Note: Descriptions are shown in the official language in which they were submitted.
M- 8559 (for. flg. )
.
i~333~V
BAC~G~OUND. 0~: THE INVENTION
~ . . . . .
There are only a relatively few pediculicides whlch are
commercially a~ailable *oday. The most popular pediculicidal -
toxicants ar~ Lindane (gamma ~enzene hexachloride)~ alathion
. .
- [~S-1,2-dicarbethoxyethyl)-O,O-dimethyl phosphorodithioa~e3,
synergized pyrethrins and Cuprex ~a combination of tetrahyd~ona
lene, copper oleate and ac~tone~ the acetone not asser~ed to be
active~c Because of increased concern about the overall saety
of some o the kno~n ectoparasitic toxicants, the search or
ne-ly sae and efective pediculicides has in~ensified recent
In addition to killing insects, a good ectoparasitic;de
sllould also destroy ova to avoid a resurgence oE the inesta~ion~
surviYing ova may hatch d~ys or ~iee~s after the initial treat-
ment. Lac~ing o~icidal activity, a pedlculicide safe to the
host usually must be re-applied until control is achie~fed~
~0 It has no-~ been found that those higher alcohols which
have a logarithm of their partition coe~-Eicient bet~een n-octan
and water of at least 0.61 exhibit pediculicidal andJor o~icidal
acti~ity. These alcohols are kno~n materials and have been in-
corporated into many pharmaceutical and costmetic prep~rationS.
~or example, ce~yl alcohol constitutes 15% of a published hair
groom gel and 61~ of a floatlng bath oil, and lauryl or ~socetyl or
dodecyl alcohol constitute about 30~ of a ~ineral oil gel.
~
1~333~0
Cetyl alcohol and lauryl alcohol are also listed und~r the
United States Food ~ Drug Administration's approved Synthetic
Flavor Substituents and ~djuvants list (21 CFR 1.1.1164). Cetyl
alcohol has been used in compositions applied to the skin tU.S.
3,226,295 and 3,943,234) and lauryl alco.hol deTivatives have been
used in parasiticides (U.S. 2,Q3~,093).
It is the object of this invention to provide nel~, safe and
effective toxicants for lice and their ova, and ~ites. This and
other objects of the invention will become apparent to those
skilled in the art from the following detailed description.
SU~I~RY OF T~IE I~NENTION
This invention relates to ectoparasiticidal to~icants and
a method of controlling ectoparasites. ~lore particularly,
the invention relates to the use of certain higher alcohols
as toxicants for lice and/or their ova and to toxicant com-
postions containing such higher alcohols.
DESCRIPTION OF T~IE PREFERRED E~IBODIhIENTS
.
The toxicants of the instant invention are monohydric
alcohols, ROH, in which R is a substituted or unsubstituted
alkyl group. The substituting moieties can be aryl, a~yloxy
halogen or the like. The R groups generally contain a~ least
4 carbon atoms and the ma~;mum number o~ carbon atoms is
not restricted but is generally 24 or less. It has been found
-that in order that the alcohols exhibit satisfactory pediculi-
cidal and/or ovicidal activity, the logarithm of the partition
coefficient (hereinafter log P) for the compound between
n-octanol and water must be at lcast 0.61. Log P values
can be obtained by consultin~ Leo et al, Chemical Revie~.,
71, 525 (1971) or calculated by the ~ethod therein des-
cribed. I~.~en pediculicidal activity is desired, it is pre-
ferred that the alcohols be unsubstitutea alkyl alcohols havin~
log P values o~ 1.16-7.13. When ovicidal activity is desired,
2.
:1133390
it is I~reEerr~(l that the alco~lols have log P values of
1.1-7.13 and ~reerably are al~yl alcohols 11avin~ lo~ P
values of 2.3-5.13. Accordingly, when both pediculicidal
an-l ovicidal activity is desire~l, it is preferred to employ
an unsubstituted alkyl alcohol having log P values of 2.13-5.1.
Typical of the monohydric alcohols which can be employed
in this invention are n-butanol, sec-butanol, iso-butanol
~but not tert-butanol), iso-pentanol, n-pentanol, n-hexanol,
n-octanol, n-decanol, n-dodecanol, hexadecyl alcollol, oleyl
alcohol, benzyl alcohol, 2-phenoxyethanol~ cyclohexanol~
4-chlorobutanol, 2-phenylethanol, and the li~e.
One or ~ore of the toxic alcohols of the present
invention can be incorporated into an active toxicant com-
position which can be in the form of a liquid~ powder, lotion,
cream, gel, aerosol spray, or foam as the result of formulation
with inert pharmaceutically acceptable carriers by procedures
well known in the art. Any pharmaceuticall~ acceptable carrier,
whether aqueous or not aqueous, which is inert to the active
ingredient can be employed. By inert is meant that the carrier
does not have a substantial detrimental effect on the pediculi-
cidal or ovicidal toxicant activity of -the active ingredient.
