GB1604622A - Use of polyoxyethylene derivatives as ectoparasiticides - Google Patents

Description

(54) USE OF POLYOXYETHYLENE DERIVATIVES AS ECTOPARASITICIDES (71) We, STAFFORD-MILLER LIMITED, of 166 Great North Road, Hatfield, Hertfordshire, a British Company, do hereby declare the invention, for which we pray at a patent may be granted to us, and the method by which it is to be performed, to be particularly described, in and by the following statement:- This invention relates to a method 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, and as adjunctive therapy to relieve pain or itch.

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 is the object of this invention to provide a new method employing safe and effective toxicants for lice and their ova.

According to the present invention there is provided a method of controlling ectoparasites or their ova which comprises applying to a substrate at least one polyoxyethylene derivative having an HLB of 2.5-13.5 and being an alkyl ether, aralkyl ether, alkyl ester or block polymer of polyoxyethylene.

For performing the method one can use an ectoparasiticidal or ovicidal toxicant composition comprising an active toxicant active against ectoparasites or their ova and an inert pharmaceutically acceptable carrier therefor, wherein the at least one derivative of polyoxyethylene is employed as the active toxicant.

The invention also provides a method of controlling ectoparasites or their ova and which involves applying with an active toxicant and adjuvant toxicant which is at least one polyoxyethylene derivative having an HLB of 2.5-13.5, and being an alkyl ether, aralkyl ether, alkyl ester or block polymer of polyoxyethylene. For this method one can use an ectoparasiticidal or ovicidal toxicant composition an active toxicant and an inert pharmaceutically acceptable carrier therefor, the composition additionally comprising the at least one derivative of polyoxyethylene.

The toxicants employed in the method of the instant invention are certain ethoxylates i.e., certain derivatives of polyoxyethylene [H(OCH2CHz)nOH]. The polyoxyethylene glycols per se have not been found to be pediculicidal or ovicidal.

For convenience, polyoxyethylene will hereinafter be referred to as POE and the number of repeating units (n) will be indicated in parenthesis where applicable.

It has been found that the 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 anesthetic 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, 4 p. 97 (1945) in a study of transpiration through insect cuticles, reported on the moisture loss of Rhodnius nymphs following treat? ment 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 effective 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 having 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 largekseries 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 Wigglesworth. We found efficacy only at concentrations several orders of magnitude greater than Maxwell and Piper. Where they reported that short ethylene oxide chain lengths were less effective than 46 moles of ethylene oxide, we discovered that the aryl alkyl ethoxylates were best at 1--3 motes of ethylene oxide, and that such compounds were good ovicides but mediocre pediculicides. Certain ethoxylates of aliphatic alcohols were much superior both as insecticides and as ovicides. Moreover, those most effective as toxicants were also found to be most effective as topical anesthetics.

The ethoxylates which we employ are well known as surface active agents and have been incorporated in many pharmaceutical and cosmetic preparations as such. For example, polyoxyethylene (4) lauryl ether is 5.5% of a washable coal tar ointment, polyoxyethylene (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.

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.

The POE derivatives which exhibit toxicant properties are the alkyl or aralkyl 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 hydropyhiliclipophilic balance (HLB) for good activity. In general, the HLB can be about 2.5 to 13.5. The alkyl ethers appear to exhibut maximum activity at an HLB in the neighborhood of 9, and the alkyl esters and block polymers at a lower HLB, excepting the alkyl diester, POE (8) 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 (1) ethylphenyl ether and POE (3) octylphenyl ether are examples of somewhat effective POE arylalkyl ethers.

Typical examples of the POE esters include POE (3) oleate, POE (2) laurate, POE (8) dilaurate, and the like. Typical examples of the block polymers include Poloxamer 401, Poloxamer 181 and the like.

