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Patent 2371925 Summary

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(12) Patent: (11) CA 2371925
(54) English Title: ANTIBACTERIAL COMPOSITIONS
(54) French Title: COMPOSITIONS ANTIBACTERIENNES
Status: Deemed expired
Bibliographic Data
(51) International Patent Classification (IPC):
  • A01N 31/16 (2006.01)
  • A01N 25/02 (2006.01)
  • A01N 25/30 (2006.01)
  • A01P 1/00 (2006.01)
  • C11D 3/48 (2006.01)
(72) Inventors :
  • TAYLOR, TIMOTHY J. (United States of America)
  • SEITZ, EARL P., JR. (United States of America)
  • FOX, PRISCILLA S. (United States of America)
(73) Owners :
  • THE DIAL CORPORATION (United States of America)
(71) Applicants :
  • THE DIAL CORPORATION (United States of America)
(74) Agent: SMART & BIGGAR
(74) Associate agent:
(45) Issued: 2009-02-17
(86) PCT Filing Date: 2000-06-08
(87) Open to Public Inspection: 2000-12-28
Examination requested: 2001-12-19
Availability of licence: N/A
(25) Language of filing: English

Patent Cooperation Treaty (PCT): Yes
(86) PCT Filing Number: PCT/US2000/015729
(87) International Publication Number: WO2000/078275
(85) National Entry: 2001-12-19

(30) Application Priority Data:
Application No. Country/Territory Date
09/338,654 United States of America 1999-06-23
09/425,521 United States of America 1999-10-22

Abstracts

English Abstract



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


French Abstract

Compositions antibactériennes à efficacité antibactérienne améliorée, qui contiennent un agent antibactérien phénolique, un tensioactif ou un alcool désinfectant et de l'eau, le degré de saturation de l'agent antibactérien dans une phase aqueuse continue de la composition étant d'au moins 25 %.

Claims

Note: Claims are shown in the official language in which they were submitted.



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CLAIMS:

1. An antibacterial composition comprising:

(a) triclosan as an antibacterial agent at a
concentration of from 0.001% to 5%, by weight;

(b) a surfactant selected from the group
consisting of an anionic surfactant, a nonionic surfactant,
an ampholytic surfactant, and mixtures thereof at a
concentration of from 0.1% to 15%, by weight;

(c) a hydrotrope at a concentration of from 2%
to 30%, by weight;

(d) a water-soluble hydric solvent at a
concentration of from 2% to 25%, by weight; and
(e) water,

wherein the antibacterial agent is present in a
continuous aqueous phase in an amount of at least 50% of
saturation concentration, when measured at room temperature,
the % saturation concentration being expressed as:

% saturation = [C/C s]×100

in which C is the concentration of the antibacterial agent
in the composition and C s is the saturation concentration of
the antibacterial agent in the composition at room
temperature; and

wherein the composition has a pH of from 5 to 8.
2. The composition of claim 1, wherein the amount of
the antibacterial agent present in the aqueous continuous
phase is 75% to 100% of the saturation concentration.


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3. The composition of claim 1, wherein the amount of
the antibacterial agent present in the aqueous continuous
phase is 95% to 100% of the saturation concentration.

4. The composition of any one of claims 1 to 3,
comprising about 0.05% to about 2% by weight, of triclosan.
5. The composition of any one of claims 1 to 4, which
is a ready-to-use composition in which the surfactant is
present in an amount of about 0.3% to about 10%, by weight
of the composition.

6. The composition of any one of claims 1 to 4, which
is a ready-to-use composition in which the surfactant is
present in an amount of about 0.3% to about 3%, by weight of
the composition.

7. The composition of any one of claims 1 to 6,
wherein the surfactant is selected from the group consisting
of a C8-C18 alkyl sulfate, a C8-C18 fatty acid salt, a C8-C18
alkyl ether sulfate having one or two moles of ethoxylation,
a C8-C18 alkamine oxide, a 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 7, wherein the surfactant
is selected from the group consisting of a C8-C18 alkyl
sulfate, a C8-C18 alkamine oxide, and mixtures thereof, and
has a cation selected from the group consisting of sodium,
ammonium, potassium, alkyl (C1-4) ammonium,
dialkyl (C1-4) ammonium, trialkyl (C1-4) ammonium,
alkanol (C1-4) ammonium, dialkanol (C1-4) ammonium,
trialkanol(C1-4)ammonium, and mixtures thereof.


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

10. The composition of any one of claims 1 to 9,
wherein the hydrotrope is present in an amount of about 5%
to about 20% by weight.

11. The composition of any one of claims 1 to 10,
wherein the hydric solvent is present in an amount of
about 5% to about 15% by weight.

12. The composition of any one of claims 1 to 11,
wherein the hydric solvent comprises an alcohol, a diol, a
triol, or a mixture thereof.

13. The composition of any one of claims 1 to 11,
wherein the hydric solvent comprises methanol, ethanol,
isopropyl alcohol, n-butanol, n-propyl alcohol, ethylene
glycol, propylene glycol, glycerol, diethylene glycol,
dipropylene glycol, tripropylene glycol, hexylene glycol,
butylene glycol, 1,2,6-hexanetriol, sorbitol, PEG-4, or a
mixture thereof.

14. The composition of any one of claims 1 to 13,
wherein the hydrotrope is selected from the group consisting
of sodium cumene sulfonate, ammonium cumene sulfonate,
ammonium xylene sulfonate, potassium toluene sulfonate,
sodium toluene sulfonate, sodium xylene sulfonate, toluene
sulfonic acid, xylene sulfonic acid, sodium polynaphthalene
sulfonate, sodium polystyrene sulfonate, sodium methyl
naphthalene sulfonate, disodium succinate, and mixtures
thereof.

15. The composition of any one of claims 1 to 3,
comprising:


-143-

(a) about 0.01% to about 0.5%, by weight, of
triclosan;

(b) about 0.1% to about 5%, by weight, of the
surfactant;

(c) about 5% to about 20%, by weight, of the
hydrotrope; and

(d) about 2% to about 15%, by weight, of the
hydric solvent.

16. The composition of any one of claims 1 to 15,
which has a log reduction against Gram positive bacteria of
at least 2 after 30 seconds of contact, as measured against
S. aureus, and has a log reduction against Gram negative
bacteria of at least 2.5 after 30 seconds of contact, as
measured against E. coli.

17. The composition of any one of claims 1 to 16, for
reducing a bacteria population on a surface.

18. The composition of claim 17, wherein the surface
is a skin of a mammal.

19. The composition of claim 17, wherein the surface
is a hard, inanimate surface.

Description

Note: Descriptions are shown in the official language in which they were submitted.



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ANTIBACTERIAL COMPOSITIONS
FIELD OF THE INVENTION

The present invention is directed to anti-
bacterial compositions, like personal care composi-
tions, including hand sanitizer gels, having im-
proved antibacterial effectiveness. More particu-
larly, the present invention is directed to antibac-
terial compositions comprising an antibacterial
agent and a surfactant or a relatively low amount of
a disinfecting alcohol, and that provide a substan-
tial reduction, e.g., greater than 99%, in Gram
positive and Gram negative bacterial populations
within one minute.

BACKGROUND OF THE INVENTION
Antibacterial personal care compositions
are known in the art. Especially useful are anti-
bacterial cleansing compositions, which typically
are used to cleanse the skin and to destroy bacteria
and other microorganisms present on the skin, espe-
cially the hands, arms, and face of the user.
Another class of antibacterial personal
care compositions is the hand sanitizer gels. This
class of compositions is used primarily by medical
personnel to disinfect the hands and fingers. The
hand sanitizer gel is applied to, and rubbed into,
the hands and fingers, and the composition is al-
lowed to evaporate from the skin. Wiping of the
composition from the skin is not necessary because
the high alcohol content of present-day hand sani-


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tizer gels leads to a fast and essentially complete
evaporation of the composition from the skin.
Antibacterial compositions in general are
used, for example, in the health care industry, food
service industry, meat processing industry, and in
the private sector by individual consumers. The
widespread use of antibacterial compositions 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 antibacte-
rial agent, a surfactant, and various other ingredi-
ents, for example, dyes, fragrances, pH adjusters,
thickeners, skin conditioners, and the like, in an
aqueous carrier. Several different classes of anti-
bacterial agents have been used in antibacterial
cleansing compositions. Examples of antibacterial
agents include a bisguanidine (e.g., chlorhexidine
digluconate), diphenyl compounds, benzyl alcohols,
trihalocarbanilides, quaternary ammonium compounds,
ethoxylated phenols, and phenolic compounds, such as
halo-substituted phenolic compounds, like PCMX
(i.e., p-chloro-m-xylenol) and triclosan (i.e.,
2,4,4'-trichloro-2'hydroxy-diphenylether). Present-
day antimicrobial compositions based on such anti-
bacterial agents exhibit a wide range of antibacte-
rial activity, ranging from low to high, depending


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on the microorganism to be controlled and the par-
ticular antibacterial composition.
Hand sanitizer gels contain a high per-
centage of an alcohol, like ethanol. At the high
percent of alcohol present in the gel, the alcohol
itself acts as a disinfectant. In addition, the
alcohol quickly evaporates to obviate wiping or
rinsing skin treated with the sanitizer gel. Hand
sanitizer gels containing a high percentage of an
alcohol, i.e., about 40% or greater by weight of the
composition, however, have a tendency to dry and
irritate the skin.
Most commercial antibacterial 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 mi-
croorganisms. The log reduction, or alternatively
the percent reduction, in bacterial populations
provided by the antibacterial composition correlates
to antibacterial activity. A log reduction of 3-5
is most preferred, a 1-3 reduction is preferred,
whereas a log reduction of less than 1 is least
preferred, for a particular contact time, generally
ranging from 15 seconds to 5 minutes. Thus, a
highly preferred antibacterial composition exhibits
a 3-5 log reduction against a broad spectrum of
microorganisms in a short contact time. Prior dis-
closures illustrate attempts to provide such anti-
bacterial compositions, which, to date, do not pro-
vide the rapid, broad range control of microorgan-
isms desired by consumers.


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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. This is especially the case for hand
sanitizer compositions which typically are not wiped
or rinsed from the skin after use. It has been
difficult to impossible to achieve a high log reduc-
tion using an antibacterial composition having a
neutral pH of about 5 to about 8, and especially
about 6 to about 8, without simultaneously incorpo-
rating a high percentage of an alcohol.
For example, WO 98/01110 discloses compo-
sitions comprising triclosan, surfactants, solvents,
chelating agents, thickeners, buffering agents, and
water. WO 98/01110 is directed to reducing skin
irritation by employing a reduced amount of
surfactant.
Fendler et al. U.S. 5,635,462 discloses
compositions comprising PCMX and selected surfac-
tants. The compositions disclosed therein are de-
void of anionic surfactants and nonionic surfac-
tants.
WO 97/46218 and WO 96/06152 disclose com-
positions based on triclosan, organic acids or
salts, hydrotropes, and hydric solvents.
EP 0 505 935 discloses compositions con-
taining PCMX in combination with nonionic and an-
ionic surfactants, particularly nonionic block co-
polymer surfactants.


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


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European Patent Application 0 604 848
discloses a gel-type hand disinfectant containing an
antimicrobial agent, 40% to 90% by weight of an
alcohol, and a polymer and a thickening agent in a
combined weight of not more than 3% by weight. The
gel is rubbed into the hands and allowed to evapor-
ate to provide disinfected hands. As illustrated in
EP 0 604 848, the amount and identity of the anti-
bacterial agent is not considered important because
the hand sanitizer gels contain a high percentage of
an alcohol to provide antibacterial activity. The
disclosed compositions often do not provide immedi-
ate sanitization and do not provide residual anti-
bacterial efficacy.
Prior disclosures have not addressed the
issue of which composition ingredient in an antibac-
terial composition provides bacterial control.
Prior compositions also have not provided an effec-
tive, fast, and broad spectrum control of bacteria
at a neutral pH of about 5 to about 8, and espe-
cially at about 6 to about 8.
An efficacious antibacterial composition
has been difficult to achieve because of the proper-
ties of the antibacterial agents and the effects of
a surfactant on an antibacterial agent. For exam-
ple, several active antibacterial agents, like phe-
nols, have an exceedingly low solubility in water,
e.g., triclosan solubility in water is about 5 to 10
ppm (parts per million). The solubility of the
antibacterial agent is increased by adding surfac-
tants to the composition. However, an increase in
solubility of the antimicrobial agent, and in turn,
the amount of antibacterial agent in the composi-


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tion, does not necessarily lead to an increased
antibacterial efficacy.
Without being bound to any particular
theory, it is theorized that the addition of a
surfactant increases antimicrobial agent solubility,
but also typically reduces the availability of the
antibacterial agent because a surfactant in water
forms micelles above the critical micelle concentra-
tion of the surfactant. The critical micelle con-
centration varies from surfactant to surfactant.
The formation of micelles is important because mi-
celles have a lipophilic region that attracts and
solubilizes the antibacterial agent, and thereby
renders the antibacterial agent unavailable to imme-
diately contact bacteria, and thereby control bacte-
ria in short time period (i.e., one minute or less).
The antibacterial agent solubilized in the
surfactant micelles will control bacteria, but in
relatively long time frames. The antibacterial
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, antibacterial agent that is
solubilized in the micelle is readily washed from
the skin during the rinsing process, and is not
available to deposit on the skin to provide a resid-


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ual antibacterial benefit. Rather, the antibacte-
rial agent is washed away and wasted.
With respect to sanitizers, hand sanitizer
gels typically contain: (a) at least 60% by weight
ethanol or a combination of lower alcohols, such as
ethanol and isopropanol, (b) water, (c) a gelling
polymer, such as a crosslinked polyacrylate mate-
rial, and (d) other ingredients, such as skin condi-
tioners, fragrances, and the like. Hand sanitizer
gels are used by consumers to effectively sanitize
the hands, without, or after, washing with soap and
water, by rubbing the hand sanitizer gel on the
surface of the hands. Current commercial hand
sanitizer gels rely on high levels of alcohol for
disinfection and evaporation, and thus suffer from
disadvantages. Specifically, current hand sanitizer
gels have a tendency to dry and irritate the skin
because of the high levels of alcohol employed in
the compositions. Also, because of the volatility
of ethyl alcohol, the primary active disinfectant
does not remain on the skin after use, thus failing
to provide a persistent, or residual, antibacterial
effect.
At alcohol concentrations below 60%, ethyl
alcohol is not recognized as an antiseptic. Thus,
in compositions containing less than 60% alcohol, an
additional antibacterial compound must be present to
provide antibacterial activity. Prior disclosures,
however, have not addressed the issue of which com-
position ingredient in such an antibacterial compo-
sition provides bacterial control. Therefore, for
formulations containing a reduced alcohol concentra-
tion, the selection of an antibacterial agent that


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provides both a rapid antibacterial effect and a
persistent antibacterial benefit is difficult.
Prior compositions also have not provided an effec-
tive, fast, and broad spectrum control of bacteria
at a neutral pH of about 5 to about 8, and espe-
cially at about 6 to about 8.
Accordingly, a need exists for an antibac-
terial composition that is highly efficacious
against a broad spectrum of Gram positive and Gram
negative bacteria in a short time period, and
wherein the antibacterial activity is attributed
primarily, or solely, to the presence of the active
antibacterial agent in the composition. The present
invention is directed to such antibacterial composi-
tions.

SiTNIIMARY OF THE INVENTION

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


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is present in an amount of at least 25% of satura-
tion, when measured at room temperature.
In another embodiment, the present inven-
tion relates to antimicrobial compositions contain-
ing an active antibacterial agent, a disinfecting
alcohol, a gelling agent, and water, wherein the
antibacterial agent is present in an amount of at
least 50% of saturation, when measured at room tem-
perature. The present invention also relates to
antimicrobial compositions containing an active
antibacterial agent, a disinfecting alcohol, a gel-
ling agent, a hydrotrope, and water, wherein the
antibacterial agent is present in an amount of at
least 25% of saturation, when measured at room tem-
perature.
Accordingly, one aspect of the present
invention is to provide a liquid, antibacterial
composition comprising: (a) about 0.001% to about
10%, by weight, of an antibacterial agent; (b) about
0.1% to about 40%, by weight, of a surfactant se-
lected from the group consisting of a C8-Cla alkyl
sulfate, a C$-C18 fatty acid salt, a C8-C18 alkyl ether
sulfate having one or two moles of ethoxylation, a
C8-C18 alkamine oxide, a C8-C18 alkyl sarcosinate, a
C8-C18 sulfoacetate, a Ce-C18 sulfosuccinate, a C$-C18
alkyl diphenyl oxide disulfonate, a CB-C18 alkyl
carbonate, a C8-C18 alpha-olefin sulfonate, a methyl
ester sulfonate, and mixtures thereof; and (c) wa-
ter, wherein the antibacterial agent is present in
the composition in an amount of at least 50% of
saturation concentration, when measured at room
temperature.


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Another aspect of the present invention is
to provide an alternative embodiment of the antibac-
terial composition, wherein the composition com-
prises:

(a) about 0.001% to about 10%, by weight,
of an antimicrobial agent;
(b) about 0.1% to about 40%, by weight,
of a surfactant selected from the group consisting
of an anionic surfactant, a cationic surfactant, a
nonionic surfactant, an ampholytic surfactant, and
mixtures thereof;
(c) about 0% to about 30%, by weight, of
a hydrotrope;
(d) about 0% to about 25%, by weight, of
a water-soluble hydric solvent; and
(e) water,
wherein the composition contains at least
one of the hydrotrope and hydric solvent, and
wherein the antimicrobial agent is present in the
composition in an amount of at least 25% of satura-
tion concentration, when measured at room tempera-
ture.
Still another aspect of the present inven-
tion is to provide another alternative embodiment of
the antibacterial composition, wherein the composi-
tion comprises:
(a) 0.001% to about 10%, by weight, of an
antimicrobial agent;
(b) 0 to about 10%, by weight, of a
surfactant selected from the group consisting of an
anionic surfactant, a cationic surfactant, a
nonionic surfactant, an ampholytic surfactant, and
mixtures thereof;


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(c) 0% to about 40%, by weight, of a
hydrotrope;
(d) 0% to about 60%, by weight, of a
water-soluble hydric solvent; and
(e) water,
wherein the composition contains at least
one of the hydrotrope and hydric solvent in an
amount sufficient to solubilize the antimicrobial
agent, and wherein the antimicrobial agent is pres-
ent in the composition in an amount of at least 25%
of the saturation concentration, when measured at
room temperature.
Another aspect of the present invention is
to provide a liquid, antibacterial composition com-
prising: (a) about 0.05% to about 5%, by weight, of
an antibacterial agent; (b) about 1% to about 40%,
by weight, of a disinfecting alcohol, like a C1_6
alcohol; (c) about 0.01% to about 5% by weight of a
gelling agent, like a colloidal or a polymeric gel-
ling agent; and (d) water, wherein the antibacterial
agent is present in the composition in an amount of
at least 50% of saturation concentration, when mea-
sured at room temperature.
Still another aspect of the present inven-
tion is to provide an alternative embodiment of the
antibacterial composition, wherein the composition
comprises:
(a) about 0.05% to about 5%, by weight,
of an antimicrobial agent;
(b) about 1% to about 40%, by weight, of
a disinfecting alcohol;
(c) about 0.01% to about 5%, by weight,
of a gelling agent;


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(d) 0.1% to about 30%, by weight, of a
hydrotrope; and
(e) water,
wherein the antimicrobial agent is present
in the composition in an amount of at least 25% of
saturation concentration, when measured at room
temperature.
Still another aspect of the present inven-
tion is to provide another alternative embodiment of
the antibacterial composition, wherein the composi-
tion comprises:
(a) 0.05% to about 5%, by weight, of an
antimicrobial agent;
(b) about 1% to about 40%, by weight, of
a disinfecting alcohol; and
(c) water,
wherein the composition contains the dis-
infecting alcohol and an optional polyhydric solvent
in an amount sufficient to solubilize the antimi-
crobial agent, and wherein the antimicrobial agent
is present in the composition in an amount of at
least 25% of the saturation concentration, when
measured at room temperature.
Yet another aspect of the present inven-
tion is to provide an antibacterial composition that
exhibits a log reduction against Gram positive bac-
teria (i.e., S. aureus) of at least 2 after 30 sec-
onds of contact.
Still another aspect of the present inven-
tion is to provide an antibacterial composition that
exhibits a log reduction against Gram negative bac-
teria (i.e., E. coli) of at least 2.5 after 30 sec-
onds of contact.


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Another aspect of the present invention is
to provide an antibacterial composition that exhib-
its a substantial log reduction against Gram posi-
tive and Gram negative bacteria, and has a pH of
about 5 to about 8.
Another aspect of the present invention is
to provide consumer products based on an antibacte-
rial composition of the present invention, for exam-
ple, a skin cleanser, a body splash, a surgical
scrub, a wound care agent, a hand sanitizer gel, a
disinfectant, a mouth wash, a pet shampoo, a hard
surface sanitizer, and the like.
A further aspect of the present invention
is to provide a method of reducing the Gram positive
and/or Gram negative bacteria populations on animal
tissue, including human tissue, by contacting the
tissue, like the dermis, with a composition of the
present invention for a sufficient time, such as
about 15 seconds to 5 minutes, to reduce the bacte-
ria level to a desired level, and to provide a re-
sidual control of bacteria levels. The composition
can be wiped or rinsed from the skin. In some em-
bodiments, the composition is allowed to remain on
the skin until the volatile components of the
composition evaporate.
The above and other novel aspects and
advantages of the present invention are illustrated
in the following, nonlimiting detailed description
of the preferred embodiments.


