invention composition deposited the active ingredient in an amount at least three times greater than the commercial product.
The data presented in the above tables show that o saturation of a topically effective compound in a present composition can be directly correlated to a log reduction of bacteria, i.e., to efficacy. For example, as shown in the prior tables, a composition having 50o saturation of TCS
in the aqueous phase demonstrates a Iog 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
75o saturated and a 1000 saturated compositeon exhibited a log reduction of greater than 4.55 (30 SUBSTITUTE SHEET (RULE 26) and 60 seconds) vs. S. aureus (i.e., a log reduction in excess of the detection limit of the assay). The 75o and~100o 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.
In addition, the compositions have an en hanced ability to deposit the topically active com pound on a treated surface, thereby providing an effective residual activity. Prior compositions did not have an.ability to effectively deposit the top-ically active compound, and the topically active compound was removed during the rinsing step, and wasted. The present compositions, therefore, have a dual benefit of a rapid, effective topical effect, and an excellent residual effect.
The topically active compositions of the present invention have several practical end uses, including hand cleansers, mouthwashes, surgical scrubs, body splashes, hand sanitizer gels, hair care products, topical medicaments, skin care products, and similar personal care products. Addi-tional types of compositions include foamed composi-d ons, such as creams, mousses, and the like, and compositions containing organic and inorganic filler SUBSTITUTE SHEET (RULE 26) materials, such as emulsions, lotions, creams, pastes, and the like. The compositions further can be used as an antibacterial cleanser for hard sur-faces, for examp~e, 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 wip-ing article. The wiping article can be used to clean and sanitize skin or inanimate surfaces.
The present 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 reduc-tion of bacteria is important in. view of the typical 15 to ~0 second time frame used to cleanse and sanitize the skin and inanimate surfaces. The com-positions also effectively deposit the topically active compound for a strong residual topical effect.
The present compositions are effective in short contact time because the topically active com-pound is present in the aqueous continuous phase of the composition, as opposed to surfactant micelles.
The active compound, therefore, is available to immediately begin providing a topical effect, and further effectively deposits on the skin, hair, or other surface to provide residual topical efficacy.
' In addition, because the topically effective com-SUBSTITUTE SHEET (RULE 26) pound is in solution as opposed to surfactant micelles, the absolute amount of topically effective compound in the composition can be reduced without adversely affecting efficacy, and the topically active compound is not rinsed from the skin with the surfactant prior to performing its antibacterial function. The topically active compound also is effectively deposited on the skin to provide an excellent residual effect. In addition, the amount of surfactant in the present topically active com-positions typically is low, thereby providing addi-tional environmental benefits.
The following examples illustrate various compositions of the present invention.
Example 21 Hand Wash Composition 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:
Ingredient Weight Percent Triclosan 0.3 Ammonium Zauryl Sulfate 0.75 Dipropylene 61yco1 5.0 , Sodium Xylene Sulfonate 10.0 Fragrance 0.05 Water q.s.

SUBSTITUTE SHEET (RULE 26) 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-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 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 sur-factant:triclosan of 2.5:1, and was at least about 90o saturated with triclosan. The composition was evaluated for antibacterial efficacy against S.
auxeus 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 excel-lent broad spectrum antibacterial activity. Also, the composition was an excellent hand wash composi-tion in an actual use test, providing both good cleansing and a smooth feel to the hands.
Example 22 Body Splash Composition 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:
SUBSTITUTE SHEET (RULE 26) Ingredient Weight Percent Triclosan 0.3 Alkyl Polyglycoside 0.3 Propylene Glycol 14.4 Sodium Xylene Sulfonate 10.0 Ethanol 10.0 Fragrance 0.05 Water q.s.

The composition is prepared by combining the triclosan, propylene glycol, fragrance, and ethanol, and admixing the components until all the triclosan is dissolved, as evidenced by the absence of undissolved solid material. The sodium xylene sulfonate then is added, and the resulting mixture is stirred until the sodium xylene sulfonate is completely dissolved. Finally, the alkyl polyglyco-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 re-duction on the skin of the user.
Example 23 Mouthwash Composition A composition in accordance with the pres-ent invention, suitable for use as a mouthwash, is prepared using the following ingredients in the following weight percentages:
SUBSTITUTE SHEET (RULE 26) Ingredient Weight Percent Triclosan 0.3 Alkyl Polyglycoside 0-3 Propylene Glycol 14.4 Sodium Xylene Sulfonate 10.0 Denatured Alcohol 10.0 Oil of Wintergreen (flavor) 0.05 Water q.s.

The composition is prepared by combining the triclosan, propylene glycol, flavor, and de-natured alcohol, and admixing the components by any 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.
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 de-sirable level of bacterial reduction on the teeth, gums, and tongue of the user.
Example 24 Wet Wipe Composition 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:
SUBSTITUTE SHEET (RULE 26) - 10~ -Ingredient Weight percent Triclosan 0.3 Ammonium Lauryl Sulfate 0.75 Dipropylene 61yco1 5.0 Sodium Xylene Sulfonate 25.0 Water q.s.

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 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.
Example 25 Hand Wash Composition A composition in accordance with the pres-ent invention, suitable for use as a hand wash, was prepared. The composition comprised the following components at the indicated weight percentages:
SUBSTITUTE SHEET (RULE 26) Ingredient i~Teight Percent Triclosan 0.3 Ammonium Lauryl Sulfate 0.75 Dipropylene Glycol 5.0 Sodium Xylene Sulfonate 15.0 water q.s.

