Note: Descriptions are shown in the official language in which they were submitted.
1056Z5Z
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United States 1,953,413 discloses an antiseptic preparation
containing p-chloro-sym.-m-xylenol incorporated in an aqueous vehicle, employing
a soap as a dispersing agent, such as the soluble alkali metal soaps of fatty
acids of corn oil, linseed oil, olive oil, castor oil, or other vegetable or
animal fatty oils. It is further taught in the sales brochure of the Ottawa
Chemical Co., Toledo, Ohio, that alcoholic solutions of p-chloro-m-xylenol
(sold under the trademark "Ottasept" as an antimicrobial additive) are soluble
in liquid soaps such as the potassium and triethanolamine salts of oleic,
ricinoleic, myristic, and coconut fatty acids. United States 3,326,808 concerns
a liquid antiseptic detergent composition containing at least one disinfectant
; agent selected from the group consisting of hexachlorophene, fluorophene,
p-chloro-m-xylenol, bithionol, biphenamine hydrochloride, and a synergistic
mixture consisting essentially of 20% of 5,4~-dibromosalicylanilide and 80% of
3,5,4'-tribromosalicylanilide, a water-soluble, non-irritating and non-sensitizing
surface-active, organic synthetic anionic detergent; a super fatting emollient
selected from the group consisting of animal, vegetable and mineral oils and
synthetic fatty acid ester oils, and a polyethylene glycol ether of a higher
fatty alcohol. (It is noted that the most widely used germicidal liquid hand
soaps heretofore have contained hexachlorophene or iodine; however, hexachloro-
phene is now out of favor because of recent disclosures relating to possible
toxicity, and iodine is undesirable because of its staining properties.) Other
~: aqueous soap-containing detergent compositions containing chloro-xylenols are
taught in United States 2,191,405, 2,906,664 and 3,370,014. United States
3,538,009 concerns an aqueous detergent composition, which may contain a
bacteriostatic agent, and which contains a mildness additive comprising the
polymerized p~oduct of 2 to 4 molecules of a monomeric C12 to C26 fatty acid,
preferably the dimer acid derived from linoleic acid, said dimer acid derived
from linoleic acid, said dimer acid having the structure
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HOOC-(Cll2 ~ CH \
CH CH-CH2-CH=CII-~CH2) -COOH
CH / ( 2)4 H3
CH
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(CH2) 4-CH3
. It has been discovered that soaps of such acids, as well as soaps of many
: other common fatty acids derived from naturally occurring vegetable and animal
` fats, such as ricinoleic and coconut fatty acids, do not operate to give
suitable bactericidal and germicidal compositions in combination with P~X,
compared to the soaps of the dicarboxylic acids embodied in this invention.
Summary of the Invention
The present invention provides a novel and useful aqueous
. antiseptic composition comprising (a) at least about 2~ by weight of p-halo-m-
~: xylenol as an antimicrobial agent and (b) at least about 5% by weight of a
.~ water soluble mono- or di-soap formed by at least partial saponification of a
diacid from the class consisting of ti) a dicarboxylic acid of the formula
C~ = C O
CH - CH
:'~' I 1,
X X
wherein x and y are integers from 3 to 9 and x and y together equal 12 and
wherein X and X~ are different members of the class consisting of hydrogen and
a carboxylic acid group and (ii) the mono or di, 3-chloro-2-hydroxy propane
sulfonate ester of the dicarboxylic acid of (i). The soaps may be of the
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1056ZSZ
partially or completely saponified diacid and may be of the sodium, potassium,
lithium, ammonium or organic amine variety. In the preferred structure x is 5,
- y is 7, X is carboxylic acid and X' is hydrogen. The diacid from which the
preferred soap is made is sold by Westvaco Corp. under the mark "Westvaco
DiAcid 1550", with the suggestion that the potassium and sodium soaps show
remarkable water solubility and that liquid soaps up to 80% solids (K soap) or
65% solids (Na soap) can be prepared. It is the reaction product of the linoleic
acid portion of a fatty acid mixture with acrylic acid as taught in United
States 3,753,968. Preparation of the mono- and bis-hydroxy propane sulfonates
is taught in United States 3,842,119. Soap compositions made from the acid
and certain salts are disclosed in United States 3,734,859.
