Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
1 15 7372
,T~ TPl' TOI~ '
~.~.
"V~T~ T';~ T(~
'~hc prese~t; inv~ntion relat~s to san~i~ation.
MOIe part;c:lLarly the present invention relates to
sani-ti7ation in the dairy inlus-Gry, for exa~ple udder
sanitization, using c~mpositions based on glutaralde-
hyàe .
One Or the best kno~ and most efficient
sterili%in~ ac;ents is glutaraldehyde. However, glutar-
a:Ldehyde sufI`~rs from certain disadvantages. Glutar~
aldehyde in 3cid solu-tion is relatively stab]e but has
very poor sterilizing activity. In alkaline solutions
it is effective but no-t ver~r stable. Attempts have
been made to overcome these disadvantages by storing
the glutaralde~yde under acid conditions and then,
just ~rior to use, adjusting the p~ of the aqueous
æolution of glutaraldehyde to alkaline. Such ac~ion,
however, i~poses an undesirable burden on the user.
Ca~eful investigations have been made into the
action o glutaraldehyde (alone and in the presence Of ot'~er
rnaterials) u~on bacterial cell forms in order to more
fully understand the parameters which govern the
effeCt;j.VenC~SS Of 3.CUeOUS glularaldeh-lde based solutions
for sterili~in~ purposes. From a study of the effect
of glut;ara1dehyde on the cellular activity of cell
~5 forms cf hscher~chia co'~i, it is ~elieved that
,
1 15'7372
-- 2 --
~lutaral~e~lyd.e ac:ts vla a com~ination Or a partial seali.n~
of the outer membIane of the cell wall and inactivation
of cell wall-associated or periplasmic-locatc-d enzymes.
It has been found that the presence of certain materials
potentiates the effective action of glutaraldehyde by
modifying the cell wall. Study of the action of sodi~m
bicarbonate (which has been the tradi-tional alkalinating
agent for converting stored acid glutaraldehyde solutions
into more actlve alkaline glutaraldehyde solutions just
prior to use) has shown that the sodium bicarbonate
does not act only as a me~ns of ch~nging the pE.
The sodium ions arising from the sodium bicarbonate
modify the cell wall. ~he sodium ions cause disrupti.on
of the loose layer and outer membrane of the cell enabling
increased uptake and penetrati.on of glutaraldehyde to
its optimum site of.action. It would appear that the
sodium ions assist in releasing enzymes from the cell
wall constituents thus rendering them nore susceptible
to inactivation by glutaralde;~yde. Similar results were
~ 20 achieved by replacing the sodi.um bicarbonate with
sodium chloride, supporting the belief that the sodium
ion action on the cell wall was as significant a
parameter as the requirement for an alkaline pH.
Further investigations were then made into the
effects of metal ions having higher valencies than
sodium. It was found that such metal ions of higher
valencies were more effective than monovalent ions such
as sodium.
.
1 15'7~72
-- 3 --
It has bcen suggcste(l (in Bri.t;ish ~tent
Specificat-ion No.1,~ 3,7~6) that d.ormant spores can be
killed by ~he use of a composition havin~ a p~i o~
less than 7 and consisting of a solvent which is watcr
or a mi~ture of water and a lower monohydric alcohol,
glutaraldehyde and dissolved quantities of certain
highly ionizable salts at temperatures above 15C. Said
specification does not clearly show the applicability
of such a method to bacteria.
It has also been proposed to incorporate various
additives into the aqueous glutaraldehyde to produce
s-table but active solutions which do not require
alkalination prior to use. For example, a composition
~or sterilizing and disinfecting has been proposed which
comprises water or a mixture of water and a monohydric
alcohol having l to ~ carbon atoms, together with
glutaraldehyde and a trivalent metal i~n. ~he composition
is preferably at a pH not above 7. Such a composition
may also include a surfactant, either as a separate
compound from the compound providing the trivalent
metal ion or as a single compound providing both the
trivalent metal ion and the surfactant components..
However, it has been foun& that the use of such compos-
itions in tke treatment of animals can lead to problems.
~or example, prolonged use of the composition as an
. udder sanitizing agent can cause widespread inclderce
. .
