Note: Descriptions are shown in the official language in which they were submitted.
-` 2 31~.5~
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1 NON-IRRITATING HYPOCHLORITE GERMICIDE
3 Backaround of the Invention
4 1. Field of the Invention ~;
Germicidal compositions which disinfect animal
6 and/or human skin are used in food processing industries,
7 surgical and other medical and veterinary practices and ;~
8 in agriculture, where teat dipping of dairy cows is ~;
9 practiced to prevent bovine mastitis (IMI). Several
10 different types of germicidal compositions are commonly ~ ;-
11 used on skin, the active ingredients in the most common
12 being: iodophors, chlorhexidines, hexachlorophenes,
13 DDBSA, caprylic acids, cecanoic acids and hypochlorites.
14 Hypochlorites have been demonstrated to be very effective
microbiocides and are widely used in food industries,
16 sanitation, water treatment and dairy farm sanitation.
17 In the particular case of bovine teat dips,
18 hypochlorites have been frequently studied to determine
19 efficacy in reducing IMI. The concentration of 4~ sodium
hypochlorite gives excellent results, both in reduction
21 of IMI and in the reduction of microbiological
22 populations on teat skin and in milk.
23 The use of hypochlorites, however, has not met with
24 wide spread acceptance in teat dip formulations, or in
other germicidal formulations used on human or animal
26
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-i
1 skin despite a much lower cost. Hypochlorite
2 formulations have been known to cause mild to severe
3 irritation, in many cases leading to chapping and/or
4 lesions on the skin.
The irritation caused by llypochlorite solutions is
6 believed to be due to the presence of excess sodium
7 hydroxicle in typical bleach or other hypochlorite
8 solutions. Commercial bleaches diluted to approximately
9 a 4~ level of sodium hypochlorite have a pH greater than
10, typically 11 to 12. This is equivalent to a
11 concentration of approximately 0.3 to 0.6 percent sodium
12 hydroxide. Many dairy herds cannot tolerate these levels
13 of sodium hydroxide and are quite susceptible to
14 irritation. It has been suggested that in order to
eliminate most of these teat irritation problems, the
16 maximum sodium hydroxide concentration be in the range
17 0.05 - 0.08%. Excess sodium hydroxide, however, is
18 necessary in order to maintain shelf stability of a
l9 hypochlorite product. As a general rule of thumb, in
order to achieve good storage stability of bleach
21 productsc an excess alkalinity of 0.1% sodium hydroxide
22 must be present for each 1% of hypochlorite. Ev~n higher
23 levels of alXali is necessary where organic compounds are
24 also includecl in the composition.
26
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1 2. Description of_the Related Art
2 An extensive discussion of various teat dip
3 germicides may be found in Pankey, "Post Milking Teat
4 Antisepsis", V~terinary Clini~s of North America: Large
Animal Practice, 335-348 (1984). Sodium hypochloritQ
6 teat dips are described as causing chapping of milkers'
7 hands and some teat irritation. A concentration of less
8 than 0.05% sodium hydroxide in the final solution is
9 stated to be necessary for satisfactory use as a teat
dip. This reference states that emollients should not be
11 added to hypochlorite teat dips "because of associated
12 problems". `
13 Hansen, ACTA Vet. 8can~. 12, 80-85 (1971) states
14 that sodium hypochlorite udder wash is well known to
cause eczema.
16 Rev. 8nlud. Anim., 7, 193-200 (1985) comparative
17 studies of various teat dip formulations, including 4%
18 sodium hypochlorite, with and without parafin additive.
19 No skin injuries were observed with either formulation
during a 21-day test period.
21 In Dialog\ File 50, Record No. 0214463 OD046-05785,
22 it is stated that Veterinaria, ~ruguay, 19, 17-19 (1983),
..
23 reports a study of the use of diluted bleach as a teat
24 dip. The abstract states that skin on some treated teats
26
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1 became dry. The residual sodium hydroxide concentration
2 in the preparation was reportedly less than the
3 recommended maximum limit of 0,.08%.