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DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
Personal care products incorporating an
active antibacterial agent have been known for many
years. Since the introduction of antibacterial
personal care products, many claims have been made
that such products provide antibacterial properties.
However, to be most effective, an antibacterial
composition should provide a high log reduction
against a broad spectrum of organisms in as short a
contact time as possible. It also would be benefi-
cial if the antibacterial compositions provided a
residual bacterial control.
As presently formulated, commercial liquid
antibacterial soap compositions provide a poor to
marginal time kill efficacy, i.e., rate of killing
bacteria. Table 1 summarizes the kill efficacy of
commercial products, each of which contains about
0.2% to 0.3%, by weight, triclosan (an antibacterial
agent), and a surfactant.
Table 1
Time Kill Efficacy of Commercial Liquid Hand Soaps
Organism
(Log Reductions after
Product 1 Minute Contact Time)

Gram Positive Gram negative Gram negative
S. aureus E. coli K. pneum.
Commercial 1.39 0.00 0.04
Product A

Commercial 2.20 0.00 0.01
Product B

Commercial 1.85 0.00 0.00
Product C



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Antibacterial hand sanitizer compositions
typically do not contain a surfactant and rely upon
a high concentration of an alcohol to control bacte-
ria. The alcohols evaporate and, therefore, cannot
provide residual bacterial control. The alcohols
also can dry and irritate the skin.
Present-day products especially lack effi-
cacy against Gram negative bacteria, such as E.
coli, which are of particular concern to human
health. The present invention, therefore, is di-
rected to antibacterial compositions having an ex-
ceptionally high broad spectrum antibacterial effi-
cacy, as measured by a rapid kill of bacteria (i.e.,
time kill), which is to be distinguished from per-
sistent kill.
The present antibacterial compositions
provide significantly improved time kill efficacy
compared to prior compositions, for example, prior
sanitizer compositions that incorporate a high per-
centage of an alcohol, i.e., 40% or greater, by
weight. The basis of this improved time kill is the
discovery that the antimicrobial efficacy of an
active agent can be correlated to the rate at which
the agent has access to an active site on the mi-
crobe. The driving force that determines the rate
of agent transport to the site of action is the
difference in chemical potential between the site at
which the agent acts and the external aqueous phase.
Alternatively stated, the microbicidal activity of
an active agent is proportional to its thermodynamic
activity in the external phase. Accordingly, ther-
modynamic activity, as opposed to concentration, is
the more important variable with respect to


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antimicrobial efficacy. As discussed more fully
hereafter, thermodynamic activity is conveniently
correlated to the percent saturation of the active
antibacterial agent in the continuous aqueous phase
of the composition.
Many compounds have a solubility limit in
aqueous solutions termed the "saturation concentra-
tion," which varies with temperature. Above the
saturation concentration, the compound precipitates
from solution. Percent saturation is the measured
concentration in solution divided by the saturation
concentration. The concentration of a compound in
aqueous solution can be increased over the satura-
tion concentration in water by the addition of com-
pounds like surfactants, solvents, and hydrotropes.
Surfactants not only increase the solubility of
compounds in the continuous aqueous phase of the
composition, but also form micelles, and can
solubilize compounds in the micelles.
The % saturation of an active antibacte-
rial agent in any composition, including a
surfactant-containing composition, ideally can be
expressed as:
% saturation = [C/Cs] xl00 s
wherein C is the concentration of antibacterial
agent in the composition and Cs is the saturation
concentration of the antibacterial agent in the
composition at room temperature. While not wishing
to be bound by any theory, applicants believe that
the continuous aqueous phase of a surfactant-con-
taining composition is in equilibrium with the
micellar pseudophase of said composition, and fur-
ther that any dissolved species, such as an antibac-


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terial active agent, is distributed between the
aqueous continuous phase and the micellar pseudo-
phase according to a partition law. Accordingly,
the percent saturation, or alternatively the rela-
tive thermodynamic activity or relative chemical
potential, of an antibacterial active agent dis-
solved in a composition is the same everywhere
within the composition. Thus, the terms percent
saturation of the antibacterial agent "in a composi-
tion," "in the aqueous continuous phase of a compo-
sition," and "in the micellar pseudophase of a com-
position" are interchangeable, and are used as such
throughout this disclosure.
Maximum antibacterial efficacy is achieved
when the difference in thermodynamic activities of
the active antibacterial agent between the composi-
tion and the target organism is maximized (i.e.,
when the composition is more "saturated" with the
active ingredient). A second factor affecting anti-
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.


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An important ingredient in antibacterial
cleansing compositions is a surfactant, which acts
as a solubilizer, cleanser, and foaming agent.
Surfactants affect the percent saturation of an
antibacterial agent in solution, or more impor-
tantly, affect the percent saturation of the active
agent in the continuous aqueous phase of the compo-
sition. This effect can be explained in the case of
a sparingly water-soluble antibacterial agent in an
aqueous surfactant solution, where the active agent
is distributed between the aqueous (i.e., continu-
ous) phase and the micellar pseudophase. For anti-
bacterial agents of exceedingly low solubility in
water, such as triclosan, the distribution is
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,
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 is also true.


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Active agent solubilized in the micellar pseudophase
is not immediately available to contact the
microoganisms, and it is the percent saturation of
active agent in the continuous aqueous phase that
determines the antibacterial activity of the compo-
sition. The active agent present in the surfactant
micelles, however, can serve as a reservoir of ac-
tive agent to replenish the continuous aqueous phase
as the active agent is depleted.
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, deter-
mines antibacterial efficacy.
The present compositions are=.antibacterial
compositions having an improved effectiveness
against both Gram negative and Gram positive bacte-
ria, and that exhibit a rapid bacteria kill. In one
embodiment, as illustrated below, an antibacterial
composition of the present invention comprises: (a)
about 0.001% to about 10%, by weight, of an antibac-
terial agent; (b) about 0.1% to about 40%, by
weight, of a surfactant; (c) an optional hydric
solvent; (d) an optional hydrotrope; and (e) water.


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In another embodiment, an antibacterial
composition of the present invention comprises: (a)
about 0.05% to about 5%, by weight, of an antibacte-
rial agent; (b) about 1% to about 40%, by weight, of
a disinfecting alcohol; (c) about 0.01% to about 5%,
by weight, of a gelling agent; (d) an optional
hydrotrope; and (e) water. The present compositions
also can contain an optional polyhydric solvent.
The compositions can further include a hydrotrope
and additional optional ingredients disclosed here-
after, like polyhydric solvents, pH adjusters, dyes,
skin conditioners, vitamins, and perfumes. The
present compositions are free of surfactants, i.e.,
contain 0% to about 0.5%, by weight, of compounds
that exhibit surface activity. The compositions
also are mild, and provide a persistent kill because
it is not necessary to rinse or wipe the composi-
tions from the skin.
The compositions of these embodiments, and
all other embodiments, have a percent saturation of
antibacterial agent in the continuous aqueous phase
of at least about 25%, when measured at room temper-
ature. The compositions exhibit a log reduction
against Gram positive bacteria of about 2 after 30
seconds contact. The compositions exhibit a log
reduction against Gram negative bacteria of about
2.5 after 30 seconds contact.
The following illustrates important, non-
limiting embodiments of the present invention.


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A. Antibacterial Compositions Containing
an Antibacterial Agent and a Surfactant
In one embodiment of the present inven-
tion, the antibacterial compositions comprise an
active antibacterial agent, a surfactant, and water.
The compositions of embodiment A exhibit a rapid
bacteria kill even in the absence of a hydric sol-
vent and a hydrotrope. The presence of a hydric
solvent and/or a hydrotrope does not adversely af-
fect the antimicrobial properties of the composi-
tion, but such optional ingredients are not neces-
sary ingredients. The compositions can further
include additional optional ingredients disclosed
hereafter, like pH adjusters, dyes, and perfumes.
1. Antibacterial Agent

An antibacterial agent is present in a
composition of the present invention in an amount of
about 0.001% to about 10%, and preferably about
0.01% to about 5%, by weight of the composition. To
achieve the full advantage of the present invention,
the antibacterial agent is present in an amount of
about 0.05% to about 2%, by weight, of the composi-
tion.
The antibacterial compositions can be
ready to use compositions, which typically contain
0.001% to about 2%, preferably 0.01% to about 1.5%,
and most preferably about 0.05% to about 1%, of an
antibacterial agent, by weight of the composition.
The antibacterial compositions also can be formu-
lated as concentrates that are diluted before use


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with one to about 100 parts water to provide an end
use composition. The concentrated compositions
typically contain greater than about 0.1% and up to
about 10%, by weight, of the antibacterial agent.
Applications also are envisioned wherein the end use
composition contains greater than 2%, by weight, of
the antibacterial agent.
As discussed above, the absolute amount of
antibacterial agent present in the composition is
not as important as the amount of available antibac-
terial agent in the composition. The amount of
available antibacterial agent in the composition is
related to the identity of the surfactant in the
composition, the amount of surfactant in the compo-
sition, and the presence of optional ingredients in
the composition.
To achieve the desired bacteria kill in a
short contact time, like 15 to 60 seconds, the con-
tinuous aqueous phase of the composition contains an
amount of antibacterial agent that is at least about
50%, and preferably at least about 75%, of the satu-
ration concentration of the antibacterial agent in
water, when measured at room temperature. To
achieve the full advantage of the present invention,
the continuous aqueous phase is about 95% to 100%
saturated with the antibacterial agent. The amount
of antibacterial agent present in the continuous
aqueous phase can be defined as the total amount of
antibacterial agent in the composition, less any
antibacterial agent present in surfactant micelles.
The method of determining percent saturation of
antibacterial agent in the composition is disclosed
hereafter.


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

(a) 2-Hydroxydiphenyl compounds
Yo
ZP yr ~70 10 (OH) (OH) n

OH
wherein Y is chlorine or bromine, Z is SOzH, NO2, or
Cl-C4 alkyl, r is 0 to 3, o is 0 to 3, p is 0 or 1, 'm
is 0 or 1, and n is 0 or 1.
in preferred embodiments, Y is chlorine or
bromine, m is 0, n is 0 or 1, o is 1 or 2, ris 1 or
2, and p is 0.
In especially preferred embodiments, Y is
chlorine, m is 0, n is 0, o is 1, r is 2, and p is
0.
A particularly useful 2-hydroxydiphenyl
compound has the structure:

Cl 0 C1
OH Cl

having the adopted name, triclosan, and available
commercially under the trademark IRGASAN DP300, from


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Ciba Specialty Chemicals Corp., Greensboro, NC.
Another useful 2-hydroxydiphenyl compound is 2,2'-
dihydroxy-5,5'-dibromo-diphenyl ether.

(b) Phenol derivatives
OH
R5 R1

O
R4 R2
R3

wherein Rl is hydro, hydroxy, Cz-C, alkyl, chloro,
nitro, phenyl, or benzyl; R2 is hydro, hydroxy, C1-C6
alkyl, or halo; R3 is hydro, C1-C6 alkyl, hydroxy,
chloro, nitro, or a sulfur in the form of an alkali
metal salt or ammonium salt; R4 is hydro or methyl,
and RS is hydro or nitro. Halo is bromo or, prefera-
bly, chloro.
Specific examples of phenol derivatives
include, but are not limited to, chlorophenols (o-,
m-, p-), 2,4-dichlorophenol, p-nitrophenol, picric
acid, xylenol, p-chloro-m-xylenol, cresols (o-, m-,
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.


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(c) Diphenyl Compounds

R'2 R'1 Rz R2
R'3 O X O R3
R'4 R'S R5 R4

wherein X is sulfur or a methylene group, R1 and R'1
are hydroxy, and R2, R' 2, R3, R'3, R4, R'õ R5, and
R'S, independent of one another, are hydro or halo.
Specific, nonlimiting examples of diphenyl compounds
are hexachlorophene, tetrachlorophene, dichloro-
phene, 2,3-dihydroxy-5,5'-dichlorodiphenyl sulfide,
2,2'-dihydroxy-3,3',5,51-tetrachlorodiphenyl sul-
fide, 2,21-dihydroxy-3,51,5,51,6,61-hexachlorodi-
phenyl sulfide, and 3,3'-dibromo-5,5'-dichloro-2,2'-
dihydroxydiphenylamine. Other diphenyl compounds
are listed in WO 98/55096.
2. Surfactant

In addition to the antibacterial agent, a
present antimicrobial composition also contains a
surfactant. The surfactant is present in an amount
of about 0.1% to about 40%, and preferably about
0.3% to about 20%, by weight, of the composition.
To achieve the full advantage of the present inven-
tion, the antibacterial composition'contains about
0.5% to about 15%, by weight, of the surfactant.


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Ready-to-use compositions typically con-
tain about 0.1% to about 10%, preferably about 0.3%
to about 5%, and most preferably, 0.5% to about 3%,
by weight, of the composition. Concentrated compo-
sitions suitable for dilution typically contain
greater than about 5%, by weight, of a surfactant.
The amount of surfactant present in the
composition is related to the amount and identity of
the antibacterial agent in the composition and to
the identity of the surfactant. The amount of
surfactant is determined such that the percent satu-
ration of the antibacterial agent in the continuous
aqueous phase of the composition is at least about
50%, preferably at least about 75%, and most prefer-
ably at least about 95%.
In this embodiment, wherein the presence
of a hydric solvent and a hydrotrope is optional,
the identity of the surfactant is important with
respect to providing a composition having a percent
saturation of antibacterial agent in the continuous
aqueous phase of at least about 50%. As illustrated
hereafter, surfactants useful in this embodiment of
the invention include anionic surfactants and se-
lected cationic surfactants. Nonionic surfactants
and anionic surfactants containing a relatively high
amount of ethoxylation are not useful in this em-
bodiment. Ethoxylated surfactants containing more
than two moles of ethylene oxide have a strong af-
finity for the antibacterial agent, and in this
embodiment substantially reduce the efficacy of the
antibacterial agent.
Accordingly, in this embodiment, the
surfactant is selected from the following classes of


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surfactants: a Ce-C1e alkyl sulfate, a C8-C18 fatty
acid salt, a Ce-C1B alkyl ether sulfate having one or
two moles of ethoxylation, a CB-C18 alkamine oxide, a
CB-C18 alkoyl sarcosinate, a C8-C1e sulfoacetate, a CB-
C1e sulfosuccinate, a CB-C18 alkyl diphenyl oxide
disulfonate, a C8-C1e alkyl carbonate, a Ce-C1e alpha-
olefin sulfonate, a methyl ester sulfonate, and
mixtures thereof. The C8-C18 alkyl group contains
eight to sixteen carbon atoms, and can be straight
chain (e.g., lauryl) or branched (e.g., 2-ethyl-
hexyl). The cation of the anionic surfactant can be
an alkali metal (preferably sodium or potassium),
ammonium, Cl-C4 alkylamcnonium (mono-, di-, tri), or
Cl-C3 alkanolammonium (mono-, di-, tri -). Lithium
and alkaline earth cations (e.g., magnesium) can be
used, but antibacterial efficacy is reduced.
Specific surfactants that can be used in
this embodiment include, but are not limited to,
lauryl sulfates, octyl sulfates, 2-ethylhexyl sul-
fates, lauramine oxide, decyl sulfates, tridecyl
sulfates, cocoates, lauroyl sarcosinates, lauryl
sulfosuccinates, linear Clo diphenyl oxide disulfo-
nates, lauryl sulfosuccinates, lauryl ether sulfates
(1 and 2 moles ethylene oxide), myristyl sulfates,
oleates, stearates, tallates, cocamine oxide,
decylamine oxide., myristamine oxide, ricinoleates,
cetyl sulfates, and similar surfactants. Additional
examples of surfactants can be found in "CTFA Cos-
metic Ingredient Handbook," J.M. Nikitakis, ed., The
Cosmetic, Toiletry and Fragrance Association, Inc.,
Washington, D.C. (1988) (hereafter CTFA Handbook),
pages 10-13,= 42-46, and 87-94.


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3. Carrier

The carrier in this embodiment comprises
water.
4. Optional Inaredients

An antibacterial composition of the pres-
ent invention also can contain optional ingredients
well known to persons skilled in the art. For exam-
ple, the composition can contain a hydric solvent
and/or a hydrotrope. These particular optional
ingredients and the amount that can be present in
the composition are discussed hereafter.
The compositions also can contain other
optional ingredients, such as dyes and fragrances,
that are present in a sufficient amount to perform
their intended function and do not adversely affect
the antibacterial efficacy of the composition. Such
optional ingredients typically are present, individ-
ually, from 0% to about 5%, by weight, of the compo-
sition, and, collectively, from 0% to about 20%, by
weight, of the composition.
Classes of optional ingredients include,
but are not limited to, dyes, fragrances, pH adjust-
ers, thickeners, viscosity modifiers, buffering
agents, foam stabilizers, antioxidants, foam
enhancers, chelating agents, opacifiers, and similar
classes of optional ingredients known to persons
skilled in the art.
Specific classes of optional ingredients
include alkanolamides as foam boosters and stabiliz-
ers; gums and polymers as thickening agents; inor-


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ganic phosphates, sulfates, and carbonates as buff-
ering agents; EDTA and phosphates as chelating
agents; and acids and bases as pH adjusters.
Examples of preferred classes of basic pH
adjusters are ammonia; mono-, di-, and tri-alkyl
amines; mono-, di-, and tri-alkanolamines; alkali
metal and alkaline earth metal hydroxides; and mix-
tures thereof. However, the identity of the basic
pH adjuster is not limited, and any basic pH ad-
juster known in the art can be used. Specific,
nonlimiting examples of basic pH adjusters are ammo-
nia; sodium, potassium, and lithium hydroxide;
monoethanolamine; triethylamine; isopropanolamine;
diethanolamine; and triethanolamine.
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 are not limited to, cocamide MEA, cocamide
DEA, soyamide DEA, lauramide DEA, oleamide MIPA,
stearamide MEA, myristamide MEA, lauramide MEA,
capramide DEA, ricinoleamide DEA, myristamide DEA,
stearamide DEA, oleylamide DEA, tallowamide DEA,
lauramide MIPA, tallowamide MEA, isostearamide DEA,
isostearamide MEA, and mixtures thereof.


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B. Antibacterial Compositions Containing
an Antibacterial Agent, a Surfactant,
and a Hydric Solvent and/or a Hvdrotroye
In another embodiment, the antibacterial
compositions comprise an active antibacterial agent,
a surfactant, and a hydric solvent and/or a hydro-
trope. The compositions of embodiment B exhibit a
rapid bacteria kill, and are essentially unlimited
in the identity of the surfactant in the composi-
tion. The solvent and/or hydrotrope assists in
solubilizing the antibacterial agent, and reduces
the affinity of the antibacterial agent to enter
surfactant micelles. Accordingly, at least 40%
saturation of the antibacterial agent in the contin-
uous aqueous phase can be achieved regardless of the
identity of the surfactant.

1. Antibacterial Agent

The amount and identity of the antibacte-
rial agent present in this embodiment of the inven-
tion is discussed above in A.1.
In addition, to achieve the desired bacte-
ria kill in a short contact time, like 15 to 60
seconds, the continuous aqueous phase of the compo-
sition contains an amount of antibacterial agent
that is at least about 40%, and preferably at least
about 50, and more preferably at least about 75%, of
the saturation concentration of the antibacterial
agent in water, when measured at room temperature.
To achieve the full advantage of the present inven-


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

2. Surfactant
The amount of surfactant present in this
embodiment of the present invention is identical to
the amount disclosed above in A.2. However, due to
the presence of a hydric solvent and/or a hydro-
trope, the identity of the surfactant is not limited
as in A.2.
In particular, the presence of a hydric
solvent and/or hydrotrope, as defined hereafter,
reduces the affinity of the antibacterial agent to
enter surfactant micelles. Accordingly, a suffi-
cient amount of the antibacterial agent is present
in the continuous aqueous phase to quickly and ef-
fectively kill a broad spectrum of bacteria regard-
less of the identity of the surfactant. In embodi-
ments wherein a hydric solvent and hydrotrope are
absent, various surfactants, like ethoxylated
nonionic surfactants, have such a strong affinity
for the antibacterial agent that the antibacterial
agent is not available for a rapid bacteria kill.
Accordingly, in this embodiment the
surfactant can be an anionic surfactant, a cationic
surfactant, a nonionic surfactant, or a compatible
mixture of surfactants. The surfactant also can be
an ampholytic or amphoteric surfactant, which have
anionic or cationic properties depending upon the pH
of the composition.
The antibacterial compositions, therefore,
can contain an anionic surfactant disclosed above in


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A.2., and more generally can contain any anionic
surfactant having a hydrophobic moiety, such as a
carbon chain including about 8 to about 30 carbon
atoms, and particularly about 12 to about 20 carbon
atoms, and further has a hydrophilic moiety, such as
sulfate, sulfonate, carbonate, phosphate, or
carboxylate. Often, the hydrophobic carbon chain is
etherified, such as with ethylene oxide or propylene
oxide, to impart a particular physical property,
such as increased water solubility or reduced sur-
face tension to the anionic surfactant.
Therefore, suitable anionic surfactants
include, but are not limited to, compounds in the
classes known as alkyl sulfates, alkyl ether suI-
fates, alkyl ether sulfonates, sulfate esters of an
alkylphenoxy polyoxyethylene ethanol, alpha-olefin
sulfonates, beta-alkoxy alkane sulfonates, alkylaryl
sulfonates, alkyl monoglyceride sulfates, alkyl
monoglyceride sulfonates, alkyl carbonates, alkyl
ether carboxylates, fatty acids, sulfosuccinates,
sarcosinates, oxtoxynol or nonoxynol phosphates,
taurates, fatty taurides, fatty'acid amide
polyoxyethylene sulfates, isethionates, or mixtures
thereof. Additional anionic surfactants are listed
in McCutcheon's Emulsifiers and Detergents, 1993
Annuals, (hereafter McCutcheon's), McCutcheon Divi-
sion, MC Publishing Co., Glen Rock, NJ, pp. 263-266.
Numerous other
anionic surfactants, and classes of anionic surfac-
tants, are disclosed in Laughlin et al. U.S. Patent
No. 3,929,678.
The antibacterial compositions also can
contain nonionic surfactants. Typically, a nonionic


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surfactant has a hydrophobic base, such as a long
chain alkyl group or an alkylated aryl group, and a
hydrophilic chain comprising a sufficient number
(i.e., 1 to about 30) of ethoxy and/or propoxy moi-
eties. Examples of classes of nonionic surfactants
include ethoxylated alkylphenols, ethoxylated and
propoxylated fatty alcohols, polyethylene glycol
ethers of methyl glucose, polyethylene glycol ethers
of sorbitol, ethylene oxide-propylene oxide block
copolymers, ethoxylated esters of fatty (CB-C18)
acids, condensation products of ethylene oxide with
long chain amines or amides, and mixtures thereof.
Exemplary nonionic surfactants include,
but are not limited to, methyl gluceth-10, PEG-20
methyl glucose distearate, PEG-20 methyl glucose
sesquistearate, C11_1s 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 ethoxylated fatty (C6-C22)
alcohol, including 3 to 20 ethylene oxide moieties,
polyoxyethylene-20 isohexadecyl ether, polyoxy-
ethylene-23 glycerol laurate, polyoxy-ethylene-20
glyceryl stearate, PPG-10 methyl glucose ether, PPG-
20 methyl glucose ether, polyoxyethylene-20 sorbitan
monoesters, polyoxyethylene-80 castor oil, polyoxy-
ethylene-15 tridecyl ether, polyoxy-ethylene-6 tri-
decyl ether, laureth-2, laureth-3, laureth-4, PEG-3
castor oil, PEG 600 dioleate, PEG 400 dioleate, and
mixtures thereof.


