CA1113855A - Antipruritic ectoparasiticide - Google Patents
Antipruritic ectoparasiticideInfo
- Publication number
- CA1113855A CA1113855A CA304,445A CA304445A CA1113855A CA 1113855 A CA1113855 A CA 1113855A CA 304445 A CA304445 A CA 304445A CA 1113855 A CA1113855 A CA 1113855A
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- Prior art keywords
- ether
- derivative
- polyoxyethylene
- alkyl
- poe
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Classifications
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N31/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic oxygen or sulfur compounds
- A01N31/02—Acyclic compounds
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N33/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic nitrogen compounds
- A01N33/02—Amines; Quaternary ammonium compounds
- A01N33/08—Amines; Quaternary ammonium compounds containing oxygen or sulfur
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
- A01N37/12—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing the group, wherein Cn means a carbon skeleton not containing a ring; Thio analogues thereof
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N39/00—Biocides, pest repellants or attractants, or plant growth regulators containing aryloxy- or arylthio-aliphatic or cycloaliphatic compounds, containing the group or, e.g. phenoxyethylamine, phenylthio-acetonitrile, phenoxyacetone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
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- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Agronomy & Crop Science (AREA)
- Pest Control & Pesticides (AREA)
- Plant Pathology (AREA)
- Engineering & Computer Science (AREA)
- Dentistry (AREA)
- Wood Science & Technology (AREA)
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- Animal Behavior & Ethology (AREA)
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- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Tropical Medicine & Parasitology (AREA)
- Public Health (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Cosmetics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
ANTIPRURITIC ECTOPARASITICIDE
ABSTRACT OF THE DISCLOSURE
Certain ethoxylates have been found to exhibit concurrent activities of particular merit in the treatment of ectoparasitic infestations.
ABSTRACT OF THE DISCLOSURE
Certain ethoxylates have been found to exhibit concurrent activities of particular merit in the treatment of ectoparasitic infestations.
Description
BACKGROUND OF THE INVENTION
Ectoparasites such as lice and mites cause pruritus or pain in their animal or human hosts. Therapy which simply kills the parasite leaves the host with subcutaneous or intradermal residues which continue to itch for significant time periods after the infestation is extinguished. Furthermore, scratching during and after the episode frequently leads to painful excoriation.
It has now been found that certain ethoxylates exhibit insecticidal and/or ovicidal activity. The same boundaries which delimit the insecticidal properties also include compositions which have a valuable degree of topical anesthetic performance.
Although chemically unrelated to any of the conventional anes-thetic configurations, these ethoxylates demonstrate topical ~' pharmacologic properties which can be variously characterized as analgesic, anesthetic or antiprurtic.
V.B. Wigglesworth (Journal of Experimental Biology, 21,3, 4p. 97 (1945)) in a study of transpiration through insect cuticles, reported on the moisture loss of Rhodnius nymphs following treatment with various surfactants. He observed that the ethoxylates of ring compounds had very little action, and that the eight mole ethoxylate of cetyl alcohol was the most .
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effecti~e surfactant be tested, the nymphs losing 48% of body weight in 24 hours. Wigglesworth failed to appreciate that this effect could be adapted to killing insects by an action ha~ing no counterpart in higher animals.
Maxwell and Piper (Journal of Economic Entomology, 61, No~ 6, Dec. 1968 p. 1633) explored the lethal activity of a large series of ethoxylates against southern house mosquito pupae. They found activity at high dilutions (in the parts per million range), but contrary to Wigglesworth, they reported greatest activity with some ethoxylates of alkylphenols.
In tests against lice and their ova, we have made certain discoveries which were unexpected in light of Maxwell and Piper, and Wigglèsworth. We found eficacy only at concentrations se~eral orders o magnitude greater than hlaxwell and Piper.
Where they reported that short ethylene oxide chain lengths were less effective than 4-6 moles of ethylene oxide, we dis-covered that the aryl alkyl ethoxylates were best at 1~3 moles of ethylene oxide, and that such compounds were good o~icides but mediocre pediculicides. Certain ethoxylates of aliphatic alcohols were much superior both as insecticides and as ovicides, Moreover, - thoso most effective as toxicants were also found to be most , effective as topical anesthetics.
The ethoxylates of this invention are well known as surface ~ acti~e agents and have been incorporated in many pharmaceutica .,~ .
and cosmetic preparations as such. For example, polyoxyetnylene (4) lauryl ether is 5.5% of a washable coal tar ointment, poly-, ....
?~l oxyethylene (23) lauryl ether is 8~ of an all purpose anionic emulsion for skin application, and a mixture of these two lauryl ethers constitutes 35~ of a commercial tar shampoo.
,, ' .
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Smith ~U.S. 2,666,728) teaches the use up to 5% of a nonionic polyethylene oxide ether of aromatic glycols in a composition for destroying lice. Lindner (U.S. 2,898,267) teaches the use of ethoxylates in emulsifiers for acaricidal compositions.
It is the object of this invention to provide new, safe ` and effective toxicants for lice and their ova. .This and other objects of the invention will become apparent to those skilled in the art from the following detailed description.
SUM~RY OP THE INVENTION
; This invention relates to ectoparasiticidal toxicants and a ~ethod of controlling ectoparasites and the pain or itch related to infestation. More particularly, the invention relates to the use of certain ethoxylates as toxicants for lice and/or their ova, and for mites, to toxicant compositions containing ;I such ethoxylates and to such ethoxylates as adjunctive therapy to relieve p~in or itch.
~! DESCRIPTION OF THE PREF~RRED EMBODIMENTS
~,`1 The toxicants of the instant invention are certain ethoxylates i.e., certain deriva~ives o polyoxyethylene ~H(OCH2CH2)nOH], The polyoxyethylene glycols per se have not been ound to be pediculicidal or ovicidal. For convenience, the polyoxyethylene will hereinafter be reerred to as POE and the number of repeating units (n) will be indicated in parenthesis where applicable.
The POE derivatives which exhibit toxicant properties are the alkyl ethers, alkyl esters and block polymers of polyoxypropylene and/or ethylenediamine. Thus, the alkyl or ester moiety, derived from a fatty alcohol or fatty acid respectively, contains 12 to 24 carbon atoms and preferably 12 to 20 carbon atoms. The alkyl .
:
... ..., _... ... ., .. _ ...........
moiety is preferably unsubstituted but can, if desired, contain an aryl substituent. The block polymers contain 6 to 100 POE
units and 30 to 112 units of polyoxypropylene.
It has been observed that the POE alkyl ethers, alkyl esters and block polymers of polyoxypropylene and/or ethylendiamine require an appropriate hydrophilic-lipophilic balance (HLB) for good activity. In general, the HLB can be about 2.5 to 13.5.