1 15 7372
-- 4
of teat cr~cking. Cracks or fissures in the deI~al
tissue of the cow's teat act as a residence poin~ for
bacterial colonies and it i.s difficu].t to pcnctrate
these points wi.th any type of water.borne disi.nf~ctant.
One factor which may produce the dermatological changes
resulting in cracking is the denuding of the skin's
natural protective fats by a process of emulsification.
The presence of some surfactants in the workin~ formul-
ations would assist this emulsi.fication.
It has now been found possible to reduce the
problem of teat cracking.
According to the present invention there is
provided a composition for santization in the dairy
industry, said composition having a pH of below 7 and
comprising: water or a mixture of water and a mono-
hydric alcohol having l to 3 carbon atoms; glutaraldehyde;
a monovalent and/or divalent and/or.trivalent metal ion;
and an emollient which is soluble in, or has been
solubilised in? the composition and which is based on wool
I 20 grease, a derivative thereo~, an alkyl branched fatty
; . acid ester or a mixture of alkyl branched fatty acid
! esters.
According to the present invention there is also
provided a method of sanitizing in the dairy industry,
which comprises applying to a site on an animal to be
treated a composltion having a pH of below 7 and
! ~ comprising: water or a mi~ture of water and a mono-
I hydric alcohol havi.ng l to ~ carbon atoms; glutar~
1 1~'737
- 5
dehyd,?;~ a monovale~t an~/or divalent and/or triva]enl;
metal ion; and an emollient which is solu~le in, or
. has been solubili%ed ;n, the composi~ion and ~/hich is
based on wool grease, a derivative thereof, ~n ~lkyl
branched ~atty acid ester or a mi~ture of alkyl branched
~atty acid esters r
The presence of the emollient in the composition
substantial'.y overcomes t'ne problem of teat cracking.
It is believed that the emollient is adsorbed into the
udder dermal tissues, producing an emoliient action
which succeeds in ~uppressing teat cracking. The
emollient conditions the skin of animals by replacing
the natural oils which may be removed, as described
above, by other constituents in the compositions.
Care must be taken in the selection of the emollient
for use in the present invention. Many of the well
known materials suitable for use-as emollients, e.g.
glycerine and propylene glycol, are totally unsuitable
for use in the present invention because, when formulated
with glutaraldehyde at acid pH, they react with the
glutaraldehyde to form a compound which does not display
microbiocidal properties. On storage, such for~ulations
gradually show a decrease in glutaraldehyde content
and sanitizing activity and are not suitable for
co~mercial manufacture.
Another approach to the inclusion of an emollient
in a formulation comprising glutaraldehyde, water or a
-
1 15'7372
-- 6 --
mixture`of water and a monohydric alcohol having l to 3
carbon atoms, ~nd a monovalent and/or divalent and/or
trivalent metal ion is the inclusion of a water-insoluble
emollient which has been emulsified in the formulation
by the addition of a suitable surface active agent.
However, such formulations containing e~ollients otherthan
those used in the formulation o~ the present inventioncan be
unsuitable as the high concentration of ions present in
~hè formulation can crack do~rn the emulsion of the emoll-
ient and disrupt the formulation into a non-emulsified
oil ~nd aqueous mixture which is not suitable for use.
It has been ~ound that the emollients sui~able
¦ ~or use in the present invention are based on ~ool grease,
a derivative thereof, an alkyl branched fatty acid ester
or a mixture o~ alkyl branched fatty acid esters. The
emollient is either soluble in~ or is solubilised in,the
composition. I~ the emollient is solub~lised in the
composition, the solubilisation is effected by means of a
sur~actant.
~ ~ 20 Wool grease is the name given to the material
1 8ecreted by sheep from sebaceous glands in their skin
so as to form a natural protective coating on the wool
fibres. It has the physical consistency of a soft
grease, i8 chemically a wax and is different from the
body fat of the animal. Wool grease may, for example,
be recovered from the wool by a washing process and may,
- for example, be refined into derivatives which have
va~ue as emollients in the present invention. Such
',',' . .
1 1 5 ~372
-- 7 --
derivati~es wlich nave value as emollients include
wool fat (.~nhydrous lanolin), 1iquid wool fat and
hydrogenated wool Lat.
.