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Numerous other nonionic surfactants are
disclosed in McCutcheon's Detergents and Ernulsifi-
ers, 1993 Annuals, published by McCutcheon Division,
MC Publishing Co., Glen Rock, NJ, pp. 1-246 and 266-
272; in the CTFA International Cosmetic ingredient
Dictionary, Fourth Ed., Cosmetic, Toiletry and Fra-
grance Association, Washington, D.C. (1991) (herein-
after the CTFA Dictionary) at pages 1-651; and in
the CTFA Handbook, at pages 86-94.
In addition to anionic and nonionic sur-
factants, cationic, ampholytic, and amphoteric sur-
factants can be used in the antimicrobial composi-
tions. Cationic surfactants include amine oxides,
for example.
Ampholytic surfactants can be broadly
described as derivatives of secondary and tertiary
amines having aliphatic radicals that are straight
chain or branched, and wherein one of the aliphatic
substituents contains from about 8 to 18 carbon
atoms and at least one of the aliphatic substituents
contains an anionic water-solubilizing group, e.g.,
carboxy, sulfonate, or sulfate. Examples of 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-carboxymethyl-dodecylamino)propane-1-
sulfonate, disodium octadecyliminodiacetate, sodium
1-carboxymethyl-2-undecylimidazole, and sodium N,N-
bis (2-hydroxyethyl) -2-sulfato-3-dodecoxypropylamine.


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More particularly, one class of ampholytic
surfactants include sarcosinates and taurates having
the general structural formula

O
R1-C-N- (CHZ) n-Y
R2

wherein R' is C11 through Czl alkyl, R2 is hydrogen or
C1-C2 alkyl, Y is CO2M or SO3M, M is an alkali metal,
and n is a number 1 through 3.
Another class of ampholytic surfactants is
the amide sulfosuccinates having the structural
formula

0 SO3-Na+
R1-NHCCH2-CH-CO2 Na+
The following classes of ampholytic sur-
factants also can be used:

ll) i CH2CO2-Na+
R CNHCH2CH2~T
ICH2CH2OH
alkoamphoglycinates


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0 CH2CO2-Na+
RIICNHCH2CH2NCH2CO2H
I
CH2CHZOH
alkoamphocarboxyglycinates
0 CH2CH2CO2-Na+
R1ICNHCH2CH2N
I
CH2CH2OH
alkoamphopropionates

O CH2CH2CO2-Na+
11 1
RICNHCH2CH2i CH2CO2H
CH2CH2oH
alkoamphocarboxypropionates



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OH
O CH2CHCH2SO3 Na+
R1~CNHCH 2CH2N
I
CHZCH2OH
alkoamphopropylsulfonates
0 CH3
RIICNH (CH2) 3N+-CH2CO2_
I
CH3

alkamidopropyl betaines
0 CH3 OH
RIICNH(CH2)3N+-CH2CHCH2SO3
I
CH3
alkamidopropyl hydroxysultaine

0
RINHCH2CHZIC-O-Na+
alkylaminopropionates


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CH2CH2CO2-
I
RNH
I
CH2CH2CO2H
alkyliminopropionates.
Additional classes of ampholytic surfactants include
the phosphobetaines and the phosphitaines.
Specific, nonlimiting examples of ampho-
lytic surfactants useful in the present invention
are sodium coconut N-methyl taurate, sodium oleyl N-
methyl taurate, sodium tall oil acid N-methyl
taurate, sodium palmitoyl N-methyl taurate, cocodi-
methylcarboxymethylbetaine, lauryldimethylcarboxy-
methylbetaine, lauryldimethylcarboxyethylbetaine,
cetyldimethylcarboxymethylbetaine, lauryl-bis-(2-
hydroxyethyl)carboxymethylbetaine, oleyldimethyl-
gammacarboxypropylbetaine, lauryl-bis-(2-hydroxy-
propyl)-carboxyethylbetaine, cocoamidodimethylpro-
pylsultaine, stearylamidodimethylpropylsultaine,
laurylamido-bis-(2-hydroxyethyl)propylsultaine,
disodium oleamide PEG-2 sulfosuccinate, TEA oleamido
PEG-2 sulfosuccinate, disodium oleamide MEA sulfo-
succinate, disodium oleamide MIPA sulfosuccinate,
disodium ricinoleamide MEA sulfosuccinate, disodium
undecylenamide MEA sulfosuccinate, disodium wheat
germamido MEA sulfosuccinate, disodium wheat germ-
amido PEG-2 sulfosuccinate, disodium isostearamideo
MEA sulfosuccinate, cocoamphoglycinate, cocoampho-
carboxyglycinate, lauroamphoglycinate, lauroampho-
carboxyglycinate, capryloamphocarboxyglycinate,


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cocoamphopropionate, cocoamphocarboxypropionate,
lauroamphocarboxypropionate, capryloamphocarboxy-
propionate, dihydroxyethyl tallow glycinate,
cocamido disodium 3-hydroxypropyl 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.
3. Carrier

The carrier in this embodiment comprises
water.

4. Optional Ingredients

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

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


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Preferred embodiments contain about 2% to
about 20%, by weight, of a hydric solvent and/or
about 2% to about 25%, by weight, of a hydrotrope.
Most preferred embodiments contain about 5% to about
15%, by weight, of a hydric solvent and/or about 5%
to about 20%, by weight, of a hydrotrope.
As defined herein, the term "hydric sol-
vent" is a water-soluble organic compound containing
one to six, and typically one to three, hydroxyl
groups. The term "hydric solvent" therefore encom-
passes water-soluble alcohols, diols, triols, and
polyols. Specific examples of hydric solvents in-
clude, but are not limited to, methanol, ethanol,
isopropyl alcohol, n-butanol, n-propyl alcohol,
ethylene glycol, propylene glycol, glycerol,
diethylene glycol, dipropylene glycol, tripropylene
glycol, hexylene glycol, butylene glycol, 1,2,6-
hexanetriol, sorbitol, PEG-4, and similar hydroxyl-
containing compounds.
A hydrotrope is a compound that has the
ability to enhance the water solubility of other
compounds. A hydrotrope utilized in the present
invention lacks surfactant properties, and typically
is a short-chain alkyl aryl sulfonate. Specific
examples of hydrotropes includes, but are not lim-
ited to, sodium cumene sulfonate, ammonium cumene
sulfonate, ammonium xylene sulfonate, potassium
toluene sulfonate, sodium toluene sulfonate, sodium
xylene sulfonate, toluene sulfonic acid, and xylene
sulfonic acid. Other useful hydrotropes include
sodium polynaphthalene sulfonate, sodium polystyrene
sulfonate, sodium methyl naphthalene sulfonate, and
disodium succinate.


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C. Antibacterial Compositions Containing
an Antibacterial Agent and a Hydric
Solvent and/or a Hydrotrope

In still another embodiment, the antibac-
terial compositions comprise an active antibacterial
agent, and a hydric solvent and/or a hydrotrope.
The compositions of embodiment C exhibit a rapid
bacteria kill, and also are essentially unlimited in
the identity of the surfactant in the composition.
The solvent and/or hydrotrope assists in solubil-
izing the antibacterial agent. Accordingly, at
least 25% saturation of the antibacterial agent in
the continuous aqueous phase can be achieved-even in
the absence of a surfactant.

1. Antibacterial Agent

The amount and identity of the antibacte-
rial agent present in this embodiment of the inven-
tion is discussed above in A.1.
In addition, similar to embodiment B, in
order to achieve the desired bacteria kill in a
short contact time, like 15 to 60 seconds, the con-
tinuous aqueous phase of the composition contains an
amount of antibacterial agent that is at least about
25%, and preferably at least about 50%, and more
preferably at least about 75%, of the saturation
concentration of the antibacterial agent in water,
when measured at room temperature. To achieve the
full advantage of the present invention, the contin-
uous aqueous phase is about 95% to 100% saturated
with the antibacterial agent.


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2. Surfactant

The surfactant is an optional ingredient
in this embodiment. However, if present, the amount
of surfactant present in this embodiment of the
present invention is 0% to about 10% by weight,
preferably 0% to about 5%, by weight. To achieve
the full advantage of the present invention, the
surfactant is present in an amount of 0% to about
2%, by weight. Due to the presence of a hydric
solvent and/or a hydrotrope, the identity of the
surfactant in this embodiment is identical to the
surfactants disclosed in B.2.

3. Carrier

The carrier in this embodiment comprises
water.

4. Optional Ingredients

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

5. Hydric Solvent and Hydrotrope
The hydric solvent and hydrotrope dis-
cussed in B.5., above, also can be utilized in this
embodiment of the invention, for the same purpose.
However, the amount of hydric solvent and/or hydro-
trope present in this embodiment can be greater than


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the amount disclosed in B.5., above, because an
additional amount of solvent and/or hydrotrope may
be necessary to solubilize the antibacterial agent
in the absence of a surfactant.
Therefore, in embodiment C, the composi-
tions can contain 0% to about 60%, by weight, of a
hydric solvent, and 0% to about 40%, by weight, of a
hydrotrope. However, the composition contains at
least one of the hydrotrope and hydric solvent.
Preferred embodiments contain about 2% to about 20%,
by weight, of a hydric solvent and/or about 2% to
about 25%, by weight, of a hydrotrope. Highly pre-
ferred embodiments contain about 5% to about 15%, by
weight, of a hydric solvent and/or about 5% to about
20%, by weight, of a hydrotrope. Most preferred
embodiments contain both a hydric solvent and a
hydrotrope.

D. Antibacterial Compositions Containing
Antibacterial Agent, a Disinfecting
Alcohol, a Gelling Agent

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

1. Antibacterial Agent

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


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in A.1. In this embodiment, the antibacterial agent
is present in an amount of about 0.05% to about 5%,
and preferably about 0.1% to about 4%, by weight of
the composition. To achieve the full advantage of
the present invention, the antibacterial agent is
present in an amount of about 0.25% to about 2%, by
weight, of the composition.

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

3. Disinfecting Alcohol
Antibacterial compositions of the present
invention contain about 1% to about 40%, by weight,
of a disinfecting alcohol. Preferred embodiments
contain about 2% to about 38%, by weight, of a dis-
infecting alcohol. Most preferred embodiments con-
tain about 5% to about 30%, by weight, of a disin-
fecting alcohol.
As defined herein, the term "disinfecting
alcohol" is a water-soluble alcohol containing one
to six carbon atoms. Disinfecting alcohols include,
but are not limited to, methanol, ethanol, propanol,
and isopropyl alcohol.


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4. Gelling Agent

The present antibacterial compositions
also contain about 0.01% to about 5%, by weight, and
preferably 0.10% to about 3%, by weight, of a gel-
ling agent. To achieve the full advantage of the
present invention, the antibacterial compositions
contain about 0.25% to about 2.5%, by weight, of a
gelling agent. The antibacterial compositions typi-
cally contain a sufficient amount of gelling agent
such that the composition is a viscous liquid, gel,
or semisolid that can be easily applied to, and
rubbed on, the skin. Persons skilled in the art are
aware of the type and amount of gelling agent to
include in the composition to provide the desired
composition viscosity or consistency.
The term "gelling agent" as used here and
hereafter refers to a compound capable of increasing
the viscosity of a water-based composition, or capa-
ble of converting a water-based composition to a gel
or semisolid. The gelling agent, therefore, can be
organic in nature, for example, a natural gum or a
synthetic polymer, or can be inorganic in nature.
As previously stated, the present compo-
sitions are free of a surfactant. A surfactant is
not intentionally added to a present antibacterial
composition, but may be present in an amount of 0%
to about 0.5%, by weight, because a surfactant may
be present in a commercial form of a gelling agent
to help dispense the gelling agent in water. A
surfactant also may be present as an additive or by-
product in other composition ingredients.


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Surfactants are omitted from the present
compositions to help avoid micelle formation, which
in turn solubilize the active antibacterial compound
and reduce its effectiveness. Similarly, preferred
gelling agents are those that do not form micelles
in particular, and do not complex or bind with the
active antibacterial agents, or otherwise adversely
effect the antibacterial properties of the antibac-
terial agent. Regardless of the identity of the
gelling agent, the amount of gelling agents and
other composition ingredients is selected such that
the antibacterial agent is present in an amount of
at least 25% of saturation, when measured at room
temperature.
The following are nonlimiting examples of
gelling agents that can be used in the present
invention. In particular, the following compounds,
both organic and inorganic, act primarily by thick-
ening or gelling the aqueous portion of the compo-
sition:
acacia, acrylates/steareth-20 methacrylate
copolymer, agar, algin, alginic acid, ammonium
acrylate copolymers, ammonium alginate, ammonium
chloride, ammonium sulfate, amylopectin, attapul-
gite, bentonite, C9-15 alcohols, calcium acetate,
calcium alginate, calcium carrageenan, calcium chlo-
ride, caprylic alcohol, carbomer 910, carbomer 934,
carbomer 934P, carbomer 940, carbomer 941, carboxy-
methyl hydroxyethylcellulose, carboxymethyl hydroxy-
propyl guar, carrageenan, cellulose, cellulose gum,
cetearyl alcohol, cetyl alcohol, corn starch, damar,
dextrin, dibenzylidine sorbitol, ethylene dihydroge-
nated tallowamide, ethylene dioleamide, ethylene


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distearamide, gelatin, guar gum, guar hydroxypropyl-
trimonium chloride, hectorite, hyaluronic acid,
hydrated silica, hydroxybutyl methylcellulose,
hydroxyethylcellulose, hydroxyethyl ethylcellulose,
hydroxyethyl stearamide-MIPA, hydroxypropylcellu-
lose, hydroxypropyl guar, hydroxypropyl methyl-
cellulose, isocetyl alcohol, isostearyl alcohol,
karaya gum, kelp, lauryl alcohol, locust bean gum,
magnesium aluminum silicate, magnesium silicate,
magnesium trisilicate, methoxy PEG-22/dodecyl glycol
copolymer, methylcellulose, microcrystallinc cellu-
lose, montmorillonite, myristyl alcohol, oat flour,
oleyl alcohol, palm kernel alcohol, pectin, PEG-2M,
PEG-5M, polyacrylic acid, polyvinyl alcohol, potas-
sium alginate, potassium aluminum polyacrylate,
potassium carrageenan, potassium chloride, potassium
sulfate, potato starch, propylene glycol alginate,
sodium acrylate/vinyl alcohol copolymer, sodium
carboxymethyl dextran, sodium carrageenan, sodium
cellulose sulfate, sodium chloride, sodium polymeth-
acrylate, sodium silicoaluminate, sodium sulfate,
stearalkonium bentonite, stearalkonium hectorite,
stearyl alcohol, tallow alcohol, TEA-hydrochloride,
tragacanth gum, tridecyl alcohol, tromethamine mag-
nesium aluminum silicate, wheat flour, wheat starch,
xanthan gum, and mixtures thereof.
The following additional nonlimiting exam-
ples of gelling agents act primarily by thickening
the nonaqueous portion of the composition:
abietyl alcohol, acrylinoleic acid, alumi-
num behenate, aluminum caprylate, aluminum dilin-
oleate, aluminum distearate, aluminum isostearates/-
laurates/palmitates or stearates, aluminum isostear-


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ates/myristates, aluminum isostearates/palmitates,
aluminum isostearates/stearates, aluminum lanolate,
aluminum myristates/palmitates, aluminum stearate,
aluminum stearates, aluminum tristearate, beeswax,
behenamide, behenyl alcohol, butadiene/acrylonitrile
copolymer, C29-70 acid, calcium behenate, calcium
stearate, candelilla wax, carnauba, ceresin, choles-
terol, cholesteryl hydroxystearate, coconut alcohol,
copal, diglyceryl stearate malate, dihydroabietyl
alcohol, dimethyl lauramine oleate, dodecanedioic
acid/cetearyl alcohol/glycol copolymer, erucamide,
ethylcellulose, glyceryl triacetyl hydroxystearate,
glyceryl triacetyl ricinoleate, glycol dibehenate,
glycol dioctanoate, glycol distearate, hexanediol
distearate, hydrogenated C6-14 olefin polymers,
hydrogenated castor oil, hydrogenated cottonseed
oil, hydrogenated lard, hydrogenated menhaden oil,
hydrogenated palm kernel glycerides, hydrogenated
palm kernel oil, hydrogenated palm oil, hydrogenated
polyisobutene, hydrogenated soybean oil, hydroge-
nated tallow amide, hydrogenated tallow glyceride,
hydrogenated vegetable glyceride, hydrogenated vege-
table glycerides, hydrogenated vegetable oil, hy-
droxypropylcellulose, isobutylene/isoprene copoly-
mer, isocetyl stearoyl stearate, Japan wax, jojoba
wax, lanolin alcohol, lauramide, methyl dehydro-
abietate, methyl hydrogenated rosinate, methyl
rosinate, methylstyrene/vinyltoluene copolymer,
microcrystalline wax, montan acid wax, montan wax,
myristyleicosanol, myristyloctadecanol, octadecene/-
maleic anhydride copolymer, octyldodecyl stearoyl
stearate, oleamide, oleostearine, ouricury wax,
oxidized polyethylene, ozokerite, palm kernel alco-


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hol, paraffin, pentaerythrityl hydrogenated rosin-
ate, pentaerythrityl rosinate, pentaerythrityl
tetraabietate, pentaerythrityl tetrabehenate, penta-
erythrityl tetraoctanoate, pentaerythrityl tetra-
oleate, pentaerythrityl tetrastearate, phthalic
anhydride/glycerin/glycidyl decanoate copolymer,
phthalic/trimellitic/glycols copolymer, polybutene,
polybutylene terephthalate, polydipentene, polyeth-
ylene, polyisobutene, polyisoprene, polyvinyl
butyral, polyvinyl laurate, propylene glycol dicap-
rylate, propylene glycol dicocoate, propylene glycol
diisononanoate, propylene glycol dilaurate, propyl-
ene glycol dipelargonate, propylene glycol distear-
ate, propylene glycol diundecanoate, PVP/eicosene
copolymer, PVP/hexadecene copolymer, rice bran wax,
stearalkonium bentonite, stearalkonium hectorite,
stearamide, stearamide DEA-distearate, stearamide
DIBA-stearate, stearamide MEA-stearate, stearone,
stearyl alcohol, stearyl erucamide, stearyl stear-
ate, stearyl stearoyl stearate, synthetic beeswax,
synthetic wax, trihydroxystearin, triisononanoin,
triisostearin, triisononanoin, triisostearin, tri-
isostearyl trilinoleate, trilaurin, trilinoleic
acid, trilinolein, trimyristin, triolein, tripalmi-
tin, tristearin, zinc laurate, zinc myristate, zinc
neodecanoate, zinc rosinate, zinc stearate, and
mixtures thereof.

