Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
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MICROBICIDAL COMPOSITIONS
BACXGROUND OF THE INVENTIQN
(a) Field of the Invention
The invention relates to microbicidal compositions
which may be formulated as solids or liquids and, more partic-
ularly, to such compositions comprising as essential activeingredients certain organic acids and salts of aliphatic
sulfates or aliphatic sulfonic acids.
(b) In~ormation Disclosure Statement
Leading hygienists urgently express the need for
fast-acting disinfectants, having a broad spectrum of micro-
bicidal activity but the active components of which are
toxicologically so innocuous that they can be employed in
the area of food hygiene without any problem. Disinfection
in~ the foodstuff industry presents a much more difficult
i5 problem than in the medical area since far fewer chemicals
can be considered. To begin with, chemicals having strong
odors or which are toxic are excluded from consideration.
Among such chemicals are the aldehydes which, although
possessing a broad spectrum of microbicidal activity, cannot
be used due to their obnoxious odor as well as their ability
to cause allergic reactions. Furthermore, the aldehydes
are extremely incompatible with soap and their activity
is reduced at temperatures below 18 C. Phenols, although
numbering among the oldest of disinfectants, also are
malodorous and toxic. - As to the per-acids, halogens and
halogen precursors, these agents develop unpleasant odors.
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Other known disinfectants such as the quaternary ammonium
salts have large gaps in their spectra of activity and are
readily inactivated by protein contamination. To~ic effects
are also encountered with guanidine derivatives while alcohols
must be used at concentrations of 60% to 80% in order to
obtain rapid disinfection. Such high concentrations of
alcohols are to be avoided in spraying large surfaces because
of the danger of explosion.
The urgent need for rapid-acting, toxicologically
unobjectionable, broad-spectrum disinfectants for destroying
agents which cause spoilage and pathogenic germs in the
foodstuff industry extends also to the household kitchen,
e.g., to dish washing, work areas, refrigerators and kitchen
utensils. Obviously, such a disinfectant also would have
advantages in the medical and sanitation areas.
U.S. Patent 2,393,866 to Wassell discloses metal
tarnish remover compositions comprising water, abrasive
particles, a polyoxyethylenediol, a tarnish-removing substance
and a metal wetting agent. Among the classes of wetting
agents disclosed are the salts of fatty alcohol sulfates.
- The tarnish-removing agents disclosed include organic acids.
Among the various specific acids disclosed is tartaric acid.
U.S. Patent 3,083,166 to Harding discloses detergent
compositions having improved detergency and brightening
properties comprising non-soap anionic or nonionic detergents,
a condensation product of formaldehyde and a carbocyclic
aryl sulfonic acid, and an organic acid. Among the classes
... . .
12~'7S~
--3--
anionic detergents disclosed are the alkali metal salts
of higher alkylsulfonic acids and the alkali metal alkyl
sulfates. Among the various specific organic acids disclosed
are hydroxyacetic acid, lactic acid and tartaric acid.
U.S. Patent 3,141,821 to Compeau discloses composi-
tions for local antisepsis comprising an anionic surface
active sulfonate and a bacteriostatic compound at a pH of
2 to 4. ~mong the classes of surface active sulfonates
disclosed are alkyl sulfonates having from 8 to 22 carbon
atoms. The pH is regulated by the addition of an appropriate
acid. Various specific acids are disclosed including tartaric
acid and hydroxyacetic acid. No specific compositions com-
prising combinations of tartaric acid and/or hydroxyacetic
acid and an alkyl sulfonate are exemplified.
U.S. Patent 3,650,964 to Sedllar et al. discloses
low foam acid sanitizer compositions comprising anionic
surfactants in acidic media. Among the classes of surfactants
disclosed are the alkali metal salts of alkyl sulfates.