4 Other references describing the use of sodium
hypochlorite as a teat dip are as follows:
"Current Concepts of Bovine ~astitis", The ~ational
7 Ma~tlti~ Council, Inc., Second Edition (1978)
8 Australia~ ~eterinary Journal, 5~, 247-251 (May,
1978)
Journal of D~iry Scie~¢e, 69, 260-266 (1986)
Rec. Nea. Vet., 153, 485-488 (1977)
11
Journal of Dairy Science, 53, 1392-1403 (1970)
12
The Veterinary Re¢ord, 645-649 (Aug. 27, 1955)
13
Journal of Dairy 8aienoe, 61, 950-955 (1978)
14
Journal o~ Dairy Researoh, 46, 601-611 (1979)
Journal o~ Dairy Baienae, 66, 161-167 (1983)
16
IIA Practical Mastitis Control Routine", Int~l. Dairy
17 Fed. (Brussels), 422-438 (1975)
18 In US 3,172,861 there are described hypochlorite :
19 bleaching compositions which include sulfonate
surfactants. There is no discussion of skin sensitivity
21 nor is there a suggestion to use the compositions as a ;.
22 `skin germicide.
23 In US 4,740,327 there are disclosed thixotropic
24 dishwashing detergents which include hypochlorite, ;~
hydroxide and a detergent which may be a C8 z2
26
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l alkyldimethyl amine oxide. There is no discussion of :
2 skin sensitivity nor is there a suggestion to use the
3 compositions as a skin germicilde.
4 : -
Summary of the Invention
6 The present invention pertains to an aqueous .
7 germicidal composition comprising: .
8 (a) an alkali hypochlorite in an amount equivalent
9 on hypochlorite basis to 2% or more NaOCl; .
(b) an alkali hydroxide in an amount effective to
11 maintain the hypochlorite concentration at a level
12 e~uivalent to at least 2% NaOCl on hypochlorite basis for
13 a period of about 6 months; :~
14 (c) an amount of emollient effective to reduce skin
irritation of the composition, the emollient having the
16 formula;
17 R1R2nXO
18 `
19 where Rl is a C16 or higher aliphatic hydrocarbon group,
R2 is a lower alkyl group, X is N, P or S, and n is 2
21 when X is N or P and 1 when X is S: and
22 ~ (d) an amount of a substantially nonirritating
23 bleach staple hydrotrope effective to maintain a stable
24 unseparated foxmulation at temperatures as low as 40F.
:::
26
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1 Detailed Description of the Invention
2 The invention will be particularly described herein
3 in the preferred embodiment as a teat dip formulation.
4 Teat dip formulation are espe~cially demanding because
they are sub;ected to wide temp,erature variations. Often
6 stored in a milkhouse or other farm building, they can be
7 subjected to temperatures as low as 35-40F (2-4C) and
8 as high as 100F ~38C). A teat dip product must remain
9 dissolved and maintain stability of the hypochlorite ion
over this wide range of temperatures. In other
11 applicat.ions a significantly smaller temperature range
12 may be tolerable.
13 The initial hypochlorite concentration of the
14 formulations should be su~ficient to maintain a
hypochlorite level equivalent to at least 2% NaOCl for at
16 least about 6 months at ambient temperature. The six
17 month requirement represents the expected minimum
18 practical shelf-life of a formulation distributed through
19 ordinary commercial channels. In some instances
shelf-lives as low as 4 months may be acceptable. A
.
21 somewhat lower minimum hypochlorite level may also be -
22 Itolerable but is considered undesirable because of the
23 risk that germicidal activity will be inadequate. Teat ~
24 ~ `'
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1 dips having hypochlorite levels less than 1% NaOCl have -i
2 been reported to show questionable results in reduciny
3 incidence of IMI.
4 In attempting to formulate hypochlorite based teat
5 dip compositions with improved stability and skin ;
6 tolerance, attempts to find sub~3titute alkaline buffering
7 salts less aggressive to the skin which would stabilize
8 bleach in low concentrations were not met by success. An
9 alternative approach, the addition of emollients, also
proved to be difficult. Emollients typically included in
11 teat dip formulations based on other germicidal agents,
12 such as ethoxylated lanolin, glycerin, isopropyl
13 myristate, isopropyl palmitate, polypropylene glycol,
14 glycol derivatives, high molecular weight alcohols,
petroleum fractions, and many others, proved unsuitable
16 for use in formulations due to a myriad of stability
17 problems such as insolubility and chemical attack by the
18 strong oxidative effects of the hypochlorite radical.
19 Most, if not all, of the common emollients available on
the market today have chemical structures which are
21 readily hydrolyzed and oxidized.
22 The applicants have nevertheless found that a
23 particular class of compounds known to be stable to
24 hypochlorites can serve as effective emollients in
alkaline hypochlorite formulations so as to significantly
26
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1 reduce irritation associated with such formulations while
2 maintaining acceptable shelf stability. The compounds
3 have the formula:
4 RlR2nX0
6 where R1 is a C16 or higher aliphatic hydrocarbon group, - -
7 R2 is a lower alkyl group, X is N, P or S, and n is 2
8 when X is N ~r P and 1 when X is S.
