Note: Descriptions are shown in the official language in which they were submitted.
~ZZ6213
ANTIMICROBIAL COMPOSITIONS
BACKGROUND OF THE INVENTION
The present invention relates to compositions useful as
antimicrobial agents. More particularly, it relates to
the enhancement of the activity of specific bus biguanide
antimicrobial compounds by the addition of amine oxides.
Numerous antimicrobial agents and compositions have been
described in the literature and these compounds have
attained widespread utility, for example, as preservatives
in the cosmetic and pharmaceutical area as well as for
cleansing purposes. Such compositions to be useful should
demonstrate high activity against a wide range of organ
nisms while exhibiting low toxicity as well as being free
from odor, easily handled and chemically stable. Not with-
standing the widespread acceptance of such compositions,
there is an ongoing search for more effective anti micro-
blat agents and compositions and, therefore, there is anteed to enhance the antimicrobial activity of known anti-
microbial agents by the addition of other compounds.
One of the objects of the present invention is to provide
a method of enhancing the antimicrobial effect of come
pounds having known antimicrobial activity.
Another object of this invention is to provide an anytime-
crabbily composition comprising one or more antimicrobial
compounds in combination with a compound which enhances
the antimicrobial activity of the antimicrobial compound.
A still further object of this invention is to provide
antimicrobial compositions effective against both gram
positive bacteria and gram negative bacteria.
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These and other objects of the invention will become
apparent from the following description.
SUMMARY OF THE INVENTION
In accordance with the present invention, there is pro-
voided compositions useful as antimicrobial agents comprise
in (A) a bis-biguanide compound selected from the group
consisting of polyhexamethylene biguanide hydrochloride
and chlorhexidine salts, and (B) an amine oxide.
The enhancing effect on the antimicrobial properties is
most remarkable when component (A) is employed with
component (El) within specific ratios and the compositions
lo of the invention can be employed as antimicrobial agents
in various personal care products.
DETAILED DESCRIPTION
There are employed as the bis-biguanide compound, a
compound selected from the group consisting of
po~ybexamethylene ~iguanide hydrochloride of the
formula:
25 HC~-NHz~CH3)3~(CH2)3~NH~C~NH~C~NH~(CH2)3~n(CH~)3~NNH~C~NH~CN
NH NH-HCl NH
wherein n is from 4.5 to 6.5, and chlorhexidine salts of
on 1,6-di-(4-chlorophenylbiguanide)-hexane of the formula:
Of NH-C-NH-C-NH-(CH2)6NH-C-NH-f-NH I
NH NH No
The salts which are useful include chlorhexidine acetate,
chlorhexidine huddler and chlorhexidine gluconate.
These compounds may be employed alone or in mixtures.
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The polyhexamethylene biguanide hydrochloride are avail-
able commercially, for example, from ICY Americas Inc.
Wilmington, Delaware under the a~e~n~me-kCosmocil CQ and
the chlorhexidine salts are also available commercially,
for example, from ICY Americas Inc., Wilmington, Delaware
under the trade name, Chlorhexidine. The bis-biguanides
should be present in the compositions of the present
invention from about 2 to 5% by weight of the total
composition, preferably from about 3 to I
The amine oxides which are useful in the compositions of
the present invention are the amidoamine oxides of the
formula:
O H SHEA
if l l
R-C-N-(CH2)3-N - JO
SHEA
wherein R is from 7 to 17 carbon atoms or mixtures
thereof.
The amidoamine oxides are available commercially, for
example, from Lyons Chemical Company, Fair lawn, New Jersey
under the trade name Barlow C and from Onyx Chemical
Company, Jersey City, New Jersey under the trade name
Ammonyx COO. The amidoamine oxides should be present in
the compositions of the present invention from about 1 to
20% by weight of the total composition, preferably from
about 4 to 8%.
In order to obtain the desired results of the present
invention the amidoamine oxide to bis-biguanide ratio
should be from about 1:2 to 4:1. If the ratio is less
than about 1:2 the enhancement effect of the amidoamine
oxide begins to diminish and if the ratio is greater than
about 4:1, the resulting compositions tend to become harsh
to the user and also are relatively expensive.
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The balance of the compositions consist of water and
may also contain minor amounts of owner components
normally found in such compositions such as chelating
agents, thickening agents, fragrances, coloring
agents and the like.
The pi of the compositions should be maintained with-
in a range of from about 4 to 8, preferably 7.0 to
7.5.