5. Optional Ingredients

a. Polyhydric Solvent

A polyhydric solvent, if present at all,
is present in an amount of about 0.1% to about 50%,


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and preferably about 5% to about 50%, by weight of
the composition. To achieve the full advantage of
the present invention, the polyhydric solvent is
present in an amount of about 10% to about 50% by
weight of the composition. In contrast to a dis-
infecting alcohol, a polyhydric solvent contributes
little, if at all, to the antibacterial efficacy of
the present composition.
As defined herein, the term "polyhydric
solvent" is a water-soluble organic compound con-
taining two to six, and typically two or three,
hydroxyl groups. The term "water-soluble" means
that the polyhydric solvent has a water solubility
of at least 0.1 g of polyhydric solvent per 100 g of
water at 25 C. There is no upper limit to the water
solubility of the polyhydric solvent, e.g., the
polyhydric solvent and water can be soluble in all
proportions.
The term "polyhydric solvent" therefore
encompasses water-soluble diols, triols, and
polyols. Specific examples of hydric solvents in-
clude, but are not limited to, ethylene glycol,
propylene glycol, glycerol, diethylene glycol, di-
propylene glycol, tripropylene glycol, hexylene
glycol, butylene glycol, 1,2,6-hexanetriol, sorbi-
tol, PEG-4, and similar polyhydroxy compounds.

b. Hydrotrope

A hydrotrope, if present at all, is pres-
ent in an amount of about 0.1% to about 30%, and
preferably about 0.5% to about 25%, by weight of the
composition. To achieve the full advantage of the


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present invention, the hydrotrope is present in an
amount of about 1% to about 20%, by weight of the
composition. The identity of the hydrotropes is
discussed in B.5., above, and is used in this em-
bodiment of the invention for the same purpose.
c. Other Optional Incrredients
Other optional ingredients discussed in
A.4., above, also can be utilized in this embodiment
of the invention, in the same amounts and for the
same purposes.
Additional optional ingredients useful in
this embodiment include skin conditioners. Examples
of skin conditioners, include emollients, such as,
cetyl myristate, glyceryl dioleate, isopropyl
myristate, lanolin, methyl laurate, PPG-9 laurate,
soy stearyl, octyl palmitate, and PPG-5 lanoate, for
example. The skin conditioner also can be a
humectant, for example, glucamine and pyridoxine
glycol, for example. Occlusive skin conditioners,
for example, aluminum lanolate, corn oil, methicone,
coconut oil, stearyl stearate, phenyl trimethicone,
trimyristin, olive oil, and synthetic wax, also can
be used. Combinations of the classes of skin condi-
tioners, in addition to miscellaneous skin condi-
tioners known to persons skilled in the art, alone
or in combination can be used. Nonlimiting examples
of miscellaneous skin conditioners include aloe,
cholesterol, cystine, keratin, lecithin, egg yolk,
glycine, PPG-12, retinol, salicylic acid, orotic
acid, vegetable oil, and soluble animal collagen.
The skin conditioners can be used alone, or in com-


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bination with a skin protectant, like petroleum,
cocoa butter, calamine, and kaolin, for example. A
skin protectant also can be used alone. Additional
examples of skin conditioners and protectants can be
found in "CTFA Cosmetic Ingredient Handbook," J.M.
Nikitakis, ed., The Cosmetic, Toiletry and Fragrance
Association, Inc., Washington, D.C. (1988) (hereaf-
ter CTFA Handbook), pages 79-85,

Antibacterial compositions of the present
invention comprising an active antibacterial agent,
a disinfecting alcohol, and a hydrotrope exhibit a
rapid bacteria kill. The alcohol and hydrotrope
assist in solubilizing the antibacterial agent.
Accordingly, at least 25t saturation of the anti-
bacterial agent in the composition can be achieved
even in the absence of a surfactant.

The antibacterial compositions of the
present invention do not rely upon a low pH or a
high pH to provide a rapid reduction in bacterial
populations. Antibacterial compositions of the
present invention can have a pH of about 4 to about
9, but at the two extremes of this pH range, the
compositions can be irritating to the skin or damag-
ing to other surfaces contacted by the composition.
Accordingly, antibacterial compositions of the pres-
ent invention preferably have a pH of about 5 to
about 8, and more preferably about 6 to about 8. To
achieve the full advantage of the present invention,
the antibacterial compositions have a pH of about
6.5 to about 7.5. In addition, the antibacterial
compositions of the present invention also do not


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rely upon a high concentration of disinfecting alco-
hol.
To demonstrate the new and unexpected
results provided by the antibacterial compositions
of the present invention, the following Examples and
Comparative Examples were prepared, and the ability
of the compositions to control Gram positive and
Gram negative bacteria was determined. The weight
percentage listed in each of the following examples
represents the actual, or active, weight amount of
each ingredient present in the composition. The
compositions were prepared by blending the ingredi-
ents, as understood by those skilled in the art and
as described below.
The following materials were used as in-
gredients in the examples. The source of each in-
gredient, and its abbreviation, are summarized be-
low:
a) Alkyl (linear) diplienyl oxide
disulfonate, Pilot Chemical Co., Santa Fe Springs,
CA, CALFAZlOL-45 (active=45.4%),
b) Alkyl polyglucoside (APG), Henkel
*
Corp., Hoboken, NJ, PLANTAREN' 2000N UP (ac-
tive=55.53%),
c) Alpha-olefin sulfonate (AOS), Stepan
Chemical Co., Northfield, IL, BIOTERGE AS-40 (ac-
tive=38.80$),
d) Ammonium lauryl sulfate (ALS), Henkel
Corp., STANDAPOLA (active level--28.3%),
e) Ammonium xylene sulfonate (AXS),
Stepan Corp., STEPANATE AXS (active=40%),
*Trade-mark


CA 02371925 2006-06-13
64267-1185

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f) Cocamidopropyl betaine (CAPB),
McIntyre Group, Ltd., Chicago, IL, MACKAM*35-HP
(est. 30% active betaine),
g) Dipropylene glycol (DPG), Dow Chemi-
cal Co., Midland, MI,
h) Disodium laureth sulfosuccinate
(DSLScct), McIntyre Group, Ltd., MACKANATE EL (ac-
tive=33.8%),
i) Disodium lauryl sulfosuccinate
(DSLrylScct), McIntyre Group, Ltd., MACKANATE LO
(active est.=40%),
j) DMDM Hydantoin (DMDM), MacIntyre
Group, Ltd., MACKSTAT DM (approx. 55%- active),
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 (99.7% CP/USP),
m) Isopropanol (IPA), Fisher Scientific,
Pittsburgh, PA, 2-Propanol, HPLC Grade A 451-4,
n) Lauramine oxide (LAO), McIntyre
Group, Ltd., MACKAMINE* LO (active=30.55%),
o) Liquid Perfume (PF),
p) Lithium lauryl sulfate (LLS), Henkel,
TEXAPON*LLS (active=28.8%),
q) Magnesium lauryl sulfate (MLS),
Stepan Chemical Co., STEPANOeMG (active=28.3%),
r) Methyl ester sulfonate (MES), Stepan
Chemical Co., ALPHA-STEP ML-40 (Sodium methyl-2
sulfo laurate and disodium 2-sulfo lauric acid)
(active=36.47%),
*Trade-mark


CA 02371925 2006-06-13
64267-1185

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s) Monoethanolamine (MEA),. Dow Chemical
Co.,
t) Monoethanolamine lauryl sulfate
(MEALS), Albright & Wilson, Cumbria, England,
EMPICOL~ LQ 33/F (active=33%),-
u) Octylphenol ethoxylate, 9-10 moles EO
(TX100), Union Carbide, TRITON X 100,
v) PEG-6ME, polyethylene glycol 300
methyl ether, available from Dow Chemical Co., Mid-
land, MI, as MPE(:~350 (active=est. 100%),
w) Poloxymer 338 (F108), BASF,
Wyandotte, MI, PLURONI(!F108 (active=est. 100%),
x) Potassium cocoate (KCO), McIntyre
Group, Ltd., MACKADET*40-K (active=38.4%),
y) Potassium laurate (KL), prepared from
lauric acid (Sigma, #L-4250, active=99.8%) and po-
tassium hydroxic_,
z) Potassium oleate (KO), Norman, Fox &
Co., Vernon, CA, NORFOX*KO (active=approx. 80%),
aa) Propylene glycol (PG), Dow Chemical
Co., USP Grade (active level=99.96%),
bb) Sodium 2-ethylhexyl sulfate (S2EHS),
xHenkel, SULFOTEX OA (active=39.68%),
cc) Sodium C12-C1e sulfate (SC12-18S) ,
Henkel, TEXAPON ZHC needles (active=90.95%),
dd) Sodium cocoamphoacetate (SCA),
McIntyre Group, Ltd., MACKAM*IC-90 (active=approx.
32%) ,
ee) Sodium cumene sulfonate (SCS), Stepan
Chemical Co., STEPANATE*SCS (active=44.6%),
ff) Sodium decyl sulfate (SDecS), Henkel,
SULFOTEX*110 (active=30.80%),
*Trade-mark


CA 02371925 2006-06-13
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gg) Sodium lauroyl sarcosinate (SLSarc),
Hampshire Chemical Co., Lexington, MA, HAMPOSYL7L-30
Type 724 (active=29.9%),
hh) Sodium lauryl ether sulfate, 1 mole
x.
EO (SLES-1), Henkel, STANDAPOL ES-1 (active=25.40%),
ii) Sodium lauryl ether sulfate, 2 mole
EO (SLES-2), Henkel, STANDAPOL7ES-2 (active
leve1=25.71%),
jj) Sodium lauryl sulfate/sodium dodecyl
sulfate (SLS/SDS), BDH Biochemical, BDH Ltd., Poole,
England, (active=99.0%),
kk). Sodium lauryl sulfoacetate (SLSA),
Stepan Chemical Co., LANTHANOI; LAL (active=72.65%),
11) Sodium octyl sulfate (SOS), Henkel,
STANDAPOL LF (active=32.90%),
mm) Sodium salt of NEODOe 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, W, RHODAPOW TDS (ac-
tive=24.65%),
oo) Sodium xylene- sulf onate (SXS), Stepan
Chemical Co., STEPANATE*SXS (active level=40-42%),
'25 pp) Triclosan (TCS), IRGASAN DP-300, Ciba
Specialty Chemicals Corp., Greensboro, NC (GC assay
on lots used=99.8-99.9% active TCS; mp=56.0-58.0
C.),
qq) Triethanolamine lauryl sulfate
(TEALS), Henkel, STANDAPOe T (active=40.1%),
rr) Tripropylene Glycol (TPG), Dow Chemi-
cal Co., Tripropylene Glycol,
*Trade-mark


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ss) p-Chloro-m-xylenol (PCMX), NIPACIDE*
PX-R, Nipa Inc., Wilmington, Delaware (about 100%
active),
tt) Glyceryl polymethacrylate and propyl-
ene glycol (LUBRAGEL DV), International Speciality
Products, Wayne, New Jersey (about 46%* active),
uu) CARBOPOL ULTREe 10 (ULTREZ 10 ),
crosslinked polyacrylic acid, BF Goodrich Specialty
Chemicals, Cleveland, Ohio (about 98% active),
vv) Diisopropylamine, Air Products and
Chemicals, Allentown, Pennsylvania (about 100% ac-
tive),
x
ww) LAPONITE XLG (lithium magnesium sil-
icate, synthetic smectite clay), Southern Clay Prod-
ucts, Gonzales, Texas (about 99% active),
xx) CELQUAT*CS230M (Polyquaternium 10},
National Starch and Chemical Company, Bridgewater,
New Jersey (about 92% active),
yy) Polypropylene glycol-9 (PPG-9), Poly-
glycol P425, Dow Chemical Company, Midland, Michigan
(about 100% active),
zz) Ethanol (Denatured Ethyl Alcohol
40B), Gold Shield, Hayward, California (about 100%
active),
aaa) Water--Unless otherwise indicated,
the water was prepared as follows: deionized (DI)
water was distilled once through a Corning AG-3
water still.
The following methods were used in the
preparation and testing of the examples:
a) Determination of Rapid Germicidal
(Time Kill) Activity of Antibacterial Products. The
activity of antibacterial compositions was measured
*Trade-mark


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WO 00/78275 PCT/US00/15729
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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 concen-
tration to use is at the discretion of the investi-
gator, and suitable concentrations are readily de-
termined by those skilled in the art. For example,
viscous samples usually are tested at 50% dilution,
whereas nonviscous samples are not diluted. The
test sample is placed in a sterile 250 ml beaker
equipped with a magnetic stirring bar and the sample
volume is brought to 100 ml, if needed, with sterile
deionized water. All testing is performed in trip-
licate, the results are combined, and the average
log reduction is reported.
The choice of contact time period also is
at the discretion of the investigator. Any contact
time period can be chosen. Typical contact times
range from 15 seconds to 5 minutes, with 30 seconds
and 1 minute being typical contact times. The con-
tact temperature also can be any temperature, typi-
cally room temperature, or about 25 degrees.Celsius.


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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 ATCC (American Type
Culture Collection) identification number, and the
abbreviation for the name of the organism used here-
after.

Organism Name ATCC # Abbreviation
Staphylococcus aureus 6538 S. aureus
Escherichia coli 11229 E. coli
Klebsiella pneumoniae 10031 K. pneum.
Salmonella choleraesuis 10708 S. choler.

S. aureus is a Gram positive bacteria, whereas E.
coli, K. pneum, and S. choler. are Gram negative
bacteria.
The beaker containing the test composition
is placed in a water bath (if constant temperature
is desired), or placed on a magnetic stirrer (if
ambient laboratory temperature is desired). The
sample then is inoculated with 1.0 ml of the test
bacteria suspension. The inoculum is stirred with
the test composition for the predetermined contact
time. When the contact time expires, 1.0 ml of the
test composition/bacteria mixture is transferred


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into 9.0 ml of Tryptone-Histidine-Tweeri 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 25f2 hours, and the colonies
are counted for the number of survivors and the
calculation of percent or log reduction. The con-
trol count (numbers control) is determined by con-
ducting the procedure as described above with the
exception that THT is used in place of the test
composition. The plate counts are converted to
cfu/ml for the numbers control and samples, respec-
tively, by standard microbiological methods.
The log reducti,on;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
90 1
99 2
99.9 3
99.99 4
99.999 5
*Trade-mark


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b) Preparation of saturated solutions of
TCS in water: A four liter flask was equipped with
a 3-inch magnetic stir bar and charged with approxi-
mately 7.5 grams (g) TCS and 3 liters (L) of water.
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 fii.tering assembly was attached
to a two liter vacuum filter flask, and filtration
was conducted in batches. The filtrate then was
transferred to another four liter flask and allowed
to cool. Typically, fine needles of TCS crystals
formed after the filtrate was stored at room 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-
cate) were analyzed by HPLC. The apparatus used to
filter the solutions was a Whatmari AUTOVZAL , with
0.45um PTFE membrane and glass microfiber prefilter,
cat. No. AV125UORG. TCS concentrations were caicu-
*Trade-mark


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- 63 -

lated using a linear regression line fit (Microsoft
EXCELO 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 0.3%, 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
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
surfactant necessary to almost completely solubilize
the 0.3% TCS was determined by use of an experimen-
tal design in which the concentration of surfactant
was serially reduced by a factor of two over a se-
ries of test samples until the approximate satura-
tion point of TCS in the surfactant was observed.
Then the difference in concentration (saturated vs.
just solubilized) was halved until a close endpoint
for TCS saturation could be determined. The satura-
tion point of TCS/surfactant compositions could be
effectively estimated with small-scale (15 to 100
mL) samples, but about 600-800 g samples were re-
quired to obtain reliable final results. The ini-
tial ranges, therefore, were established with


CA 02371925 2001-12-19
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- 64 -

small-scale samples, and the final concentrations
were determined using larger-scale samples.
d) Preparation of compositions contain-
ing TCS and a solvent or solvent/hydrotrope combina-
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 crys-
tallize. In compositions containing a solvent,
hydrotrope, and surfactant, the TCS was dissolved in
the solvent as above, and then the hydrotrope and
surfactant were added to the TCS/solvent solution.
The resulting mixture then was diluted to the batch
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, Califor-


CA 02371925 2001-12-19
WO 00/78275 PCT/US00/15729
- 65 -

nia, USA). This method also was used with solutions
very near to saturation to enhance observation of
small amounts of crystals formed on the bottom of
containers.
Table 2 summarizes the results of time
kill tests performed on TCS/water compositions. Two
series of results, I and II, demonstrate the effect
of % saturation in TCS/water compositions, i.e.,
that within a given test series, reduction in %
saturation produces a concomitant reduction in time
kill efficacy.


CA 02371925 2001-12-19
WO 00/78275 PCT/US00/15729
- 66 -

-ri
0
0 U

H 1J Ln oo
Ei r-I N
14
ri O N H
O
=ri 0 1D cM
= l- r~
O y'
-1 Ul A N O
-rl G1^~
rA
O a1 UI Vl
L(1 L(1
O z rl
U p ~ .N (N ~ uNi Ln Ln
f~l
H N ri 00
}~ . . ~ . . 01 G)
rl O O O o N O
4J V
t0 Q
\ a p kD
tn ,~ 0 Ln ao
V Cry = ~ O
N
0
H Ln A r-i 0
0
4.- U
(d U) m m
ya Ln un u1
p7 \ ~ .-i ~-+
4.)
ro -ri ,.l M ko l0 kO
~y 14 rl O r N
rl O 0 O 0 r-1 O
0
44
m
v -rl 01 '-I N
91
N ~ 1A A rl 0
a
~ ro ~ m Ea
Ln u) Ln
-rl aJ r cn rn r)
m o O o m N
y~ . . .
r1 O ~ o. o.
ri O
Ei

N a r ~n ~o
0 0 0 0
b v) \?~ rxi m ~ ~ 0)
H F bi A 0) ri ko rn

O 'd 'b
- - tl - rd
t~ 4-) - i-) -
m o~i m rt u~i ro
~ m ta
a cW dP oVo
~ 0 o aa o or
0 in 0 o O
un

H
H H


CA 02371925 2001-12-19
WO 00/78275 PCT/US00/15729
- 67 -

Comparing the data in Tables 2 and 3 shows
that at the very lowest concentration of TCS (i.e.,
to 10 ppm), the efficacy of time kill is reduced
compared to samples containing higher levels of TCS.
5 For example, a sample in Table 2 containing 0.93 ppm
TCS has a log reduction of 0.44 after 15 seconds vs.
E. coli, whereas a sample in Table 3 containing 484
ppm TCS had a log reduction of 4.13 after 15 seconds
vs. the same organism. This effect is more apparent
at shorter-contact time periods. Another example,
in more complex compositions is illustrated in sam-
ples in Table 3, i.e., 50 ppm TCS (est.)/l0oPG/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 min-
ute. The data in Table 3 also show differences in
efficacy when different solvents/hydrotropes are
used with approximately the same TCS concentrations.


CA 02371925 2001-12-19
WO 00/78275 PCT/US00/15729
- 68 -

w I:v r- 00 r- co i-n r- Ln
Lfl N M r l0 M l0 M l0 l0 lD N ~ [- M Ol ~ ~
=rl r-I
Ei = O
M O d~ d~ ~M d~ d d~ d~
O ~ I O
/\ N A A A A A A A

O
U
w 0 in o Ln in o ui i.n in
M r I ("1 rl M r I r1 rl
\ \ \ \ \ \ \ \ \
V 61 M [- OD rl N LI) L(1 L(1
4J N N ri d~ M N ~zv N M
m
>4 d d' V A d~ d~ d~ O O
m
0
~4
4J
0
N 01 [- l~ l- l0 01 l- O\ M
~
ro M ~-1 d~ rl cM \O r-1 d~ ~-=I M ~zv (`'7
,~y+>1, dl O d' Lf) M LIl M Lfl lzv O N ~ O
n A A A A A A A A n
~ N
~a ro
4J o Ln O in in o in Ln in
H M rl r--I M -I rl r-I
\ \ \ \ \ \
> U tD l~ lo Ol t- 01 u1 0
O O :v r-I lzv l0 rl ~t rl N
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A A A A A n

~
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m 4J ol. r~ FC w 04 w w a, a w a w w
i'Y a QI O\P O\w G\p O\p O\p 0\0 0\0 C\w 6\0 0\0
,1a N 1.1 H H lJ) r-I l0 (Y) C) Lfl N O O O U) m
Id > 0 o\o o\o OD 0 00 Lfl N O L(1 O O O o\o o\o
E-I rl fd L- [-
O Lj = = '-1 N= ~f'= ~= l~ O = = O= Ln= L!l Ln
' H ~--~ m O
CA ,7+ N d' d' d' d' di di L11 Ill l-
41 ji
a) a) L,
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V a o df OJ r-I (N O O. ~ O O ~ o
H ~
N O M L11 [- lp 0p H
r-I rl
r-I r-I


CA 02371925 2001-12-19
WO 00/78275 PCT/US00/15729
- 69 -

r=' r-i N Lf) OD t11 l0 l0 L-
=~i 00 M H M 01 Ol rl
r4 (D C) n -I M O [r O A O
r=I
'H
ti
O
U
w o o
u1 = ~
Lf) G1 N ~ N
N
4.) W
Ul ~ n o
N
a
0
$4
+)
0
$4 Ci 11' 0 Lfl N Ul al ~ ~ ~
=rl l0 , O d~ O LI) , = O
O M O O ^ O
\ Q)
ro ro
4J
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rn
r1 U d' u1 M M
O O ~ o o
N
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U
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P. U) JI U) i ~C >C U U U) U)
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4J i ow o\0 o\0 \0 1-=4 > r7 7 c~7 7 a w
F' o ~n ~n a a a a w a ra ra
o\o o\o oW o\o o\o o\o o\o o\o
=~, O O O O 0 O lf1 Ln
(N N
r-i r-I

1o!o!o!o!o
~ H
O O O N
Ln LI) LIl


CA 02371925 2001-12-19
WO 00/78275 PCT/US00/15729
- 70 -

{~. ~ fM r-I rl [- O\ ~ (Y1 V~ l0
rl N Ifl M N I(1 M N Lfl
~ n r1 (+'1 N N N A A O rn
~==I
H
O
o LO C) in in C) LO in in
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V \ \ \ \ \ \ \ \ \
O N 'v l0 O\ m N 0) l- ~zv
4.) tp Lfl H U) N L- O\ l0 H M
rA N H r-I r-I r-I N N O ri
>4
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m
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ro a
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Eõ4 M I~v Ln L- \D 00
N O
r-I r-I
r I r-1


CA 02371925 2001-12-19
WO 00/78275 PCT/US00/15729
- 71 -

00 rn
0 N
^ rI A
r=1
N
0
o O (D 0
M m m
\ \ \
Q1 l- Lf) lD
(1) 4.) N r-I CN = M
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m
0
p
4J
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s4 M 0,
m
A o A o
\ o
ro a~
ro a,
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0 0 m
Ln Lr)

rl N


CA 02371925 2006-06-13
64267-1185

- 72 -

Many compositions of the present invention
contain a surfactant, which potentially can reduce
the efficacy of the antibacterial agent. The fol-
lowing examples show the unexpected benefits
achieved by compositions of the present invention.
Exa=le I

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

*Trade-mark


CA 02371925 2001-12-19
WO 00/78275 PCT/US00/15729
- 73 -

14
~ ~
~
=.~
01 v
.,.~ N
~ OD 0 0 {1
G) M H H N
~ N
4J A O O O
0 0
p p~ N
0 tr
(d
N
N
J.1 =='I
ro ti '~ O o o 0
~
~ V d N 0 0
.~ A 0 0 0 4-)
p 0
m U
a ro 4J
rn
a w a ~ o N ro N N
A r-I U
H
w
0
G
0
rl
o 4-'
.rl (a
a~

~ ~ ~ ~ ~ ~ ~
rz:
P d U
m v
a
~ 4.) ~ ~
cn 0 co
cd 4-)

~ O `~ .~ ~ +
U r. uo 0
=r'~ ~i -r'I
{d U1 (~ J 1
M E ~
U)
11 E~ = rd
V U)
b ~ i ~
0 U op
w
a
.: N m


CA 02371925 2001-12-19
WO 00/78275 PCT/US00/15729
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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 100% saturation, offers signif-
icantly greater antibacterial efficacy than any of
the three commercial products tested, against Gram
positive and against Gram negative microorganisms,
both of which can present a significant health
threat to consumers.