AlkoxylatiGn of wool grease or derivatives thereof
with a suitable agent, e.g. ethylene oxide or propylene
oxide, produces derivatives-which-may, for example, be
soluble in water and use~ul as emollients in the
present inventïon. In such instances the polyalkylene
oxide condensate produced preferably has a minimum
average chain length of approxi~ately 15 alkoxyl units.
-- The emollient is preferably a polvalkylene oxide
derivative of either wool grease or a derivative of
wool grease such as wool fat, liquid wool fat or
hydrogenated wool fat. Suitable emollients include the
polyalkylene oxide derivatives of wool fat, such as
ethoxylated wool fat, particularly when the degree of
ethoxylation is within the range of 40 to 70 mols of
ethylene oxide. However, any other water-soluble
polyalXylerLe oxide derivative of wool fat may be
employed.
The emollient used in the present invention is
preferably one which is soluble in aqueous solution as
no solubili~ation of the emollient will be required.
¦ Such emollients which are soluble in aqueous solution
! 25 include the polyall~ylene oxide derivatives of wool
grease and the polyalkylene oxide derivatives of wool
grease derivatives such as wool fat, liquid wool fa~
hydro~en~ted ~rool fat ~nd chlorin~ted wool fat~
,
115 7372
The water-soluble polyalkyleIle oxide dcrivatives
of wool grase and the water-soluble polyalkylene oxide
derivatives of wool grease derivatives can tolerate
high electrolyte concentrations and in the working
formulations they are stable and may be stored for
considerable periods of time without loss of glutaral-
dehyde content or sanitizing activity and without
disruption of the formulation.
The polyal~ylene oxide derivatives of wool grease
and the polyalkylene oxide derivatives of wool grease
derivatives also have the adv&ntage that they possess
non-ionic surfactant properties. Thus, in addition
to their emollient action on the skin of the animal,
they enhance the microbiocidal action of the glutaral-
dehyde because of a synergistic action in combination
with the glutaraldehyde and metal lons. This means that
the quantity of glutaraldehyde present in the mixture
may be reduced to produce the desired microbiocidal
effect.
It is possible, with the polyalkylene oxide
derivatives of wool grease and the polyalXylene oxide
derivatives of wool grease derivatives, to solubilize
further quantities of the water-insoluble emollients
sucn as wool fat and alkyl branched fatty acid esters
~5 w1thout additional quantities of surface acti~e agents.
.
1 15'7372
g
Examples of water-insoluble derivatives of wool grease
which may be used in the present invention include: wool
fat; wool alcohols; liquid wool fat, e.g. Arganol* 60
produced by Westbrook Lanolin Limited; hydrogenated wool
fat, e.g. Satulans* produced by Croda Chemicals Limited;
and esterified wool fats such as the isobutyl derivative
of liquid wool fat, e.g. Arganol* 40 produced by Westbrook
Lanolin Limited.
Examples of water-soluble derivatives of wool grease
which may be used in the present invention include: eth-
oxylated wool grease such as Aqualose* WG 75 produced by
Westbrook Lanolin Limited; alkoxylated wool fats such as
ethoxylated wool fat, e.g. Aqualose* L75 or Aqualose* L30
produced by Westbrook Lanolin Limited; alkoxylated liquid
wool fats such as Aqualose* LL 100 produced by Westbrook
Lanolin Limited; and alkoxylated wool alcohols such
as propylene oxide derivatives of wool alcohols, e.g.
Solulans* PB produced by Amerchol U.S.A., or ethoxylated
wool alcohols, e.g. Aqualose* W20 produced by Westbrook
Lanolin Limited.
Examples of commercially available solubilized
derivatives of wool grease include: Aqualose* SLW
which is produced by Westbrook Lanolin Limited and is
a blend containing approximately 20~ by weight liquid
wool fat solubilized with ethoxylated wool alcohols; and
Aqualose* SLT which is also produced by Westbrook Lanolin
* Trade Mark
B
.
.
,
:
1 1 5 73~2
-- 10 --
Limited and is a blend containing approximately 25%
by weight of natural liquid wool fat solubilized with
ethoxylated straight chain fatty alcohols.