One or more of the toxic ethoxylates 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 substantial detrimental effect on the pediculicidal 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 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 50 ZO 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 concentration of ethoxylate in the composition required to provide an effective 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 /O may be required to obtain an effective 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 24"C). Ten young adult 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 cnE 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 immediately plunged into the beaker containing the tap water. The patch is vigorously 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 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 30"C holding chamber.

Ovidical 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 30"C 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 pouring, the mesh patch is placed into the beaker, 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 removed and placed on paper toweling for one minute. The patch is then placed in a petri dish which 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.

In both the pediculicidal and ovicidal two minute immersion test, controls are run in identical manners to that described, with room temperature (240C) tap water substituted for the sample to be tested. The results of the tests reported are net results.

In the following tables, the results of pediculicidal and ovicidal testing for various toxicantso this invention are set forth. The materials were tested in undiluted form (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., polyethylene glycol (PEG) and other ethoxylates not within the scope of this invention are also set forth.

TABLE I 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 54 PEG 12 12 25 35 35 16 PEG 32 32 (1) 20 0 (2) .0 PEG 75 75 (1) 15 0(2) 14 TABLE II Pediculicidal and Ovicidal Activity for a Series of Alkyl Ethoxylate Ethers % Mortality Pediculicidal Ovicidal Compound HLB Neat C Neat C POE (1)lauryl ether 3.6 100 40 100(3) 100 POE (2) oleyl ether 4.9 100 10 100(3) 100 POE (2) stearyl ether 4.9 100 40 100 33 POE (3) oleyl ether 6.6 100 10 100 41 POE (3) tridecyl ether 8 100 20 100 100 POE (4) myristyl ether 8.8 100 35 100(3) 100 POE (5) oleyl ether 8.8 100 15 100 8.3 POE (4) lauryl ether 9.5 100 30 100 83 POE (6) tridecyl ether 11 100 30 100 0 POE (6.5) tridecyl ether 11.6 100 15 100 34 POE (6) lauryl thioether 11.6 100 20 100 0 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 13.6 100 20 100(3) 19 POE (10) lauryl thioether 13.9 15 5 30 0 POE (12) lauryl ether 14.5 20 5 100 0 POE (20) isohexadecyl ether 15.7 (1) 0 11(2) 2 POE (23) lauryl ether 16.9 (1) 69 (2) 3 TABLE III Pediculicidal and Ovicidal Activity for Some Arylalkyl Ethoxylate Ethers % Mortality Pediculicidal Ovicidal Compound HLB Neat C Neat C POE (1) octylphenyl ether 3.6 80 10 100(3) 66 POE (3) octylphenyl ether 7.8 15 5 82 (3) 34 POE (10) nonylphenyl ether 13.4 20 5 82 (3) 0 TABLE IV Pediculicidal and Ovicidal Activity for Ethoxylate Mono and Diesters % Mortality Pediculicidal Ovicidal Compound HLB Neat C Neat C POE (2) oleate 3.5 70 75 100(3) 14 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 (1) 40 (1) 23 POE (4) laurate 8.6 10 15 14 5.9 POE (4) sorbitol 9 5 20 77 21 septaoleate POE (8) dilaurate 10 80 10 23 38 POE(12)distearate 10.6 (1) 40 (1) 24 POE (20) stearate 15 (1) 0 (1) 0 POE(100)stearate 18.8 (1) 0 (1) 5 TABLE V Pediculicidal and Ovicidal Activity for Ethoxylate Block Polymers Having the General Structure Type Outlined for Each Section A) based on structure type

% Mortality 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 15 7 22 7 10.8 10 0 0 41 B) based on structure type

% Mortality Pediculicidal Ovicidal x y z HLB Neat C Neat C 3 30 3 3 10 0 70 0 13 67 13 4 - 10 0(2) 1.2 6 67 6 5 55 0 80 84 8 30 8 7 0 50 8.4 0 21 67 21 8 (1) 10 0(2) 4.5 13 30 13 15 5 20 0 17 38 54 38 15 (1) o (2) 19 122 47 122 27.5 (1) 40 (1) 4.5 C) based on structure type