Included in the various acids disclosed is hydroxyacetic
acid. No specific compositions are exemplified which include
a combination of hydroxyacetic acid or any organic acid
with an alkali metal salt of an alkyl sulfateO
British Patent Specification No. 938,908 discloses
a process for sterilizing and disinfecting frui~. A composi-
tion disclosed for comparative purposes comprises a 2~ aqueoussolution of the sodium salt of lauryl sulfate,
hydroxyquinoline, salicylic acid, acetic acid and tartaric
acid, and sodium propionate.
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British Patent Specification No. 962,469 discloses
anhydrous acid denture cleaner pastes comprising an anhydrous
base and sulfonic acid. The pastes may contain other ingredi-
ents such as a surfactant. Several compositions are exempli-
fied which contain, inter alia, sulfamic acid and sodiumlauryl sulfate.
Australian Patent Specification No. 287,889 dis-
closes anionic and non-ionic detergent baths containing
a pH adjusting additive. Among the classes of anionic
detergen~s disclosed are the alkyl sulfonates. The p~l
adjusting additive may be an organic or inorganic acid.
Included among the specific organic acids disclosed is
tartaric acid. No specific compositions containing an alkyl
sulfonate and an acid are exemplified.
Chemical Abstracts 91, 44537p, discloses tabletted
cleaning compositions for maxillary prosthesis comprising
a phosphate or polyphosphate, a carbonate or bicarbonate,
a salt of a weak organic acid, a detergent, an antimicrobial
agent and a polyethyleneglycol. A specific composition
exemplified contains, inter alia, tartaric acid and a
detergent. The detergent is not specifically identified.
Chemical Abstracts _ , 182892x discloses sprayable
cleaning compositions for removing soils and stains ~rom
hard surfaces containing sodium dihydrogen phosphate as
well as oxallc acid, tartaric acid and/or citric acid. A
specifically exemplified composition includes, inter alia,
sodium stearyl sulfate and oxalic acid.
759
DETAILED DESCRIPTION INCLUSIVE OF T~E
PREFERRED EMBODIMENTS
It has now been found that the combination of
alkyl sulfonates and/or alkyl sulfates with one or more
organic acids described hereinafter displays an unexpectedly
broad spectrum of microbicidal and virucidal activity in
very low use concentrations at which the individual components
of the combination do not exhibit any microbicidal activity.
Such combinations possess no acute toxicity and are practi-
cally odorless.
Thus, for example, the minimum .inhibitoryconcentration (MIC) for sorbic acid against Staphylococcus
aureus is 0.7~, and against Escherichia coli it is 0.2%.
However, with a mixture of 1 part of sorbic acid with 4
parts of a mixture of C8_18 alkyl sulfonates, killing is
effected within 15 minutes at a sorbic acid concentration
of only 0.004Z% in the case of Staphylococcus aureus and
only 0.0150% in the case of Escherichia coli. The MIC values
for benzoic acid against Staphylococcus aureus and Escherichia
coli are 0.1~ and 0.125% respectively whereas with a mixture
of 1 part benzoio acid with 4 parts of a mixture of Cg_lg
alkyl sulfonates, concentrations of benzoic acid of 0.0075~
and 0.0300% .suffice to kill Staphylococcus aureus and
Escherlchia coli respectively within 15 minutes.
By using suitable combina~ions of the acids
employad in this invention, the spectrum of activity can
be extended even to the allegedly resistant mildew fungi
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such as Aspergillus niger, Asperqillus fumigatus and
Penicillium expansum.
Thus in one aspect this invention provides a
microbicidal composition comprising as essential components:
S (A) an organic acid selected from the group consisting of
benzoic acid, benzoic acid substituted by a methoxy substi-
tuent or a methyl substituent, 2-furancarboxylic acid,
ascorbic acid, pyruvic acid, sorbic acid and cyclohexane-
sulfamic acid and mixtures of said acids; and (B) a
water-soluble salt of an alkyl sulfate or alkyl sulfonic
acid wherein alkyl in each case contains from 8 to 18 carbon
atoms.