The composition was prepared by first admixing the triclosan and dipropylene glycol until homogeneous (about 5 minutes). After the triclosan was completely dissolved, as evidenced by the 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, 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 90o saturated with triclosan. The composition was evaluated for its antibacterial efficacy against S.
aureus, E. coli, K. pneum., and S. cho.Ier. using a time kill test, and a contact time of 30 seconds.
The composition exhibited log reductions of >3.59, >4.49, >3.20, and >4.27 against the four test organ-isms, respectively.
Thus, the composition exhibited an excel-lent broad spectrum antibacterial activity. In addition, the composition was an excellent hand wash composition in an actual use test, providing bath good cleansing and a smooth feel to the hands.
SUBSTITUTE SHEET (RULE 26) 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 18 was compared to the sole example disclosed in W098/01110. In both com-positions, the active antibacterial agent was tri-closan (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 W098/01110 was tested at 50o dilution, in accordance with the test procedure for viscous~com-positions. The following data summarizes the per-cent of active antibacterial agent in each composi-tion at the test dilution (i.e., test dilution is 1000 for the composition of Example 18 and 50o for the example of W098/01110), and the log reduction observed in the time kill test at a contact time of 30 seconds.
Composition~ TCS Log Reduction at 30 seconds S. aureus E. coliK. pneina.S, choler.

Example 0.3 >4.60 >4.50 9.21 >4.68 WO 98/011100.5 3.29 0.29 1:00 0.45 This example demonstrates the superior time kill performance of a composition of the pres-ent invention compared to a prior composition, especially against Gram negative bacteria. 'This superiority is demonstrated even through the compar-SUBSTITUTE SHEET (RULE 26) ative 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 2? 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 25 was compared to a composition disclosed in W096/06152. W096/06152 discloses effective compositions comprising TCS, an anionic surfactant, a hydrot.rope, a hydric solvent, and further comprising an organic acid, specifically citric acid. W096/06152 contains additional pH
adjusting agents, such as monoethanolamine and sodium hydroxide. Further, the examples disclosed in W096/06152 all have a pH of 4 or 9.1, with no examples having a desirable, neutral pH of about 7.
A pH of about 7 is desired for compositions con-tacting skin or inanimate surfaces because composi-tions 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 I of W096/06152 (hereafter referred to as composition 27-A) was prepared. For comparison, composition 27-A was prepared as above, except that the pH was adjusted, to 7 by the addition of further SUBSTITUTE SHEET (RULE 26) monoethanolamine (this composition hereafter re-ferred to as composition 27-B). To provide an additional comparison, the composition of Example 3 of W096/06152 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 27-C). The table below summarizes the results of'a time kill test on the compositions of this example against the bacteria indicated at a contact time of 30 seconds.
Log Reduction at 30 seconds S' E. FC. S.

Composition p8 ~ TCS aureus coli pn~r~. choler.

Example 25 7.1 0.3 >4.54 >4.25 3.67 >4.77 Comparative 4 0.075 -- -- >4.89 --Comparative 7 0.075 -- -- G.07 --Comparative 7 0.15 4.44 2.91 0.28 4.67 This example demonstrates the superior time kill performance of a composition of the pres-ent invention compared to prior compositions, es-pecially with respect to Cram negative bacteria at a pH of about 7. From the data presented in this example, it can be concluded that the compositions of W096/06152 rely substantially on a relatively extreme pH (either 4 or 9, as disclosed) to achieve a desirable, rapid and broad spectrum reduction of bacterial populations. This is in contrast to Example 18 of the present invention, which provides a rapid broad spectrum bacteria kill at the desir-able pH of about 7.
SUBSTITUTE SHEET (RULE 26) Example 28 Antibacterial Composition Containincr PCN~
An antibacterial composition in accordance with the present invention containing p-chloro-m-xylenol (PCMX) as the active antibacterial agent was prepared. The composition contained the following components in the indicated weight percentages:
Ingredient WeigYit Percent PCMX 0.1 Ethanol 13.42 Water q.s.

The composition was prepared by first mix-ing the PCMX and ethanol to completely solubili~e the PCMX (about 5 minutes). After the PCMX was completely dissolved, as evidenced by the absence of undi~ssolved solid material, the water was added, and the composition was stirred until homogeneous (about 5 minutes).
The composition was at least about 90a saturated with PCMX. The composition was evaluated for antibacterial efficacy against S. aureus, E.
c~Ii, K. pneum., and S. choler. using a time kill test. Against S. aureus, the composition exhibited a log reduction of 4.16 in 30 secondse against E.
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 seconds and against S. choler, the composition exhibited a log reduction of >4.04 in 30 seconds.
Thus, the composition exhibited an excellent broad Spectrum antibacterial activity.
SUBSTITUTE SHEET (RULE 26) Example 29 Antibacterial Composition Containing PCI~
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 the indicated weight percentages:
Ingredient Weight Percent PCMX -0.3 Ammonium Lauryl Sulfate O.g Water . . q.s.