Example 2

This example demonstrates that the anti-
bacterial activity of an inventive composition is
attributable to the active antibacterial agent, as
opposed to the surfactant. Test compositions A-i
and A-2 were prepared. Composition A-1 is a solu-
tion containing 0.3% triclosan, 1.35% ammonium
lau"ryl sulfate, with the balance being water. Com-
position A-1 is 100% saturated with triclosan.
Composition A-2 is a "placebo," i.e., an aqueous
1.35% ammonium lauryl sulfate solution that is free
of the active antibacterial agent.


CA 02371925 2001-12-19
WO 00/78275 PCT/US00/15729
- 75 -

~ 0 m .G r O
M O
.,~
~ E
d rn U)
N N M ,~
11 0, d~ .
n O
Ln
1J l0 lll
fd U rI N
O M O
.0
4.1
U
=d N
N
. .
o ro M M
A A
0
-.l
4.)
b o
(D 0
4.)
cd
N
dP
dP
rt
N o
o M o
r-1
.,~
Ei
4J
U
~ --I N
b
o
$4


CA 02371925 2001-12-19
WO 00/78275 PCT/US00/15729
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The inventive composition A-i clearly
provided an excellent, broad spectrum antibacterial
activity, whereas the "placebo" composition A-2
exhibited an extremely limited spectrum of activity.
Composition A-2 has especially poor efficacy against
Gram negative organisms. Control of Gram negative
organisms is of particular concern to consumers
because such organisms present a significant health
threat. The excellent broad spectrum activity of
composition A-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 0.0872% by
weight triclosan, 47.5% aqueous PG, and the balance
being water. Composition A-3 was 100% saturated
with triclosan and is a composition of the present
invention. Test composition A-4 was a "placebo"
consisting of 47.5% PG, by weight, and the balance
water. This example illustrates an added advantage
of including an optional hydric solvent in the 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
further demonstrates that the antibacterial activity


CA 02371925 2001-12-19
WO 00/78275 PCT/US00/15729
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of a present composition is unambiguously attribut-
able to the presence of the antibacterial agent.


CA 02371925 2001-12-19
WO 00/78275 PCT/US00/15729
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rl
, i 0 N t~
rl U
(N o
m
~
.,~
4J
N t!1
lll
0 a o
U
m x
O
M N
4õ) N lfl
~ V d~ N
o
0 r]
-1
4J
U
'~ tq
Ln
0 ro ~
A
0
-rl
4J
o 0
H
4J
td
N
dP
dP
ro N
UJ o
~
rl (D o
o
.r{

+J
U
ro M d4
o ~ F:C
p


CA 02371925 2001-12-19
WO 00/78275 PCT/US00/15729
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Example 4

This example illustrates that composition
of the present invention provide an acceptable sani-
tization efficacy even though the compositions con-
tain a relatively low concentration of disinfecting
alcohol. Examples B-1, B-3, and B-5 contain 0.15%,
by weight, triclosan, at 100% saturation. Examples
B-2, B-4, and B-6 are comparative examples contain-
ing 0% triclosan.


CA 02371925 2001-12-19
WO 00/78275 PCT/US00/15729
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a)
~D O 1 O M O O
W O ~ ~ O O O '"{
ro
CQ
N
Ln Lll 0 M Lfl -V
rl I 0 0 ro
pq O O:v O O O
Cq
N
00 U
ep O ~ r-I M ~j al O N r=I O p rl

bl cn
~
m

A
N
v M Ln O ~ M N
dP H O O ro
00
~ O N ~ O O 0 ~
CQ
N
LI)
N O ~ ~ O O
al O M O O O '-I
(d
a)
rl Ln M Ln
00 ~ O O ro
O O O O
r-I
0
N
rl ri U2
U H
ro
11 r ro
Ci A N 0 a =
-rl U] rl ~ rl 0 U
N 0
ro a ~ n w ai ~
dl (a H -H ~I 1J (d
a ~+ i-) a-~ a, ro
H H w A ~D 0 a :3:


CA 02371925 2001-12-19
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The following table summarizes the results
of a time kill test at 15 seconds.

Log Reductions at 15 seconds

Example S. aureus E. coli K. pneum. S. chol.
B-1 >4.61 >4.78 >4.51 >4.49
B-2 >4.61 >4.78 >4.51 >4.49
B-3 >4.00 >4.44 >4.20 >3.92
B-4 2.50 1.20 >4.20 >3.92

B-5 >4.39 3.29 1.37 1.30
B-6 0.10 0.0 0.35 0.34
These results show that acceptable sanitization
efficacy is achieved, even with reduced levels of
disinfecting alcohol and other polyhydric solvents.
Furthermore, the compositions of the present inven-
tion provide a persistent antibacterial benefit
because of the nonvolatile nature of the active
ingredient, triclosan, whereas presently marketed
compositions do not provide a persistent antibacte-
rial activity.
In particular, Examples B-3 through B-6
demonstrate that the rapid antibacterial activity of
the present compositions is attributable mainly to
the antibacterial agent, e.g., triclosan, as opposed
to a disinfecting alcohol. This is in contrast to
prior art disclosures. For example, composition B-3
contains only 28% ethanol, yet exhibits excellent
broad-spectrum antibacterial activity at 15 seconds.
Composition B-5 contains no alcohol, yet exhibits
excellent antibacterial activity against S. aureus
and E. coli. Prior art teachings rely on a high


CA 02371925 2001-12-19
WO 00/78275 PCT/US00/15729
- 82 -

alcohol concentration (i.e., >40%) to achieve a
fast, broad-spectrum antibacterial activity.
Example 5
This example illustrates the effect of the
identity of the surfactant on the antibacterial
activity of the composition. The test results sum-
marized below were performed on a wide variety of
compositions containing either an anionic surfactant
or representative cationic, anionic/nonionic,
amphoteric, and nonionic surfactants. The percent
saturation of TCS in the compositions of this exam-
ple is at least about 90%.


CA 02371925 2001-12-19
WO 00/78275 PCT/US00/15729
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=~-.
o "H
u El + + + + +
+ + + + + +
N + + + + + +
IY) ~ + + + + + + + O 0 + 0 0
y
N ^~

ro El + + + + + + + + + + +
+ + + + + + + + + + + +
N + + + + + + + + + + + +
b~ ~. + + + + + + + + + + + +
N i
1.I
m ~ 0 ~ 4J u) O N
(U v- un tq ttY -W U 1~
4J r-+ ~4 o a~ w rt ~4 ro
fa :j rl ~' +J r-i 4-4 L~i
v-+ Cf~ ro Q) ~v a rt ~j =-+ 0
-i a -W x - w U2 ;:j a, 4-4
rd 4) -i m ~ r-i
q U~ 7 N u-a ~ a) 0 -1 ;j H
~-f "O u] >1 -1 0 c1> >. U
O ~ j H U >1 U 0 ~+
>1 (0 E (n x ~ m ~+ 0 ~+ k m
~+ (a 41 0 >1 ro :J U a) 0 ~n
r-i-j w U -rl ro iJ ro
b ~a E 0 cn >. I a) N ~-+ E rn a cn
a a G a 4-) N_ r. Q H 0 w
co v
rq ra 9 U =ri E -=-4
~ ~ u1
G s' . W 0 EU) E E E ;j U)
a.) 0 4-) H ;j ]C tlo ~j ;j =.4 N >1 -ri 4.)
q -~ E a) -- E -~+ w ~+ -H -H (d J., ro rts
f0 'o ~ =.=1 0 'd N ;j ''o 'd JJ JJ J-) O L;
41 0 ?-i a) =ri 0 u] (a 0-- 0- -H 0 a) cn =r-i
U rn H-W 'd u) -- a U) u) cn u) a a 2: m
ttl dP r0 0 U cn dP O
W aa cn Ln ul or w cn aa ai dP w (L) aP -1 dP cn w or U) Ln U
~I w a (+1 Lfl r-i ln JJ L(7 Lfl 'o Lfl (~ Lfl ra lfl 0 w N~-1
. ~ . ~ . :j p . b . . W . ul . ,a . X . (d
U] =--1 ~ r-I ~-' H CJ) U) 0) 4-4 ri N`-' N~-' r-I `=-' f-I (14 `--' rI CJ)
U
C'.
0
U
~ ~ ~ W ul U) cf) cl) (n U) co cf)
(1) U U U U U U U U U U U U
D H H H H H H H H H H H H
-r=1 dP cW oW Ow dP cw dP oW ow oW ow ow
J-1 (+1 m f+1 m M f+1 M rn rn m m M
V . . . . . . . .
~ o 0 0 0 0 0 0 0 0 0.
0 0

=r-I -r-I =rl =ri =-1
Ii U U U U U
r. ~ G A r_:
O O O O O
=rl =r-i =ri =r-I -r-I
9 ~ U ~ ~ ~ ~ ~ ~


CA 02371925 2001-12-19
WO 00/78275 PCT/US00/15729
- 84 -

.N
H L~
O ==i
U Fj
= H
O 0 0 0 0 O O 0 0 0 0
(d S + + +
+ + + + + (~ f0
= e-{ + + + + + \ +
\
+ + + + + + A O
i ~
N fr' ri l~ 4) .`~i 4)
1J U) ~ ta 4-) 4) U) U
rts .~ cn w m G 4-) rts
1J 04- JJ ri 1! -.i rd 4a
4) =r-I u) Q) ~-1 ::j U) (0 C"+ 4)
i-i
U q d 0 N-- U] U li 0 1.)
td ~ U] ,4 ,' .-1 (a (1) 44 to U]
0 E O r-i a..~ 1 ~4 0 CU r-i L+- d~
i) w rl >. W U1 4) 4 ;j rl rl ~
rl a -1 s4 w J., 04 cn ~j >1 ~t M
'd -- >. a rl a 41 e U) ?-1 i N
o cn 0 4 cn >1 cn w -~ ro a 0
ul N ;J q ~4 " N 0 0 =ri
rl 4..1 (d -- .'j 11 I U ~-I 44
,~r a 4) 'Fr
'C ~ ~+ ~ a N a w ?-~i w u 0 04 ~ ~ r ~ z
0 ;j (t 0 ~J a 'ci 0 FC 71 x
fd (IS 4) 4-4 f0 e N fu Ua ri
a qr-i -r-i q :j r-i a ;J E ~ E rA E v
4+ -ri ;j rc$ -,I -ri 0 -1 (15 4 ~$ -- a) ~l 4-)
a m O U ro E E o 10 U a -li cn r. =H rt
ro ~ -- -ri u) U 0 1 ~l w 0 0 ~ 10 - rn v r-+
aJ -ri q -~ 0 U) r-i -1-t cn U FC 0 -1 f 0 >.
U rd O q U) =O U) U) E cn SC
Cd O FC r-i u1 0 ckO ~ O-1 dP dP W dP N - 0
w m u] U'O dP w in N tA O ui r~ Ln LL Ln u] aa r-i A. cn da Q
Sd a -r-1 tf) ri N.LJ 5 (N U [- N O Lf) U Lfl a 0 14
0 owU) dP X = :3 - (d dP I .u) =U . 9 =~n . 2: = ro
UI r-I r=1 O rl Ul r=i W rl N H - r-I `-' r-I `--' r-I `-' rl `-' N C.1
U
G.'
0
U
Ul U] U) cO M U] U) U) Cm Cn U)
N U U U U U U U U U U U
> F H p E~ H p E+ H E-4 H H
-I ap uw da dP oW cw cw aw op dP cw
41 m cel f=1 (+1 m m r'1 f=1 M (==1 f=)
V . . . . . . .
O 0 0 O 0 O O O. O. O. O.
U U U
4) =ri =rl =r-1
~ O. 0 .0
+J 0 0 D U 0
a z z H -r-i z
ro ~ ~ k ~,
4-1 U U U U U U) U) U U U U
U =ri -r-I =r-I -r-I =r-I 11 41 -r-I =r-1 =ri . =-I
ro G G A q ~ 0 0 r. G G r.
w 0 0 0 0 0 4 J., 0 0 0 0
14 =rq-I -prl =rl -qr1 -r-1 04 =ri =qri =rl
N ~C rC FC ~ aC FC r~ FC ~C ~


CA 02371925 2001-12-19
WO 00/78275 PCT/US00/15729
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=~-.
O =-I
U Fj
H
O
lii .. O 0
a1
~
N -~
~ N
ro
H +
+ O O
U
04

~ U N
i.l 1-) 4) Ul O
Q) U) 0 0
}- a U .-i
:3 H
a -- cn
~
~ ~ ,~' o
~
rt - -i (s 04
i~ o 0 -~ r, 00
~
=ri U .x >C
U A N ~ 0 41
w u~i v0-4 dP 0
$4 N rl Lf1 J-1
3 = ~j - do Ul
U] r-I Cf] N 0)
Li
r-I
r-i
U -r1
0 U U) M m E
Ul U U U -~
> p H p
=rl w ow da
a.) rn m m q
U -r=1
~y O 0 (D
A
0
H -.i 'L7
1.) 0 3-+
q Z rn rn m m m
ro-- U U a,m 0) m m m
y.) U H -,..i 0 . . . .
V -H C," -f. r-I m N r~ O O
10 L; 0 0 A A n A V
w 0 -H -r-i
N ~ r. G .. +
vi z 0 z 0 a,+++
x++o


CA 02371925 2001-12-19
WO 00/78275 PCT/US00/15729
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The results summarized above demonstrate,
unexpectedly, that antibacterial agents and anionic
surfactants form highly effective antibacterial
compositions when the % saturation of antibacterial
agent in the composition is high, i.e., at least
50%. In addition, it was observed that, within a
homologous series of surfactants, efficacy can vary
(i.e., in the sodium alkyl sulfate homologous se-
ries, sodium lauryl sulfate and sodium octyl sulfate
yielded high efficacy formulas). The efficacy with
respect to the cation also is unexpected (i.e.,
sodium, ammonium, and triethanolammonium lauryl
sulfates provided high efficacy formulas, whereas
lithium and magnesium lauryl sulfates did not).
Example 6

The following table summarizes the effect
of surfactant identity on the antibacterial activity
of the composition. This example expands upon the
data provided in Example 5. The table includes
results of tests performed on a wide variety of
compositions containing either anionic surfactants
or representative examples containing cationic,
anionic/nonionic, amphoteric, and nonionic surfac-
tants.
The results demonstrate that various an-
ionic 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,
sodium 2-ethylhexyl sulfate and lauramine oxide.


CA 02371925 2001-12-19
WO 00/78275 PCT/US00/15729
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However, it is possible that the high activity of
the lauramine oxide containing composition was due
primarily to the surfactant.
Series I (Lauryl Sulfates) demonstrates
efficacy effects attributed to the cation. The
sodium lauryl sulfate had the highest efficacy,
wherein ammonium, monoethanolammonium and
triethanolammonium exhibited intermediate efficacy.
Lithium and magnesium sulfates exhibited low effi-
cacy. Potassium lauryl sulfate was not tested be-
cause of its low solubility at room temperature.
Comparing Series I (Lauryl Sulfates) and
Series II (Other Alkyl Sulfates) shows that efficacy
varies within a homologous series (i.e., sodium
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 (EO) in surfactants tends to inactivate TCS.
The activity of SLES-1 and SLES-2 vs. S. aureus is
attributed to the anionic ("lauryl sulfate-like"
character) of these anionic/nonionic surfactants.
The results for Series V (Miscellaneous
Surfactants) shows that these compositions exhibit
moderate to low activity, with the exception of
lauramine oxide. The portion of high activity of


CA 02371925 2001-12-19
WO 00/78275 PCT/US00/15729
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LAO is attributed to the surfactant alone because of
its quasi-cationic character. The remaining
surfactant/TCS compositions in Series V showed var-
ied activity vs. S. aureus (Gram positive) and very
little activity vs. E. coli (Gram negative).


CA 02371925 2001-12-19
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N M L- [-
~.' O 00 31 d~ LIl ~--I
M rl
=rl 1O %O Lfl = cr N = = = M m
~y M O~ O1 O 0 00 Lfl d~ d~ = N = C)
-r=I = = = = M r-I = A A A IT = O =
\ \ \ \ r-I \ O
ry r=I W N M \ N = 00 0
O \ \ \ \ [- \ \ M r- r ui \ w \
O ~n w r-i m 0 ao \ \ in oo v w v rn 0 w
O fyl lfl M = L11 M r-i V~ = = = = lfl = O
= f+1 = . = C) = lfl = d~ d' W = O =
{A r-i r-i 0 r=1 = 0 A A A A 0 i O
v d r r rn d m rn
01 Q1 01 O) M aD m M O)
ryl -rl . . . . M M . =.-i = . = f~l Lfl
M f=1 M (='1 O [- OD d~ M d~ = 00
~ A A A A = = A = A A A M =
{i r=I \ \ \ \ d~ M r-I \ r-I \ \ \ A N
q\ ~r d ~ r \ \ = ~ m \ a rn m \ \
ro m o) rn m m m M %o m m m ~ rn
o = = = = N ~ \ \ = r = = = N 0
= M M M M M = = ~ ~ d~ = d~ M d~ =
A A A A N (14 i i A rl A A A M N
U]
00
U) U)
q v [-4 W W U r-i
tis N N N U]
U] Ul U]
U) U) tlf 1-) U]
4-~i . ~ r-4-4 i W U] ~ N N U]
14 ) U] ~$ rl JJ J..) 'L$ U] i
:3 a a co :J m ro a) N
Efl Ul uo N N UI 4.4 44 'L3 ri
4-3 u -1 4-) in co r-i U) v
(a rs a) (a O o a-- 4-)
=-~ N N 4-4 w 1.) w m cn U] m ((S
4-) 4-) r-i r-i ~-4 c6 -4 N w N
(s rt 0 ro ;:S w 0 r-i r-i i-) r-i 4
=rl 44 va m fA r-i (0 r-i U) U1 N >+ >1 c0 ~l ft
v1 ,~ 0 A-3 iJ X X v-i cn u-i
r-i r-i U] r-1 td ro N N ri ri
En En >1 >+ ?. 4-4 w ,.O 4 ::l r-I
=~ ~4 s4 -ri S4 r-i -1 , -i U) 71 r-i r-i ::1 E ==-1 >1 ~$ >1 U
>+ ,1 r0 rd ro E 74 ro N U] ,t,' ri N r-I
U JJ S-I ~-I r-I r-i r-I f0 0 r-i J-1 JJ TS ,r
H 0 -1 0 r-i (d rt N 41 U H ,k
N ca ro E E A 0 r-i E >. 7. ~ I N ~4 r-i
-rl r-i r-i ;:1 ~% (u .{-'. ~l 11 1) N N 'LS 11 (d
N E E G' G'i JJ ~'i Ul 0 0 E E E E~ E
O 0 N 4-1 =r-1 N 0 ~j ~l 0
bi E E 0 (U 4 G m -1 -ri ri -H =11
'C) G'i r-i J-) 01 4) 'd 'o 'o 'c$ 'c$
0 0 rt m O ~4 -ri fd 4.) =r-i -1 0 0 0 0 0
m cn A. E E w o o ~n uQ u~ ~n ~n
4) Op Op I.() ln Ow Ow Op Op m ril Oh Oh Gp Uw Op
,[i w M M Lh Ul Lfl Lfl Lfl lfl L(1 Lfl U)
yJ m . . . . . . . . U1 o1c op . . . . .
0 rl r-I rl r-I r-I r-I r-I r-i ~ l!1 u1 Ol O~ N N rl
W 'T-
m U U U U U H U U U U U
'J = ~ E-1 U~ E-i H E-A E-1 '~= H co E-~ U] E-~ H E-~
f-, ~n ~n cn ~n cn x m ~n cn ~n cn
=ri U ow U oY~ Cw Gw Cw Uw U Gw U Cw Uw Gw
JJ (y ~==~ M E-1 f~l M M m Cl E-I (='1 f~l M
. = . = 4) . dp = cp
U 0 ~'= = dP
0 O 0 C) O O 0 O 0 O O O O
a
~ H
H H
U U tll =-1 r-I N =-1 =-I 0 0 O 0 0 0 0 0 0 0
11 -ri =~-i -r=I r=I -rl =ri ri ri =rl .=i
w