Examples of suitable commercially available alkyl
branched fatty acid esters or mixtures thereof include:
PCL* liquid which is marketed by Dragoco Company and is
a mixture of alkyl branched chain fatty acid esters; and
Neo-PCL* which is marketed by Dragoco Company and is a
mixture of an alkyl branched chain fatty acid polyglycol
ester with 4 moles of ethylene oxide and an alkyl phenol
polyglycol ether as a solubilizer.
The amount of emollient used can, for example, be
as low as 0.1% weight/volume, e.g. at least 0.5% weight/
volume, based on the composition. The emollient can, for
example, be used in amount of up to 15% weight/volume,
e.g. up to 10% weight/volume, based on the composition.
However, it is preferred to use substantially 2% weight/
volume of the composition. Such concentrations are based
on the solution as used in the treatment. It is, however,
possible to provide the composition in a concentrated form
which may be diluted, for example, ten times, prior to use.
The composition of the present invention contains
a monovalent and/or divalent and/or trivalent metal ion.
In the case of monovalent ions it is preferred to use
alkali metal ions, in the case of divalent ions it is pre-
ferred to use alkaline earth metal ions, and in the case
* Trade Mark
115 73r?2
of trivalent metal ions it is preferred to use those
of Group IIm of the Periodic Table of the Elements
~e.g. aluminium). ~he metal ions can be introduced i
salt form. Examples of suitable salts of monovalent
5~ metal ions include halide ~e.g. chloride), sulphate,
nitrate, acetate and citrate salts of sodium and
potassium. Examples of sùitable salts of divalent
metal ions include halide (e.g. chloride), sulPhate,
nitrate, acetate and citrate salts of magnesium and
soluble salts of calcium includin~ chloride and acetate
- salts of calcium. Examples of suitable salts of
trivalent metal ions include aluminiu~ acetate,
aluminium chlor~de and aluminium chlorohydrate.
For the sake of convenieDce, the present invention
will hereinafter be particularly described with
reference to the use of A~3+ or Mg2~ as the metal ion.
However, monovalent or other divalent or trivalent
¦ metal ions may be used.
I The presence of A~+ or Mg2+ in aaueous glutaral-
¦ 20 dehyde solutions has been found to increase glutaral-
¦ dehyde inactivation of cellular alkaline phosphatase by
I caus;ng a drift of the enzyme towards the outer membrane.
I A still further increase in activity nas been
demonstrated when a surfactant, preferably of the
anionic t~pe, is added to the aluminium-glutaraldehyde
or magnesium-glutaralde`nyde formulation and this effect
s related to increa~ed upta~e of the disinfectant.
~ 1 15'737~
-12_
As mentione(l above, acidic sclutions of glu~araldei)yde
have very slow activity. Tlowcvt:r, it llas been found
that an aclueolls acidic solution of glutaraldehyde
containing A~3+ or Mg2+ has comparable activity to an
aqueous solution of glutaraldehyde made alkaline by the
presence of, for example, sodium bicarbonate.
Study of the effect of varying concentrations of
Ae3~ or Mg2+ on the effectiveness Gf the glutaraldehyde
solution has shown increasing effectiveness up to abou~
0.2 molar but no significant increase for concentrations
over 0.2 molar. However,concentrations as high as 0,5 rrlolar
may be used. It is preferred to use a concentration of
Aa3~ or Mg2~ of at least 0.15 Molar. However, concent-
rations as low as 0.05 Molar may, for example, be used.
Extrapolation of investigations on bacteria to spores
has shown similar results.
The incorporation of a surfactant into the
glutaraldehyde-Ae3+ or glutaraldehyde-Mg2+ solution
potentiates the effect of the glutaraldehyde. Indeed
it has been found that in some cases a synergistic
effect is achieved when compared with aqueous glutar-
aldehyde containing Ae3+ or Mo2+ or surfactant alone.
The ~ount of surfactant present may, for ex-rple,
be a~ least 0.017' by weight, e.g. at least 0~1~ by weightJ
of the compositionO The surfactant rnay, for example,
be prcsent in an arlount of up to 1~^~' by Yeight~ e.g. up
to 5,~ by ~ieight,of the composition.
1 15'7372
--l 3-
~ he preforred surfactan~s are anionic. Suitable
anionic suIfRctants include detergents ,lhich are
ionizable at the p~ of acid solutions of glutaraldehyde.