10~ The composition was prepared by first com-biasing the PCMX and water, then adding the ammonium lauryl sulfate and mixing the components for such time as to completely admix the components and dis-solve the PCMX (about 2 hours).
The composition was at least about 900 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 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 SUBSTITUTE SHEET (RULE 26) should be imposed as are indicated by the appended claims.
SUBSTITUTE SHEET (RULE 26) Appendix A
Fragrance Compounds Balm Mint Extract Benzyl Cmnamate Acetyl Hexamethyl Baim Mint Oil Benzyl Saticyfate Tetralm Amyl Acetate Bay Oit Bitter Almond Od Amyl Saucyfate Benzaldehyde Calendula-Od Anethole BenzyLAcetate ~ - Camellia Oit Arnse Oil Benzyl Alcohol Camphor 4nnatto Benzyt Benzoate , Caraway 08 Cardamom Oil Juniper Tar Pentadecalactone Carvone Lavender Oit Peppermint Extract Chamomile Oil Leinongrass O~ Pepperinmt Oil Lemon Oil ~ P henethyl Alcohol Cinnamon oa Lovage Oil' ' Pine Oit Citral Maficaria Oit Pine Tar Oil Cloveleaf Oit Menthot~ . Rose Extract Clove 08 Menthyt Acetate Rosemary Oil Coriander Oii Menthyt Lactate Rose Oii Coumari n Menthyl Salicylate Rue Od Cumin Extract Methyldihydrojasmonate Sage Oil p-Cymene Methyl Eugenol Sambucus Extract Dimethyl Brassylate Methyl Rosinate Sambucus Oii Dipentene Nutmeg Oil Sandalwood Oil Ethylene Brassylate Ocotea Cymbarum Oil Sassafras Oil Ethyl Vanillin Olibanum Sweet Marjoram Oil Eucalyptol Olibanum Extract Tar Oil Eucalyptus Oil Orange Extract Tea Tree Oil Eugenol Orange Flower Oil Terpmeol ' Orange Flower Water Thyme Oil Ginger Oil Orange 01 Thymol Gum Benzoin Orange Peel Extract Vanilla Hops OiF Orris Root Extract Van~Iin Isoamyl Acetate Parsley Seed Oil Yarrow Oil SUBSTITUTE SHEET (RULE 26) Appendix B
Hair Conditioning Agents Aliantoin Acetyl MethionineMethionine Ammonium Hydrolyzed Anima!~Methyt Hydroxymethyl Protein Oleyl p~cazolme ~. ACetylated Lanolin Hydroxyethyi Stearam~de-MIPAMineral Oif Acetylated Lanolin AlcoholHydroxytated Lanolin Mmk Oil Acetylated Lanolin RianoteateHyc~oxyphenyi GlycinamideMink Wax D,'hyd~oxyethyi Oleyl Glyclnate Dihydroxyethyl5oya Glycinate OihvdroxvethVt Sovamine Montan Acid wax Dioleate _. : , . . Isobutylated Lanolin Montan Wax Od Steary! Glyanate Isodecvl isononanoate Dihydroxyethyl _ D(hydr_oxyethyl Taeowamine' Caprytoyt Hydrolyzed Oieate Animal Keratin Isononyl isononanoate Amodimethicone '~ ~ ~ ' DihydEoxyethys i allow Isopropyl Lanolate .
Glycinate ' Dimethicone Copalyol Isopropyl Myristate ' Dimethyi Lauramme OleateIsopropyl Palmitate Myristammopropiomc Acid , Disornum Caproamphodiacetate~ Myristoyi Hydrolyzed Animal Protein Disodmm CaproamphodipropvonateAv~~,~l Mynstoyl Sarcosme Disodium Caprytoamphod~acetate Niacin Avocado Oii Unsaponifiables Disodium CapryloamphodlpropionateBalsam Canada N~acinamide Oisodium CocoamphodiacetateBalsam Oregon Nonfat Dry Milk ;

Disodium CocoamohodioroAionate ~~ ~ Norvahne Camauba - ' - Casein , Disodium Isostearoamphod~propionate- Ceresin Disodium Lauroamphod~acetate Coal Tar Disoamm LauroamphodipropionateIsostearoyi Hydrolyzed .. -Animal Protein Disodmm Oleamido MIPA-SuftosucanateJapan Wax Oleamioopropyl D~methytamme Hydrolyzed Disodmm OleoamphodipropionateJojoba Butter Animal Protein Disodium StearoamtahodiacetateJojoba Oil "' ' ..

Jojoba Wax Dried Egg Yolk Juniper Tar Egg Keratin Oleovl Hvdrolvzed Animal Prr~tem Egg Powder Lanolin Egg Yolk Lanolin Alcohol Ethyl Ester of Hydrolyzed Oleyl Lanoiate Animal Protein Ethyl Glutamate Lanolin Linoleate Olive 0d Lanolin OLI Olive Od Unsaponfiables Ethyl Morrhuate Lanolin Rianoleate Ouncury Wax , Ethyl Sennate Lanolin Wax ~~ T~

f Sulfur ~yb~.ly ~

c~lutamic Aad Com p Cydomethicone C12-16 Atcohols Glyceryl Distearate - ' Calaum Pantothenate ~d Glyceryf Lanolate CanaehiVa wax GlycerylTrioctanoate _ _~~;9--- _ Glycery! TriundecanoateLauraminopropionic Acid Paimrtoyl Animal Collagen Amino Acids Glyane Lauroamphodipropiomc Palm~toyt Hydrolyzed Acid Animal Protein Glycol Oleate Lauroyl Hydrolyzed AnimalPalmfto;~i HydPolyzed Protein Milk Protein ~

GI col Ricmoleate Dicapryloyl Cystine DEA
Paim Kemelam~de Henna Extract Diethylaminoethyl PEG-,5Palm Kemelam~de MEA
Laurate Hinowtiol Diethylene TrfcaseihamidePalm Kefneiamide MIPA

Histidine =c: w. ~w ~- -, - , . Panthenoi -Hybrid Saf~ower Oil Lauryl Glycol , Panthenyl Ethyl Ether Hydrogenated Joloba Lauryl Mynstate Panthenyi Ethyl Ether Wax Acetate Hydrogenated Lanolrn Lauryi Palmitate Pantothenic'ACid Hydrogenated Rice Bran Cocaminobutyric Aad ' ' ;
Wax Coa~rninopropionic Add Hydrolyzed Animal Elastin' . CocoamphodipropioriicPEG-5 Hydrogenated Lanolin Acid Hydrolyzed Anunal Keratin~ ' Coco-Hydrolyzed'AnirrialPEG-10 Hydrogenated Lanolin Protein Hydrolyzed Animal Protein_ -- - - . . - PEG-20 Hydrogenated Lan~lw , Hyqrolyzed Casein .-~~r : - ~ PEG-24 Hydrogenated Lanolin ~