Detailed Descrlption of the Invention
The aqueous antiseptic soap of this invention comprises, as
essential ingredients, from about 5 to about 50% by weight based on the weight
of the total composition (preferably from 8 to 18%) of the sodium, potassium,
lithium, ammonium or organic amine soap of the above-described dicarboxylic
acid or the halo-substituted propane sulfonate ester thereof, from about 2 to
10% by weight (preferably from 2 to 5%) of P~MX as an antimicrobial agent and
from about 30 to about 90% by weight (preferably from 60 to 80%) of water.
The potassium and amine soaps wherein the diacid is saponified to from about
50% to 75% are preferred since such compositions are less basic and more soluble
than soaps containing other cations; the trithanolamine soaps are of particular
value because they are less irritating to the skin.
i The composition of the present invention is prepared by
dissolving in water appropriate amounts of (i) PHMX as an antimicrobial and ~ii)
the soap described above to provide ingredient concentrations within the expressed
ranges. At the lower concentrations of antiseptic (i.e. below about 2% by
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weight) the composition is less bactericidal (i.e. at times only partial kills
are experienced) while compositions containing more than 2% (preferably at
least 3.75%) by weight of the antimicrobial are completely bactericidal (i.e.
100% kill). Although the defined antimicrobial is only sparsely soluble in
water its water solubility is enhanced by the presence of the partially or fullysaponified soap. In addition it has been found that the presence of minor
amounts (i.e. 1-5%) of an alcohol or glycol supplementary solubilizer will aid
the solubility of the PHMX and improve the stability of the final composition
during storage.
During the mixing operation it has been found essential to add
. the ingredients to the water. Reversal of the recommended order of addition,
i.e. adding the water last, has been observed to result in compositions
ineffective as bactericides presumably due to micellization that masks the
antimicrobial. The preferable order of addition of ingredients is to first
combine the antimicrobial and solubilizer (where used) and add this mixture
~ to the required water containing (i) part of the alkali (intended to saponify
- the diacid) and (ii) the chelating agent where appropriate. Thereafter the
remainder of the alkali to form the soap is added, followed by optional
ingredients such as surface active agents, emollients, perfumes and the like.
A final pH adjustment is made by addition of more alkali or diacid to provide
a pH of about 6 to about 10.
Solubilization of the PHMX
. _ _ _ . . _
As noted, the presence of the diacid soap identified above
enhances the solubility of PHMX in water. Thus the amount of PHMX that may be
solubilized in any given formulation of the present invention will depend upon
the concentration of the diacid soap; it will also depend upon the nature and
concentration of any supplementary solubilizer that may be present. Finally
it has been observed that the effectiveness of the final composition as a
bactericide is generally directly proportional to the solubility of the PHMX in
water.
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The Drawing
The drawing is a plot defining solubility limits and bactericidal
effectiveness of related concentrations of p-chloro-m-xylenol (PCMX) and Westvaco
: .
Diacid 1550. In the drawing, percentage of Diacid is plotted as abscissa
against the percentage of p-chloro-m-xylenol (PCMX) as ordinate using compo-
sitions that otherwise contain the ingredients of the soap of Example 1. The
Example uses isopropyl alcohol at a 5% by weight level as a supplementary
solubilizer. Curve "A" represents the solubility limit of the PCMX in the
system; above curve A, the PCMX component crystallizes out. Curve C represents
10 the dividing line between complete bactericidal versus partial bactericidal
activity, i.e. concentrations within the area between curves A and C represent
concentrations that are 100% bactericidal in nature whereas those below C are
generally less than 100% bactericidal. Concentrations of diacid soap and PCMX
between curves C and B represent preferred concentrations not only because of
high bactericidal activity but also because of the high shelf-life of the
resulting compositions.
,:~
It will be obvious to those skilled in the art that the curves
will depend upon the identity of the critical components and the supplementary
solubilizer. However from this teaching those skilled in the art can readily
~ 20 determine the most effective proportion of ingredients for any combination.