% Mortality Pediculicidal Ovicidal x y HLB Neat C Neat C 18 2 2 5 20 79 0 12 2 3 45 0 73 (3) 11 21 7 3.5 30 0 100(3) 53 26 8 5 5 0 100(3) 49 13 4 7 0 20 58 0 26 24 13 85 0 - 20 8 7 16 0 20 0 28 Notes to Tables I-V (1) solid-could not be tested at 100% (2) 50% (w/w) in ethanol (3) pad noted to be coated with 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 (I) lauryl ether HLB=3.6 10 55 15 40 20 80 30 85 40 80 50 95 B. POE (2) oleyl ether HLB=4.9 10 30 15 10 20 35 30 15 40 20 50 35 C. POE (2) stearyl ether HLB=4.9 10 0 15 40 20 80 30 50 40 100 50 100 D. POE (3) oleyl ether HLB=6.6 15 10 20 15 30 60 40 70 50 100 60 100 E. POE (3) tridecyl ether HLB=8 10 25 15 20 20 95 30 95 40 100 50 100 F. POE (4) myristyl ether HLB=8 10 75 15 35 20 90 30 100 40 100 50 100 G. POE (4) lauryl ether HLB=9.5 10 15 15 30 20 55 30 80 40 85 50 60 H. POE (6) tridecyl ether HLB=l 1 10 40 15 30 20 65 30 75 40 35 50 55 Concentration, % (w/w) Mortality, % I. POE (6.5) tridecyl ether HLB= 1.6 15 15 20 25 30 5 40 35 50 30 60 60 J. POE (7) lauryl ether HLB=12.5 15 0 20 10 30 20 40 20 50 35 60 40 K. POE (9) lauryl ether HLB=13.6 15 20 20 25 30 15 40 25 50 70 60 50 L. POE (12) lauryl ether HLB=14.5 15 5 40 0 50 15 60 30 70 45 M. POE (23) lauryl ether HLB=16.9 15 0 20 0 30 0 40 0 50 0 60 5 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) Mortality, % A. POE (2) oleyl ether HLB=4.9 5 0 10 10 20 35 30 90 40 100 60 100 80 100 100 100 B. POE (4) lauryl ether HLB=9.5 5 5 10 5 15 45 20 100 80 100 90 100 100 100 The ovicidal activity of various compounds set forth in Table II as a function Df concentration was determined in a diluted system containing 25% isopropanol ind water q.s. The results are shown in Table VIII.

TABLE VIII Concentration, % (wAw) Mortality, % A. POE (1) lauryl ether HLB=3.6 1 100 3 100 5 100 7 100 9 100 B. POE (3) tridecyl ether HLB=8 10 100 15 100 20 100 30 100 40 100 C. POE (4) myristyl ether HLB=8.8 10 27 15 100 20 100 30 92 40 100 50 100 D. POE (6) tridecyl ether HLB=1 1 10 0 15 0 20 16 30 44 40 14 50 3 E. POE (12) lauryl ether HLB=14.5 15 0 30 0 40 0.2 50 5 60 2 70 0 F. POE (23) lauryl ether HLB=16.9 15 3 20 10 30 4 40 5 50 0 60 5 Table IX reflects the resulting pediculicidal and ovicidal activity of a 15% (w/w) concentration of POE (4) lauryl ether with variation of isopropanol and water content.

TABLE IX % Mortality % w/w Isopropanol % w/w Water Pediculicidal Ovicidal 25 60 30 83 20 65 30 21 15 70 15 19 10 75 15 15 5 80 95 100 1 84 20 100 0 85 45 10 As can be seen from Table IX, the 15% concentration of POE (4) lauryl ether exhibited synergistic pediculicidal activity when the isopropanol was about 1-5%.