The active alcohol is incorporated into the toxicant com-
positlon used to treat the substrate ~human or animal) in need o
such treatment, believed to be in need of such treatment, or desired
to be prophylactically protected in an effective toxicant amount
By such amount is meant the amount which will cause at least
75% of the ectoparasites e~posed in the two minute immersion
tests described below to die within 24 hours in the case of lice
and within 2 weeks in the case of the ova. Tlle minimum con-
centration of alcohol in the composition re~uired to provide
~11333go
an e ~fective tox;c ar,loun-t vclries considera~ly depending on the
particular alcohol, the particular inert pharmaceutically
acceptable carrier being employecl and any other in~redients ~;hich
are present. Thus, in one case a 10% concentration may suffice,
while in other cases, concentrations as high as 30 to 40~ may
be required to obtain an effective toxic dose. The alcohols
can also be employed as an adjuvant toxicant in a preparation
which otherwise exhibits pediculicidal and/or ovicidal activity.
In such preparations, the term "effective toxic dose" means
tllat amount which ~îll increase the mortality rate by about 20~
in the standard i~mersion test.
The t~o minute i~mersion test referred to above is carried
out as follows:
Pediculicidal activity: A 50 ml beaker is filled ~ith
tap ~ater and allowed to come to room temperature (about 24C).
Ten young adult male and ten young adult female lice (Pediculus
humallus corporis) of the same age group and from the same stock
colony are placed on a 2x2 cm coarse mesh-patch. The sample to be
'tested, maintained at room temperature, is shakell until homogeneous
and placed into a 50 ml beaker. The mesh patch is placed into
the sample immediately af~er pouring, allowed to submerge, and
after t~o minutes is removed and immediately plunged into the
beaker containing the tap water. The patch is vigorou51y agitated
every ten seconds and after one minute,the patch is removed and
placed on paper toweling. The lice are then transferred to a
4x4 cm black corduroy cloth patcll and this point of time is con-
sidered zero 110UrS. Thereafter, the'corduroy patch is placed in
a petri dish ~hich is covered and stored in a 30C holding chamber.
Ovicidal activity: 15 adult, 5 to 10 day old, female
lice (Pediculus humanus corporis) are placed Oll a 2x2 cm nylon
1133390
S]l patC}l ~'}l;Ch is placed in a petri dish, covered and main-
tained in an incubator at 30C for 24 hours. The adult lice
are then removed and the numbsr of plump, viable eggs and
shriveled, non-fertile eggs on the patch are recorded. The sample
to be tested, mailltained at room temperature, is shaken until
homogeneous and poured into a 50 ml beaker. I~mediately after
the pouring, the mesh patch is placed into the beaker, allo~ed
to submerge, and after t~o minutes is removed and immediately
plunged into a 50 ml beaker containing tap ~ater at room
temperature (about 24C). The patch is vigorously agi~ated
every ten seconds and after one minute, the p~tch is re~oved
and placed on paper toweling for one minute. The patch is then
placed in a petri dish WhiC}l is covered and stored in the 30~C
incubator. Fourteen days following treatment, the number of
hatched eggs and the number of shriveled or unhatched eggs is noted. I
In hoth the pediculicidal and ovicidal t~o minute immersion
tests,controls are run in identical manners to that described
with room temperature ~24C~ tap ~ater substituted for the
sample to be tested. The results of the tests reported are net
results.
In the following tables i and 2, the results of pediculi-
cidal and ovicidal testing, respectively, for various alcohols
of this invention and other alcohols are set fortll. The alcohols
were tested in undiluted form tlO0% alcohol), as a 25~ solution
in water, and in a solution containing 15% of the alcohol, 25%
L~S
isopropanol and 60~ r- ("15/25/G0"~. The results are set forth
in terms of percent mortality.