The alkyl ethers appear to exhibit maximum activity at an HLB
in the neighborhood of 9, and the alkyl esters and block polymers ; 10 at a lower HLB, excepting the alkyl diester, POE (8j dilaurate, having an HLB value of 10.
~ Exemplary of the POE alkyl ethers of the present invention are'; POE (1) lauryl ether, POE (2) oleyl ether, POE (2~ stearyl ether, POE (3) oleyl ether, POE (3) tridecyl ether, POE (4) myristyl ` ether, POE (5) oleyl ether, POE (6) tridecyl ether, POE (10) oleyl ether, and the like. POE (l)ethylphenyl ether and POE
(3) octylphenyl ether are examples of somewhat effective POE
aryl alkyl ethers.
Typical examples of the POE esters include POE (3) oleate, POE (2) laurate, POE (8) dilaurate, and the like. Typical ~: B examples of the block polymers include Poloxamer~ 401, Poloxame~tM
;j 181 and the like.
One or more of the toxic ethoxylates 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 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 ;~
.' .
.
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. . . , i . -,,~ 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 carrier may also be additive or synergistic to the ,~ primary active ingredient.
The active ethoxylate is incorporated into the toxicant '`
composition used to treat the substrate in need of such treat- , ment, 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 50~ of the ectoparasites exposed 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 ova, The minimum con-centration of ethoxylate in the composition required to provide an efective toxic amount varies considerably depending on the , particular ethoxylate, the particular inert pharmaceutically acceptable carrier being employed and any other ingredients which '~ are present. Thus, in one case a 10~ concentration may suffice, while in other cases, concentrations as high as 30 to 40% may ,, 20 be required to obtain an e~fective toxic dose.
, The two minute immersion test referred to above is carried ',-" out as follows: ' Pediculicidal activity: A 50 ml beaker is filled with tap water and allowed to come to room temperature (about 24C), Ten young adult male and ten young adult emale lice tpeaiculus 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 room 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 immsdiately plunged into the .
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~ 3~
beaker containing the tap water. The patch is Yigorously agitated e~ery ten seconds and after one minute the patch is remo~èd and placed on paper toweling. The lice are then transferred to a 4x4 cm black corduroy cloth patch and this point of time is con-sidered zero hours. Thereafter, the corduroy patch is placed in a petri dish which 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 on a 2x2 cm nylon ~¦ mesh patch which is placed in a petri dish, covered and maintained in an incubator at 30C for 24 hours. The adult lice are then ¦ removed and the number o 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 bea~er. Immediately after the pouring, the mesh patch is placed into the beaXer, allowed to submerge, and after two minutes is removed and immediately plunged into a 50 ml beaker containing tap water at room temperature (about 24~C). The patch is vigorously agitated every ten seconds and after one minute, the patch is remo~ed and placed on paper toweling for one minute. The patch is then placed in a petri dish which is covered and stored in the 30C incubator. Pour-teen tays following treatment, the number of hatched eggs and the number of shriveled or unhatched eggs is noted.
In both the pediculicidal and ovicidal two minute immersion test, controls are run in identical manners to that described, with room temperature (24C) tap water substituted for the sample to be tested. The results of the tests reported are . j .
net results.
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. . .. . . .. ..
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~n the following tables, the results of pediculicidal -and ovicidal testing for various toxicants of this invention are set forth. The materials were tested in undiluted for~
neat) or in a combination ~C) containing 15% (w/w) compound, - 25% isopropanol and 60% water. For comparative purposes, results achieved with the unmodified ethoxylate, i.e., poly-' ethylene glycol (PEG) and other ethoxylates not within the scope of this invention are also set forth.
Table 1. Pediculicidal and ovicidal activity for ethoxylate alcohols having a general structure type H(OCH2CH2)nOH-,, ' ' ' , , ' , Mortality Pediculicidal Ovicidal ~.,, - , Compound n Neat C Neat C
diethylene glycol 2 0 5 0 S4 ;~ PEG 12 lZ 25 35 35 16 PEG 32 32 (1) 20 0(2) 0 PEG 75 75 ~1) 15 0(2) 14 ~'' ' ' .
. . , 1....................................................... .
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:: .
~ 7 -~3e~
Table II. Pediculicidal and ovicidal activity for a series of alkyl ethoxylate ethers.
.
: .
. % ~lortality ~ .
Pediculicidal OvicidaL
Compound HLB NeatC Neat C
POE (1) lauryl ether 3.6 10040 100(3) 100 POE ~2) oleyl ether 4.9 10010 100~3) 100 : :
:~ POE (2) stearyl ether 4.9 100. 40 100 : 33 POE (3) oleyl ether 6.6 10010 100 41 .. . . . .
POE (3).tridecyl ether 8 10020 100 100 POE (4) myristyl ether 8.8 10035 100~3) 100:
POE (5) oleyl ether 8.8 10015 100 8.3 POE (4) lauryl ether 9.5 10030 100 83 POE (6) tridecyl ether 11 10030 100 o POE (6.5) tridecyl ether- 11.6 100 15 100 34 POE (6) lauryl thioether 11.6 100 20 100 n POE (10) oleyl ether 12.4 100 10 ~ 5 68 . .
POE (7) lauryl ether 12.5 100~4) 0 100(4) 36 POE (8) lauryl thioether 13.4 75 20 67 0 POE (9) lauryl ether 15.6 ioo 20 100~3) 19 POE (10) lauryl thioether 13.9 15 5 30 0 POE (12) lauryl ether 14.5 . 20 5 100 o POE (20) isohexadecyl ether 15.7 (1~ o llt2) 2 POE ~23) lauryl ether 16.9 (1) o 69(2) 3 ... .~
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. i Table III. Pediculicidal and ovicidal activity ~or some : arylalkyl ethoxylate ethers.
% Mortality Pediculicidal Ovicidal Com ound HLB Neat C Neat C
, P
POE (l) octylphenyl ether 3.6 80 lO lOO~3) 66 POB (3) octylphenyl ether 7.8 15 5 82(3) 34 ~: POE (lO) nonylphenyl ether 13.420 5 82t3) 0 ,,.
.. " :
. Table IV. Pediculicidal and ovicidal activity for ethoxylate mono and diesters.
. ' ' ' ~'.
... ~ Mortality ' Pediculicidal- Ovicidal Compound HLB Neat C Neiat, C
POE (2) oleate 3.5 70 75 lOO~3) 14 1 .. POE (2) laurate 6.0 25 20 100~3) 6.5 ~, POE (8) dioleate 7.2 40 0 7.3 28 :: . POE (2) laurate 7.4 95 55 100~3) 8.3 ~ .
' POE (8) distearate 7.8 ~l) 40 ~l) 23 '~1 POB t4) laurate 8.6 lO 15 14 5.9 ~! 20 POE (4) sorbitol '~! septaoleate 9 5 20 77 21 POE (8) dilaurate lO 80 lO 23 38 ~ -POE (12) distearate lO.6 (l) 40 (l) 24 ?ij POE (20) stearate 15 (l) o (l) o POE (lOO) stearate 18.8 (l) o (l) 5 '.' ..