9 Suitably Rl is a C16 - C22 hydrocarbon group and R2 is
. . :
10 methyl or ethyl. Most preferably Rl is palmityl or ~`~
11 stearyl, R2 is methyl and X is nitrogen. Such preferred
.: . .
12 amine oxide compounds are well known materials which are
13 commonly used as surfactants in cosmetics, toiletries,
. . .
14 shampoos, bath oils and detergents. They are nonionic in ~
.:. .
neutral to alkaline solutions and stable to bleach.
16 In teat dip formulations, at least, it has been ~ ~ `
17 found that the amine oxide compounds useful in the `~
18 invention are not ~ully soluble in alkaline aqueous
19 bleach solutions. In order to fully solubilize the amine
20 oxide it is also necessary to include as an additional`~
21 ingredient a bleach stable hydrotrope. Applicants have
22
23
24
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1 found that compounds of the formula:
2 ~ ;
3 ~~ 'S2
7 where R3 is lower alkyl and m is an integer of 0-3, and A
8 is Na or K, are especially preferred. Suitable such
9 hydrotrope compounds include sodium xylene sulfonate,
sodium tolvene sulfonate, sodium benzene sulfonate,
11 sodium cumene sulfonate and corresponding potassium
12 ~alts. While the hydrotrope need not be limited to such
13 aryl sulfonate compounds, it is important that this ~`
14 ingredient also not irritate the skin. Sodium xylene
sulfonate is a preferred non-irritating bleach stable
16 hydrotrope compound useful in this invention.
17 The invention is illustrated by the following
18 non-limiting examples.
19
Example 1
21 A series of samples were prepared to determine the
22 ~uantity of a bleach stable hydrotrope, sodium xylene
.,
23 sulfonate, required to prevent the separation and
24 instability of palmityldimethyl amine oxide in a 4%
sodium hypocblorite solution upon cold storage. Freezing
26
s~
1 of hypochlorite solutions should be avoided so as not to -
2 effect the hypochlorite stability. A criterion for
3 stability was taken to be solutions remaining clear
4 without evidence of separation upon storage for one month
5 at 38F. An arbitrary amount of 3% active ;~
6 palmityldimethyl amine oxide was chosen as an amount
7 thought to pro~ide adequate emollient to the skin, yet
8 still keep the cost of the potential product well below
9 other competing teat dips. Levels as low as 2% may still
give acceptable emollience. The upper limit is limited
11 only by cost and solubility concerns. All ingredients ~;
12 were mixed in the order given as in Table I. ``
13 Table 1.
14 Ingredient/Composition I II III IV
1 5 .: . ~
Deionized Water 59.5%w/w 57.0 54.5 52.0 -~
16
Sodium Xylene ~-~
17 Sulfonate 40% 2.5 5.0 7.5 10.0 ; `
18 Palmityldime.thyl amine
oxide 30% lO.0 10.0 10.0 10.0
19 ;
Bleach (15% sodium ~ ~
hypochlorite w/w)27.0 27.0 27.0 27.0 ~ ;
21 Caustic Soda 50% 1.0 1.0 1.0 1.0
22 ~-
Compositions III and IV were stable upon cold storage. ~`-
23 Compositions I and II were opaque and separation
24
occurred.
26 ~ - ~
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1 It was also observed that viscosity was greatly
2 controlled by the amount of sodium xylene sulfonate
3 present. In these samples, an increase of sodium xylene
4 sulfonate proportionately caused a ~ecrease in viscosity.
For example, in the series of formulae an increase of
6 sodium xylene sulfonate of 2.5% decreased the viscosity
7 by about one order of magnitude. This relationship is
8 demonstrated in Table II.
Table II.
11 Formula I II III IV
_ _ .
12
Sodium Xylene2.5% 5.0% 7.5% 10.0
13 Sulfonate 4Q%
14 Viscosity in
Centipoise (cps) >10,0000-1000 c100 <10 ,
16 It is typical of many teat dip formulae to include a
17 viscosity thickener. It is thought that such a practice ~
18 especially in post milking teat dips may actually ~ ~,
19 increase the microbicidal efficacy of the product by
allowing the product to remain on the teat without
21 dripping off. It may also serve to increase the contact ,~
22 ,,time of the active microbicidal agent against ''
23 microorganisms by increasing the time it takes for the,,
24 product to dry. In the hypochlorite teat dip, by varying ,
the ratios of the hydrotrope, sodium xylene sulfonate to
26
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.
s~
1 the emollient, palmityldimethyl amine oxide, the
2 viscosity can be controlled to the degree desired. In
3 the examples above, formulae III and IV would be
~.
