Note: Descriptions are shown in the official language in which they were submitted.
~LV~
.
BACKGROUND OF TE~E INVENTION
There are only a relatively few ectoparasiticides
which are commercially available today. The most popular
pediculicidal toxicants are Lindane tgamma benzene hexa-
chloride), Malathion [(S-1,2-dicarbethoxyethyl)-0,0-dimethyl
phosphorodithioate], synergized pyrethrins and Cuprex (a
combination of tetrahydronapthalene, copper oleate and acetone,
the acetone not asserted to be active). Sulfur, LINDANE, benzyl
and crotamiton are the best known agents for scabies. Because
of increased concern about the overall safety of somé of the
Xnown ectoparasitic toxicants, the search for new, safe and
ef~ective ectoparasiticides has intensified recently.
It has now been found that certain polyols are
effective ovicides, miticides and, depending on formulation
are also pediculicidal. The polyols are well known compounds
but the insecticidal and/or ovicidal activity thereof has not
been previously known. 2-ethyl-1,3-hexanediol is well known
as an insect repellent (cf. U.S. 2,407,205 and 3,836,672) and
is in wide commercial use as such.
It is the object of this invention to provide new,
safe and effective toxicants for insects and their ova. This
and other objects of the invention will become apparent to those
skilled in the art from the following detailed description.
- 30
., ~
-- 1 --
~ .
109~9
SU~ RY OF T~IE INVENlION
This in~ention relates to ectoparasiticidal
toxicants and a method of controlling ectoparasites, other
biting insects and mites. More particularly, the invention
relates to the use of certain polyols as to~lcants for lice,
mites, and/or their ova and to toxicant compositions con-
taining such polyols.
DESCRIPTION OF ~HE PREFERR~D E~lBODIMENTS
_ _ .
Certain polyols which are diols whose hydroxyl groups
are in non-vicinal positions, preferably 1,3-diols, have been
found to exhibit satisfactory activity. Exemplary polyols are
2-methyl-2,4-pentanediol, 2-ethyl-1,3-hexanediol, 1,3-butan~diol,
1,3-heptanediol and 1l3-nonanediol. One or a combination o* the
toxic polyols of the present invention can be incorporated into
an active toxicant composition which can be in the form of a
liquid, powder, lotion, cream, gel or aerosol spray, or foam as
the result of formulation with inert pharmaceutically acceptable
carriers by procedures well known in the art. Any pharmaceutically
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 substantlal detrimental
effect on the insecticidal, miticidal or ovicidal toxicant
ac*ivity of the active ingredient.
The active polyol is incorporated into the toxicant
composition used to treat the substrate (human, animal or
inanimate) in need of such treatme~t, belie~ed *o 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 50% mortality of the ecto-
parasites or their ova. Wi*h respect to lice and their ova,
2.
the standard two minute in-mersion tests are described below.
The minimum concentration of polyol in the composition
required to provide an efective toxic amount varies con-
siderably depending on the particular polyol, the particular
inert pharmaceutically acceptable carrier being employed and
any other ingredients ~hich are present. Thus, in one case
a 10~ concentration may sufice, while in other cases, con-
centrations as high as 30 to 40~ may be required to obtain a~
effective toxic dose.
The two minute immersion tests referred to above
are carried out as follows:
Pediculicidal activity: A 50 ml beaker is filled
with tap water and allowsd to come to room temperature
(about 24C~. Ten young adul* male and ten young adult female
lice (Pediculus humanus 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 roo~ temperature~
is shaken until homogeneous and placed into a 50 ml beaker.
The mesh patch is placed into the sample immediately after
pouring, allowed to submerge, and after two minutes is removed
and immediately plunged into the beaker containing the tap
water. The patch is vigorously agitated every ten seconds and
af*er one minute the patch is removed and p~aced on paper
toweling. The lice are then transferred to a 4x4 cm blac~
corduroy cloth patch and this point of time is considered
zero hours. Thereafter, the corduroy patch is placed in
a petri dish which is covered and stored in a 30Q holding
chamber for 24 hours.
Ovicidal activity: 15 adult, 5 to 10 day old,
female lice (Pediculus humanus corporis) are placed on a
. . _ _ . . . ~
2x2 cm nylon mesh patch which is placed in a petri dish,
covered and maintained ill an incubator at 3DC for 24 hours.