The most effective toxicants of 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 duration of about 0.54 hours (average four tests was two hours) in a modified Cole and Rose rabbit eye irritiation test (J. Lab. & Clin. Med. 15:239, 1929). In contrast, POE (23) lauryl ether did not exhibit any activity in the same test. In general, the preferred alkyl ethers exhibit anesthetic, analgesic or antipruritic activity at concentrations of at least 1% and are preferably employed for this purpose at about 1-10%.

The miticidal activity 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 depression slide containing ten adult mixed sex mites, Psoroptes equi var. cuniculi. The slide is positioned at a distance of ten inches horizontally and four inches below the activator of 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 shaken until homogeneous and placed in the mechanical pump spray device. The primed activator 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. Miscroscopic observations are noted at 0, 1, 3, and 24 hours post treatment. Controls are run in an identical manner as that described using water or the diluting agent, and net mortality results are reported.

Table X shows the miticidal activity of a 50% (w/w) concentration of the named compounds in isopropanol.

TABLE X Compound HLB Miticidal Activity, % POE(l)laurylether 3.6 100 POE (2) oleyl ether 4.9 80 POE (4) myristyl ether 8.8 L00 POE (4) lauryl ether 9.5 100 POE (6) tridecyl ether 11 90 POE (10) oleyl eether 12.4 100 POE(12) lauryl ether 14.5 100 As noted, various end use formulations can be prepared. Some typical formulations are set forth and the amounts recited are percentages by weight: Liquid pediculicide and ovicide suitable for mechanical spray application or inunction POE (8) dilaurate 15 Isopropanol 60 Water 25 Liquid pediculicide and ovicide 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 10 POE (1) lauryl ether 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 (4) lauryl ether 20 Water 72 Isobutane 8 Pediculicidal and ovicidal gel POE (2) oleyl ether 15.0 Isopropanol 25.0 Carbomer 940 0.5 Triethanolamine 0.38 Water 59.12 Illustrative Examples will now be given of the use of the compounds with adjunctive toxicants. In each instance there is first given the formulation and activity of a composition without adjuvant.

% w/w % Pediculicide % Ovicide Isopropanol 25 75 Phenyldimethicone 25 cs 9 Polysorbate 80 7 Water 59 Isopropanol 25 100 POE (4) lauryl ether 15 Phenyldimethicone 25 cs 9 Polysorbate 80 . 7 Water 44 Isopropanol 25 10 60 Dimethicone 100 cs 5 Polysorbate 80 7 Water 63 Isopropanol 25 90 100 POE (4) lauryl ether 15 Dimethicone 100 cs 5 Polysorbate 80 7 Water 48 Isopropanol 25 30 83 POE (4) lauryl ether 15 Water 60 Isopropanol 100 Cs 25 100 93 Dimethicone 100 cs 5 POE (4) lauryl ether 15 Polysorbate 80 7 Water 48 Various changes and modifications can be made: the various embodiments disclosed herein are for the purpose of further illustrating the invention but are not intended as limiting. Throughout this specification and claims, all temperatures are in degrees Centigrade and all parts and percentages are by weight unless otherwise indicated.

WHAT WE CLAIM IS: 1. A method of controlling ectoparasites or their ova which comprises applying to a substrate at least one derivative of polyoxyethylene, the derivative having an

**WARNING** end of DESC field may overlap start of CLMS **.

Claims (21)