~ ~ .
:. 9 , ...... _ _ -TABLE V. Pediculicidal and ovicidal activity for ethoxylate block polymers having the general structure type :
outlined for each section.
i'~'' . ' ' , . .
A) based on structure type HO(CHCH20)x(cH2cH2o)y(cHc~2o) z ; - .
. % ~lortality Pediculicidal Ovicidal : . x _y__ z HLB Neat C Neat C
. . . _ .
18 14 18 4.5 10 0 56 4.8 12 . 23 12 8.4 5 0 0 lS
7 22 . 7 10.8 10 0 . O 41 ... .
,. . .
B) based on structure type Ho~cH2cHzo)x(cHcl~2o)y(cH2c~l2o)zH
: CH3 : .
. % ~lortality ::' Pediculicidal Ovicidal ~, . x _y_ z HLB Neat C Neat C
3 30 . 3 3 10 0 70 0 ~.
13 67 13 4 _ 10 ~t2) 1.2 6 67 6 5 55 0 80 . 84 . 8 30 8 7 0 50 8.4 O
21 67 . 21 8 (1) 10 0~2) 4.5 , 13 30 13 15 5 20 0 . 17 ~' 38 5~ 38 15 (1) 0(2) 19 122 47 122 27.5 (1) 40 ~1) 4.5 :~ .
.
.
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C) based on structure type C~13 C~13 H(ocH2cH2)y~ocH2cH)x / (CHcH2o)x(cl{2cH2o)yH
C~13 / \ CH3 H(ocH2cH2)y(oc~l2cHlx (C~CH20)x(CH2CH20)yH
% ~1ortality . . Pediculicidal Ovicidal x y HLB Neat C Neat C
_ ;:. 12 2 3 ~5 0 73(3)ll 21 7 3.5 30 0 l00(3)53 .
26 .8 . 5 5 . 0 . l00(3)49 13 4 7 0 : 20 58 O
,; . .
~`i 26 24 13 85 0 - 20 ., 8 7 16 0 20 0 28 , . ' ' ' ' ' ", Notes to Tables I-V
(l) solid - could not be tested at 100%
. (2) 50% (w/w) in ethanol (3) pad noted to be coated ~Yith compound at . conclusion of test (4) 90% (w/w) in water The pediculicidal activity of various compounds set forth in Table II as a function of concentration was determined in a diluted system containing 25% isopropanol and water q.s. The results are shown in Table VI.
.
-, TABLE VI
': Concentration, %~w/w) Mortality, $
,' A. POE ~1) lauryl ether HLB = 3.6 -. 20 80 . SO . 95 ' B. POE (2) oleyl ether HLB - 4.9 IO 10 30 ~ ~
. 15 10 . ~ ~.
~
~ 20 35 `
.
! 30 15 :
.
^ 40 20 C. POE (2) stearyl ether HLB ~ 4.9 ' 10 o : 15 40 . 20 30 50 i .
: 50 100 ,'' ' ' ' ' I .
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. .. .. 1~
.: ' - ~
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D. POE (3) oleyl ether HLB- 6,6 . 70 ` 100 .
E. POE t3) tridecyl ether HLB = 8 -. 15 . 20 ` : .95 i `. 100 ,;! .
F. POE ~4) myristyl ether HLB ~ 8 , 10 75 . 90 ~ 40 100 ,:
G. POE (4) lauryl ether HLB = 9.5 , . 40 85 ~: . 50 60 .,. , . - .
~ -13-~ ~. .
: : :
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il. POE (6) tridecyl ether HLB = 11 ~-~ 30 75 . 35 . ' - I . POE (6 . 5) tridecyl ether HLB = 11. 6 ~, J. POE (7) Iauryl ether HLB = 12 . 5 ; 15 . 0 ; 20 10 . 35 ', , ' ', K. POE t9) lauryl ether ~ILB = 13 . 6 lS 20 ~5:
.
lS
: 40 25 . 60 . 50 . . . . . .
P~-L. POE (12) lauryl ether HLB = 14.5 . 0 . 15 .
: 70 45 M. POE (23) lauryl ether HLB = 16.9 . . 0 ;~ 10 30 . 0 . 0 .: , .
The pediculicidal activity of two ethoxylated alkyl ethers as a function of concentration when diluted with water was determined and the results are set forth in Table VII, ' . . ' ' . ' , ..
, . .
~,, ' ',' :, , . :
TABLE VII
Concentration, % (w/w) ~lortality, A. POE (Z) oleyl ether ~ILB = 4.9 .
O :~
. . 10 10 ' .
. . 100 100 100 , ' ' .
B, POE (4) lauryl ether HLB - 9.5 . S
' 5 , . ..
lS 45 100 ' ' 100 .
The ovicidal activity of various compounds set forth in Table II as a unction of concentration was determined in a diluted system containing 25~ isopropanol and water q.s.
The results are shown in lable VIII.
'~
~3E. `~3 TABLE VIII
.
- . Concentration, ~ tw/w) ~ ~lortality -A. POE (1) lauryl ether ~ILB = 3.6 100 ~ .
',:
B. POE t3) tridecyl ether HLB = 8 . lq ' 10 100 . 15 100 , . 40 100 .
C. POE (4~ ~yristyl ether HLB = 8.8 , : 10 27 .; , . , : 15 100 .
.20 40 100 i; . .
D. .POE (6) tridecyl ether HLB = 11 ;~ . 10 0 ',. , 15 , O' 4~
: 40 14 , 50 3 .
.
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-E. POE (12) lauryl ether HLB - 14.5 ~:
O
0.2 ' 50 ' 5 ~ , 60 , 2 O
:~, F. POE ~23) lauryl ether HLB = 16.9 lQ 20 10 . .
" , . SO ' . O .
. '`' ' '' . ':
Table IX reflects the resulting pediculicidal and .
ovicidal activity of a 15~ (w/w) concentration of POE t4) lauryl ether with variation af isopropanol. and water content . ..
., .
TABLE rx % ~ortality % w/w isopropanol % w/w water Pediculicidal Ovicidal ~ . 25 60 30 83 .: 20 65 30 21 , , .. . .
~ 1 84 20 100 . , : 0 85 45 10 .
. ~ .
-.
: .
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~ s can be seen from Table IX, the 15% concentration of POE (4) lauryl ether exhibited synergistic pediculicidal activity when the isopropanol ~as about l-S~.