The adult lice are then removed and the number of plump,
viable eggs and shriveled non-fertile eggs on the patch are
recorded. The sample to be tested, maintained at room
temperature, is shaken until homogeneous and poured into a
- 50 ml beaker. Immediately after the pou~ing, the mesh patch
is placed into the beaker, allowed to submerge, and a~ter two
minutes is remo~ed and immediately plunged into a 5~ ml ~eaker
containing tap water at room temperature ~about 24C~. The
patch is vigorously agîtated every ten seconds and after ~ne
minute, the patch is removed and placed on paper toweling for
one minute. The patçh is then placed in a petri dish which
is covered and stored in the 30C incubator. Fourteen days
following treatmen~, a number of hatched eggs and the number
- o shriveled or unhatched eggs is noted.
In both the pediculicidal and ovicidal two minute
immersion tests, controls are run in identical manners to that
described with room tempelature ~24C) tap water substituted
for the sample to be tested. The results of the tests repor~ed
are net results.
It will be appreciated that the polyols of this
invention can be utilized as adjunct toxicants in compositions
which are otherwise insecticidal and/or ovicidal. In such
compositions, the term "effective toxic amount" means the
amount which will cause at least 20~ increase in the mortality
of the ectoparasites exposed in the two minute ;mmersion test
relative to the same composition without the polyol.
.. . .. .... ........ .... . . . ..... ..
li~)g78~
In the following table 1, the pediculicidal and
ovicidal activ.ity o~ several polyols, tested in undiluted
form in the two minute immersion test is se~ forth. Com-
parative results for other polyols are also set forth.
TABLE 1
Mortality, ~
Polyol OvicidalPediculicidal
2-me*hyl-2,4-pentanediol 100 o
- 2-ethyl-1~3-hexan~diol 100 100
sorbitol (70~ s~l'n) 10
1,2-ethanediol 35 0
1,2-propanediol 14
- 1,3-butanediol 1~0 1
1,3-heptanediol . 100 82
1,3-nonanediol 100 47
It will be noted that the instant polyols are
excellent o~icides from Table 1. The hexanediol is also an
excellent pediculicidal toxicant. It was further surprisingly
found that the pentanediol, while not pediculicidal in un-
diluted form, imparted pediculicidal acti~ity to compositionswhich would not otherwise exhibit such activity~ e.g., aqueous
aliphatic alcohol solutions and a~ueous aliphatic ester
solutions. This fact is shown in the data pr`esented b010w.
Additionally~ it has been observed that the instant polyols
are effective toxicants towards the rabbit ear mite, the m
vitro surrogate for testing toxicants for the sarcopic mite.
Accordingly, the diols can be used to prepa~e compositions
which are both ovicidal and scabicidal and, in the case of the
hexanediol, also pediculicidal.
ll.t.~9 789
Table 2 sets orth the results of testing three
polyols at a 15~ concentration in combination with 25%
isopropanol and 60% water. For comparative purposes, it should
be noted that the combination of 25~ isopropanol and 75~ water
results in zero percent ped;culicidal mortality in the same
test.
Table 2
~ortality, %
Polyol O~icidalPediculicidal
. _ _
2-methyl-2,4-pentanediol 59 15
2-ethyl-1,3-hexanediol 17 70
1,3-butanediol 44 5
In the following Table ~, the results of the two
minute immersion test for ovicidal and pe~icullciaal actlvity
for the three compounds a~ a concentration of 25~ in com-
bination with 15~ isopropyl myristate and 60~ water is set
forth. For comparison, it should be noted that 15~ isopropyl
myristate emulsi~ied in 85~ water exhibit~ zero percent
pediculicidal toxicity.
Table 3
~rtat itya
Polyol Ovicldal Pediculicidal
2-methyl-2,4-pentanediol 34 95
2-ethyl-1,3-hexanediol 44 100
1,3-butanediol 100 0
1~09~789
: ~ The ovicidal activity o~ a t~o minute immersion of
2-ethyl-1,3-hexanediol as a unction o-E concentration was
determined in a ~ormulation which contained 25% ~w/w)
isopropanol and water q.s. to 100~. The results are shown
. in Table 4.