Hydrolyzed Human PlacentalLi~oieic ~ACid PEG-30 Hydrogenated:Lanblin Protein Hydrolyzed Silk Linoiei;iic Acid PEG-70 Hyd_rogenated-Lariolin ~

Hydrolysed Soy Protein .bil ' Animal Collagen Nmino Lmseed Aads j Hydrolyzed, Vegetable _ i Animal Elastm Amuio Protein Goconut'Ot ~ . Adds: ~ i Hyctrolyzecj-Yeast . , ~'~>~~'- - j , ~Ariiinal.Keratln _ , Am~io AaCs . T_ry p -:~::=: 1 H dro Metnicone ed Yeast Prbtein l ..~...:._.-: =.... , Y . yz . _. ..:;.; ~' SUBSTITUTE SHEET (RULE
26) Petrolatum Soluble Animal Collagen Phenylalarnne _ Phenyl Tnmethicone Soybean Oil Soybean Oil tJnsaponifiables PPG2-Buteth-3 Spualane PPG-3-Buteth-5 Squalene PPGS-Buteth-7 PPG-7-Buteth-10 Stearyl Alcohol PPG9-8uteth-12 Sutfur PPG12-Buteth-i 6 Sweet Almond Oil PPG-15-Buteth-20 Synthetic Wax PPG-20-Buteth-30 Threonine PPG-24-Buteth-27 Tripaba Panthenol PPG-26-Buteth-26 PPG-28-Buteth-35 PPG-33-Buteth-45 PPG4 Butyl Ether ' PPG5 Butyl Ether PPG9 Butyt Ether PPG14 Butyl Ether Vegetable O~

PPG-15 Butyl Ether Wheat Germamidopropylam~ne Oxide PPG16 Butyl Ether Wheat Germ On PPG-18 Butyl Ether Zetn PPG-22 Butyl Ether Zinc Hydrolyzed Animal Protein PPG-30 Butyl Ether PPG-33 Butyl Ether PPG-40 Butyl Ether pPG53 Butyl Ether Pyridoxine Dicapryfate Pyndoxine Dilaurate Pyndoxine Dioctenoate Pyridoxine Dipalmitate Pyridoxine Tnpalmitate Resorcinol Acetate R~Ge Bran Wax 5afftower Oil Sal~cyhc Acid Senne Sesame Oil Shea Butter Unsaponifiables Shellac Wax Silk SUBSTITUTE SHEET (RULE 26) Apperidix C
Ultraviolet Light Absorbers Allantoin PABA Benzyl Sahcylate Isoamyl p-Methoxyannamate Amsonlc Acid 8omelone Isobutyf PABA

Benzophenone-1 Bumetnzole Isopropylbenzytsahcylate Benzophenone-2 Butyl Metnoxyd~benzoylmethaneIsopropyl Methoxyannamate Benzophenone-3 Butyl PABA Menthyl Antnranlate Benzophenone-4 Cinoxate Menthyl Sahcylate Benzophenone-5 Octoaylene Benzophenone-6 Digalloyl Tnoleate Octnzoie Benzophenone-7 Drometrizole Octyl Dimethyt PABA

8enzophenone-8 Ethyl Dihydroxypropyl PABA Octyl Methoxyannamate Benzophenone-9 Ethyt Dasopropytannamate Octyl Sahcylate Benzophenone-10 Etocrylene PABA

Benzophenone-11 Glycery! PABA

Benzophenone-12 Glycol Sahcylate Tnpaba Panthenol 3-Benzyhdene CamphorHomosalate SUBSTITUTE SHEET (RULE 26) - zoo -Appendix C
Skin Care Agents Acetyl Trioctyl Citrate Dihydrophytosteryl Hydrogenated Lard Glyceride Octyldecanoate Apricot Kernel Oil PEG-6Dihydroxyethyl SoyamineHydrogenated Lard Glycerides Esters Dioleate Arachidyl Propionate Dihydroxyethyl TallowamineHydrogenated Palm Glycerides Oleate Avocado Oil Diisobutyt Adipate Hydrogenated Palm Kernel Glycendes Bay 0~7 Diisocetyl Adipate Hydrogenated Palm Oil Glyceride Behenyl Erucate Diisodecyt Adipate Hydrogenated Palm Oil Glycerides Hisphenyihexamethicone Diisopropyl Adipate Hydrogenated PaIm/Palm Kernel Oit Butyl Acetyl RicinoleateDiisopropyl DilinoleatePEG-6 Esters Butyl Myristate Diisopropyl Sebacate Hydrogenated Polytsobutene Butyl Oleate Diisostearyl Adipate Hydrogenated Soybean Oil Glycendes Butyl Stearate Diisostearyl DilinoleateHydrogenated Soy Glycende C18~6 Aad Glycol Ester Diisostearyl Malate Hydrogenated Tallow Giycende 012-15 Alcohols BenzoateDilauryl Citrate , Hydrogenated Tallow Glycende Citrate 012-15 Alcohols Lactate Dimethicone Copolyoi Hydrogenated Tallow Glycende Lactate 012-15 Alcohols OctanoateDimethiconol Hydrogenated Tallow Glycendes 014-15 Alcohols Dioctyi Adipate Hydrogenated Tallow Glycendes Citrate 015-18 Giycot Dioctyl Dilinoleate Hydrogenated Vegetable Glycende 018-20 Glycol isostearateDioctyl Sebacate , Hydrogenated Vegetable Glycendes 014-16 Glycol Palmitate Dioctyt Succiriate Hydrogenated Vegetable Glycendes Ct 3-14 Isoparaffin Dipropylene Glycol Phosphate , Dibenzoate 013-16 Isoparaffin Ditridecyl Adipate Hydroxytated Lanolin , 020-40 Isoparaf6n Dodecyttetradecanol Hydroxyoctacosanyl Hydroxystearate , 011-15 Pareth-3 Oleate Ethyl Arachidonate Isoamyl Laurate 011-15 Pareth~ Stearate Etnyl Laurate Isobutyl Mynstate 017-15 Pareth-12 StearateEthyl Linoleate Isobutyl Patmitate , 012-15 Pareth-9 HydrogenatedEthyl Linolenate Isobutyl Peiargonate Tallowate 012-15 Pareth-12 Oleate Ethyl Morrhuate Isobutyl Stearate 030-46 PisGne Oil Ethyl Myristate . Isocetyl Alcohol ~