~he pKa values would generally be less than 4,
preferably less than 3.5. ~ne anionic surfactants may,
for example, be alkyl sulphates or alkylaryl sulphonates.
~he alkyl sulphates usually have 8 to 18 carbon atoms
in the alkyl group, for e~ample, lauryl or deodeGyl
sulphate. ~he anionic surfactant is usually employed
in an amount of less than 10% by weight, preferably less
than 5% by weight, of the composition when using an
alkyl sulphate.
Non-ionic surfactants such as the ethoxylated
fatty alcohols or ethoxylated alkylphenols may be used.
Preferably the fatty alcohol or alkyl phenol has been
ethoxylated to a degree of greater than 9 moles of
ethylene oxide. However, use of a non-ionic surfactant
with Ae~+ or Mg2+ has been found not to be as effective
- as use of an anionic surfactant (as sodium salt) with
A~3+ or Mg2~. The non-ionic surfactant is usually
employed in an amount of less than 3,~ by weight,
preferably 0.5 to 1.5% by weight of the co position.
Use of fairly high concentratio~s of Ae~+ or Mg2+
(or indeed monovalent or other divalent or trivalent
metal ion) salts and fairly high concentrations of
3ur~actants can, however, lead in some instances to a
sa~ting out effect resulting in precipitation from the
1 15'7372
-14-
solution. '~his prob]em can, however, be overcome by
employin~ the Ae3+ or Mg2+ and surfactant as a sin~le
compound. When using such s;ng]e compounds, the
monovalent, divalent or trivalent metal ions are cations
of s~rf~ct~nts, preferably anionic surfactants.
EXamples of such compounds are aluminium dodecyl or
lauryl sulphate, aluminium dodecyl or lauryl benzene
sulphonate, magnesium dodecyl or lauryl sulphate and
magnesium dodecyl or lauryl benzene sulphonate. Indeed,
if a single compound is used it is possible to produce
effective formulations of glutaraldehyde containing
less than the desired 0.15 Molar concentration of
Ae3~ or Mg ~, even as low as 0.001 Molar.
'~he concentration of glutaraldehyde in the aqueous
solution affects the time required for sanitization.
The concentration of glutaraldehyde is usually from
0.005/0 to 10%, but preferably less than 0.5%, by weight
of the composition~ -
'~he composition of the present invention may also
contain a small quantity of an organic acid such as
citric acid, propionic acid, tartaric acid or maleic
- acid. The organlc acid, if used~ i3 present in an
amount suf~icient to ensure an acid pH for the fo~ul-
ation.
The compositions of the present invention are
temperature dependent in use~ Increasing te~perature
leads to lncreasing activity and indeed a synergistic
,' .
115 ~372
,5
effect may be observecl. ~rhe compositiorls ~Ire usually
employed at a temperature of at lea~t ambient ternperature.
If a mixtllre of water and alcohol is used in the
composition of the present invention, the alcohol may,
for example, be isopropanol. The presence of an
alcohol, or indeed any other organic solvent, can be
used to control the viscosity of the solution or produce
a humectant èffect.
~he co~po~ition of the present invention may
further comprise a corrosion inhibitor.
~ he col-lpositior. of the present inventior. may be
used in saniti~ation in the presence of metallic,
particularly ferrous, articles. IIowever, at the acid
pH of the composition, many of the conventional
additives for rust inhibition have been demonstrated to
be ineffective. It has further been demonstrated that
the sulphate or sulphonate derivati-res of hydroxy
carboxylic acids, such as those derived from ricinoleic
- and hydroxy stearic acids, are effective corrosion
inhibitors for the formulations of this invention.
~he aforementioned sulphate and sulphonated derivatives
of hydroxy carboxylic acids are also anionic surfactants.
It is further possible by the use of the said carboxylic
acids to present the preferred ion, anionic surfactant
and corrosion or rust inhibitor in the form of a single
compound. The amount of corrosion or rust lnhibitor
1 15 7372
-1 6-
employed i~; usllrLlly 0~1 to 5~o by weifrh1., pre~ ?I'
to 2~ b~ weil~ht, and more ~re~erably subst~ntiall~
by weight, of the composit.ion. A par'icularl~ useful
i~libitor is sulphated caster oil (marketed by Ellis
Jones & Co.), preferably in the presence of an or~an~c
acid (eOg. citric acid) to ensure an acid pH.