The present invention is more particularly described
and explained by means of the following examples:
EXAMPLE I
An antimicrobial composition is prepared as follows:
a Methuselah (hydroxypropyl methyl cellulose) solution
containing 1.9 g., active sufficient to provide 0.75%
wow Methuselah in the finished product is added to 75
g. deionized water and mixed until homogeneous. To
this solution is added 50 g. active of a 20% active
polyhexamethylene biguanide hydrochloride sold under
the trade name Cosmocil CQ by ICY Americas Inc., Wit-
mington, Delaware, followed by the addition of 0.25g. Versene 100 and 16.75 g. of 30% active cocoamido-
propyldimethyl amine oxide. The pi is adjusted to
6.0 using 15% Hal and the total is adjusted to 250 g.
by the addition of deionized water. The resulting
composition is of the following formula:
% w/w
Cosmocil CQ 4.00
Versene 100 0.03
hydroxypropyl methyl
cellulose 0.75
cocoamidopropyldimethyl 2.00
amine oxide
deionized water us to 100
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EXAMPLE II
An antimicrobial composition is prepared according to the
procedure of Example I except the cocoamidopropyldimethyl
amine oxide is eliminated and replaced with deionized
water.
EXAMPLE III
An antimicrobial composition is prepared according to the
procedure of Example I except the Cosmocil CQ is elm-
noted and replaced with deionized water
EXAMPLE IV
An antimicrobial composition is prepared according to thepr~cedure of Example I except that 33.25 g. of cocoamido-
propyldimethyl amine oxide are utilized resulting in a 1:1
ratio of amine oxide to Cosmocil CQ (on an "active"
basis).
EXAMPLE V
An antimicrobial composition is prepared according to the
procedure of Example I except that 66.6 g. of amine oxide
are utilized resulting in a 2:1 ratio of amine oxide to
Cosmocil CQ (on an "active" basis).
EXAMPLE VI
A screening technique is used to test the compositions in
Examples I-V. This technique consists of preparing 2-fold
or 4-fold serial dilutions of the compositions of each
Example. Allocates of these dilutions are then inoculated
with a mixed suspension of gram positive bacteria or a
mixed suspension of gram negative bacteria. The inoculm
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density is adjusted to yield approximately 107 bacteria/ml
of sample. Portions of the inoculated sample are then
tested for viable bacteria at zero-time (immediately after
inoculation), 6 to 8 minutes, 15 minutes, 30 minutes and
60 minutes after inoculation. This testing involves
placing a calibrated 0.01 ml transfer loop into the
inoculated sample and removing a remeasured portion which
is then streaked on a solid growth medium (ajar) and
incubated for a period of 48 hours at a temperature of
35~C. After the incubated period, the plates are examined
for the presence or absence of growth. Any amount of
growth on the line of streak is considered as positive
growth. When the compositions of Examples I-V are tested
according to the above procedure the following results are
lo obtained. These results are expressed in terms of the
minimum inhibitory concentration required for complete
kill expressed in micrograms per milliliter (mcg/ml).
TABLE I
Composition Gram Positive Gram Negative
time minutes time minutes
0 6-8 15 30 60 0 6-8 15 30 60
Example I >104 104 156 39 <19 2500 312 39 <19 <19
Example II >104 5000 625 78 156 2500 39 <19 <19 <19
Example III >104 >104 5000 1250 1250 >104 >104 >104 >104 >104
Example IV >104 625 19 <19 <19625 <19 <19 ~19 <19
Example V >10 4 1250 19 <19 it 5000 <19 <19 <19 <19
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These results clearly demonstrate the antimicrobial ad van-
taxes of the compositions of the present invention, i.e.,
the compositions of Examples I, IV and V.
EXAMPLE VII
An antimicrobial composition is prepared according to the
procedure of Example I and is of the following
formulation:
wt/wt
Chlorhexidine gluconate 4.00
Versene 100 0.03
15 hydroxypropylmethyl cellulose 0.75
cocoamidopropyldimethyl 4.00
deionized water us to 100
The pi of the above formulation is adjusted to l6.0 with
dilute Hal.
EXAMPLE VIII
An antimicrobial composition is prepared according to the
procedure of Example VII except that the cocoamidopropyl-
dim ethyl amine oxide is utilized in a 1:2 ratio of amine
oxide to chlorhexidine gluconate (on an "actves" basis).
EXAMPLE IX
An antimicrobial composition is prepared according to the
procedure of Example VII except the cocoamidopropyldi-
methyl amine oxide is eliminated and replaced with
deionized water.
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EXAMPLE X
An antimicrobial composition is prepared according to the
procedure of Example VII except the chlorhexidine
gluconate is eliminated and replaced with deionized
water.
EXAMPLE XI
The compositions of Examples VII, VIII, IX and X are
tested according to the procedure of Example VI and give
the following results.
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--10--
Various other features and embodiments of the present
invention not specifically set forth will be obvious to
those skilled in the art, all of which may be achieved
without departing from the spirit and scope of the
invention as defined by the following claims.
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