CapryliclCapriGOiglycerylEthyl Palmitate isocetyt Isodecarioate Succinate CapryliGCapric GlyceridesEthyl Pelargonate Isocetyl Palmitate , CaprytidCapriGlsosteanrJAdipicEthyl Persate Isocetyl Stearate Triglycendes Cetearyl Alcohol Ethyl Stearate Isocetyt Stearoyl Stearate Cetearyl Isononanoate Fish Glycerides Isodecyl Hydroxystearate Cetearyl Octanoate Glyceryl Behenate Isodecyl Isononanoate Cetearyl Patmitate Glyceryl Caprate Isodecyl Laurate Cetyl Acetate Glyceryl Caprytate Isodecyf Myristate Cetyi Alcohol Glyceryl Caprylate/CaprateIsodecyl Neopentanoate ' Cetylarachidol Glyceryl Cocoate Isodecyl Oleate Cetyi Esters Glyceryi Dilaurate Isodecyl Paimitate Cetyl Lactate Glyceryl Dioleate lsohexyl Laurate Cetyl Myristate Glyceryl Distearate Isohexyl Palmrtate Cetyt Octanoate Glyceryi Erucate Isononyl Isononanoate Cetyl Paimitate Glyceryl HydroxystearateIsopropyl Isostearate Cetyl Ricinoleate Glyceryl Isostearate Isopropyl Lanolate Cetyt Stearate Glyceryl Lanolate Isopropyl Laurate Coco-Caprylate/Caprate Glyceryf Laurate Isopropyl Linoleate Cocoglycerides Giyceryi Linoleate Isopropyl Metnoxycmnamate Coconut AJCOhoI Glyceryl M.yristate Isopropyl Mynstate Corn Oil PEG-6 Esters Glyceryf Oteate Isopropyl Oleate Cottonseed Glyceride Glyceryi Palmitate Isopropyl Paimrtate Lactate Cottonseed Oil Giyceryl Rianoleate Isopropyl Ricinoleate CyGomethicone Glyceryl SesquioleateIsopropyl Stearate Decyl Alcohol Glyceryi Stearate Isopropyl Tallowate Decyl Isostearate Glyceryl Stearate Isostearyl Alcohol Citrate Decyt Oleate Glyceryl Stearate Isostearyl Benzoate Lactate Decyl Succinate Glyceryl Triacetyl isostearyl Isostearate Hydroxystearate Decyttetradecanot Glyceryl Triacetyl Isostearyl Lactate Ricinoleate Dibutyl Adipate Glyceryl TrioctanoateIsostearyl Neopentanoate , Ditiutyf Sebacate Glyceryt TnundecanoateIsostearyl Palm~tate Di-012-15 Alcohols AdipateGlycol Dioctanoate Isotndecyl Isononanoate Dicapryi Ad~pate Glycol HydroxystearateLaneth-9 Acetate Dicetyl Adipate Glycol Oleate . Laneth-10 Acetate Diethylen2 Glycol DibenzoateGlycol Ricinoleate Lanolin Diet ~yl Palmitoyl AspartateGlycol Stearate Lanolin Alcohol Diethyl:Sebacate Neptyiundecanol Lanolin Oil DihexyLA'dipate Hexyl Laurate Lanolin Wax Dihydrochdlesteryi OctyldecanoateHydrogenated Coco-GlyceridesLard Glycerides SUBSTITUTE SHEET (RULE 26) Laureth-2 Benzoate Octyl Myristate PPG-5 Lanolin Wax Glycende Lauryl Alcohol Octyl Palmrtate PPG-9 Laurate Laury4 Glycol Octyl Pelargonate PPG-4 Lauryt Ether Lauryl Isostearate Octyl Stearate PPG-3 Mynstyl Ether Lauryl Lactate Oleyl Acetate PPG-4 Mynstyl Ether ~ , Lauryl Mynstate Oleyl Alcohol PPG26 Oleate Lauryt Palmitate Oleyl Arachidate PPG-36 Oleate Methyl Acetyl R~cinoleateOleyl Erucate PPG-10 Oleyl Ether Methyl Caproate Oleyl Lanolate . PPG-20 Oleyl Ether Methyl Caprylate Oleyl Myristate PPG23 Oleyl Ether Methyl Caprytate/CaprateOleyl Oleate PPG30 Oleyl Ether Methyl Cocoate Oleyl Stearate PPG-37 Oleyf Ether Methyl DehydroabietatePalm Kernel Alcohol PPG-50 Oleyl Ether Methyl Glucose Ses4uioleatePalm Kernel Glycendes PPG-9-Steareth~

Methyl Glucose SesquistearatePalm Oil Glycerides PPG-1 t Stearyl Ether Methyl Hydrogenated PEGS CapryliGCapnc GlycendesPPG-t 5 Stearyl Ether Rosinate Methyl HydroxystearatePEG-2 Castor Oil Propylene Glycol Isostearate .