`~` 113339~
Table 1
- Pediculicidal Rating
100~ 25%
Alcohol Log P AlcoholSolution lS/25/60
Methanol.-0.66 0 0
Ethanol -0.32 45 . 0
isQ-Propanol-0.12 65 0 0
n-Propanol0.34 70 0 o
t~rt-Butanol0.37 80 O O
sec-Butanol0.61 95 0 35
iso-Butanol0.65 95 40 0
n-Butanol 0.88 100 20 . 0
Benzyl Alcohol 1.10 90 0 5
iso-Pentanol1.16 100 55 80
2-Phenoxy-
ethanol1.16 100 5 5
Cyclohexanol1.23 100 20
A-Chloro-
butanol1O27 100 0 20
2-Phenyl- -
ethanolla 36 100 0 80
n-Pentanol1.40 100 10 75
n-Hexanol 2.03 100 5 85
n-Octanol 3.15 100 10 85
n-Decanol 4.15 100 20 gs
n-Dodecanol5.13 100 10 ioo
Hexadecyl
Alcohol~ 7.13 100 40 go
Oleyl Alcohol 7.47 100 0 40
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1133390
Table II
Ovicidal Rat~
Alcohol Log p lOO~ Alcohol25~ Solution15/25/60 _
~lethanol -0.66 4 27 0
Ethanol -0.32 4 7 - 13
iso-Propanol -0.12 . 1 O
n-Propanol 0.34 27 23
tert-Butanol 0.37 16 17 O
sec-Butanol 0.61 10 46 32
iso-Butanol 0.65 0 58 2
N-Butanol 0.88 48 17 2
~enzyl Alcohol1.10 100 100 . 29
iso-Pentanol 1.16 100 52 - O
2-Phenoxyethanol 1.16 100 100 100
Cyclohexanol 1.23 100 57
4-Chlorobutanol1.27 100 100 100
2-Phenylethanol1.36 100 ~ 100 3~
n-Pentanol 1.40 100 67 35
n-Hexanol 2.03 100 100 100
n-Octanol 3.15 100 . 100 100
n-Decanol 4.15 100 100 100
n-Dodecanol 5.13 100 100 100
Hexadecyl Alcohol'7.13100 75 29
Oleyl Alcohol 7~47 l4 0 20
7 ~ ... ..
113339(~
The miticidal activity of the instant toxicants was determined
as follo~s. Into a one cubic foot chamber, held at room temperature,
is placed a covered microscope depression slide containing
ten adult mixed sex mites,P~roptes equi var. cuniculi.
The slide is positioned at a distance of ten inches horizontall~ -
and four inches below the activator of a mechanical spray
device and uncovered. The mechanical p~mp spray de~ice delivers
50 micrograms of sample per depression of the activator.
The sample to be tested, maintained at rcom tempera*ure, is
shaken until homogenous and placed in the mechanical pump
spray device. The primed activ~tor is depressed twice, releasing
100 micrograms of spray mist into the closed chamber. The
mist is allowed to settle and the slide containing the mites
is removed and covered. This point of time is considered
zero hours. The covered slide `is then held at room temperature
for 24 hours. Microscopic observations are noted at 0, l,
3, and 24 hours post treatment. Controls are run in an identical
~anner as that described using water or the diluting agent ?
and net mortality results are reported.
TABLE III
~liticidal Rating
50~ Solution in
Alcohol log P 100~ Alcohol Isopro~anol
iso-Propanol -0.12* 0
sec-Butanol 0.61 50
n-Butanol 0.88 100
Benzyl Alcohol 1.10 100
Cyclohexanol 1.23 - lO0
2-Phenylethanol 1.36 lO0
n-Pentanol 1.40 100
n-~lexanol 2.03 lO0
~lexadecyl Alcohol~ 7.13* lO0
Oleyl Alcohol 7.47* 30
,, .
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:~33390
Tlle log P values sct forth in the foregoing tables I, II
and III are those set forth in the aforementioned Leo
et al article except for the values starred ~hich were
calculated using standard methods. The log P value for
hexadecyl alcohol is a calculated value and the actual
figure is dependent on the degree of branching o the
alkyl moiety.
As noted above, various end use formulations can be
prepared. Some typical formulations are set forth below
and the amoun~s recited are percentages by weight:
Clear calorless liquid suitable for mechanical spray
application or inunction
Isopropyl alcohol - 65
~lexadecyl alcohol 15
IYater 20
Clear s}iampoo
Isopropyl alcohol 25
n-Dodecanol lS
Triethanolamine lauryl sul-Eate 20
Water 40
Lotion
Isopropyl alcohol 25
Hexadecyl alcohol 15
Carbo~ypolymethylene 0.1
Triethanolamine 0.1 -
Water 59.8
g
1~33390
cream
Isopropyl alcohol 25.0
Isopentanol . 15.0
Glyceryl monostearate 22.5
Sorbitan monostearate 1.5
. - Polysorbate 60 3.5
Xanthan gum 0.2
: Water 32.3
Quick Breaking Aerosol Foam
Mono and diglycerides from the
glycerides o~ edible fats 8
n-Octanol 15
Isopropanol 25
Glycerine 3
: Isobutane 8
Water 41
Powder -
~' 4-chlorobutanol 10
- Talc . 9O
Stick
Sodium stearate . 8.0
Sorbitol 3.5
Isopropanol 25.0
Ethanol 39.0
n_Decanol 15.0
Water 9 5
. .
.
-10 -
~133390
.
Gel
Carboxypolymethylene 1.5
Isopropyl alcohol . 25.0
4-Chlorobutanol 10.0
Polysorbate ~0 4.0
Triethanolamine 3.0
Water 56.5
Various changes and modifications can be made in the
instant invention without departing from the spirit and
scope thereof. The various embodiments set forth herein
were for the purpose of further illustrating the invention
and were not intended to limit it. Throughout this specifi-
: cation and claims, all parts and percentages have been by
weight and all temperatures in degrees Centigrade unless
otherwise indicated.
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