Table 4
Concentration, ~w/~) . Ova ~ortality, %
9.4
9-7
15- 17
: 20 66
: 30 l~
40 100
f Tn Table S, the results of the two minute immersion
test for ovicidal activity of the five polyols as a unction
:~ of concentration in water q.s. to 100~ was determined.
;.~ . Table 5
~ 2-.~iethyl-2,4-pentanediol, ~ w/wOva ~ortality,_~
" ~ .
100 100
68
74
. 70 52
39
71
66
53
52
36
` 11~g7~39
2-EthYl-1,3-hexanediol ~ w/w Ova ~lortalityL %_
100
100
42
43
46
63
1, 3-Butanediol, % w/w Ova Mortali~,
10D . 100
go 94
. 90
100
94
86
30 - 76
;: 20
~ 10 21
- '~
1, 3-Heptanediol, ~ (w~w) in
20 2~ isopropanol and ~ater q.s. ûva ~lortality,
; 50 100
lû0
- 9.4
` 10 ` - 12 . 2
1109789
1,3-Nno~a~odiol, % ~w/~Y) in
25% isopro~ol and water q.s. Ova Mortality,
100
100
100
100
97
The miticidal acti~ity of the instant polyols was -
determined as *ollows. Into a one cubic foot chamber, held
at ~oom temperat~re, is placed a co~ered microscope depression
slide containing ten adult mixed sex mites, Psoroptis ~
`.~ var. can~culi. The slide is positioned at a distanc~ of
ten inches horizontally and four inches below the activator
of a me~hanical spray de~ice and uncove~ed~ The merhanical
; ................................................................... . pump spray de~ice delivers 50 micrograms of sample per de-
pression of the activator. The sample to be tested, main- -
tained at room temperature, is shaken un$il homogeneous and
placed in the mechanical pump spray device. The primed acti-
vator is depressed ~wice, releasing 100 micrograms ~f spray
mist into-the closed chamber. The mist is allowed to settle
and the slide containîng the mites is remo~ed and co~ered.
This point of time is considered zero hours. The covered
slide is then held at room temperature fo~ 24 hours. ~liscro-
scopic observations are noted at 0, 1, 3, and 24 hours post
treatment. Cont~ols are run in an identical manner as *hat
described using water or the diluting agent, and net
mortality results are reported. In Table 6, the acti~ity of
a SD~ ~w/w) concentration of the polyols ln water ~lY) or
isopropanol tI) is reported.
97 8 9
Table 6
Polyol ~ite ~lortality,
` 1,3-butanediol 100 (~J)
2-methyl-2,4-pentanediol 90 tw)
2-ethyl-1,3-hs~anediol 100 (I)
1,3-heptanediol 100 (I)
1,3-nonanediol 100 ~I)
Some typical end use formulations for the polyols
of this invention are as follows:
~lear liquid suitable for pediciculicidal, ovicidal and
miticidal mechanical spray application or inunction. -
;~
2-Fthyl-1,3-hexa~ediol 75
Isopropanol 25
Clear liquid o~icidal shampoo
1,3-Butanediol 50
Triethanolamine lauryl sul~ate 20
Water 30
: Quick Breaking Ovicidal Aerosol Foam
Mono and diglycerides from the
glycerides of edible fats8
Isopropanol 25
1,3-nonanediol 20
1,2,3-Propanetriol 5
~Yater 34
Isobutane 8
.~
10 .
789
Ovicidal ~erosol Spray
2-~lethyl-2,4-pentanediol 50
Isopropanol 25
~ater 10
Isobutane 15
,
. O~icidal Cream
., .
- Cetyl alcohol 3.0
2-Ethyl-1,3-hexanediol 30.
Glyceryl monostearate 8.0
: 10 Sorbitan monostea~ate 8.0
Xanthan gum 0.3
Wat0r 5~ 7
Various changes and modifications can be made in
the instant in~ention without departing from the spirit and
scope thereo. The various embodi~ents which were described
herein were set forth for the purpose of further illustrating
the invention but ~ere not intended to limit it~ Unless
otherwise stated, all parts and percentages have been by
weight and all temperatures in degrees Centigrade throughout
this specification and claims.
- 11.