Methyl Laurate PEG3 Castor Oil Propylene Glycol Hyd~oxystearate Methyl tinoleate PEG-4 Castor Oil Propylene Glycol Laurate Methyl Myristate PEGS Castor Oil Propylene Glycol Myristate Methyt Oleate PEG-8 Castor Oil Propylene Glycol Mynstyl Ether Methyl Palmftate PEG-9 Castor Oil Propylene Glycol Myristyt Ether Acetate Methyl Pelargonate PEGt 0 Castor Oil Propylene Glycol Oleate Methyl Rianoleate PEG10 Coconut Oil Esters Propylene Glycol Rianoleate Methyl Rosinate PEG-5 Glyceryl TrbsostearatePropylene Glycol Soyate ~ ' Methyl 5tearate PEGS Hydrogenated Castor Propylene Glycol Stearate Od , Mineral Oil PEG7 Hydrogenated Castor Silica Sdylate , Od Mink OiI PEG-5 Hydrogenated Com Soybean 01 Unsapon~hables Gtycendes ' Myreth-3 Caprate PEG8 Hydrogenated Fish Soy Sterol Glycendes Myreth-3 Laurate PEG20 Methyl Glucose 5esqmstearateSoy Sterol Acetate Myreth-3 Mynstate Pentaerythr'ttyl Rosmate Spualene Myreth-3 Palmdate Pentaerythrityt TetraoctanoateStearoxytnmethylsllane Myristyi Alcohol Pentaerythrttyl TetraoleateStearyl Acetate Myristyleccosanol PPG-4-Ceteth-1 Stearyl Alcohol Myristyleicosyl StearatePPG-8-Ceteth-1 Steary! Citrate Myristyl IsostearatePPG-8-Ceteth-2 Stearyl Lactate Myristyl Lactate PPG-10 Cetyl Ether Sucrose Oistearate Myristyl LignoceratePPG10 Cety1 Ether PhosphateSutfunzed Jojoba Oil Myristyl Myristate PPG-28 Cetyt Ether Sunflower Seed Od Glycendes Myristyl NeopentanoatePPG-30 Cetyl Ether Tall Oil Glycendes Myristyloctadecanoi PPG50 Cetyi Ether Tallow Glyceride Myristyl Propionate PPG-17 Dioleate Tallow Glycendes Myristyl Stearate PPG-3 Hydrogenated Castor TndeCyl Alcohol Oil Neopentyl Glycol PPG-30 Isocetyl Ether Trusocetyl Citrate Dicaprate Neopentyl Glycol PPG-5 Lanolate Tnisostea'nn PEG-6 Esters Oioctanoate Nonyl Acetate PPG-2 Lanolin Alcohol EttierTnmethylsdylamodimethicone Octyl AcetoxystearatePPG-5 Lanolin Alcohol EtherTriolem PEG-6 Esters Octyldodecano ! PPG-10 Lanolin Alcohol Tns(Tnbutoxysiloxy)Methylsilane Ether Octyldodecyl NeodecanoatePPG-20 Lanolin Alcohol Undecytpentadeca~oi Ether - -Octy1 HydroxystearatePPG-30 Lanolin Alcohol Vegetable Glycendes Ether Phosphate Octyl Isononanoate PPG-5 Lanolin Wax ~ Wheat Germ Glycendes Adenosine Phosphate Desamido Animal Collagen Hydrolyzed Human Placental Protein Adenosine TriphosphateDicapryloyl Cys4ne Hydrolyzed Mucopolysacchandes Alanine ~ Diethyl Aspartate Hydrolyzed Siik -Albumen Diethylene Tncasemamide Hydrolyzed Soy Protein Aldioxa Diethyl Glutamate Hydrolyzed Vegetable Protein Allantoin Dihydrocholesterol Hydrolyzed Yeast Protein Altantoin Ascorbate Dipalmitoyl Hydroxypro6ne Hydroxylated Lanolin Allantom Biotin Disodium Adenosine Tnphosphate.

Allantoin Calcium Dried Buttermilk Isobutylated Lanolin Pantothenate Oil Allantoin GalacturonicDried Egg Yolk Acid Allantoin GlycyrrhetinicEgg Acid Allantoin PolygalacturonicEgg Oil Isostearyl Diglyceryl Acid Succinate Aloe Egg Yolk Keratin Animal Collagen AmmoEgg Yolk Extract Laneth-4 Phosphate Acids Animal Elastin AminoEthyl Aspartate Laneth-5 Acids Animal Keratin AminoEthyl Ester of Hydrolyzed Acids Animal Protein Arginine. Ethyl Glutamate La~osterol Asparagine Ethyl 5erinate Lard Glycerides Aspartic Acid Ethyl Urocanate SUBSTITUTE SHEET (RULE 26) Ct0-tt Isoparaffin C10-13 Isoparaffin P~92 , PPG-16 Butyl Ether C1 t-12 tsoparaffin PPG-t5 ~ PPG-18 Butyl Ether C11-13 Isoparaffin PPG-17 PPG-22 Butyl Ether C12-14 Isoparaffin PPG-20 PPG24 Butyl Ether Camphor ~ PPG-26 PPG-30 Butyl Ether Glyceryl Lanolate ' p~ PPG-33 Butyl Ether Glyane ppG~ PPG-40 Butyl Ether Glycogen ~ . PPG-2-Buteth-3 PPG53 Butyl Ether PPG-2 Isostearate , PPG-3-Buteth-5 ppG_10 Methyl Glucose Hexamethyldisiloxane ppGS-Buteth-7 Ether ppG20 Methyl Glucose Hexyl Nicotinate PPG-7-Buteth-10 ~ Ether Methyl Glucose Ether Acetate ppG-20 Human Placental ProteinPPG-l2BButeth-26 .
PPG2 tvlyfistyl Ether fkopionate Hyaluronie Acid pp~j ~~~~~20 Pregnenolone Acetate Hydrogenated Animal PPG-20-Buteth-30 Tocophieryl Acetate Glycende ~