In a second aspect this invention provides a
microbicidal composition which comprises as essential
components: (A) tartaric acid or glycolic acid: (B) benzoic
acid or 2-furancarboxylic acid; and (C) a water-soluble
salPt of an alkyl sulfate or alkyl sulfonic acid wherein
alkyl in each case contains from 8 to 18 carbon atoms.
The microbicidal compositions of the invention
are active over a wide temperature range. Their activity
at low temperatures is particularly advantageous for disin-
fecting cold rooms and refrigerators.
The alkyl sulfates and alkyl sulfonates employed
in the invention are primary or secondary alkyl sulfates
or sulfonates in which the alkyl group contains from 8 to
18 carbon atoms, preferably from 10 to 16 carbon atoms.
The cation of the alkyl sulfates and alkyl sulfonates is
alkali metal, e.g., sodium and potassium, ammonium, or substi-
tuted ammonium such as mono-, di- and triethanolammonium.
4~75~
The sodium alkyl sulfates and alkyl sulfonates are preferred.
Mixtures of alkyl sulfates and/or alkyl sulfonates can be
employed.
The compositions of the invention can contain
one or a mixture of two or more organic acids as follows:
benzoic acid, benzoic acid substituted at the 2, 3 or 4-
position by a methoxy or methyl substituent, 2-furancarboxylic
acid, asorbic acid, pyruvic acid, sorbic acid and cyclohexane-
sulfanic acid; or a mixture of tartaric and/or glycolic
acid with benzoic acid or 2-furancarboxylic acid.
The weight ratio of alkyl sulfate or alkyl
sulfonate to organic acid in the compositions of the invention
can range from 50:1 to 1:50, preferably from 7:1 to 1:7,
and more preferably from 9:1 to 1:1. The selection of a
particular ratio will depend on the pKa-value of the acid
to be employed, as well as on the pH value dèsired in the
use solution. The pH of the use solution should be between
about 0.1 and 5Ø Optimal microbicidal activity is obtained
in a pH range of 2 to 4.
The compositions of the invention can be
formulated as solids, i.e., in granular or finely divided
(powdery) form, which are prepared for use by dissolving
in an aqueous medium. Alternatively they can be formulated
as liquids in aqueous medium, either in a form ready for
usa or in the ~orm of a concentrate which can be prepared
for use by appropriate dilution in water. The concentrates
generally will contain from about 20~ to 40% by weight of
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the active ingredients, i.e., the acid and alkyl sulfate
or sulfonate. The concentration of active ingredients in
the use solution should be sufficient to provide effective
microbicidal activity as can be readily determined by one
skilled in the art. The use solutions can be used safely
and without danger in the household.
If the water solubility of a particular acid
to be employed is limited, it is desirable to include an
alcohol in the liquid forms of the compositions of the
invention in order to aid in solùbilizing the acid. Alcohols
which can be used are, for example, ethyl alcohol, n-propyl
alcohol, isopropyl alcohol and 1,2-propanediol. The alcohols
also provide for faster drying of the compositions after
application to a surface.
The compositions of the invention can optionally
contain, in addition to the alkyl sulfates and sulfonates,
other surfactants of the anionic, non-ionic and ampholytic
types. Thus, if desired, anionic surfactants of the fatty
alcohol ether sulfate type, e.g., sodium lauryl myristyl
ether sulfate in combination with sodium chloride may be
added in order to increase the viscosity of a use solution.
If foam regulation of a use solution is desired, a non-ionic
surfactant such as a fatty alcohol polyglycol ether with
a suitable degree of ethoxylation can be employed.
Other optional ingredients which can be included
in the compositions of the invention are corrosion inhibitors
such as the phosphonic acids, low temperature stabilizers,
enzymes, additional antimicrobial agents, perfumes, colorants,
~244'7S~
solubllizers, pH-regulating agents, salts and, for the prepar-
ation of solid forms of the compositions, fillers such as
sodium sulfate.