The most efective toxicants o~ this invention have also been found to exhibit topical anesthetic activity. Thus, for example, one drop of 5% aqueous POE (4) lauryl ether caused an onset of corneal anesthetic action in about 5-8 minutes with a duration of about 0.5-4 hours ~average four tests was two hours) in a modified Cole and Rose rabbit eye iritiation test (J. Lab. ~ Clin. ~led. 15:239, 1929). In contrast, POE (23) lauryl ether did not exhibit any activity in the same test. In general, the preerred alkyl ethers exhibit anesthetic, analgesic or antipruritic activity at concentrations o at least 1~ and are preferably employed for this purpose at about 1-10~.
The miticidal acti~ity of some of the instant toxicants was determined as follows. Into a one cubic foot chamber, held at room temperature, is placed a covered microscope de-pression slide containing te~ adult mixed sex mites, Psorop~es equi var. cuniculi. The slide is positioned at a distance of ten inches horizontally and four inches below the activator o~
a mechanical spray device and uncovered. The mechanical pump spray device delivers 50 micrograms of sample per depression of the activator. The sample to be tested, maintained at room temperature, is sha~en until homogeneous and placed in the mechanical pump spray device. The primed activator is de-pressed 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 co~sidered zero hours. The covered slide is then held at room temperature for 24 hours. .liscroscopic observations ar~
noted at 0, 1, 3, and 24 hours post treatment. Controls are , . , . ... , . . . . = . .. .. . ... . .. .. . . ... . . ..
- . ~
3~
run in an identical manner as that ~escribed using water or the diluting a~ent, and net mortality results are reported.
Table X shows the miticidal activity of a 50~ twJw) concentration of the named compounds in isopropanol.
TABLE X
'Compound HLB Miticidal Activity,~
POE ~1) lauryl ether 3.6 ~ 100 POE (2) oleyl ether 4.9 80 POE (4)'myristyl ether 8.8 100 POE (4) lauryl ether 9.5 100`
POE (6)' tridecyl ether 11 90 POE (10) oleyl ether 12.4 100 , POE (12) lauryl ether 14.5 100 .
' As noted, various end use formulations can be prepared.
Some typical formulations are set ~orth and the amounts recited are, percentages by weight:
.. . . .
, Liquid pediculicids and ovicide suitable ~or mechanicsl ' '" spray application or inunction.
POE (8) dilaurate 15 ,, 20 Isopropanol 60 ,Water 25 , , :
Liquid pediculicide and ouicide shampoo '~
POE (4) lauryl ether 26.0 , , POE (23) lauryl ether 7.7 ,~ Isopropanol 7.7 Benzalkonium chloride 0.2 Water 58.4 ~, . ~ -- , . ., --Ovicidal powder : POE (3) tridecyl ether 3 - .
Pyrophyllite . 97 .
Pediculicidal and ovicidal powder : POE tl) lauryl ether 10 .~ Prophyllite 90 .~ . ..
: Pediculicidal Stick . POE (2) oleyl ether 15.0 Sodium stearate 8.0 Sorbitol 3.5 .~ Isopropanol 25.0 ; Ethanol . 39.0 Water 9.5 ~ . . .
:. Pediculicidal and ovicidal quick breaking aerosol foam ' POE t4) lauryl ether 20 . Water 72 ~: . Isobutane 8 .
Pediculicidal and ovicidal gel POE (2) oleyl ether 15.0 Isopropanol 25.0 Carbomer 940 (7'r~de~ar~) 0 5 . ~ ,~ . . .
.~. Triethanolamine 0.38 Water 59.12 : , .
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....... ,.. ,,,, , ~
lL13~
As noted, various changes and modifications can be made in the instant invention without departing from the spirit and scope thereof. The various embodiments disclosed herein were made for the purpose of further illustrating the invention but . were not intended to limit it. Throughout this specification `~ and claims, all temperatures are in.degrees Centigrade and all -parts and percentages are by weight unless otherwise indicated.
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Ectoparasites such as lice and mites cause pruritus or pain in their animal or human hosts. Therapy which simply kills the parasite leaves the host with subcutaneous or intradermal residues which continue to itch for significant time periods after the infestation is extinguished. Furthermore, scratching during and after the episode frequently leads to painful excoriation.
It has now been found that certain ethoxylates exhibit insecticidal and/or ovicidal activity. The same boundaries which delimit the insecticidal properties also include compositions which have a valuable degree of topical anesthetic performance.
Although chemically unrelated to any of the conventional anes-thetic configurations, these ethoxylates demonstrate topical ~' pharmacologic properties which can be variously characterized as analgesic, anesthetic or antiprurtic.
V.B. Wigglesworth (Journal of Experimental Biology, 21,3, 4p. 97 (1945)) in a study of transpiration through insect cuticles, reported on the moisture loss of Rhodnius nymphs following treatment with various surfactants. He observed that the ethoxylates of ring compounds had very little action, and that the eight mole ethoxylate of cetyl alcohol was the most .
:' .
. :"
: - ~- :
effecti~e surfactant be tested, the nymphs losing 48% of body weight in 24 hours. Wigglesworth failed to appreciate that this effect could be adapted to killing insects by an action ha~ing no counterpart in higher animals.
Maxwell and Piper (Journal of Economic Entomology, 61, No~ 6, Dec. 1968 p. 1633) explored the lethal activity of a large series of ethoxylates against southern house mosquito pupae. They found activity at high dilutions (in the parts per million range), but contrary to Wigglesworth, they reported greatest activity with some ethoxylates of alkylphenols.
In tests against lice and their ova, we have made certain discoveries which were unexpected in light of Maxwell and Piper, and Wigglèsworth. We found eficacy only at concentrations se~eral orders o magnitude greater than hlaxwell and Piper.
Where they reported that short ethylene oxide chain lengths were less effective than 4-6 moles of ethylene oxide, we dis-covered that the aryl alkyl ethoxylates were best at 1~3 moles of ethylene oxide, and that such compounds were good o~icides but mediocre pediculicides. Certain ethoxylates of aliphatic alcohols were much superior both as insecticides and as ovicides, Moreover, - thoso most effective as toxicants were also found to be most , effective as topical anesthetics.
The ethoxylates of this invention are well known as surface ~ acti~e agents and have been incorporated in many pharmaceutica .,~ .
and cosmetic preparations as such. For example, polyoxyetnylene (4) lauryl ether is 5.5% of a washable coal tar ointment, poly-, ....
?~l oxyethylene (23) lauryl ether is 8~ of an all purpose anionic emulsion for skin application, and a mixture of these two lauryl ethers constitutes 35~ of a commercial tar shampoo.
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Smith ~U.S. 2,666,728) teaches the use up to 5% of a nonionic polyethylene oxide ether of aromatic glycols in a composition for destroying lice. Lindner (U.S. 2,898,267) teaches the use of ethoxylates in emulsifiers for acaricidal compositions.
It is the object of this invention to provide new, safe ` and effective toxicants for lice and their ova. .This and other objects of the invention will become apparent to those skilled in the art from the following detailed description.