Hydrogenated Honey PPG24-Buteth-27 Tocopheryf Linoleate Hydrogenated Palm 01 PPG26-Buteth-26 T,ocoplieryl NicoUnate -Hydrogenated Tallow PPG-28-Buteth-35 Sucanate Betame Tocophieryl Hydrogenated TallowtrimoniumPPG-33-Buteth-45 : TridecyI~SaI~cylate Chlonde ~

Hydrogenated Laneth-5 PPG-4 Butyl Ether Tndecyl Stearate Hydrolyzed'Animal ElastinPPG-5 Butyl Ether Tryptophan ~

Hydrolyzed Animal KeratinPPG9 Butyl Ether . Tyrosine Hydrolyzed Anunal ProteinPPG14 Butyl Ether Undecylenyl Alcohol , Hydrolyzed Casein PPG-15 Butyl Ether Undecylpentadeaanol , Whey Protein Pyridoxine DicaprylateUric Acid ! anic Acid Uro Whole Dry Milk Pyridoxine Dilau~at~ec Witch Hazel, Distillate~ Vegetable Oil pY~doxxir::e Dioctenoate Witch Hazel Extract R etmyl ACetara Pyridoxine Dipalmitate P
i t i Linoleic Acid PEGS Hydrogenated al Lanolin ta e Retinyl n Ribonucleic Acid inolernc Acid PEG-10 Hydrogenated L Lanolin _ PEG-2 Milk Solids Methionine Orotic Acid PEG-6 Soya Sterol 2-Methyl-4-Hydroxypyrrolidme Undecylenate Norvaline Phenylalanine Milk Serum Albumin polyglyceryl-2 LanolinPYhdo~ne T~ipalmrta~C
Alcohol Ether _ Resoranol Aartate Serum Proteins ~ Sutfurized Jojoba Silk Oil ~

, Tall Oil Sterol Acetyiated Castor Oil Acetytated Lanofin Acetylated -Glycol Stearate Acetylated Lanolin Alcohol Acetylated Hydrogenated Cottonseed' Acetylated Lanolin Rtcinoleate Glycende . Acetylated Lard Glycende Acetyiated Hydrogenated Lard Glyceride Acetylated Palm Kemel Glycendes Acetylated Hydrogenated Tallow Glycende Acetylated Sucrose Distearate Acetylated Hydrogenated Tallow Glycerides w Acetylated Hydrogenated Vegetap~le Gfyceride SUBSTITUTE SHEET (RULE 26) Apricot Kernel Oil Hydrogenated Rice Bran Propylene Glycol Diundecanoate Wax .Avocado Oil Hydrogenated Shark Liver Rapeseed Oil 0~4 Avocado Oil UnsaponifiablesHydrogenated Soybean Oil Rapeseed O~I
Unsaponifiables Batyl Alcohol Hydrogenated Tallow Rice Bran Od Batyl Isostearate Hydrogenated Vegetable Rice Bran Wax Od Batyl Stearate Isobutylated Lanolin Oil Safflower Oil Bayberry Wax Isostearyl Erucate Sesame Oil BisphenylhexamethiconeIsostearyl Stearoyl StearateShark LNer Oil Butter ~ Jojoba Butter Shea Butter C18-36 Aad TriglycerideJojoba Oil Shea Butter Unsaponri5ables C30-48 Piscine Oii Jojoba Wax Shellac Wax C10-18 Triglycendes Lanolin Linoleate Soybean Oil CaprytiCiCapnGlsosteariC/AdipicLanolin Ricinoleate Soybean Od Unsaponif~ables Tnglycerides Lard Soy Sterol Acetate Caprylic/CapriclLauricLauryt Stearate Squalane Triglyceride Caprytic/CapridLinoleicLinseed Oil 5tearoxy Dimetn~cone Tnglyceride CapryticJCapnc/StearicMenhaden 0!I Stearyl Caprytate Triglycende CapryliGCapric TriglycerideMethicone Stearyl Caprylate/Caprate Castor 011 Mineral 01 Stearyl Erucate Chaulmoogra Oit Mink 0!t Stearyt Heptanoate Cherry Plt Oil Mink Wax Stearyl Octanoate Cocoa Butter Monnga Oit Stearyl Stearate Coconut Oil Neatsfoot Oil 5tearyl Stearoyl Stearate Cod Liver Oil Octyldodecyl Mynstate Sunflower Seed Oil Coin Oil Octyldodecyl Stearate Sweet Almond Od Cottonseed Oil Octyldodecyl Stearoyl StearateSynthetic Jojoba OU