4 acceptable in this regard. Formula II was gooey and
tackey and formula I became gel-like. The viscosity of
6 formula I and probably that of formula II would preclude
7 its use as a teat dip but offers possible application for
8 other skin infection applications such as for use on
9 hands of hospital or food processing personnel. ;
1~ .` '~ '::.
11 Exam~le 2
12 The emolliency of amine oxides improves with an
13 increase in the number of carbon atoms in the long chain
14 alkyl group; in order of increasing carbons and
15 emolliency is lauryl, myristyl, palmityl or cetyl, and ` -
16 stearyl groups. It was found that several percent of
17 myristyldimethyl amine oxide was stable under cold
18 storage in a 4~ hypochlorite system without a hydrotrope.
19 As mentioned, significant amounts of palmityldimethyl
amine oxide could be solubilized with sodium xylene
21 sulfonate, stearyldimethyl amine oxide could not be
22 cooled into solution and stabilized by sodium xylene
23 sulfonate alone.
24
26 ;
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1 Stearyldimethyl amine oxide can be coupled into
2 solution if both palmityldimet:hyl amine oxide and sodium
3 xylene sulfonate are both included as ingredients. Other
4 shorter chain amine oxides ~i.e. where R1 is Cl014) can
also be used to facilitate the dissolution of
6 stearyldimethyl amine oxide, but the amine oxide with the
7 palmityl group is preferred to maximize skin emolliency.
8 An example of a stable composition employing
9 stearyldimethyl amine oxide is given below which again
provides for 3% active emollient.
11 Deioni2ed Water ........................... 52.6%
12 Sodium xylene Sulfonate 40% ............... 10.0%
13 palmityldimethyl amine oxide 30% .......... 8.0%
14 stearyldimethyl amine oxide 25% ........... 2.4%
Bleach (sodium hypochlorite 15%) .......... 27.0%
16 The above formulation remained clear at one week at 38F.
17
18 Example 3
19 A series of 4% sodium hypochlorite compositions
containing various levels of palmityldimethyl amine oxide
21 and sodium xylene sulfonate were prepared. In the
22 following tests it was the objective to determine the
23 amount o~ sodium hydroxide (or any salt providing the
24 hydroxyl radical) to stabilize the hypochlorite, and
prevent undesirable interactions between the emollient
26
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1 and hydrotrope with the hypochlorite. In each
2 composition the weight percent of sodium hydroxide was
3 determined by testing. A series of samples of varying
4 alkalinities for each composition was then prepared by
calculating the amount of caus,tic soda (50% NaOH) to add
6 to each sample to boost the alkalinity to the desired
7 level. Each sample was then tested for weight percent
8 sodium hydroxide and weight percent sodium hypochlorite.
9 Some of these samples were then stored at 75F. and
tested again at 4 months to determine shelf-life
11 stability at slightly higher than room temperature
12 conditions. All samples were also subjected to
13 accelerated aging testing by storing them at 50C for a
14 period of 8 days, which is roughly equivalent to 6 months
at room temperature (approximately 72F). These
16 composition~ and their stability results are listed in `
17 Table III.
18 ~
19 , .
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22
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o o o o. o 8 ~ ~ ~ ,~ ~ ~`
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~~" ~ O Go~ ~ 5 5 5 ~ ~ ~ ~
o, o o. o ~ o o~ . ~- ~ ~o ~ ~ , ~
~r ~ ~ ~ o ~ ~ ~ ~ ~ ~ ~
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,_~ ~ o o ~ ~ o. ~o ,, ..
~ o o o o ~ 8 C~ ) .
X~ o ~ i O .'.`
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~-( ~ O ~ ~ C'`l ~~ O O .' .
~ o o o. o. ~ 8 o o ::
o o o ~ o
. ~ oo o. o o ~ ~o ~ ` oo
O O ~ O ~ G~ _~ ~ ~
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o o o o ~ ~ ~~ ~o ~ ,.
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o o ~
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1 The control composition was diluted 15% hypochlorite
2 without emollient or additional alkalinity adjustments.