SUM~RY OP THE INVENTION
; This invention relates to ectoparasiticidal toxicants and a ~ethod of controlling ectoparasites and the pain or itch related to infestation. More particularly, the invention relates to the use of certain ethoxylates as toxicants for lice and/or their ova, and for mites, to toxicant compositions containing ;I such ethoxylates and to such ethoxylates as adjunctive therapy to relieve p~in or itch.
~! DESCRIPTION OF THE PREF~RRED EMBODIMENTS
~,`1 The toxicants of the instant invention are certain ethoxylates i.e., certain deriva~ives o polyoxyethylene ~H(OCH2CH2)nOH], The polyoxyethylene glycols per se have not been ound to be pediculicidal or ovicidal. For convenience, the polyoxyethylene will hereinafter be reerred to as POE and the number of repeating units (n) will be indicated in parenthesis where applicable.
The POE derivatives which exhibit toxicant properties are the alkyl ethers, alkyl esters and block polymers of polyoxypropylene and/or ethylenediamine. Thus, the alkyl or ester moiety, derived from a fatty alcohol or fatty acid respectively, contains 12 to 24 carbon atoms and preferably 12 to 20 carbon atoms. The alkyl .
:
... ..., _... ... ., .. _ ...........
moiety is preferably unsubstituted but can, if desired, contain an aryl substituent. The block polymers contain 6 to 100 POE
units and 30 to 112 units of polyoxypropylene.
It has been observed that the POE alkyl ethers, alkyl esters and block polymers of polyoxypropylene and/or ethylendiamine require an appropriate hydrophilic-lipophilic balance (HLB) for good activity. In general, the HLB can be about 2.5 to 13.5.
The alkyl ethers appear to exhibit maximum activity at an HLB
in the neighborhood of 9, and the alkyl esters and block polymers ; 10 at a lower HLB, excepting the alkyl diester, POE (8j dilaurate, having an HLB value of 10.
~ Exemplary of the POE alkyl ethers of the present invention are'; POE (1) lauryl ether, POE (2) oleyl ether, POE (2~ stearyl ether, POE (3) oleyl ether, POE (3) tridecyl ether, POE (4) myristyl ` ether, POE (5) oleyl ether, POE (6) tridecyl ether, POE (10) oleyl ether, and the like. POE (l)ethylphenyl ether and POE
(3) octylphenyl ether are examples of somewhat effective POE
aryl alkyl ethers.
Typical examples of the POE esters include POE (3) oleate, POE (2) laurate, POE (8) dilaurate, and the like. Typical ~: B examples of the block polymers include Poloxamer~ 401, Poloxame~tM
;j 181 and the like.
One or more of the toxic ethoxylates 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 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 ;~
.' .
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. . . , i . -,,~ 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 carrier may also be additive or synergistic to the ,~ primary active ingredient.
The active ethoxylate is incorporated into the toxicant '`
composition used to treat the substrate in need of such treat- , ment, 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 50~ of the ectoparasites exposed 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 ova, The minimum con-centration of ethoxylate in the composition required to provide an efective toxic amount varies considerably depending on the , particular ethoxylate, the particular inert pharmaceutically acceptable carrier being employed and any other ingredients which '~ are present. Thus, in one case a 10~ concentration may suffice, while in other cases, concentrations as high as 30 to 40% may ,, 20 be required to obtain an e~fective toxic dose.
, The two minute immersion test referred to above is carried ',-" out as follows: ' Pediculicidal activity: A 50 ml beaker is filled with tap water and allowed to come to room temperature (about 24C), Ten young adult male and ten young adult emale lice tpeaiculus 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 room 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 immsdiately plunged into the .
.: .
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beaker containing the tap water. The patch is Yigorously agitated e~ery ten seconds and after one minute the patch is remo~èd and placed on paper toweling. The lice are then transferred to a 4x4 cm black corduroy cloth patch and this point of time is con-sidered zero hours. Thereafter, the corduroy patch is placed in a petri dish which 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 on a 2x2 cm nylon ~¦ mesh patch which is placed in a petri dish, covered and maintained in an incubator at 30C for 24 hours. The adult lice are then ¦ removed and the number o 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 bea~er. Immediately after the pouring, the mesh patch is placed into the beaXer, allowed to submerge, and after two minutes is removed and immediately plunged into a 50 ml beaker containing tap water at room temperature (about 24~C). The patch is vigorously agitated every ten seconds and after one minute, the patch is remo~ed and placed on paper toweling for one minute. The patch is then placed in a petri dish which is covered and stored in the 30C incubator. Pour-teen tays following treatment, the number of hatched eggs and the number of shriveled or unhatched eggs is noted.
In both the pediculicidal and ovicidal two minute immersion test, controls are run in identical manners to that described, with room temperature (24C) tap water substituted for the sample to be tested. The results of the tests reported are . j .
net results.
. .
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~n the following tables, the results of pediculicidal -and ovicidal testing for various toxicants of this invention are set forth. The materials were tested in undiluted for~
neat) or in a combination ~C) containing 15% (w/w) compound, - 25% isopropanol and 60% water. For comparative purposes, results achieved with the unmodified ethoxylate, i.e., poly-' ethylene glycol (PEG) and other ethoxylates not within the scope of this invention are also set forth.
Table 1. Pediculicidal and ovicidal activity for ethoxylate alcohols having a general structure type H(OCH2CH2)nOH-,, ' ' ' , , ' , Mortality Pediculicidal Ovicidal ~.,, - , Compound n Neat C Neat C
diethylene glycol 2 0 5 0 S4 ;~ PEG 12 lZ 25 35 35 16 PEG 32 32 (1) 20 0(2) 0 PEG 75 75 ~1) 15 0(2) 14 ~'' ' ' .
. . , 1....................................................... .
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Table II. Pediculicidal and ovicidal activity for a series of alkyl ethoxylate ethers.
.
: .
. % ~lortality ~ .
Pediculicidal OvicidaL
Compound HLB NeatC Neat C
POE (1) lauryl ether 3.6 10040 100(3) 100 POE ~2) oleyl ether 4.9 10010 100~3) 100 : :
:~ POE (2) stearyl ether 4.9 100. 40 100 : 33 POE (3) oleyl ether 6.6 10010 100 41 .. . . . .
POE (3).tridecyl ether 8 10020 100 100 POE (4) myristyl ether 8.8 10035 100~3) 100:
POE (5) oleyl ether 8.8 10015 100 8.3 POE (4) lauryl ether 9.5 10030 100 83 POE (6) tridecyl ether 11 10030 100 o POE (6.5) tridecyl ether- 11.6 100 15 100 34 POE (6) lauryl thioether 11.6 100 20 100 n POE (10) oleyl ether 12.4 100 10 ~ 5 68 . .