CA 02371925 2001-12-19
WO 00/78275 PCT/US00/15729
- 90 -

r M l0 ~l
r~
C) N N r 0
=rl M = = 0 N (N cr kO = kO
= = O = d O
r 0 C)
ry 0 O = =
i-{ rl rl \ \ \ i M A 0 N \ O
O\ \ 00 M C) \ \ \ \ r-I O~ \
U N t11 C) N (n C) N H = H M
O M = = = i-1 00 r 0
= d~
= M = 0 O O = = = = \ C)
0 I I t O O rl 0 C) O
IT C) 0) L(1 0)
~. M rl M N d
tlQ =rl = m N = ri w r-I = = = LIl
0 ~7 OD Lfl O w 00 N d' O r-I
i =
~ A = = i = = = A A
S~ rl \ 0 C) \ f+l r-i O \ \ \ O
\ \ U)
R1 fA M U1 l0 H dD kO 00 M N 'IV w
O = Lfl N = 0 C) r-I = = = H
~ . 0 . . d~ d~ O =
A C) O O. A A I O
r-I
1
~
W N
tn
m 0
~
+- W ~- w
m ~
V~ rl W N
0 4J

41 Z
U i ~
ro Q) N
11 U1
1a (t 1J
w v ro
a~ o ul w x
0W O ~ N A
=,i - ~ i fo
U1 N N N N JJ ~4 U
~ v a) v iJ 41 iJ v w o
4-) .u 4--) rts rd m ~v O
~ 0 tld ~ t[S ~4 S4 4 -1 11 rl
U N N N ~ ~ N .~ >C
U1 m 0 ~ r-i ~ rt rd rd
U a.- U 0 0 0 r-i r1 rl ~ rl N
~ ~ ~ +1 ~ E 0)
'd -rl -r-I -rl -ri -rl -r-I =ri 0
N U) ~n ~n U) rn ~n rn ro ~ ~ O
~I UI U) U) U) U] UI U) +3 -ri
b1 t~ r0 rtf rq (0 r0 tt V Lf -r-I Sv
,.) -W ~ .u ro 0 ro x
H 0 0 0 0 0 0 0 0 w cA -r-i 0 0
+' a 04 04 04 04 a a 1+ ro N 4J
s~ ro :3 w 0 U
N ~ dP dP dp dp dP dp oW ta LI1 U] dp 0
~ ~ L(1 O Lf) lfl O 0 O N ~ O A.
Q A rl rl N N N M M a -I rl N d~

v ~n m U) m cn b m m U) U)
> = H H CU-i ~n H CU-1 U) +J U H [U-q C-U~
-rl U dP oW oW U oW dp U a dp oW o`P dp
43 0 ~ m M M ~ M M ~ U 0 M f"1 f~l C~l
U O
O O O O O O O o O O C)
-II
~ H y
H H U \ U \ U U
i U=rl -rl
U=r1 U-r
m W -r-I A =ri ~-,' =.-1 ~,' C'.
G) . . G) r. O r. O G O 0
C) =rI 0 0 0 0 0 =rl 0-14 0-,1 0-1 -rt
$4 -~ r~ -H r~ -,j 0 q
E-1 rn (n z ~ z ~ z z


CA 02371925 2001-12-19
WO 00/78275 PCT/US00/15729
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(+1 (n lfl
lp O H N
=ri = m O kO 00 = N M M = ri 0
[- = r-i f+1 0 N ~'rl N O 10
. p . . . . . i . p
A
'-1 rl \ d~ \ 0 O \ O O O O i
O \ ri \ ui \ \ m \ \ \ t- \ \
U~ l0 00 0 N 10 O r-i 00 aD H r-I r-i
O = H 0 (+1 = rl N r-i N 0
= M 'IV = O= = = 0 = = = O=
= =
A O 0 O O O ~ O 0
Lf1 O M h
N kO N 0 ri
!q -rl = l0 m l0 00 m . d~ . = =
d~ 00 = O kO 0D d~ O O O O
= ~ i
~ A . lzv = A
G{ ~==I \ c~l A V~ (11 r7 \
"a \ Ul \ \ \ \ \ d~ \ \ Lf1 OA O
RI fA N lfl lfl 10 01 10 cN l- r-i 0 rl
O = Lf) O 0) L- r-i = M [- = =
M rM = = = = = W = . O O O
!!~ A M d' N r-i t+) A r-i N
N
1J
~ U 1J O
GGG111 U 0 0
r-i U] r-I
~
>1 N U] U)
v] a fa -ri
~4 u)
C!~ Q N N
ro a 4.)
+J U) a) rt FC
cu w 0 co X ~C
(0 ro -r-i a U] 0 U fYl
~ 4..~' -r~ i U u' w
:j ru U 0 U
t11 rl U Ul N ~ N
=rl ::1 0 1.1 N Q1 1.1
m ua U) v, (o a) +J 4 rd (D 0
~ 0 0 -1 J-) ,J (s a 4J 0 a
a o 0 U w 0 (1) (u 0 -H a) -1 r~
ro ~ `~ ro o ~ ~ rt ~
u) m 4 0 w r-i f=- 0 N N
4-1 4-4 r-i ;:I U1
q U) U1 -1 C~+ 0
.i L~ tl >. 'o ~ ~ U
~ =11 0 ~-i rn 0 0 (d >1
m SC X ~+ 0 c0 S4 -ri U) 0 0 r-i
EU-N 0 0 b ~ ~ ~ r-i t U .~ a) 44 0 P+ ~
G) N N r-i E~ ~-I U) r-i S4 U 0 r-i
-I ~ 0 r= ~ a1 0 r0 rd 0
+3 =~ -~ rz ~J -~ ro U E =H 04
m V. E E :J -ri r-i Cd q 0 E
H cd co i -r-I '-d 0 >1 4 =rl -.i (t ~
tT 43 ~+ ~-i 'd 0 cn E .S' . 0+ r-+ TS U ~
A U ~ 0 U) -ri ~ r-i .~ 0 0 X
H 4"~ r-i r-I ~ 'Ld ~ 'd ~ ~ O d' U] U f0
3=1 w cW dP 0 oW rl I oW oW
N da aa in aa in En ow in U O in in ow
.{y N Lfl lll N lfl N O N r-i N L- lfl
yl = . . . . op = = aW 0 . .
0 r-I r~ r-I H r-i rl N H M`--' rI r-I N
0
~ ~ ~ ~ ~ ~ ~ ~ m U)
N 0 U U U U U U U U U U
> = cd H ~ H H H H H H H H H
r-f ow U ow da ow aW ow dP an da ow or
-rl U
4.1 Q ~ M ~ r"1 r'1 c1 M N1 M M ~ c*) M r~l
U O
a' U rj p 0 0 0 O O 0 p O H p p p
~ U U
~ -rl =ri
U \ U ~4 ~i U
-rl U U U=r-I U U U U N a) =H
tl! C'. -r-I =ri =rl 0 =ri r-i =.i -r=I 4-1 4.1 r.
G) 0 r. r. G O q q 0 q 0 0 0
N -.i =rq 0 0 0-~ 0 0 0 0 4 4 -H
~ ~ z ~ ~ ~ ~ z


CA 02371925 2001-12-19
WO 00/78275 PCT/US00/15729
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Example 7

This example illustrates the effect of %
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 % 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/SOS compositions
vs. S. aureus) show a substantial decrease in anti-
bacterial activity with decreasing % saturation.
Also, 100% saturated samples (0.15%TCS/0.67%ALS) and
(0.15%TCS/4.0%SOS) have an antibacterial activity
approaching that of 100% saturated samples contain-
ing 0.3% TCS. In these two examples, the effects
are seen clearly for organisms wherein the sur-
factant does not show a strong placebo kill effect.


CA 02371925 2001-12-19
WO 00/78275 PCT/US00/15729
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00
~=~ ,,;
A A A A
~,~ \ \ \ \ \
-n , ~r
0
A w d a d
A A A A
>, O N
L(1 0) M C. l0 ~O 10 l0 l0
1.1 =H =ri o) 00 lt7 rl kD M d~
U U '-i Ei = . = .
=ri :j O M N rl ri M i cr d~ d~ d~ d~ N
44 U .q \ \ \ \ \ \ \ \ \ \ \ \
W m \ 01 r-I l- m O l- l0 l0 NV M [-
(Y~ a . O M kO M C) rl 0 M M ~ ~ Lfl
la 0 t~l ri O O O ~--I O VW M ~
=,~ a
aJ
U
c0
.4
.,~
r 14, ~r w ~v w w
a U~ (.~. Ol 01 O1 O~ 01 Ol Ol O1 O~ m m m d~ d~ N M O
w O=r~ 0 O 00 d~ N
0) r4 M M m m f"1 m M m rn m m = = = = =
O 1.4 A A A A A A A A A A A A m M rl ~--I M
rl \ \ \ \ \ -- \ \ \ \ \ \ \ \ \ \ \
~, rt1 \ L- [- l- L- r L- 14, d' d' w lq~ Orn Ol O1 w 0
fA 01 m 01 (n O) m 01 01 0', O'A m m M Ifl lll 01 (A
O
C.
-1 Cl~ M M rn m M M f"1 M M m M m M M N r1 O N
b A A A A A A A A A A A A
N
4J
ro
rn
rn
U
H
dP 4J
44 f..' (A U) In U) U] U) U) U] U) U) U) U) U] U) U) U] (q
o ro a a a a a a a a 0 0 0 0 0
+~ 9 ~ g m m rn m m m rn cn m cn m
41 U aa uw aa 9P dP dw av da cW an oW ow cw ar aP oW ow
ri ie Ln U) in in t- Ln o 0 O O o o U) Ln U) Ln o
m w M M M M kO M l0 l0 w w OD w r [- [- l- O
w w
yõi :3 H rt o r-i r r~ -1 r-i r-+ in in Ln in
pq ul

JJ o O O O O o O o o
cU m r Un (3) r in m r in
u] \ r-i
o1P r H L(1 \ o o
\ r H lf1 \ \ \ l- H Lf1
N N r-I ~ O N N rl ~ N N rl
pw M = = ~ M r+ M
Ul 0 O 0 C) O O 0 O O O O
U
EH


CA 02371925 2001-12-19
WO 00/78275 PCT/US00/15729
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m A
cy \ w
. O
QQ M d~
A
V O
11 vi ri
0 W 'd U rl
w a o
ri b1 M
c0 0
H
N
1J
U
lU
.A
-I
4J
m o
=rl M
r' 1{ 0
0 'a H
~y Ib \ (`~1
0 N N
=rl O
iJ tr~ v
ro
~
4J
~
U
Ei
dP 4J
"' m
0 o
4, U)
yJ U oW
u (a ~
4) 44 r
w
w u)
Gt~

a.)
ro
tn 0
dP
0
dP
rn
U
F


CA 02371925 2001-12-19
WO 00/78275 PCT/US00/15729
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Example 8

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


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WO 00/78275 PCT/US00/15729
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ri
o w Un r
.G N rn
,~ V . . .
M rl
x v~

-.~
4.)
N %1O (N L(1 00 [-

a M M O
0
m
N
O
M
J-) U cr d M

p n A
=rl W
4J
U
m y
a a
w m N
O
N
a ro M M M
A A
0
.rl
43
(d o 0
~4 o O 0
:j -4
4-)
b
m
dP
dP
td
~A M rI 0
0
ri 0 0 0
U
.,~
H
tJ
U
0 ~ ~


CA 02371925 2001-12-19
WO 00/78275 PCT/US00/15729
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This example illustrates two important
features of the present invention. First, the abso-
lute amount of triclosan, or other antibacterial
agent, is less important than the percent saturation
of antibacterial agent in the composition. For
example, composition A-6 (containing 0.10% tri-
closan) was at least as effective as composition A-5
(containing 0.3% triclosan). The important feature
is that both compositions were 100% saturated with
triclosan. Second, Example 5 also clearly showed
that the active antibacterial agent is responsible
for the excellent broad spectrum antibacterial ac-
tivity. Compositions A-5 and A-6 of the invention
clearly outperformed the "placebo" composition A-7,
which did not contain an active antibacterial agent.
Example 9

This example demonstrates that a hydric
solvent and hydrotrope can impart activity to an
otherwise inactive surfactant and antibacterial
agent composition. In the following table, all
percentages are by weight, and the balance of all
compositions is water. Composition B contains 1.35%
ammonium lauryl sulfate (ALS) and 0.3% triclosan
(TCS). Composition C contains 1.35% ALS and 0.0%
TCS. Composition D contains 0.25% ALS, 14.4% DPG,
10.0% SXS, and 0.3% TCS, and Composition E contains
0.25% ALS, 14.4% DPG, 10.0% SXS with 0.0% TCS.
Compound F contains 2.5% alkyl polyglucoside (APGTM)
with 0.3% TCS. Compound G contains 0.3% APG, 14.4%
dipropylene glycol (DPG), 10% sodium xylene sulfon-
ate (SXS), and 0.3% TCS. Compound H contains 0.3%


CA 02371925 2001-12-19
WO 00/78275 PCT/US00/15729
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APG with 14.4% DPG, 10% SXS, and 0.0% TCS. Composi-
tion I contains 1.25% sodium cocoamphoacetate (SCA)
and 0.3% TCS. Composition J contains 0.25% SCA,
14.4% DPG, 10.0% SXS, and 0.3% TCS. Composition K
contains 0.25% SCA, 14.4% DPG, 10.0% SXS, and 0.0%
TCS. Composition L contains 1.75% cocamidopropyl
betaine (CAPB) and 0.3% TCS. Composition M contains
0.25% CAPB, 14.4% DPG, 10% SXS, and 0.3% TCS. Com-
position N contains 0.25% CAPB, 14.4% DPG, 10% SXS,
and 0.0% TCS. Composition 0 contains 4% octoxynol-9
(TRITON X-100TM , TX100). Composition P contains
0.75% TX100, 14.4% DPG, 10.0% SXS, and 0.3% TCS.
Composition Q contains 1.25% sodium lauryl ether
sulfate (1 EO, SLES-1) and 0.3% TCS. Composition R
contains 0.25% SLES-1, 14.4% DPG, 10.0% SXS, and
0.3% TCS.


CA 02371925 2001-12-19
WO 00/78275 PCT/US00/15729
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N OD OD 0) 0) Lfl M
111 O M H kO 00 l0 H [- L!1
rl N N ON = = = = lf) = = = C)
~ ry O = O d~ d~ d~ = 'v O cM
.r{ Q l0 m A A A A I A
U \ \ \ \ \ \ \ \ \ \ \
~ 0) [- OD m 0) C) 0) L- M 0
M O fM d~ l0 Ul ~O rl l~ O~
. . . . . . . . .
.~ rl O d~ N ~T N
H I A A A A I A
V.
O
.rl
43 r
V r- O rn 0)
0) 0) 00 d1 H 10 ~--1 N M DO
y . . . LI) N = (14 = = pp
4) ~ 0 (l1 M M = = IdM = O 114 =
a {=1 l0 A A A r-i rl A r-1 I A O
J \ \ \ \ \ \ \ \ \ \ \
~ ro m r r C) H 0) a% rn in m w
o O 01 m 00 M rl 10 r1 1-I m O0
a ~, = = = . . . .
Cl~ `=' M Nl M rl rl C~ ~--I O lzr 0
A A A A A
C'.
0
.rj
J.1 O 0 C) O C) O
dp ro 0 o C) 0 0 0 0 o
y~
p ~ t ~ t t ~ t
~
ro
ul
ul cn
~ ~ x x ~
aa dW ~ ~ m dP aP
0 0 0 0 o C)
y o 0 0 0 0 0
r-I r-I

~ ~ A A ~ A A UUi Q A
F. Ln Ln v d ~n v~ Ln v w
~..~ M M ' ' . . . N
d d = d d
r-I
H 11 N ~ -i r-I H
N
~ ~
~ U U U
o a a U) cl)
oW aP dP dP oW aP
u) u, u, Ln
N N M M N N
O O O O O O
fd
~
O M O M C) M Nl O M M O
rl (jP
V O O O O O O O O O O
.rf
14
N

0
=,i
1.)
.rl
m PO U A W f~ C7 x ri ] x
0
~
0
CU


CA 02371925 2001-12-19
WO 00/78275 PCT/US00/15729
- 100 -

-q l~ m ko ko
r-I 'H ~A l0 = 10 :r v =
rl N O = V' = = ~, = V'
.r.{ Q t0 O A O n 0 A
~ V \ \ \ \ \ \ \ \
01 r-i f1 kO m [-
~ O (N L, N IT
U')
~ v . .
O. V~ ~+1 0 O
A A
0
-rl
41
m 01 O1% 14
tQ .. 0 m Lf1 If) ao rl OD
b GU = = cm H tfl = =
y N O o d~ = = = d
A O o o A A
p \ \ \ \ \ \ \ \
b, roM 01 Om kO 10 m o, -t
p O 0 m r r-i Ln
a ~, . . . . . . .
tr~ o w o o O ~ w
~ A A A
0
=,-1
.u 0 0 o 0 0
c0 0 0 0 o 0 0
~'
: t t ~ t t
a.)
cd
m
cl)
ui vi aa
dp da O O
0 0 0
o o 0 .-i
4.)

a a
m P4 q q o W aQa
s~ u ~ dw ~ a w
a ~n ~ ~
H L It 'IV dp ul ri
rl ri d~ N
{d r-I
Q) 0 H
r-I
O
o ~ ~ H a
6p dp In
Ul U) N N lf)
N
O O 0 O
Cd
m
0 m m O M m M M
rl dp
= = = =
U 0 o O o o O o
=rl
14
N

0
=rj
iJ
-rl
w aE z o a a a
0
0
U


CA 02371925 2001-12-19
WO 00/78275 PCT/US00/15729
- 101 -

The results of the time kill tests summa-
rized in the above table very surprisingly show that
the use of a hydric solvent and hydrotrope can im-
part a high antibacterial activity to surfactant/TCS
combinations which alone exhibit only low to moder-
ate efficacy (i.e., compare efficacy of composition
F vs. G; I vs. J; L vs. M; and Q vs. R). The hydric
solvent and hydrotrope also can render active compo-
sitions more active in shorter contact times (i.e.,
compare composition B vs. D). Especially surprising
is the observation that a hydric solvent and hydro-
trope can impart antibacterial efficacy against E.
coli even in a composition containing a nonionic
surfactant, i.e., octoxynol-9 (compare compositions
0 vs. P). This result is unexpected because poly-
ethoxylated surfactants are known to inactivate
phenolic antibacterial agents.

Example 10
This example demonstrates the importance
of % saturation in compositions containing a hydric
solvent and hydrotrope. As observed in surfactant/-
TCS compositions, the relative % saturation of the
antibacterial agent in the continuous aqueous phase
of the composition also greatly influences the anti-
bacterial activity of compositions containing a
hydric solvent and hydrotrope. As the results sum-
marized below illustrate, this influence on antibac-
terial activity is especially apparent with respect
to the Gram negative bacterium, K. pneum.


CA 02371925 2001-12-19
WO 00/78275 PCT/US00/15729
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0
.r.,
~
rtf o F' O ~
o cn o 0 3 0
1-i v v
4.i r ~ 3
cd
~
~
co
~ ~ ~ ~ ~ ~ ~ U)
o\ \ \o o\o cn co cn
0 0 0 0 0 ow o\o o\0
m O o 0
yJ o o O O o
H rl H o O O
Q A Q Q Q Q C) f21
lzM o\ o\ o\
H = Ln LO Ln
$4 r-I H r-I H N N N N
ri)

o\o oW o\o oW 00
o\o o\o o\
Ln O O O N L(1 O O
N lIl 0 O
~ N ln LIl
O O r-I rl

W
O M M M O M m M O
rl dP = = =
C) O O o 0 0 0 0 0
Ei

0
.rl
4J
.,-l
W U) H ~D > 3 >C ~+ N
0
134
r4
0
U


CA 02371925 2001-12-19
WO 00/78275 PCT/US00/15729
- 103 -

Ln Ln
a0 OD ~ 01 m N N
= U~ OD co m Ol N Lfl
O M M
0 t0 A A m n d~ m M N
'4 \ \ \ \ \ \ \
N Ln Ln rn M Orn o
O 40 OD ~ 1-1 00 M OD
.M. . . .
M m M N ~:v N N H
A A

OA M I-
OD l0 Ol 0
m ri
r"'~ ry \ n \ \ \
'rl (~ m \ M 01 O
O ~ d 00 N
m
~ Qfi `-' N N O O
4-1

0
.rl
41
U
~ rn rn rn
b .=. Lf) Lf1 lf) ol
m M Ul lfl
(~' ey O 't d' :v
Otc A A A 0 U1 01 Q1 m N
a O L!1 Ul L(1 d~
w M
A A A
N N
UJ .-. lD ~O ri O~
Ul M N
O M M
~ 1D A A N H
=,~ \ \ \ \ \
ro rn N N l- 0
O lo ko lo f-i
,~ . . . .
C!~ V M M ri ri
A A
0
-ri
4J
-r=I
W U] E-~ J > 3 >C ?+ N
0

O
U


CA 02371925 2001-12-19
WO 00/78275 PCT/US00/15729
- 104 -

From the above data, it is clear that an
increase in antibacterial efficacy, as measured by a
time kill test, is associated with an increasing %
saturation of the antibacterial agent in the aqueous
phase of a given composition. This example further
shows that compositions containing an antibacterial
agent, surfactant, hydric solvent, and hydrotrope
are effective when a high % saturation of active
antibacterial agent is maintained.