3 The alkalinity was 0.6% NaOH. All compositions remained
4 clear and homogeneous, even among those formulations -~
which were not stable to hypochlorite. Most organic
6 material incorporated into hypochlorite systems cause
7 rapid decomposition of the hypochlorite. However,
8 hypochlorite ions are relatively stable in the presence
9 of certain organic matter. Criteria for acceptable
stability in these examples were to remain above 2% NaOCl
11 or roughly 50% NaOCl retention for samples stored for 8 ;~
12 days at 50C. Such products would remain efficacious for
13 a period of at least 6 months at room temperature. By
14 this criteria compositions A, C, F, G, H and I are not ~:r `~
acceptable compositions. Compositions A, F, G and I
16 decomposed completely due to insufficient alkalinity,
17 while composition C and I experienced excessive
18 hypochlorite decay. In fact, sample C was tested again `-
19 at 10 days storage at 50C, the level of NaOCl had
20 quickly *allen to just a trace (<0.1%). ; -~
21 For samples which exhibit good stability to
22 hypochlorite, most of the drop in strength is seen
23 immediately after they are prepared. For example, on ~ ~;
24 average, compositions B, C, D, E, J, K, L, M and O lost
about 10-15% of their initial hypochlorite strength after
26
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1 only 1-1/2 days storage at 50~C (not shown in table).
2 After this, the hypochlorite strength decreased more
3 slowly. This is typical of many hypochlorite solutions
4 containing hypochlorite stable organic material. The
control sample did not experience this initial drop, it
6 decreased slowly and steadily, and as expectPd stability
7 was excellent at 90% retention.
8 Sample K was also testecl again at 10 days. The
9 NaOCl retention was still quite good at 53%. Sample O
lo was tested after 2 weeks storage at 50C (equivalent to
11 about one year at room temperature) and found to have
12 retained approximately 50% of its NaOCl. Compositions J,
13 K, L, and M, which contain about twice the emollient and
14 hydrotrope levels as samples D and E and have equivalent
alkalinities, have about as good retention of
16 hypochlorite at 50C storage. However, in some
17 formulation~ emollient and hydrotrope levels do affect
18 stability. Sample B at 0.8% NaOH retained greater than
19 50% of its NaOCl level, whereas sample H also at 0.8%
with twice the emollient and hydrotrope, was unstable.
21 No significant improvement in stability was seen for
22 alkalinities greater than 0.95% NaOH up to 1.2% NaOH. To
23 minimize skin irritation due to the aggressiveness of
24 NaOH, therefore, it i5 preferred that the alkalinity not
exceed 0.95~ NaOH.
26
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1 Some of the compositions, were also stored at 75F
2 for a 4-month period. Compositions B, C, D, and E
3 exhibited excellent stability to NaOCl up to retentions
4 as high as 80%, even at alkalinities as low as 0.8% NaOH.
Compositions J and L at 75F storage showed good NaOCl
6 stability, though not as good as the compositions with
:,.. . .
7 half the emollient levels. `
9 Example 4
As noted in example 2 above, amine oxide compounds
11 where the long chain alkyl group Rl is less than C16 are ;~
12 more readily solubilized in aqueous alkaline bleach.
13 However, such compounds alone do not provide adequate
14 emollience to overcome the irritating effect of the
15 composition. ~ -
16 Formulation J in Table III was field tested as a
17 teat dip on cows for a one month period. An identical
18 formulation except that myristyldimethyl amine oxide was
19 used in place of palmityldimethyl amine oxide was
similarly tested, as was the control composition P. At
21 the end of the month teats dipped in composition J were ;~
22 found to have actually softened compared to the control.
23 The formulation based on myristyldimethyl amine oxide,
24 however, caused even greater irritation of the teats on ~
25 which it was used than did the control. -
26
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1 Although the invention has been examplified using
2 sodium hypochlorite, hydroxide and hydrotrope, it will be
3 appreciated that corresponding salts of other alkalî ions
4 may be used, especially potassium salts, without
departing from the invention.
6 From the foregoing it can be seen that with `
7 judicious choice of levels of hydrotrope, emollient, and
8 level of excess hydroxide, relatively stable germicidal
9 hypochlorite 6ystems can be formulated. For other
intended applications skilled persons can readily
11 formulate and test alternative composition ingredients
12 and ratios under various storage conditions to ensure
13 adequate shelf life and efficacy for such applications.
14 The present disclosure should be considered an
exemplification of the principles of the invention and is
16 not intended to limit the invention to the particular
17 embodiments illustrated herein.
18
19
21
22
23
24
26
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