POE (7) lauryl ether 12.5 100~4) 0 100(4) 36 POE (8) lauryl thioether 13.4 75 20 67 0 POE (9) lauryl ether 15.6 ioo 20 100~3) 19 POE (10) lauryl thioether 13.9 15 5 30 0 POE (12) lauryl ether 14.5 . 20 5 100 o POE (20) isohexadecyl ether 15.7 (1~ o llt2) 2 POE ~23) lauryl ether 16.9 (1) o 69(2) 3 ... .~
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. i Table III. Pediculicidal and ovicidal activity ~or some : arylalkyl ethoxylate ethers.
% Mortality Pediculicidal Ovicidal Com ound HLB Neat C Neat C
, P
POE (l) octylphenyl ether 3.6 80 lO lOO~3) 66 POB (3) octylphenyl ether 7.8 15 5 82(3) 34 ~: POE (lO) nonylphenyl ether 13.420 5 82t3) 0 ,,.
.. " :
. Table IV. Pediculicidal and ovicidal activity for ethoxylate mono and diesters.
. ' ' ' ~'.
... ~ Mortality ' Pediculicidal- Ovicidal Compound HLB Neat C Neiat, C
POE (2) oleate 3.5 70 75 lOO~3) 14 1 .. POE (2) laurate 6.0 25 20 100~3) 6.5 ~, POE (8) dioleate 7.2 40 0 7.3 28 :: . POE (2) laurate 7.4 95 55 100~3) 8.3 ~ .
' POE (8) distearate 7.8 ~l) 40 ~l) 23 '~1 POB t4) laurate 8.6 lO 15 14 5.9 ~! 20 POE (4) sorbitol '~! septaoleate 9 5 20 77 21 POE (8) dilaurate lO 80 lO 23 38 ~ -POE (12) distearate lO.6 (l) 40 (l) 24 ?ij POE (20) stearate 15 (l) o (l) o POE (lOO) stearate 18.8 (l) o (l) 5 '.' ..
~ ~ .
:. 9 , ...... _ _ -TABLE V. Pediculicidal and ovicidal activity for ethoxylate block polymers having the general structure type :
outlined for each section.
i'~'' . ' ' , . .
A) based on structure type HO(CHCH20)x(cH2cH2o)y(cHc~2o) z ; - .
. % ~lortality Pediculicidal Ovicidal : . x _y__ z HLB Neat C Neat C
. . . _ .
18 14 18 4.5 10 0 56 4.8 12 . 23 12 8.4 5 0 0 lS
7 22 . 7 10.8 10 0 . O 41 ... .
,. . .
B) based on structure type Ho~cH2cHzo)x(cHcl~2o)y(cH2c~l2o)zH
: CH3 : .
. % ~lortality ::' Pediculicidal Ovicidal ~, . x _y_ z HLB Neat C Neat C
3 30 . 3 3 10 0 70 0 ~.
13 67 13 4 _ 10 ~t2) 1.2 6 67 6 5 55 0 80 . 84 . 8 30 8 7 0 50 8.4 O
21 67 . 21 8 (1) 10 0~2) 4.5 , 13 30 13 15 5 20 0 . 17 ~' 38 5~ 38 15 (1) 0(2) 19 122 47 122 27.5 (1) 40 ~1) 4.5 :~ .
.
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C) based on structure type C~13 C~13 H(ocH2cH2)y~ocH2cH)x / (CHcH2o)x(cl{2cH2o)yH
C~13 / \ CH3 H(ocH2cH2)y(oc~l2cHlx (C~CH20)x(CH2CH20)yH
% ~1ortality . . Pediculicidal Ovicidal x y HLB Neat C Neat C
_ ;:. 12 2 3 ~5 0 73(3)ll 21 7 3.5 30 0 l00(3)53 .
26 .8 . 5 5 . 0 . l00(3)49 13 4 7 0 : 20 58 O
,; . .
~`i 26 24 13 85 0 - 20 ., 8 7 16 0 20 0 28 , . ' ' ' ' ' ", Notes to Tables I-V
(l) solid - could not be tested at 100%
. (2) 50% (w/w) in ethanol (3) pad noted to be coated ~Yith compound at . conclusion of test (4) 90% (w/w) in water The pediculicidal activity of various compounds set forth in Table II as a function of concentration was determined in a diluted system containing 25% isopropanol and water q.s. The results are shown in Table VI.
.
-, TABLE VI
': Concentration, %~w/w) Mortality, $
,' A. POE ~1) lauryl ether HLB = 3.6 -. 20 80 . SO . 95 ' B. POE (2) oleyl ether HLB - 4.9 IO 10 30 ~ ~
. 15 10 . ~ ~.
~
~ 20 35 `
.
! 30 15 :
.
^ 40 20 C. POE (2) stearyl ether HLB ~ 4.9 ' 10 o : 15 40 . 20 30 50 i .
: 50 100 ,'' ' ' ' ' I .
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D. POE (3) oleyl ether HLB- 6,6 . 70 ` 100 .
E. POE t3) tridecyl ether HLB = 8 -. 15 . 20 ` : .95 i `. 100 ,;! .
F. POE ~4) myristyl ether HLB ~ 8 , 10 75 . 90 ~ 40 100 ,:
G. POE (4) lauryl ether HLB = 9.5 , . 40 85 ~: . 50 60 .,. , . - .
~ -13-~ ~. .
: : :
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il. POE (6) tridecyl ether HLB = 11 ~-~ 30 75 . 35 . ' - I . POE (6 . 5) tridecyl ether HLB = 11. 6 ~, J. POE (7) Iauryl ether HLB = 12 . 5 ; 15 . 0 ; 20 10 . 35 ', , ' ', K. POE t9) lauryl ether ~ILB = 13 . 6 lS 20 ~5:
.
lS
: 40 25 . 60 . 50 . . . . . .
P~-L. POE (12) lauryl ether HLB = 14.5 . 0 . 15 .
: 70 45 M. POE (23) lauryl ether HLB = 16.9 . . 0 ;~ 10 30 . 0 . 0 .: , .
The pediculicidal activity of two ethoxylated alkyl ethers as a function of concentration when diluted with water was determined and the results are set forth in Table VII, ' . . ' ' . ' , ..
, . .
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TABLE VII
Concentration, % (w/w) ~lortality, A. POE (Z) oleyl ether ~ILB = 4.9 .
O :~
. . 10 10 ' .
. . 100 100 100 , ' ' .
B, POE (4) lauryl ether HLB - 9.5 . S
' 5 , . ..
lS 45 100 ' ' 100 .
The ovicidal activity of various compounds set forth in Table II as a unction of concentration was determined in a diluted system containing 25~ isopropanol and water q.s.
The results are shown in lable VIII.
'~
~3E. `~3 TABLE VIII
.
- . Concentration, ~ tw/w) ~ ~lortality -A. POE (1) lauryl ether ~ILB = 3.6 100 ~ .