In view of their bactericidal, mycobactericidal,
fungicidal, virucidal and desirable cleaning properties,
the compositions of the inventions find utility not only
in the home and with respect to foodstuffs in which case
appropriate acids can be selected such as condiment acids,
e.g., tartaric acid, and acids expressly permitted as
additives in foodstuffs, but also are useful in appropriate
concentrations as instrument, hand and skin disinfectants
in hospitals, as well as in industry and agriculture. Their
application in the field of dermatology also is possible.
For use as hand and skin disinfectants or in
dermatology, the compositions can be formulated, by techniques
standard in the art, as semi-solids, i.e., as paste-like,
creamy or gel-like compositions. The alkyl sulfate or
sulfonate employed in such compositions must be
skin-compatible such as, for example, the triethanolamine
salt of decyl sulfate. In formulating such compositions
adjuvants such as organic and inorganic thickening agents,
alcohols, fragrances and ointment bases can be employed.
Toxicological studies of the alkyl sulfates
and sulfonates employed in this invention demonstrated an
oral LDso (mouse) of 2100 mg/kg which is physiologically
unobjectionable.
The compositions of the invention are highly
active, toxicologic`ally unobjectionable disinfectants which
~4~S9
--10--
are particularly useful as microbicidal agents in the field
of foodstuffs and in the household. They can be applied
to the surfaces to be treated by well known procedures such
as spraying, swabbing, immersion, etc.
The invention is illustrated by the following
examples without, however, being limited thereto.
The compositions of the invention exemplified
below were tested for antimicrobial activity in accordance
with the methods of the DGHM (Richtlinien f~r die Pr~fung
chemischer Disinfektionsmittel der Deutsches Gesellschaft
f~r Hygiene and Mikrobiologie) against two or more of the
following bacteria, mold and fungi:
I. Staphylococcus aureus
II. Escherichia coli
15 III Pseudomonas aeruginosa
.
IV. Proteus
V. Klebsiella
VI. Penicillium expansum
VII. Aspergillus niger
~ VIII. Aspergillus fumigatus
IX. Candida albicans
_
X. Tricophyton matagrophytes
The above-listed microorganisms are hereinafter
identified by the above-designated Roman numerals.
;759
Example 1
An aqueous composition, ready for use, was prepared
containing the following ingredients:
Ingredient Weiqht~Percent
L-~+)-Tartaric acid 0.5
Benzoic acid 1.0
Sodium alkyl sulfonate
(mixture of C10-16) 2.0
Ethyl alcohol 20.0
' Water (deionized) 76.5
10096
pH 2.65
The antimicrobial and anti-viral test results
for the composition of Example 1 were as follows:
1. Bactericidal Effect
(Suspension test; killing time in minutes)
Concentration Microorganism
(%) I II III IV V
2.5 2.5 2.5 2.5 2.5
2.5 2.5 2.5 2.5 2.5
3 2.5 15 2.5 2.5 15
1.5 2.5 >60 5 5 >60
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2._ngicidal Effect
(Suspension test; killing time in minutes)
Concentration Microorganism
~ VII IX
100 2.5 2.5 2.5
2.5 2.5 2.5
2.5
>60 >60 15
3. Virucidal Effect v. poliomyelitis virus
10Time (minutes) Reduction of Titer, logl-n
>8
>8
>8
>8
15 4. MYcobacterium smegmatis was killed within 60
minutes.
5. Killlng of bacteria on PVC and lacquered wood
surfaces at room temprature and at 40C.
The numbers listed in the time columns below
represent the number of colonies of the
microorganismr the first referring to the PVC
surface and the second to the lacquered wood
surface (e.g., 29/0 denotes 29 colonies on the
PVC surface and 0 colonies on the lacquered wooden
surface).