Example 11

This example, in conjunction with Example
10, illustrates the effect of % saturation of TCS in
compositions containing a hydric solvent, hydro-
trope, and surfactant. As previously observed with
simple surfactant/TCS compositions, the relative %
saturation of the antibacterial agent in the compo-
sition also influences the antibacterial activity of
a composition containing a hydric solvent and/or a
hydrotrope. From the data summarized in the table
of Example 10 and the following table, it is clear
that a substantial gain in antibacterial efficacy
(as measured by a time kill test) is associated with
an increasing % saturation of the antibacterial
agent in a given type of composition. The tables
demonstrate this effect from two different perspec-
tives. The table in Example 10 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.


CA 02371925 2001-12-19
WO 00/78275 PCT/US00/15729
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In the table of Example 10, the information relating
to % saturation is relative because % saturation is
difficult to directly calculate. Even using this
qualitative data, the effect of % saturation of TCS
is clear from both tables for all organisms tested.


CA 02371925 2001-12-19
WO 00/78275 PCT/US00/15729
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~ ri ri r-I r-I H
r-I
-1 00 co 00 00 00 00 co
r., . . . . . .
=rl M M M M M M M
N
0) l0 A n A A A A A
\ \ \ \ \ \ \ \ \
H ~O 0 m Lf1 O
~ ~ M
00 m
.~{
E ^ cn m M N N N ~
0
-{
4.1 Ifl L(1 l!1 lfl
U tQ Ln LI1 II1 111 Ln tJl l!1 m
",J' fq = = = = 0 0 rl 01
'd Ol O d' d~ d~ d' . = = =
Q) 1~ l0 A A A A m N rl
(4 :3 \ \ \ \ \ \ \ \ \
fd W lfl Lf1 Lfl lfl N kO ~44 N
bi 0 Ln in Ln in C) 0) rn r
0 M . . . . . . .
m Cl~ `-' ~ n' A ~ M ri r-1 rl
q
o
4.)
E ~ ~
O
w ~ ''i
~
0 O
rt
V s~ o o ri O o o in
-'i 0 ~ r-i O) OD l- l0 Lfl d~ N
1J 1d b
fd b1 N
dp
J.1 4-1
fd
N
dP
aa
o ~
0 43
U O U] [!) U] U] cn U] U] CO
b?~ ~A o~ da o~ ~ da ~ oW ~
x t) ul ul t11 Lfl ul Lt1 ul u1
ri . . . . . .
aai q ~ .
= o O O O O O o 0
A N 'd
cn ul In co cn U)
4,i o b- >C DC >C >C DC x ~C >C
=ri M 0 C!) Ul CO tA tA CA v] u]
> H oW oaP dP dP dP aP aP dP
.rf V Ln L(1 l11 lf) u1 Ln l11 u1
y) .ri ~I r-I r-I rl r-I r-I rl .1 H

o w w w w a a w a
~ oQW dQP o~W d Aa dQP dAP aQa
ui Ln Ln uO ui Ln Ln Ln
oY'

IO M N O O 00 C- k0 M
m r-1 l- M O 111 O 1o O
O -t M fn m N N r-i r-i
~
U O O o o O O O O
.,~
~
E


CA 02371925 2001-12-19
WO 00/78275 PCT/US00/15729
- 107 -

Example 12

This example illustrates the effect of
different levels of hydric solvent and hydrotrope on
antibacterial efficacy. In particular, the data
summarized below demonstrates the effect of varying
the relative amounts of hydric solvent and hydro-
trope. It should further be noted that the addition
of a perfume (PF) and/or a preservative (DMDM) to
the composition has only a modest effect, if any, on
the antibacterial efficacy of the compositions.


CA 02371925 2001-12-19
WO 00/78275 PCT/US00/15729
- 108 -

IV Ln Ln Ln Ln
r-, r o ao 00
ao 00
d
O d M M
O l0 A O A A A A A
\ \ \ \ \
V N d4 kD N Lfl lf1 O l-
O rl M 00 a0 Ln H
. . . . . .
N~ d~ O N M M M N
A A A

~ d~ Ol 01 r-I
r-I 6~ OD (3) C7 [~ 0 10 ~O 10 L- r-i H
V'
~ N = M [- O 10 Ol l0 0 M ~ = = OD N M =
lo A . O O . = M. r-I O . . N. M. n M A M A . . . ~
n N d1 A
4) \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \
(~ N d' ri M Q1 00 Lfl L- 01 01 r-I N It H
E 00 N (3) [- m ~D l0 OD [- O
O ri (") d~ ~
M
t O O N N O 0 0 r-I M M M 0 rl M
A A A A
O
y w l- ao Ln Ln Ln Om
w = r-I rl = = = Ln
r-i o d4 = = d~ d~ V =
b p%c A o =44 n n n lzv
y U \ \ \ \ \ \ \ \
a+ N V 10 Ol O) 01 (3) N
= O d' N d~ LIl ul tfl d~
p0 M . . .
p 114 O. N d~ d~ V~ rn
A n n n
M N N
01 .-. kO d' d' %.O kO r-I Oll
,.7 N = O Lll = = M N
G) O ("1 = = M M = =
o A O rl n n N ri
~ \ \ \ \ \ \ \ \
1{1 N M M rl N N [~ O
O \O O M kO kO kO rl
M . .
b~ `=' fl1 O rl M M rl ri
A n n

~C >C X >C >C >C x ~C x X X x x ~
U1 Ul fJl U) U] Ul U] U) U] Cl) U) U] U) ~
oW oW dP oW oW dP oW A. oW dP dP oW oW op
~ O O O O O O l!1 O lf) O O tfl O ~
U)
N
4J k ?~ O O O O O O N Lfl l- O O N Ul ~
~ ~ rl r-I r-i ri rl ri r-1 r-I rl N rl rl rl ~
~ O O C7 U U CJ U = C7
y0~ ~ C A A A A A A A A A A A A A A
oW do do oW d. dP o1p eW oW o`P oW dP oW op
p ~ d d a a `r o o 0 o o in in in
H
A q ui in Ln ui Ln r ~ ~ ~
w ow 0

9 ~ ~ ~ ~ ~ ~ ~ ~
aP o~ oW dP oW ul Lfl t.f) u1 lfl Lfl lfl Lfl F
N 0i o o ~
N u
O O p '-{ ~ O O O O O O O O ~
~
(d N
N
p O O M r'1 Cl O M Cl nl M ("1 M M M M
rl dP
V U~ O O O O O O O O O O O O O O O
O
11
H

0
.,~
N U A W m E+ A > ~ CO U A W [*a C7 pC H
O u
A
ri
O
U


CA 02371925 2001-12-19
WO 00/78275 PCT/US00/15729
- 109 -

r w a
~ .. 0) 0 0
~ o r~ d v
r-4 A A A
0 \ \ \ \
m r v~ w
V o 0) 0 0
N `~ M d d~
A A A

~ r-I H r-I O~ 0) r r
Ql N V~ dI N d' 0) kD kO m ~ r~l l0 ri rl
H .~ E N d~ r~1 0~ ON kO kO d~ ~ V~
W 4 M M 4 4
%O A rl m A A N O N n A A rl rl A A
~ (,~' \ \ \ \ \ \ \ \ \ \ \ \ \ \
(Q4 N r-I 00 r \ r-1 r-I r N ON m r-i r r r
0 O d' O 01 r- r-I Q) N 10 w r-I .-i
DC O O N O O N m m rn O O I~v
A A A A A A A
0
.,1 r ao 0o ao
yJ Lfl rn M r r r
V 'M N
-1 o d' -W
b Q ~O A A A A A A
4) U \ \ \ \ \ \ \
py al r Ir 00 0o ao
Ln o ri r r r
tn [~ M
0
A A A A A
tlJ r. l0 O
p m r m
N o
3~ ~o A rn o
p \ \ \
rtl m r m
o r o r
. .
tq r.,~ ri o

~ ~ ~
rn (1) U) cn U) ~n ~n cn ~n ~n ~n ~n m x x >c
~ ~C ~C >C ~C >C C ~C SC u] c~ ~ j ~ u tn U) u)
U) Uo C!] U~ U) U] U] U] Un U) dp dP dP
p oW dp dp dP oW dp dP o'P dp dp dp oW dp O O O
~ O 0 lfl O lfl O C) lfl O t!) O O O O ,
0 0 O
O O N Ln r O N lfl r O Ln Ln Ln r-I N N
~ N r-I ri rl r-I N ri rl ri rl N -I r-I rl

Ri C7 C7 C7 C7 C~ C7 C7 C7 c7 C~ C7 C7 c7 c7 a a a
~ a a a a a a a a a a a a a w Q A A
~ ~ A G] A A C] A A A ~1 C] ,A ,AP dp dp dp
ow da dp aa dp aP dp aa aa aa o 0 0
H 0 0 0 C) 0 Lfl Ul Lf1 I.f) ~ o o O , ,
~ r Ln ui in in in r r r r r 'n 'n "n O O O
r-i
N
cn cn U~ u~ u~ ~n cn cn rn cn U) m ~n m m
O g ~ ~ ~
oN
oW dp da dP dP dw cw dP dP dP aP dp
Ln o O o 0 0 0 0 0 0 0 ~ ~ ~ in Ln in
. . . . . . . . . . r r r
H
0 0 0
m
Q M ("1 fv) M m (=1 m M M f~l m fn (+1 0 M M 0
r-1 dp
V O O O O O O O O O O O O O O O O O
.ri
11
E-1

F'a
0
.rf
J.)
'~ h x a Z 0 w a rx M Ei :3: X >+ N
~' h x a z 0 w a a ul H 3 >C >+ N
0
0
U


CA 02371925 2001-12-19
WO 00/78275 PCT/US00/15729
- 110 -

a~o
0
U
O
= M
N

r=1
r=~ ~ 10
O
..i . M
F p4
0
Ln
=,~ _
y~ rn 00
U cN
~ O d
.d Q tD A 0
py m ul ao
= O 01 N
V4 O
O `-' d'
a A
mo

ro m
a
= M

~
x
Ul
dP
m a
,~
o),,
(D
rl
m
ro dP r-i
-4
tn
w vi
~ rI a
~
a~
4,
0
aP o
Ln
t-
O
~
w
O
~ dp ri o
U o 0
.,.~
F

CS
0
.rj
43
O pq
~
0
U


CA 02371925 2001-12-19
WO 00/78275 PCT/US00/15729
- 111 -

It was observed that for compositions S,
T, and U, the antibacterial activity against S.
aureus and K. pneum. increases, especially, with a
decreasing wt% of ALS surfactant (i.e., an increase
in % saturation of TCS). Compositions CC, HH, MM,
and RR demonstrate that about 15% SXS, or more, is
preferred to exhibit high activity against K. pneum.
in compositions containing a hydric solvent and a
hydrotrope. This observation suggests that the
hydrotrope may be acting as an adjuvant for the TCS
because the time required for a substantial antibac-
terial kill, i.e., log reduction of at least 2, is
reduced.

Example 13

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


CA 02371925 2001-12-19
WO 00/78275 PCT/US00/15729
- 112 -

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


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;:v
~ o 0 ~ 0o ~ c0 ~ ~ 0 0 o
m = w
O d~ = d~ ' M M
%o A 0 A A
A M A A p \ \ \ A \ n ~ A
\ v v \
m w w w \
O r-I M O Ln 00 Ln 0~ 0 ~ 0 0 0
. . . . . . .
d4 O d~ N M M
A A n n n n
~--I 01 r 00 Ol M [- ~ ~ M
U! = M 0 00 1.0 O) 10
O d
.r4
4) l0 A O 0 n M rl 0 ~--I
C' \ \ \ \ \ \ \ \ \ \ \
Ol d~ d~ rl M ON 00 0
Lf)
O ~--I M 40 N ~ 0
-~ M
H W O m~ O N N O O 0
0 00 0) Olt 0 0
.rj [- M 00 LIl lfl Lfl O) l- L- O
4.) H . ~ = . = Ln . .
V -i O d~ = w = w v~ d~ = d~ d~ '
A 0 A w A A A 14 A A
U \ \ \ \ \ \ \ \ \ \ \ A
~ N w 00 01 m 01 m N 0 0 a' . O V~ N M "zr lfl L(1 Lfl ~r I- [-
0)
r4 v
tn . . . . . . . . . d~ O. d~ N d~ d~ d~ M It

p A A A A A A A M 0 N N ON m

tlo %,O W 00 IV k0 ~O H O\ lf) lfl m
"~' (A = 0 = lfl ' = M N = ' rl
Q) O m ' M = M cn = = d~ d~ =
to A O A rl A A N r-i A A N
~ \ \ \ \ \ \ \ \ \ \ \ \
fd !Q m f~) 0 ri N N L, 0 m m 0
O l0 O 00 M kO ~O l0 H L(1 lfl [-
. . . . . . . . . .
C!~ `-' M O M rl m M r-1 r-1 d' d~ rl
A A A A A A

m ~ ~ L7 U C7 ~ C7 [*-~ 0 [~ C7 [*-~
m ~n a
u~i o o ~ ~ ~ 04 A ~ u~i ~ u~i ~ u~i
U] U] U) ~t U) dp C!) oW U) 1 O 11 d4 O
o X .11 ?C w >C .41 o d. o 141 o
$4 r-I r-I U) ~ U] ~~ d' U] ' C!] =(!~ H H H
oW dp dP rl dp W dP V~ dP
o 0 0 0 r-i o -1 0 , co , cl) , co
H a w o o o ui o . o o ~~ ~~ a ~
~ ~q H ~ ~ v) ~ a~ ~ ~ aw ~ ow ao
N dp dp dp g dP o Gw 0 aa o
A U) Ln u1 ut u1 p ill = Ln = Un '
4=1 ' N N N N 'p dp N 0 N 0 N 0
0 d+ -14
. . . ' r-1 r-I = r-i = r-I = ri
H O O O O O O O
dp
ri) U) ri) En ri) U)
N
ai U o o [U-~ U H CU-~ CU-~ U H CU-~ U
O -4 U)
dp E-~ ow dp aP E~ aa aa H
ri (O O O M o1 M M M dP It M dP
U U o = o = = ' O = = o
0 0 0 0 0
~
Ea
p
.,i
~ U A w w 0 x H h x a
m U Q w w 0 H h x a
p U Q w w 0 ~x H h x a
~
0
U


CA 02371925 2001-12-19
WO 00/78275 PCT/US00/15729
- 114 -

0 0 r ~ ~ ~ ~ r
O N O OD 00 QO 00 00 00
~ ~ N r{
O d~ cM = m fn (1) m f'n M
0 t0 A A A A A A A A A
\ \ \ \ \ \ \ \ \ \
GO O 0 O~ L- [- l~ [- l- [~
V O N ~ N N CO DO QO DO 00 OD
M = = . . . . . . .
N m M M r'~1 r='1 M
A A A A A A A A
Ln N Ln OD L- N M OD [-
~ N Ln l0 Lf)
01 m kO M w r-i l,
.r4 A t"1 0 m m rv) d' '~M r=1
C~' \ \ \ \ \ \ \ \ \
m \ r-1 \ lfl O w N o kO t+1
~ O ~ ri 10 r-I d~ ~M M 00 l0
M
E Q( `-' cn ri m 0 N r-I r-I Pn N N
F'.
p rl -I r-i r-1 r-1 N N N
~ .-. L~ [- L- l0 ~ kO ~O 0 10
V
,~ =i O IV 4 ~v 4
p~v A A A A A A A A A A
U \ \ \ \ \ \ \ \ \
a N r-I r-I r-I \ r-I \ H N N N
O [- L~ I- l0 ~D l0 ~O 10
M . . . = . . . . .
p dp
A A A M A A A A A
L~ L-
V~ . Ql N N N
Ln
0 ~ O . . ~ . . .
N O = = d' d' V~ d~ d'
1.~ tD ~'ll /~ h A A A A
O \ r \ \ \ \ \ \ \ \ \
ro 60 r, OD 0) N ri ri 00 f'1 ~"1 M
O r-i M l- N N N N
A M
A A A A A

N C7 G4 Lu LV Cc Cia 0 LV C7 G+ G4 - Cu
Id w w w a w ~ ~ a
aA da q aaw w aP
aP ui ao ~n w o Oõ , d, o oõ o d, o a, o o O O o o N o
N zp o o = o o = 0 o d~ 0 O o = 0 = o
v = w o
~ -1
~ v~ " rt '
~ ~ " ~ ~ ~ ~ ~n ~ cn ~ ~ m ~
H ~n a~ " u~ u] U) ' un ~ m ~ (1) ~) 4 Cn ~ cA cn F-1 ul
N aa o o dP o o o4w o aa o 4 o FaaC o
dP da da aP
4-1 N O p O Ln O p O Ln O ~ O I~ O M O O ~ O
Q C~ 0 r-i 0 r-I O r-i O r-1 0 r-1 O r-i
dP

ttl U U U U) U U U U U U
m E-~ p E+ U E-q H P H E-+ H
O ao ar aa H dP aP da dP dP dv
r-I M fn m oW m m m f~1 P7 Nl
V = . O = . . . . .
=rl 0 O O 0 0 O 0 O 0
w
F
0
.A
o ~ o w a a c~n C~ -+ 3
~
0
U


CA 02371925 2001-12-19
WO 00/78275 PCT/US00/15729
- 115 -

r m
ao in in 0 w
m . = ~ N OD M r
~ O M Cl = = = ~,.~ =
%D A A f~l M N n N
0 \ \ \ \ \ \ \ \
m r orn rn d li rn
V O 00 LIl O N Ol ~ (3)
M . . . . . .
rii`=' M M N M (D N 0
A A

Lf1 N ~O M 10 0
F~= W r-I r ri l0 N l!1 O
7 O = = =
4) 1D M n r-I M N M N
q \ \ \ \ \ \ \
(]r lfl \ 00 r Lf1 OA 01
~ M O1 N d~ H
P1
Eõ4 N O H O ri 0
0 N rI
.1"1 kO M 00 M 00
V =~=1 W = = a, O N Ln rl
H o d~ v
,d O'o A A
U A d ~r A
\ \ \ \ \ \ \
O
a N r-1 0 O \ r
o %D rn ~ ~
~
0 M ~"1 M M M
m d, T
A A

M M r r r r
tq -. (N QO 0 0 0 0 0
a W . r-i
C) O ~v M = 4 W d~ d~
~ t0 A A N A A A A
.7 \ \ \ \ \ \ \ \
f(~ fq M M OO r r r r
O N CU 0 0 0 0
~ . = .
Cl~ ~ V~ ("1 r=I V~ d~ d~ d~
A A A A A A
" ~ a a a ~-~1 -~~1 a r'' a a a a' a
~ A~ A d~a A dP Q ~ A ow C] ~ fa dP
aa ui da ui da aa ui ow da in
','jd ~ wOQ ~OQ O 00 in Ln0
~ r ~ O A W O Lf1 Lf1 O r r O
ac
O ~ v] "n m`n u~ co u~ c~ u) u1 u~
~ ~ ~ oW oW dB ~ da ~ dP ~ oW ~
.L: to dP O ow O Lf1 Ln ul t(1 , Ln ul
4.) Ln O Ln r r r r
= r r
0 O
H = r-, Or-i OO O
dP

O
cd U U ul U U U U
Fi O ow a~a E-i a~ ~
a aa ow d~w
rl c~l M odP M M M M
.
V 0
=rl 0 0 O O O 0
w
H
G'.
0
.r{
41
O >4
N f~A U fa
p
O
U


CA 02371925 2001-12-19
WO 00/78275 PCT/US00/15729
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Examnle 14

This example shows that other hydric sol-
vents can be used in a composition of the present
invention.