',:
B. POE t3) tridecyl ether HLB = 8 . lq ' 10 100 . 15 100 , . 40 100 .
C. POE (4~ ~yristyl ether HLB = 8.8 , : 10 27 .; , . , : 15 100 .
.20 40 100 i; . .
D. .POE (6) tridecyl ether HLB = 11 ;~ . 10 0 ',. , 15 , O' 4~
: 40 14 , 50 3 .
.
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-E. POE (12) lauryl ether HLB - 14.5 ~:
O
0.2 ' 50 ' 5 ~ , 60 , 2 O
:~, F. POE ~23) lauryl ether HLB = 16.9 lQ 20 10 . .
" , . SO ' . O .
. '`' ' '' . ':
Table IX reflects the resulting pediculicidal and .
ovicidal activity of a 15~ (w/w) concentration of POE t4) lauryl ether with variation af isopropanol. and water content . ..
., .
TABLE rx % ~ortality % w/w isopropanol % w/w water Pediculicidal Ovicidal ~ . 25 60 30 83 .: 20 65 30 21 , , .. . .
~ 1 84 20 100 . , : 0 85 45 10 .
. ~ .
-.
: .
.
~ s can be seen from Table IX, the 15% concentration of POE (4) lauryl ether exhibited synergistic pediculicidal activity when the isopropanol ~as about l-S~.
The most efective toxicants o~ this invention have also been found to exhibit topical anesthetic activity. Thus, for example, one drop of 5% aqueous POE (4) lauryl ether caused an onset of corneal anesthetic action in about 5-8 minutes with a duration of about 0.5-4 hours ~average four tests was two hours) in a modified Cole and Rose rabbit eye iritiation test (J. Lab. ~ Clin. ~led. 15:239, 1929). In contrast, POE (23) lauryl ether did not exhibit any activity in the same test. In general, the preerred alkyl ethers exhibit anesthetic, analgesic or antipruritic activity at concentrations o at least 1~ and are preferably employed for this purpose at about 1-10~.
The miticidal acti~ity of some of the instant toxicants was determined as follows. Into a one cubic foot chamber, held at room temperature, is placed a covered microscope de-pression slide containing te~ adult mixed sex mites, Psorop~es equi var. cuniculi. The slide is positioned at a distance of ten inches horizontally and four inches below the activator o~
a mechanical spray device and uncovered. The mechanical pump spray device delivers 50 micrograms of sample per depression of the activator. The sample to be tested, maintained at room temperature, is sha~en until homogeneous and placed in the mechanical pump spray device. The primed activator is de-pressed 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 co~sidered zero hours. The covered slide is then held at room temperature for 24 hours. .liscroscopic observations ar~
noted at 0, 1, 3, and 24 hours post treatment. Controls are , . , . ... , . . . . = . .. .. . ... . .. .. . . ... . . ..
- . ~
3~
run in an identical manner as that ~escribed using water or the diluting a~ent, and net mortality results are reported.
Table X shows the miticidal activity of a 50~ twJw) concentration of the named compounds in isopropanol.
TABLE X
'Compound HLB Miticidal Activity,~
POE ~1) lauryl ether 3.6 ~ 100 POE (2) oleyl ether 4.9 80 POE (4)'myristyl ether 8.8 100 POE (4) lauryl ether 9.5 100`
POE (6)' tridecyl ether 11 90 POE (10) oleyl ether 12.4 100 , POE (12) lauryl ether 14.5 100 .
' As noted, various end use formulations can be prepared.
Some typical formulations are set ~orth and the amounts recited are, percentages by weight:
.. . . .
, Liquid pediculicids and ovicide suitable ~or mechanicsl ' '" spray application or inunction.
POE (8) dilaurate 15 ,, 20 Isopropanol 60 ,Water 25 , , :
Liquid pediculicide and ouicide shampoo '~
POE (4) lauryl ether 26.0 , , POE (23) lauryl ether 7.7 ,~ Isopropanol 7.7 Benzalkonium chloride 0.2 Water 58.4 ~, . ~ -- , . ., --Ovicidal powder : POE (3) tridecyl ether 3 - .
Pyrophyllite . 97 .
Pediculicidal and ovicidal powder : POE tl) lauryl ether 10 .~ Prophyllite 90 .~ . ..
: Pediculicidal Stick . POE (2) oleyl ether 15.0 Sodium stearate 8.0 Sorbitol 3.5 .~ Isopropanol 25.0 ; Ethanol . 39.0 Water 9.5 ~ . . .
:. Pediculicidal and ovicidal quick breaking aerosol foam ' POE t4) lauryl ether 20 . Water 72 ~: . Isobutane 8 .
Pediculicidal and ovicidal gel POE (2) oleyl ether 15.0 Isopropanol 25.0 Carbomer 940 (7'r~de~ar~) 0 5 . ~ ,~ . . .
.~. Triethanolamine 0.38 Water 59.12 : , .
~"' , '' .
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-21 :
....... ,.. ,,,, , ~
lL13~
As noted, various changes and modifications can be made in the instant invention without departing from the spirit and scope thereof. The various embodiments disclosed herein were made for the purpose of further illustrating the invention but . were not intended to limit it. Throughout this specification `~ and claims, all temperatures are in.degrees Centigrade and all -parts and percentages are by weight unless otherwise indicated.
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Claims (29)
1. A method of controlling ectoparasites or their ova which comprises applying to a human or animal host believed in need of such control, an effective toxic amount of at least one derivative of polyoxyethylene having an HLB of about 2.5-13.5, said derivative selected from the group consisting of the alkyl ethers thereof, the aryl alkyl ethers thereof, the alkyl esters thereof and the block polymers thereof containing 6-100 polyoxyethylene units and 30-112 units of polyoxypropylene.
2. The method of claim 1 wherein the alkyl or ester moiety of said derivative contains 12 to 24 carbon atoms.
3. The method of claim 2 wherein said alkyl or ester moiety contains 12 to 20 carbon atoms.
4. The method of claim 3 wherein said derivative is said alkyl ether.
5. The method of claim 4 wherein said derivative is selected from the group consisting of polyoxyethylene (3) tridecyl ether, polyoxyethylene (4) myristyl ether, polyoxyethylene (2) oleyl ether, and polyoxyethylene (1) lauryl ether.
6. The method of claim 4 wherein said derivative is polyoxyethylene (4) lauryl ether.
7. The method of claim l wherein said derivative is employed in combination with an inert pharmaceutically acceptable carrier.
8. The method of claim 7 wherein said carrier is an aqueous carrier.
9. The method of claim 7 wherein said derivative is said alkyl ether and is employed at a concentration of at least about 1% whereby topical anesthetic, analgesic or antipruritic activity is present.