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a)Room temperature
Microorganism Time (minutes)
_ 10 30 60_
I 0/0 0/0 0/0 0/0
II 0/0 0/0 0/0 0/0
III 0/0 / / /
IV G/0 0/0 0/0 0/0
V 29/0 0/0 0/0 0/0
10 b)4C
Microorganism Time (minutes)
I _ 15 30 60_
II 0/0 0/0 / /
III 0/0 0/0
15IV
V 100/17 0/0 0/0 0/0
6. Killing of fungi on PVC and lacquered wood surfaces
at room temperature and 4C.
The numbers listed in the time columns below
have the same meaning as in paragraph 5) above.
a) Room temperature
Microorganism Time (minutes)
5 15 30 60
V~ 0~0 0/0 0/0 0/0
25VII 0/0 o/0 0/0 0/0
IX 0/0 0/0 0/0 /
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b) 4C
MicroorganismTime (minutes)
5 15 30 60
VI 27/0 0/0 0/0 0/0
VII 0/0 / / /
IX 0/0 0/0 0/0 0/0
Example 2
A composition was prepared containing the following
ingredients:
Ingredient Weight-Percent
Sodium dodecyl sulfonate 20
L-(~)-Tartaric acid 5
Benzoic acid 5
Ethyl alcohol 15
15 - Water (deionized) 55
100%
- The antimicrobial test results for the composition
of Example 2 are given in Table 1.
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e 8 ~ ~ ~
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Example 3
A solid ~powdery) composition was prepared
containing the following ingredients:
Ingredient Weight-Percent
S Sodium lauryl sulfonate 10
Sodium decyl sulfate 10
L-(~)-Tartaric acid 3
2-Furancarobxylic acid 5
Sodium sulfate 72
Example 4
A composition was prepared containing the following
ingredients:
Ingredient Weiqht-Percent
Sodium alkyl sulfonate
(mixture of C10-16)
Cyclohexanesulfamic acld 0.9
Water (deionized) 96.1
100
pH 2.12
The antimicrobial test results for the composition
of Example 4 are given in Table 2.
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U~ U~
~ U~
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o H ~
H
E3
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1'-'
.~ U~
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U~ ~ ~ ~ o
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o
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a) ..
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h . o\O
o~ o U') ~D '
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h O
0
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Example 5
A composition was prepared containing the following
ingredients:
Ingre_ient Wei~ht-Percent
Sodium alkyl sulfonate
~mixture of C10-16) 3 00
1,2-Propanediol 5.00
L~ Ascorbic acid 0.88
Water (deionized) 91.12
100%
pH 2.95
The antimicrobial te~t results for the composition
of Example 5 are given in Table 3.
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tQ
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o
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Example 6
A composition was prepared containing the following
ingredients:
Ingredient Weight-Percent
Sodium alkyl sulfonate
(mixture of C10-16) 3'
2-Furancarboxylic acid 0.56
1,2-Propanediol 5.00
Water (deionized) 91.44
100
pH 2.54
The an~imicrobial test results for thë composition
of Example 6 are given in Table 4.
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H I ~ t~ `J U'l O O
Ei ~ ~
.~
~ ~ U~
ooH ¦ ~1 u~ U7 0 0 0
h
a) ,,
,~
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.,1
.~ .
E~ .~
U~
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o
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S~ ` ~ . . , , o~O
O ~ ~ ~ ~ O
~: o ~
a) ,,
o
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0
O
o
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Example 7
A composition was prepared containing the following
ingredients:
Inqredient Weight-Percent
Sodium alkyl sulfonate (C10-16) 3.00
Pyruvic acid 0 44
1,2-Propanediol 5.00
Water (deionized) 91.56
100
pH 2.18
The a~timicrobial test results for the composition
of Example 7 are given in Table 5.
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Example 8
A composition was prepared containing the following
ingredients:
Ingredient _ Weight-Percent
Monoethanolamine dodecyl sulfate 3.00
Glycolic acid 0.38
Benzoic acid 1.00
Ethyl alcohol 20.00
Water (deionized) . 75 62
100
pH 2.6
The antimicrobial test results for the composition
of Example 8 are given in Table 6.
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