The present invention will now be further
described with reference to, but is in no manner limited
to, the following examples.
EXAMP~E 1.
1.5% by weight of solubilized liquid wool fat
was heated and dispersed in warm water and allowed to
cool. 0.5% by weight glutaraldehyde and 2.0% by weight
sodium chloride were then added and the mixture was
made up to 90% of the desired volume with water. Citric
acid was added to give a pH of appro~imately 5.0 and
the re~sultant mixture was made up to 100% of the desired
volume with water. The resulting formulation was
satisfactorily used in the santizing of cows' udders.
The solubilized liquid wool fat used in this
Example was Aqualose S~T which is marketed b~ Westbrook
I~nolin Limited and is a mixture of natural liquid wool
fat (approximately 25C~ by weight) and an ethoxylated
fatty alcohol (approximately 75~ by weight).
E.~AM I.E 2.
0.1~' by weight glut~raldehyde, 4.0C~ by weight
magnesium chloride hexahydrate and 2~C;, by weight
.
.
1 1 5 7372
,~
etho~lated ~rool fat were dispersed in ~rater. Citric
acid was added in an amount sufficient to give a pH of
approximately 5Ø The resulting formll]ation was
Successfully used as a saniti7.ing formulatior. for dairy
pur~ose;.
EXAMPIE 3.
0.5% by weight glutaraldehyde, 4.0% by weight
magnesium chloride hexahydrate, 2.0% by weight etho~y-
lated wool fat and 10.0,o by weight isopropanol were
dispersed in water. Citric acid was added in an amou~t
sufficien to give a pH of approximately 5Ø The
resulting formulation satisfactorily used in the sanit-
izing of cows' udders.
EXAMPLE 4.
_
0.5% by weight glutaraldehyde, 7 0C,' by weight
magnesium lauryl sulphate, 3.0~.~ by weight ethoxylated
wool fat and 0.5% by weight citric acid were dispersed
in water. The formulation so produced was effective in
the sanitization of co~s' udders.
EXAMPL~ 5.
0.1% by weight glut~raldehyde, 4~0, by weight
magnesium chl~ride he~ahydrate and 1.5-~o by weight Neo-
PCI.~/clter-soluble were dispersed in water. Citric
acid was added in an amount sufficient to give a pH of
approximately 5Ø The resulting formula-tio~ was
successfully used as a sc~nitizing agent for dairy
pur,poses .
l l5'7372
_18-
~.XAMPLE 6.
1.0,'.by weight of solubilized liquid wool fat
wa~ heatecl and dispersed in warm water and allo~red to
cool. 0.55'~by weight glutaraldehyde and 2.0% by weight
sodium sulphate were added and the mixture made up to
90% of the desired volume with water. Citric acid was
then added to ~ive a pH of approxima-tely 5.0 and the
resultant mixture made up to 100% of the desired volu~e
with water. ~he resulting formulation was satisfactorily
used in the sanitizin~ of cows' udders.
In this Example the solub~ ed liquid wool fat
was Aqualose SLW which is marketed by Westbrook Lanolin
~imited and is a mixture of natural liquid wool fat
~approximately 20% by weight) and ethoxylated wool
alcohols (approximately 80% by weight).
~ ~ . . ... ..
~XAMP~
3% by weight of ethoxylated wool alcohols was heate~
and dispersed in warm water and allowed to cool. 0.4
by weight glutaraldehyde and 1,~ by weight aluminium
- 20 acetate were added and made up to the ~esired volume with
water. The resulting formulation had a pH of less than
7 and was satisfactorily used for saniti~ing cow~s udders.
E2~PIE 8
2% by weight of ethoxylated wool grease (Aqualose
WG 75) was heated and dis~ersed in warm water and allowed
to cool~ 0.3/~ by weight glutaraldehyde and 3~J by ~eight
.. .
115 7372
-19-
magnesium ch~oride hexahydrate were added and ~adc up to
the d.esircd vol~me with ~rater. The resulting formulation
had a pH o-f less than 7 and was satisfactorily used for
. sanitizing cows' udders.
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