; Supplementary Solubilizers
The use of small amounts of alcohols and glycols as supplementary
solubilizers for PHMX has been discussed above. While up to 20% by weight of
supplementary solubilizer will be found effective in making compositions of the
present invention, usually the minimum amount will be employed not only because
of safety (flash-point) and cost considerations but because such substances tend
to defat the skin, causing dryness. Thus the use of from 1 to 5% by weight of
supplementary solubilizer is preferred. Among suitable supplementary solubilizers
are alcohols, glycols and sulfonated fatty acids such as
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1 056252
~i hexylene glycol, ethylene glycol, sulfonated oleic acid and the like.
In addition to increasing the solubility of the PHMX in water,
the presence of the solubilizer appears to enhance the antimicrobial properties
of the PHMX so that a concentration of PCMX as low as about 2% by weight has t
been found effective to provide bactericidal protection (equivalent to the action
; of 50 ppm available chlorine) whereas in the absence of the solubilizer about
3.75% by weight of antimicrobial is required to reach such a level of effective-ness.
Optional~In~_edients
o There are a number of ingredients which may be optionally in-
cluded in the germicidal soap of this invention, some of which enhance per-
formance and others of which are cosmetic in nature. Suitable ingredients for use
as skin conditioning agents, surface-active agents, organic chelating agents,
perfumes and thickening agents are well known to those skilled in the art. Thus
from about 1 to about 5% by weight of a polyhydric alcohol such as glycerol or
sorbitol is useful as an additive to provide skin conditioning or emollient
properties. As a surface-active agent the composition of present invention will
usually have incorporated therein from about 0.5 to about 15% by weight (pre-
ferably from 1 to 3% by weight) of an amphoteric or anionic surface-active agent,
for example, alkyl imiazolinium decarboxylate sodium salt, alkyl benzene sulfonate,
alkyl sulfate, alkyl benzene sulfate, alkyl sulfonate, alkyl ether sulfonate or
like anionic sulfonated detergent; higher concentrations, e.g. 10% by weight,
are often useful when high foam generation is desired. A particularly preferred
detergent is a sodium salt of a lauryl sulfate of an alkylphenoxypoly (ethyleneoxy)
ethanol made from naturally occurring lauric acid.
For some applications, the use of from about 0.05 to about 5% by
weight of an organic chelating agent to enhance the biological activity by
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` ~056ZSZ
sequestering water hardness or other metal ions from the system is beneficial.
Representative chelating agents are the alkali metal salts of ethylene diamine-
tetraacetic acid, the sodium salt of hydroxyethylene diamine triacetic acid,
l-hydroxy-ethylidene-1, l-diphosphonic acid, nitrile triacetic acid, sodium
salts of gluconates, hepta gluconates and citrates. Conventional water soluble
perfumes may also be desirably added to enhance the attractiveness of the
germicidal hand soap, for example, in amounts ranging from about 0 to 2% by weight.
Thickeners may be used to adjust the viscosity of the final
product. Carboxymethylcellulose, carboxyethylene ether cellulose and the like
are suitable and may be added in sufficient quantity to provide a wide range of
products from a liquid to a thick paste.
.:
Supplementary antimicrobial agents can also be added to the
composition. While such additions have been found useful in reducing the amount
of PHMX necessary to provide antimicrobial activity, none has been observed to
make the PHMX bactericidal below a concentration of PHMX of about 2% by weight.
Suitable supplementary animicrobials are "Irgasan DP-300" (manufactured by
the Chemical Division of the Ciba~Geigy Corporation), "Troysan 142" (made by
the Troy Chemicals Co.) and "Santophen 1" (made by the Monsanto Corp.)
pH Adjustment
Since the composition is intended for topical application to
the skin, a pH adjustment close to neutral or slightly alkaline is recommended.
Generally this is done by addition of aqueous alkali (such as potassium hydroxide)
to the final composition to provide a pH from about 6 to about 10.5. While a
higher pH can be used, the increased alkalinity tends to reduce the antimicrobial
activity and to increase irritability of the composition upon application to theskin.