CA 02371925 2001-12-19
WO 00/78275 PCT/US00/15729
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00 lfl l(1 14
N 00 M a) m m
O
ri~ I I 1 n N N A A N I I
0 I I 1 \ -1 OC) r- I I
U 0 N Ln N N
~ M . . .
U~ v M M M H
d N N N O)
0) 0)
.
O
A M n n '~
p\ i i i \ \ \ \ \ \ i i
eo ui
r o ~ o N OD Ln I~
E Q( - rq H O m M 0
gi m M lfl r-i r-I
Q r r- 0 00 Ln '^ 14 r-i o u)
.~ N N
+J -i o w v d d+ d
V Q tG A A A A A A V A A n n N M
U \ \ \ \ \ \ \ \ \ \
fA M m O Lfl 00 rl ~--I ON l0
O L- l- l0 ~ U4 L!1 d~ d' ~ ~--I 10
m ~v N 14 d~ ri r-I
tn A A zv A M A A M N
0
a
rn rn m q4 w
y r. ~ U) m rn am ao ao r-i -1
m a) w r-i . . . . . = o a,
Q p = = = d~ M M M m m
= V~ = d~
3~ ~O M M r-I A A A A A A A M A m A
\ = \ \ \ \ \ \ \ \ \ \ \ \ \
RI N d~ ON L- m 01 0N N rl L, rl
0 N Lfl l- 01 m ON QO 00 N r-I l0 rl
M . .
M . 13. N.
M . (".1 !'~1 . M
'cM N O . . (")
G~ `=~ d~ V~ W
A A A A A A A A A
~ ~ ~ x U) U) ~ ~ ~
r-i ~ N U) U] U] cn Uo ~, Ul Ul U] U~ U)
~X ar aP aa dP A. ao dP aa ao
~~ o 0 0 0 , o 0 0 0 0
q ~ F E~ O o 0 0 0 0 o o U) Ln Lf)
N 04 aa da ~4 .
_1 ~ o a) o U) 104
N 4-~i oX oX ar a w a a
w fn u) a a a a d, oa a dP ~
dp dp aP dP A. oW p dp
o C7 0 0 0 0 0 0 0 o 0 0 0
Ln E-+ u) o a o R' o 0 0 o N o o 0 0
~--I 4 ri rl N N N N N

C r- r
O 4 0 cn c~ tn c~ ~
dp >' o o in 1-i an aP dp
aa
Lf1 trl oW dp oW dp N oW dp ~ O
r O~ o ui ui ui ui Ln
o 0 0 O o 0 0 O o 0
c0
m
Q M m O m M M ~ O rl M O M 0 M
rl 0)p . . . . . . . . . . . . .
u o 0 0 0 0 0 0 0 0 0 0 0 0 0
.11
w
H

0
.ri
" w G4 0 x ~"i h x ~l 0 w a x
w w 0 x H h x a ~ 0 04 a rx
w 0 W. H h x a x 0 04 a x
w C3+ C~ x H h x a ~ 0 04 a x
0
U


CA 02371925 2001-12-19
WO 00/78275 PCT/US00/15729
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~r. M r4,
O
o~ , o 0
\ \ \
A m r, t~
V O ul ri
O.
C)

Dd m kO \ O
p, m ' N o
M
.rl ~ v O
F o
a
O ch ri ,-~
'rl =~i N ~O O~ N
1.1 ~y O
V O %O r-I 0 O
~ U \ \ \ \
~ W 01 l0 ~0
a O [~ r-I O
IY~ M
Ul 0 O 0
0
a
tq .. M Ln Ln
N N
N 0
N O d~
A
n
\ \ \ \
R1 f0 a0 d4 m
O N N ,n
, . .
N d N
n

x >~ x
Cf] U) CQ
dp oW dp
fA O 0 0
y1
(y' Lf1 Lfl l11
m
'd U U C7
$1 oN dP dp
bl 0 0 O
H O O. O
r-I r-I rl
11
m
.ri co U] U]
O FC
aP
dp dp
O 0) 0)
O O O
c~
m
O O N 0
=
rl dp
0 o 0
.,a
14
E-4

C'.
0
-rl
4J
-rl
O M H
~
O
U


CA 02371925 2001-12-19
WO 00/78275 PCT/US00/15729
- 119 -

In addition to the observation that other
solvents (e.g., PG and TPG) can be used in composi-
tions of the present invention, products JJJJ
through 0000 illustrate another effect of relative
saturation of antibacterial agent in the system.
The relative % saturation (highest to lowest) of the
first three compositions is JJJJ>KKKK>LLLL. Compo-
sition KKKK has one-third the amount of TCS as com-
position JJJJ solubilized in the same level of ALS
(0.5%), and compositions LLLL contains 0% TCS.
Significant reductions in activity were observed
with respect to K. pneum. and S. choler. when the
relative % saturation of TCS in the composition
decreases. It also was observed that when the rela-
tive % saturation is essentially equal (i.e., about
100%), the activity remains essentially constant
even though the absolute amount of TCS in the compo-
sition is decreased (i.e., compare Compositions MMMM
to NNNN). These data further support the observa-
tions with respect to the importance of % saturation
set forth in Example 7.
In addition, a comparison of composition
IIII to composition TTTT shows that composition TTTT
contains slightly less ALS (0.9% vs. 1.0% for IIII),
the same amount of PG (10.0%), and one-half the
amount of SXS (5.0% vs. 10.0% for IIII). Experimen-
tal observations indicated that compositions IIII
and TTTT were at or near 100% saturation. However,
the log reductions of E. coli were considerably
lower (about 4 log) for Composition TTTT. This
observation further supports the data set forth in
Example 8 wherein minimum level of hydrotrope may be


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- 120 -

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

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

Table 4

Composition ~ by weight (as active substance)

TCS Ethanol PPG-9 DPG Water
15-A 0 25.86 11.5 -- Balance
(control)

15-B 0.10 25.86 11.5 -- Balance
15-C 0 23.0 -- 11.18 Balance
(control)

15-D 0.10 23.0 -- 11.18 Balance


CA 02371925 2001-12-19
WO 00/78275 PCT/US00/15729
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Table 5
Composition Log reduction @ 15 sec/30 sec

S. aureus S. coli K. pneum. S. chol.
15-A 0.55/1.73 0.18/0.43 1.15/0.71 2.51/4.24
15-B 3.27/>4.43 3.75/>4.51 1.33/3.10 4.09/4.34
15-C 0.01/0.0 0.17/0.12 0.4/0.11 0.18/0.17
15-D >4.43/>4.43 3.20/3.48 3.19/4.03 2.86/3.99

Example 15 illustrates the surprisingly
high efficacy of compositions of the present inven-
tion (15-B and 15-D), wherein high log reductions
are observed against both Gram positive and Gram
negative bacteria, even for compositions containing
less than 26% ethanol. The results are in contrast
to compositions described in prior disclosures,
wherein high alcohol concentrations (i.e., greater
than about 40%) are relied upon to achieve a high,
broad spectrum antibacterial activity.

Example 16

Example 16 shows that compositions of the
present invention provide excellent, broad spectrum
antibacterial activity, even at further reduced
alcohol concentrations. Accordingly, composition
16-A containing 0.15% TCS, 11.18% ethanol, 25.71%
DPG, the balance being water (as weight percent of
active compounds), was prepared. For comparison, an
identical control composition 16-B was prepared,
except composition 16-B was free of TCS. The fol-
lowing table summarizes the results of antibacterial


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WO 00/78275 PCT/US00/15729
- 122 -

efficacy of compositions 16-A and 16-B by time kill
tests.

Composition Log reduction @ 15 sec/30 sec

S. aureus S. coli K. pneum. S. chol.
16-A 4.54/>4.69 >4.78/>4.78 3.63/>4.11 1.12/1.31
16-B 0.88/0.97 0.36/0.37 0.0/0.0 0.0/0.0
Example 16 further demonstrates that the
concentration of alcohol in the present compositions
can be reduced to very low levels without sacrific-
ing antibacterial activity. Accordingly, composi-
tions that provide excellent antibacterial efficacy,
and that do not dry the skin, can be prepared.
Prior compositions that relied on a high alcohol
concentration for antibacterial activity dried the
skin, and often caused skin irritation.
Example 17

Example 17 demonstrates that highly effec-
tive compositions of the present invention can in-
corporate p-chloro-m-xylenol (PCMX) as the antibac-
terial active agent. Composition 17-A was prepared
by admixing 0.1% PCMX, 13.42% ethanol, and the bal-
ance water (as weight percent of active compounds).
The antibacterial efficacy of composition 17-A was
evaluated by a time kill test and exhibited log
reductions against S. aureus, E. coli, K. pneum.,
and S. chol., at 30 seconds contact time, of 4.16,
>4.34, 3.99, and >4.04, respectively. Thus, compo-
sition 17-A is a highly effective antibacterial


CA 02371925 2006-06-13
64267-1185

- 123 -

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

Examvle 18
Example 18 illustrates a composition of
the present invention containing a cationic gelling
agent, CELQUAT CS-230M. Composition 18-A was pre-
pared by admixing 0.15% TCS, 28% ethanol, 11.18%
DPG, and 2% CELQUAT*CS-230M, and the balance was
water (as weight percent of active compounds, except
CELQUATi, which is as-is"). The antibacterial effi-
cacy of composition 18-A was evaluated by a time
kill test. Composition 18-A demonstrated the fol-
lowing log reductions against S. aureus, E. coli, K.
pneum., and S. chol., at 30 seconds contact time of
>3.83, 4.33, >4.43', and >3.55, respectively. Thus,
composition 18-A is a highly effective antibacterial
composition, even though the composition contained a
very low concentration of ethanol.
Example 19

Compositions of the present invention can
contain a wide variety of gelling agents, hydric
solvents, and antibacterial active agents, illus-
trated by the following examples. In Table 6 below,
all weight percentages are as active material, ex-
cept where indicated by a"*," which indicates an
"as-is" weight. The compositions were prepared by
mixing and gel preparation techniques well known to
persons skilled in the art. The compositions exhib-
ited acceptable clarity, stability, and performance.
*Trade-mark


CA 02371925 2001-12-19
WO 00/78275 PCT/US00/15729
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r-I O~
ri Ul
= N ~
h O ~ N r-i
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H
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CA 02371925 2001-12-19
WO 00/78275 PCT/US00/15729
- 125 -

Ln
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CA 02371925 2001-12-19
WO 00/78275 PCT/US00/15729
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The data presented in all the above tables
and examples show that % saturation of antibacterial
agent in the aqueous phase of the composition can be
directly correlated to a log reduction of bacteria.
For example, as shown in the prior tables, a compo-
sition having 50% saturation of TCS in the aqueous
phase demonstrates a log reduction versus S. aureus
of 1.96 (30 seconds) and 3.05 (60 seconds) and a log
reduction versus E. coli of 2.45 (30 seconds) and
greater than 3.81 (60 seconds). A 75% saturated and
a 100% saturated composition exhibited a log reduc-
tion of greater than 4.55 (30 and 60 seconds) vs. S.
aureus (i.e., a log reduction in excess of the de-
tection limit of the assay). The 75% and 100% satu-
rated compositions exhibited a log reduction of 3.40
(30 seconds) and greater than 3.81 (60 seconds) and
greater than 3.81 (30 and 60 seconds) vs. E. coli,
respectively. Accordingly, the present antibacte-
rial compositions can be characterized as exhibiting
a log reduction of at least about 2 (after 30 sec-
onds) or at least about 3 (after 60 seconds) vs. S.
aureus, or of at least about 2.5 (after 30 seconds)
or at least about 3.5 (after 60 seconds) vs. E.
coli.
The antibacterial compositions of the
present invention have several practical end uses,
including hand cleansers, mouthwashes, surgical
scrubs, body splashes, hand sanitizer gels, and
similar personal care products. Additional types of
compositions include foamed compositions, such as
creams, mousses, and the like, and compositions
containing organic and inorganic filler materials,
such as emulsions, lotions, creams, pastes, and the


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like. The compositions further can be used as an
antibacterial cleanser for hard surfaces, for exam-
ple, sinks and countertops in hospitals, food ser-
vice areas, and meat processing plants. The present
antibacterial compositions can be manufactured as
dilute ready-to-use compositions, or as concentrates
that are diluted prior to use.
The compositions also can be incorporated
into a web material to provide an antibacterial
wiping article. The wiping article can be used to
clean and sanitize skin or inanimate surfaces.
The present antimicrobial compositions
provide the advantages of a broad spectrum kill of
Gram positive and Gram negative bacteria in short
contact times. The short contact time for a sub-
stantial log reduction of bacteria is important in
view of the typical 15 to 60 second time frame used
to cleanse and sanitize the skin and inanimate sur-
faces.
The present compositions are effective in
short contact time because the antibacterial agent
is present in the aqueous continuous phase of the
composition, as opposed to surfactant micelles. The
antibacterial agent, therefore, is available to
immediately begin reducing bacterial populations,
and further is available to deposit on the skin to
provide residual antibacterial efficacy. In addi-
tion, because the antibacterial agent is in solution
as opposed to surfactant micelles, the absolute
amount of antimicrobial agent in the composition can
be reduced without adversely affecting efficacy, and
the antibacterial agent is not rinsed from the skin
with the surfactant prior to performing its antibac-


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terial function. In addition, the amount of
surfactant in the present antibacterial compositions
typically is low, thereby providing additional envi-
ronmental benefits.
The following examples illustrate various
compositions of the present invention.

Example 20

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 Lauryl Sulfate 0.75

Dipropylene Glycol 5.0
Sodium Xylene Sulfonate 10.0
Fragrance 0.05

Water q.s.
The composition was prepared by admixing
the dipropylene glycol, TCS, and fragrance until
homogeneous (about 5 minutes). After the triclosan
was completely dissolved, as evidenced by the 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 min-
utes). Finally, the ammonium lauryl sulfate and


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water were added to the resulting solution, and the
composition was stirred until homogeneous (about 5
minutes ) .
The composition had a weight ratio of
surfactant:triclosan of 2.5:1, and was at least
about 90% saturated with triclosan. The composition
was evaluated for antibacterial efficacy against S.
aureus and E. coli using a time kill test. Against
S. aureus, the composition exhibited a log reduction
of >4.07 in 30 seconds, while against E. coli the
composition exhibited a log reduction of 3.90 in 30
seconds. Thus, the composition exhibited an 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 21

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:


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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 reduc-
tion on the skin of the user.
Example 22

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:


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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 dena-
tured 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 desir-
able level of bacterial reduction on the teeth,
gums, and tongue of the user.
Example 23

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:


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Ingredient Weight 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 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 mate-
rial (i.e., a commercial paper towel) then was
dipped by hand into the composition to form a wet
wipe article, suitable for wiping and cleaning sur-
faces, for example, hands. The article formed an
excellent wet wipe and the impregnated antibacterial
composition was freely expressed from the web to
provide a broad spectrum antibacterial activity.


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Example 24

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:

Ingredient Pleight 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
90% saturated with triclosan. The composition was
evaluated for its antibacterial efficacy against S.
aureus, E. co1i, K. pneum., and S. choler. using a
time kill test, and a contact time of 30 seconds.


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The composition exhibited log reductions of >3.59,
>4.49, >3.20, and >4.27 against the four test
organisms, respectively.
Thus, the composition exhibited an
excellent broad spectrum antibacterial activity. In
addition, the composition was an excellent hand wash
composition in an actual use test, providing both
good cleansing and a smooth feel to the hands.

Example 25

Comparison to a Previously
Disclosed Composition

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


CA 02371925 2001-12-19
WO 00/78275 PCT/US00/15729
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Composition ~ TCS Log Reduction at 30 seconds

S. S. K. S.
aureus coli pneum. choler
Example 18 0.3 >4.60 >4.50 4.21 >4.68

WO 98/01110 0.5 3.29 0.29 1.00 0.45
This example demonstrates the superior
time kill performance of a composition of the pres-
ent invention compared to a prior composition, espe-
cially against Gram negative bacteria. This superi-
ority is demonstrated even through the comparative
composition contained substantially more active
antibacterial agent compared to the inventive compo-
sition. Thus, an inventive composition utilizes the
active agent more efficiently, as illustrated in a
higher log reduction using a reduced concentration
of antibacterial agent.
Example 26

Comparison to a Previously
Disclosed Composition

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


CA 02371925 2001-12-19
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dium hydroxide. Further, the examples disclosed in
WO 96/06152 all have a pH of 4 or 9.1, with no exam-
ples having a desirable, neutral pH of about 7. A
pH of about 7 is desired for compositions contacting
skin or inanimate surfaces because compositions of
pH substantially different from 7, such as 4 or 9.1,
have a greater potential to damage the surfaces they
contact. Accordingly, the composition of Example 1
of WO 96/06152 (hereafter referred to as composition
26-A) was prepared. For comparison, composition
26-A was prepared as above, except that the pH was
adjusted to 7 by the addition of further monoeth-
anolamine (this composition hereafter referred to as
composition 26-B). To provide an additional compar-
ison, the composition of Example 3 of WO 96/06152
was prepared, except that it was prepared at a pH of
7 by the addition of further monoethanolamine (this
composition is hereafter referred to as composition
26-C). The table below summarizes the results of a
time kill test on the compositions of this example
against the bacteria indicated at a contact time of
seconds.

Composition pH ~ TCS Log Reduction at 30 Seconds
25 S. B. K. S.
aureus coli pneum. choler.

Example 24 7.1 0.3 >4.54 >4.25 3.67 >4.77
Comparative 4 0.075 -- -- >4.84 --
26-A

Comparative 7 0.075 -- -- 0.07 --
30 26-B

Comparative 7 0.15 4.44 2.91 0.28 4.67
26-C



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This example demonstrates the superior
time kill performance of a composition of the pres-
ent invention compared to prior compositions, espe-
cially with respect to Gram negative bacteria at a
pH of about 7. From the data presented in this
example, it can be concluded that the compositions
of WO 96/06152 rely substantially on a relatively
extreme pH (either 4 or 9, as disclosed) to achieve
a desirable, rapid and broad spectrum reduction of
bacterial populations. This is in contrast to Exam-
ple 18 of the present invention, which provides a
rapid broad spectrum bacteria kill at the desirable
pH of about 7.

Example 27

Antibacterial Composition Containing PCMX

An antibacterial composition in accordance
with the present invention containing p-chloro-m-
xylenol (PCMX) as the active antibacterial agent was
prepared. The composition contained the following
components in the indicated weight percentages:

Ingredient Weight Percent
PCMX 0.1
Ethanol 13.42

Water q.s.
The composition was prepared by first
mixing the PCMX and ethanol to completely solubilize
the PCMX (about 5 minutes). After the PCMX was
completely dissolved, as evidenced by the absence of


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undissolved solid material, the water was added, and
the composition was stirred until homogeneous (about
minutes).
The composition was at least about 90%
5 saturated with PCMX. The composition was evaluated
for antibacterial efficacy against S. aureus, E.
col, K. pneum., and S. choler. using a time kill
test. Against S. aureus, the composition exhibited
a log reduction of 4.16 in 30 seconds; against E.
coli the composition exhibited a log reduction of
>4.34 in 30 seconds; against K. pneum. the composi-
tion exhibited a log reduction of 3.99 in 30 sec-
onds; and against S. choler. the composition exhib-
ited a log reduction of >4.04 in 30 seconds. Thus,
the composition exhibited an excellent broad spec-
trum antibacterial activity.

Example 28

Antibacterial Composition Containing PCMX
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 0.8

Water q.s.


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WO 00/78275 PCT/US00/15729
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The composition was prepared by first
combining the PCMX and water, then adding the ammo-
nium lauryl sulfate and mixing the components for
such time as to completely admix the components and
dissolve the PCMX (about 2 hours).
The composition was at least about 90%
saturated with PCMX. The composition was evaluated
for its antibacterial efficacy against S. aureus and
E. coli using a time kill test. Against S. aureus,
the composition exhibited a log reduction of >3.57
in 30 seconds; and against E. coli the composition
exhibited a log reduction of >4.17 in 30 seconds.
Thus, the composition exhibited an excellent broad
spectrum antibacterial activity.
Obviously, many modifications and varia-
tions of the invention as hereinbefore set forth can
be made without departing from the spirit and scope
thereof, and, therefore, only such limitations
should be imposed as are indicated by the appended
claims.

Representative Drawing

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Administrative Status

For a clearer understanding of the status of the application/patent presented on this page, the site Disclaimer , as well as the definitions for Patent , Administrative Status , Maintenance Fee  and Payment History  should be consulted.

Administrative Status

Title Date
Forecasted Issue Date 2009-02-17
(86) PCT Filing Date 2000-06-08
(87) PCT Publication Date 2000-12-28
(85) National Entry 2001-12-19
Examination Requested 2001-12-19
(45) Issued 2009-02-17
Deemed Expired 2011-06-08

Abandonment History

There is no abandonment history.

Payment History

Fee Type Anniversary Year Due Date Amount Paid Paid Date
Request for Examination $400.00 2001-12-19
Registration of a document - section 124 $100.00 2001-12-19
Registration of a document - section 124 $100.00 2001-12-19
Application Fee $300.00 2001-12-19
Maintenance Fee - Application - New Act 2 2002-06-10 $100.00 2002-05-06
Maintenance Fee - Application - New Act 3 2003-06-09 $100.00 2003-05-06
Maintenance Fee - Application - New Act 4 2004-06-08 $100.00 2004-05-04
Maintenance Fee - Application - New Act 5 2005-06-08 $200.00 2005-05-09
Maintenance Fee - Application - New Act 6 2006-06-08 $200.00 2006-05-05
Maintenance Fee - Application - New Act 7 2007-06-08 $200.00 2007-05-23
Maintenance Fee - Application - New Act 8 2008-06-09 $200.00 2008-05-21
Final Fee $558.00 2008-12-04
Maintenance Fee - Patent - New Act 9 2009-06-08 $200.00 2009-05-19
Owners on Record

Note: Records showing the ownership history in alphabetical order.

Current Owners on Record
THE DIAL CORPORATION
Past Owners on Record
FOX, PRISCILLA S.
SEITZ, EARL P., JR.
TAYLOR, TIMOTHY J.
Past Owners that do not appear in the "Owners on Record" listing will appear in other documentation within the application.
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Document
Description 
Date
(yyyy-mm-dd) 
Number of pages   Size of Image (KB) 
Abstract 2001-12-19 1 51
Claims 2001-12-19 25 535
Description 2001-12-19 139 4,045
Cover Page 2002-06-13 1 28
Claims 2006-06-13 7 214
Description 2006-06-13 139 4,142
Claims 2007-07-12 5 143
Claims 2008-04-01 4 127
Cover Page 2009-01-27 1 29
PCT 2001-12-19 17 662
Assignment 2001-12-19 7 271
Correspondence 2002-06-11 1 15
Prosecution-Amendment 2008-01-11 2 69
Prosecution-Amendment 2007-01-18 3 118
Prosecution-Amendment 2005-12-13 5 211
Prosecution-Amendment 2006-06-13 30 1,137
Prosecution-Amendment 2007-07-12 10 359
Prosecution-Amendment 2008-04-01 7 230
Correspondence 2008-12-04 1 39