Dihydrogenated Tallow Oleostearine Synthetic Wax Phthalate Diisostearyl DilinoleateOleyi Lanolate Tall Oil DGinoleic Acid Oleyl Linoleate Tallow Dimethicone Olive Husk Oil Tallow Glycendes Dioctyl Dilinoleate Otnre Oil Tncapnn Ditridecyl Dilmoleate Olnre Oil Unsaponrfiables Trihydroxysteann Egg Oil Paim Kernel Oil Tri~sononanom Erucyl Arachidate Palm Oil Triisopropyl Triiinoleate Erucyl Erucate Paraffin Tnisosteann Ethiodized Oil Peach Kernel Oil Tnisostearyl Tnl~noleate Glyceryl Tribehenate Peanut Oil Tnlaunn Glycol Dibehenate Pengawar Djambi Od Trilauryl Curate Grape Seed Oil Pentadesma Butter Trilnole~c Acid Hazel Nut Oil Pentaerythrityl HydrogenatedTnlinolein Rosmate Hexadecyl Methicone Pentaerythrity! Tetraab~etateTnmethytolpropane Triisostearate Hexanediol Distearate Pentaerythrityl TetrabehenateTnmethylolpropane Triactanoate Hybrid Safflower Oil Pentaerythrityl TetrastearateTnmethylsdoxysilicate Hydrogenated C6-14 Pentahydrosqualene Trimynstin Olefin Polymers Hydrogenated Castor Petrolatum . . Tnoctyt Cstrate Oil Hydrogenated Coconut Phenyl Trimethicone Tnole~h Oil Hydrogenated CottonseedPristane , Tnoleyl Phosphate Oil Hydrogenated Jotoba Propylene Glycol DicaprylateTnpatmitin Oil Hydrogenated Jojoba Propylene.Glycol Dicaprylate/DicaprateTnsteann Wax Hydrogenated Lanolin Propylene Glycol DicocoateTnstearyi Citrate Hydrogenated Lard Propylene Glycol DilaurateVegetable Oil Hydrogenated Menhaden ~ Propylene Glycol DiOCtanoateWalnut Oil Oil Hydrogenated Palm KernelPropylene Glycol D~pelargonateWheat Bran Lipids Oil Hydrogenated Palm OII Propylene Glycol DistearateWheat'Genn Oil Hydrogenated.Peanut~:Oi4 SUBSTITUTE SHEET (RULE 26)

Claims (18)

WHAT IS CLAIMED IS:

1. A topically active composition com-prising (a) about 0.001% to about 5%, by weight, of a topically active compound;
(b) about 0.1% to about 15%, by weight, of an anionic surfactant;
(c) about 0.5% to about 35%, by weight, of a hydrotrope;
(d) about 0.5% to about 25%, by weight, of a water-soluble hydric solvent;
(e) 0% to about 5%, by weight, of a co-surfactant selected from the group consisting of a nonionic surfactant, an ampholytic surfactant, and mixtures thereof; and (f) water, wherein the topically active compound is present in the composition in an amount of at least 25% of saturation concentration, when measured at room temperature.

2. The composition of claim 1 wherein topically active compound is water-insoluble and is selected from the group consisting of an antibac-terial agent, an antidandruff agent, a sunscreen, a medicament, a skin conditioner, a hair conditioner, a vitamin, an emollient, an antioxidant, a fra-grance, an antiacne agent, a skin protectant, an external analgesic, an ultraviolet light absorber, and mixtures thereof.

3. The composition of claim 1 wherein the antibacterial agent is present in an amount of at least 50% of saturation concentration.

4. The composition of claim 1 wherein the antibacterial agent is present in an amount of at least 75% of saturation concentration.

5. The composition of claim 1 comprising about 0.01% to about 1.5% by weight, of the top-ically active compound.

6. The composition of claim 1 wherein the surfactant is present in an amount of about 0.3%
to about 80, by weight of the composition.

7. The composition of claim 1 wherein the anionic surfactant comprises a C8-C18 alkyl sul-fate, 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 C8-C18 alkyl sarcosinate, a C8-C18 sulfoacetate, a C8-C18 sulfosuccinate, a C8-C18 alkyl diphenyl oxide disulfonate, a C8-C18 alkyl carbonate, a C8-C18 alpha-olefin sulfonate, a methyl ester sulfonate, and mixtures thereof.

8. The composition of claim 1 wherein the hydrotrope is present in an amount of about 30 to about 30% by weight.

9. The composition of claim 1 wherein the hydric solvent present in an amount of about 2%
to about 20% by weight.

10. The composition of claim 1 wherein the hydric solvent comprises an alcohol, a diol, a triol, and mixtures thereof.

11. The composition of claim 1 wherein the hydrotrope is selected from the group consisting of sodium cumene sulfonate, ammonium cumene sul-fonate, 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 sul-fonate, disodium succinate, and mixtures thereof.

12. The composition of claim 1 having a pH of about 5 to about 8.

13. The composition of claim 1 comprising about 0.01% to about 0.5%, by weight, of a nonionic surfactant, an ampholytic surfactant, or a mixture thereof.

14. The composition of claim 1 comprising about 0.001 to about 5.0% of a water-insoluble top-ically active compound, about 5o to about 15% di-propylene glycol, about 10% to about 20% sodium xylene sulfonate, about 0.5% to about 5% ammonium lauryl sulfate, and 0% to about 5% cocamidopropyl-betaine.

15. The composition of claim 1 wherein upon dilution of one weight part of the composition with 0.33 to 3 parts of water, by weight, a phase separation is observed within one hour.

16. A method of cleaning a surface and depositing a topically active compound on the surface comprising contacting the surface with a composition of claim 1, then rinsing the composition from the surface.

17. The method of claim 16 wherein the surface is a skin or hair of a mammal.

18. The method of claim 16 wherein the surface is a hard, inanimate surface.