* Trademark
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1(~56Z5Z ?
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Test Procedures
In the Examples that follow the bactericidal efficacies of the
various compositions are determined using the standard A.O.A.C. tests as set
forth in Methods of Analysis, 11th Edition (1970) pg. 65, that is, the Available
Chlorine Germicidal Equivalent Concentration Tests against the test organisms
Staphylococcus aureus (ATCC 6538) and Salmonella Typhosa (ATCC 6539).
Examples
~ The following Examples are intended to illustrate the invention.
They are not intended to limit it in any manner.
Example 1
The following ingredients are mixed together in a mixing vessel
with agitation:
Ingredients % by Weight
Water 63.95
EDTA (1) * 0 10
Natrosol 250 HR (2) 0 20
Potassium Hydroxide (45% solution) 5.00
Ottasept Technical (3) 3.75
Isopropyl Alcohol 5.00
Westvaco Diacid 1550 (4) 10.00
Sodium Lauryl Sulfate (30%) (5) 10.00
- Glycerol 2.00
(1) Sodium salt of ethylenediaminetetraacetic acid
(2) Hydroxyethylene ether of cellulose
(3) Para-chloro-meta-xylenol
(4) 5-Carboxy-4-hexyl-2-cyclohexene-1-octanoic acid
(5) Alipal CO 433*(Ciba-Geigy) from naturally occurring
lauric acid.
In mixing the above ingredients, the chelating agent (EDTA) is
first added to the water followed by the alkali. Sufficient alkali is used to
form slightly in excess of that required to form the half soap. Thereafter the
bactericide (p-chloro-m-xylenol) is stirred in followed by the solubilizer
(isopropyl alcohol) and the diacid (Westvaco Diacid) to form a stable complex.
*Trademark
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Then the surface actiVe agents, builders, emollients, perfumes and the like are
; added as desired.
:
The composition is tested on Salmonella typhosa (ATCC No. 6539)
using Letheen Broth. Sodium hypochlorite is used as a control. The results
:'t where "+" indicates growth and "-" indicates absence of growth~ are given below:
. .,
~ Example 1
~.
- Subculture Series
Germicide 1 2 3 4 5 6 7 8 9 10
. ,:
; Sample A - - +
Sample B
Control Conc. ppm Subculture Series
(NaOCl) Avail. C1
~, --- -- -- 1 2 3 4 5 6 7 8 9 10
.; ~ _ _ _ _ _ _ _ _ _ _
200 - - ~ ~ ~ + + + + +
t- 100
_ _ + + + + + + + +
".,~
; Comparative Control
Culture Resistance to Phenol
Dilution Intervals in Minutes
5 min. 10 15 min.
1:80 +
~, 1:90 + +
1 :100 + + +
From the above it will be noted that the composition of Example
1 is more effective as a bactericide against Salmonella typhosa than chlorine at
a concentration of 200 ppm where the culture resistance to phenol is 1:80.
: The composition of this Example 1 is further tested on Staphylo-
coccus aureus (ATCC No. 6538) with the following results
Example 1 Subculture Series ;
Germicide 1 2 3 4 5 6 7 8 9 10
. Sample C - - - - - - +
: Sample D - - - +
Sample E - - - - + - - +
Sample F
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Control Concn. ppm Subculture Series
NaCCl ~vail. C1 l 2 3 4 5 6 7 8 9 10
. 200 ~ ~ ~ ~ ~ + + + + +
, 100 -- -- -- + + + + + + +
';
. -
_ Comparative Control
; Culture Resistance to Phenol
Intervals in ~inutes
Dilution 5 min. 10 min. 15 min.
1:60
1:70 +
1:80 +
From the above it will be noted that the composition of Example
1 is more effective as a bactericide against Staphylococcus aureus than chlorine
at a concentration of 200 ppm where the culture resistance to phenol is 1:70.
` While a technical grade of the PCMX was used in this Example, a
more pure, recrystallized form is available and may be used. The recrystallized
form is preferred in applications where a low odor level is important.