**WARNING** start of CLMS field may overlap end of DESC **. 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 (4) lauryl ether 20 Water 72 Isobutane 8 Pediculicidal and ovicidal gel POE (2) oleyl ether 15.0 Isopropanol 25.0 Carbomer 940 0.5 Triethanolamine 0.38 Water 59.12 Illustrative Examples will now be given of the use of the compounds with adjunctive toxicants. In each instance there is first given the formulation and activity of a composition without adjuvant. % w/w % Pediculicide % Ovicide Isopropanol 25 75 Phenyldimethicone 25 cs 9 Polysorbate 80 7 Water 59 Isopropanol 25 100 POE (4) lauryl ether 15 Phenyldimethicone 25 cs 9 Polysorbate 80 . 7 Water 44 Isopropanol 25 10 60 Dimethicone 100 cs 5 Polysorbate 80 7 Water 63 Isopropanol 25 90 100 POE (4) lauryl ether 15 Dimethicone 100 cs 5 Polysorbate 80 7 Water 48 Isopropanol 25 30 83 POE (4) lauryl ether 15 Water 60 Isopropanol 100 Cs 25 100 93 Dimethicone 100 cs 5 POE (4) lauryl ether 15 Polysorbate 80 7 Water 48 Various changes and modifications can be made: the various embodiments disclosed herein are for the purpose of further illustrating the invention but are not intended as limiting. Throughout this specification and claims, all temperatures are in degrees Centigrade and all parts and percentages are by weight unless otherwise indicated. WHAT WE CLAIM IS:

1. A method of controlling ectoparasites or their ova which comprises applying to a substrate at least one derivative of polyoxyethylene, the derivative having an

HLB of 2.5-1 3.5 and being an alkyl ether, aralkyl ether, alkyl ester or block polymer of polyoxyethylene.

2. A method according to Claim 1 wherein the alkyl ether or ester moiety of the derivative contains 12 to 24 carbon atoms.

3. A method according to Claim 2 wherein the alkyl ether or ester moiety contains 12 to 20 carbon atoms.

4. A method according to any one preceding claim wherein the derivative is an alkyl ether.

5. A method according to Claim 4 wherein the derivative is polyoxyethylene (3) tridecyl ether, polyoxyethylene (4) myristyl ether, polyoxyethylene (2) oleyl ether, or polyoxyethylene (1) lauryl ether.

6. A method according to Claim 4 wherein the derivative is polyoxyethylene (4) lauryl ether.

7. A method according to any one of Claims 4 to 6 wherein the alkyl ether is employed at a concentration of at least 1% whereby topical anesthetic, analgestic or antlpruritic activity is present.

8. A method according to Claim 7 wherein the concentration is 1-1 0%.

9. A method according to any one preceding claim wherein the derivative is employed in combination with an inert pharmaceutically acceptable carrier.

10. A method according to Claim 9 wherein the carrier is an aqueous carrier.

11. A method of controlling ectoparasites or their ova by applying to a human or animal host an active toxicant, which comprises applying with said active toxicant an adjuvant toxicant which is at least one derivative of polyoxyethylene, the derivative having an HLB of 2.5-13.5 and being an alkyl ether, aralkyl ether, alkyl ester or block polymer of polyoxyethylene.

12. A method according to Claim 11 wherein the alkyl ether or ester moiety of the derivative contains 12 to 24 carbon atoms.

13. A method according to Claim 12 wherein the alkyl ether or ester moiety contains 12 to 20 carbon atoms.

14. A method according to any one of Claims 11 to 13 wherein the derivative is an alkyl ether.

15. A method according to Claim 14 wherein the derivative is polyoxyethylene (3) tridecyl ether, polyoxyethylene (4) myristyl ether, polyoxyethylene (2) oleyl ether, or polyoxyethylene (1) lauryl ether.

16. A method according to Claim 15 wherein the derivative is polyoxyethylene (4) lauryl ether.

17. A method according to any one of Claims 14 to 16 wherein the alkyl ether is employed at a concentration of at least 1% and wherein topical anesthetic, analgestic or antipruritic activity is present.

18. A method according to Claim 17 wherein the concentration is 1-1 0%.

19. A method according to any one of Claims 11 to 18 wherein the derivative is employed in combination with an inert pharmaceutically acceptable carrier.

20. A method according to Claim 19 wherein the carrier is an aqueous carrier.

21. A method of controlling ectoparasites or their ova substantially as herein described and which uses a polyoxyethylene derivative.