10. The method of claim 9 wherein said concentration is about 1-10%.
11. In a method of controlling ectoparasites or their ova by applying to a human or animal host an active toxicant thereto, the improvement which comprises applying with said active toxicant, an effective toxic amount of at least one derivative of polyoxyethylene having an HLB of about 2.5-13.5, said derivative selected from the group consisting of the alkyl ethers thereof, the aryl alkyl ethers thereof, the alkyl esters thereof and the block polymers thereof containing 6-100 polyoxy-ethylene units and 30-112 units of polyoxypropylene as an adjuvant toxicant.
12. The method of claim 11 wherein the alkyl or ester moiety of said derivative contains 12 to 24 carbon atoms.
13. The method of claim 12 wherein said alkyl or ester moiety contains 12 to 20 carbon atoms.
14. The method of claim 13 wherein said derivative is said alkyl ether.
15. The method of claim 14 wherein said derivative is selected from the group consisting of polyoxyethylene (3) tridecyl ether, polyoxyethylene (4) myristyl ether, poly-oxyethylene (2) oleyl ether, and polyoxyethylene (1) lauryl ether.
16. The method of claim 14 wherein said derivative is polyoxyethylene (4) lauryl ether.
17. The method of claim 11 wherein said derivative is employed in combination with an inert pharmaceutically acceptable carrier.
18. The method of claim 17 wherein said carrier is an aqueous carrier.
19. The method of claim 14 wherein said derivative is said alkyl ether and is employed at a concentration of at least about 1% whereby topical anesthetic, analgesic or anti-pruritic acitivity is present.
20. The method of claim 19 wherein said concentration is about 1-10%.
21. In an ectoparasiticidal or ovicidal toxicant compo-sition comprising an active toxicant and an inert pharmaceutically acceptable carrier therefor, the improvement which comprises said composition additionally comprising an effective toxic amount of at least one derivative of polyoxyethylene having an HLB of 2.5-13.5 selected from the group consisting of the alkyl ethers thereof, the aryl alkyl ethers thereof, the alkyl esters thereof and the block copolymers thereof containing 6-100 poly-oxyethylene units and 30-112 units of polyoxypropylene, as an adjuvant toxicant.
22. The composition of claim 21 wherein said alkyl or ester moiety has 12-24 carbon atoms.
23. The composition of claim 22 wherein said alkyl or ester moiety has 12 to 20 carbon atoms.
24. The composition of claim 23 wherein said derivative is said alkyl ether.
25. The composition of claim 24 wherein said derivative is selected from the group consisting of polyoxyethylene (1) lauryl ether, polyoxyethylene (2) oleyl ether, polyoxyethylene (3) tridecyl ether, and polyoxyethylene (4) myristyl ether.
26. The composition of claim 24 wherein said derivative is polyoxyethylene (4) lauryl ether.
27. The composition of claim 24 wherein said ether is present in an amount of at least about 1% wherein said composition exhibits anesthetic, analgesic or antipruritic activity.
28. The composition of claim 27 wherein said amount is about 1-10%.
29. The composition of claim 21 wherein said carrier is an aqueous carrier.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US80201277A | 1977-05-31 | 1977-05-31 | |
US802,012 | 1977-05-31 |
Publications (1)
Publication Number | Publication Date |
---|---|
CA1113855A true CA1113855A (en) | 1981-12-08 |
Family
ID=25182613
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA304,445A Expired CA1113855A (en) | 1977-05-31 | 1978-05-30 | Antipruritic ectoparasiticide |
Country Status (10)
Country | Link |
---|---|
JP (1) | JPS545031A (en) |
AU (1) | AU522579B2 (en) |
BE (1) | BE867612A (en) |
CA (1) | CA1113855A (en) |
CH (1) | CH630229A5 (en) |
DE (1) | DE2823593A1 (en) |
FR (1) | FR2392601B1 (en) |
GB (1) | GB1604622A (en) |
PH (1) | PH17653A (en) |
SE (1) | SE443491B (en) |
Families Citing this family (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5026734A (en) * | 1989-01-12 | 1991-06-25 | Browning Henry A | Method of controlling fungus, mites, worms, termites, nematodes and other insects |
GB2281697A (en) * | 1993-09-14 | 1995-03-15 | Euro Celtique Sa | Laxative compositions in capsules |
US6596291B2 (en) * | 1997-12-05 | 2003-07-22 | Thomas A. Bell | Compositions and methods for treating surfaces infected with ectoparasitic insects |
JP3970072B2 (en) * | 2002-03-27 | 2007-09-05 | 日本製紙株式会社 | Sliding agent for clear coating and clear coated paper coated with the same |
JP6509547B2 (en) * | 2013-12-19 | 2019-05-08 | 大日本除蟲菊株式会社 | Pest control agent and pest control method using the same |
JP6611440B2 (en) * | 2014-08-22 | 2019-11-27 | 花王株式会社 | Aqueous hair cleanser |
EP3108941B1 (en) * | 2015-06-23 | 2018-05-09 | Symrise AG | Compositions comprising polyalkylene glycol derivatives |
JP6936910B2 (en) * | 2016-05-17 | 2021-09-22 | 大日本除蟲菊株式会社 | Pest egg killing agent |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS50123821A (en) * | 1974-03-18 | 1975-09-29 | ||
JPS5238019A (en) * | 1975-09-16 | 1977-03-24 | Katayama Chem Works Co Ltd | Repellents against marine fouling animals |
-
1977
- 1977-10-18 GB GB32134/77A patent/GB1604622A/en not_active Expired
-
1978
- 1978-05-18 PH PH21155A patent/PH17653A/en unknown
- 1978-05-24 AU AU36432/78A patent/AU522579B2/en not_active Expired
- 1978-05-26 CH CH574978A patent/CH630229A5/en not_active IP Right Cessation
- 1978-05-30 BE BE188153A patent/BE867612A/en not_active IP Right Cessation
- 1978-05-30 FR FR7816048A patent/FR2392601B1/en not_active Expired
- 1978-05-30 DE DE19782823593 patent/DE2823593A1/en active Granted
- 1978-05-30 CA CA304,445A patent/CA1113855A/en not_active Expired
- 1978-05-31 JP JP6445978A patent/JPS545031A/en active Granted
- 1978-07-25 SE SE7808133A patent/SE443491B/en not_active IP Right Cessation
Also Published As
Publication number | Publication date |
---|---|
SE443491B (en) | 1986-03-03 |
GB1604622A (en) | 1981-12-09 |
DE2823593C2 (en) | 1988-05-19 |
AU3643278A (en) | 1979-11-29 |
DE2823593A1 (en) | 1978-12-14 |
BE867612A (en) | 1978-11-30 |
SE7808133L (en) | 1980-01-26 |
AU522579B2 (en) | 1982-06-17 |
CH630229A5 (en) | 1982-06-15 |
JPS6337768B2 (en) | 1988-07-27 |
PH17653A (en) | 1984-10-23 |
FR2392601A1 (en) | 1978-12-29 |
JPS545031A (en) | 1979-01-16 |
FR2392601B1 (en) | 1987-09-11 |
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