Utility
; The composition of the present invention is useful as a surgical
hand scrub, an anti-microbial soap, as a skin antiseptic or as a health care
personnel hand wash. Among other locations the present composition has been
recommended for use in official establishments operating under the Federal meat
and poultry products inspection program. In such use, the composition is dis-
pensed from adequate dispensers located a sufficient distance from the processing
line to preclude accidental product contamination. The hands need not be washed
prior to the use of the composition, but afterwards must be thoroughly rinsed
with potable water. The composition as it is proposed for use in official
establishments is free rinsing and, will not deleteriously affect
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the meat and/or poultry being p~oce5sed.
.. In Examples 2 to 14 presented below in Table 1, various com-
positions within the sCope of the invention are illustrated. Each iS effective
; as a bactericide. In each of the Examples of Table 1 except Example 11, the
dicarboxylic acid is Diacid 1550; in Example 11, the dicarboxylic acid is the
. bis-hydroxypropane sulfonate of Diacid 1550. The letters "N.M.I' in the Table
indicates that the value was not measured. In Example 14 there are additional
ingredients not listed in the Table as follows: 2.0% by weight of 2,4,4-tri-
chloro-2-hydroxy-diphenyl ether (supplementary antimicrobial) and 5.0~ by
.. 10 weight of propylene glycol (as supplementary solubilizer).
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~xample 15
While PCMX is the preferred microbial for use in compositions of
the present invention, other para halogenated meta-xylenols have been found
effective. Thus in tests using parabromo-m-xylenol as the microbial against
Salmonella typhus, three out of ten bottles displayed an effective kill, equi-
valent to available chlorine at a 100 ppm concentration.
In Table 2, a series of Comparative Control compositions are
listed which are presented to illustrate the critical nature of the antimicrobial
and dicarboxylic acid combination of the present invention. None of the
compositions of Table 2 is an effective bactericide despite the close similarity
of the formulations to those of Table 1. In Table 2 the various superscripts
("a" through "n") are used to identify the carboxylic acid and antimicrobial
employed. These are identified as follows:
(a): ricinoleic acid (12-hydroxyoleic acid)
(b): para-chloro-m-xylenol
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(c): a mixture of 75% dimer acid (C36 dibasic acid) and
22% trimer acid (C54 tribasic acid) with 3~ monobasic
acid (C18 fatty acids), sold as "Empol 1022" by Emery
Industries, described in United States 3,538,009.
. 20 (d): Westvaco Diacid, 1550
CH = CH
CH3(CH2)5 - CH CH - (CH2)7COOH
CH - CH
I
COOH
(e): polyethylene glycol ester of above dicarboxylic acid (d)
* Trademark
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(f): 1-(3-chloroalkyl)-3,5,7-triaza-1-azoniaadamantane
; chloride, sold as "Dowicide 100*", germicide by
Dow Chemical Co.
:
(g): an isomer of 1-(3-chloroalkyl)-3,5,7-triaza-1-
azonia-adamantane chloride, sold as "Dowicide 200*"
germicide by Dow Chemical Co.
: (h): aqueous solution of an amine and 1,2-benziso-thiazolin-3-one, sold as "Proxel CRL*" germicide
by ICI America, Ltd.
(i): sodium salt of 2-mercaptopyridine-N-oxide, sold
as sodium omidine germicide by Olin Corp.
(j): tris(hydroxymethyl)nitromethane, sold as Tris
Nitro* germicide by Commercial Solvents Corp.
(k): 3,5-dimethyltetrahydro-1,3,5-2H-thiadiazine-2-
thione, sold as "Troysan 142*", by Troy Chemicals
.,~ Co.
(m): ortho-benzyl-para-chlorophenol, sold as 75% sol-
; ution~in isopropanol under the mark "Santophen l*"
' by Monsanto Corp.
(n): distilled coconut acid, a blend of 8% caprylic,
7% capric, 48% lauric, 18% myristic; 9% palmitic,
2% stearic, 8% oleic and 1% linoleic; sold as
"Emery 621*" by Emery Industries.
- 16 -
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Many equivalenL modi~ications will become apparent to those
. skilled in the art from a reading of the above without a departure from the
. inventive concept.
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