1 604 853 10 PATENT SPECIFICATION «= 1 604 853 (21) Application No. 32135/77 (22) Filed 18 Oct. 1977 (as) G1) Convention Application No 802013 (32) Filed 31 May 197 in (33). United States of America (US) (44) Complete Specification Published 16 Dec. 1981 (51) INT. CL? A6IK 31/80 AOIN 55/00 (52) Index at Acceptance ASB 170 353 35Y 38Y 391 H ASE 202 236 503 509 510 A (72) Inventors: MYRON JORDAN LOVER ARNOLD JACK SINGER DONALD MICHAEL LYNCH WILLIAM EDWARD RHODES IIL (54) USE OF SILOXANES AS ECTOPARASITICIDES (71) We, STAFFORD MILLER LIMITED, of 165 Great North Rood, Hatfi Hertfordshire, a British Company, do hereby declare the invention, for which we pray that 2 patent may be granted to us, and the method by which itis to be performed, to be particularly described, in and by the following statement:- ‘This invention relates 10 ectoparasiticidal toxicants and a method of controlling ectoparasites. More particularly, the invention relates to the use of linear siloxane polymers as toxicants for lice and/or their ova. "There are only a relatively few pediculicides which are commercially available today. The most popular pediculicidal toxicants are Lindane (gamma benzene hexachloride), Malathion_[(S-12-dicarbethoxyethy!)-0,0-dimethyl phosphorodithioate], synergized yrethrins and Cuptex (a combination of tetrahydronaphthalene, copper oleate and Eeetone, the acetone not asserted t0 be active). Because of increased concern about the Overall safety of some of the known ectoparastic toxicants, the search for new, safe and effective pediculicides has intensified recently. Many species of insects encase their ova in protective sheaths which are impregnable to most toxicants. The “gestation” period of the egg is often relatively long in comparison to the life eyele ofthe adult forms. ‘Thus, an agent effective only against adults must persis for the lifetime of the developing ovum or must be reapplied as successive hatching occurs. Ttis the object ofthis invention to provide a new safe and effective method for controlling 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 linear Siloxane polymer having a viscosity of less than 20,000 centistokes. Such @ method can be carried out using an ectoparasticidal or ovicidal toxicant composition comprising an active toxicant active against ectoparasites or their ora and an fnert pharmaceutically acceptable carrier therefor, the active toxicant being at least one linear siloxane polymer having a viscosity of less than 20,000 centistokes. "The method may also be carried out using an ectoparasitical or ovicidal toxicant composition comprising an active toxicant and an inert pharmaceutically acceptable carrier, ‘Wherein said composition further contains at least one linear siloxane polymer having 2 Viseosity of less than 20,000 centistokes as an adjunct toxicant, This composition can be Used in’ method of controlling ectoparasites ot their ova provided by the invention and comprising applying to substrate an active toxicant in an inert pharmaceutically feceptable carrier, wherein the active toxicant is applied with at least one linear siloxane polymer having a viscosity of less than 20,000 centistokes as an adjuvant toxicant. iit has been found that the linear siloxane polymers exhibit pediculicidal andor ovicidal activin Th onan employed in he method of this iventon ree nx sloxane palmer having a viscosity of ese than 20,00 centitoke, preferably less than 10,00 centistokes and most preferably 1,000 centistokes or less. The polymers are characterized by repeating units 10 1510 1s 20 25 30 35 40 45 30 55 60 1,604,853 SiO in which each R is individually alkyl or ay. In most commercially valle pélysiloxanes, the R groups are usually methyl or a combination of methyl and phenyl, i.e, Gimethicones (CTFA official name for dimethylpolysiloxanes) and phenyldimethicone. The instant toxicants include simethicone which is 2 mixture of fully methylated linear siloxane polymers containing 93-99% dimethicone units stabilized with trimethylsiloxy [(CH,) SiO-} end blocking units and 4-4.5% silicon dioxide. Simethicone is widely used” as_ an antiflatulent. The polysiloxanes used in this invention are relatively inert pharmacological- ly, are chemically stable and are non-corrosive. ‘One or more of the toxic polymers can be incorporated into an active toxicant composition which canbe in the form of liquid, powder, lotion, cream, gel or sero! 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 inet vo 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 active polymers are incorporated into the toxicant composition used to treat the substrate (human or animal) in heed 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 a least 50% ofthe 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 case of the ova. The minimum concentration of polymer required to provide an effective toxic amount varies considerably depending on the particular polymer, the particular inert pharmaceutically acceptable carrier being employed and any other ingediets which represent. Thus, ong cas a 10% concentration may sfc, while in other cases, concentrations as high as 25% may be required to obtain an effective toxic dose. Usually, the polymer will be used in concentrations of about 5 to 100% and most preferably al concentrations of about 10 to 100%. ‘The instant polymers can also be employed as an adjunct toxicant in a preparation which otherwise exhibits pediculcidal and/or ovicidal activity. In such preparations, the term “effective toxic dose” means that amount which will increase the mortality rate by atleast about 20% in the standard immersion tests. “The two minute immersion tests 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 20°C). Ten young adult male and ten young adult female lice (Pediculus humanus corporis) ofthe same age group and from the same stock colony are placed on a 2x2 cm coarse mesh path. The sample to be tested, maintained at room fempeatre,shaten unl homogeneous and paced it a ml baker. The mah patch fs pla ced 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 Daich is vigorously agitated every fen seconds and afer one minute the patch removed 4nd placed on paper toweling. The lice are then transferred to a 4x4 cm black cordut cloth patch and this point of time is considered zero hours. Thereafter, the corduroy pat. is placed in a petri dish which is covered and stored in a 30°C holding chamber. Wvicidal activity: 15 adult, 5 to 10 day old, female lice (Pediculus humanus corporis) are placed on a 2x2 em nylon’ mesh patch which is placed on a petri dish, covered and aintained in an incubator at 30°C for 24 hours. The adult lice are then removed and the ‘number of plump, viable eges and shriveled non-fertle 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 fn placed on pape oweling for one minute, The paths then placed in a pet ish 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 unfatched eggs is noted, In both the pediculicidal and ovicidal two minute immersion tests, controls are run in identical manner to that described with room temperature (24°C) tap water substituted for the sample to be tested. The results of the tests reported are net results ‘The pediculicidal and ovicidal activity of various toxicants of the instant invention were tested in the two minute immersion tests described above. The ratings set forth represent the percent mortality observed. The polymers were evaluated in undiluted form (UD) or in 2 ebmioination (C)-containing 15 (ww) percent polymer, 25% isopropanol and 60% aqueous cartier. 10 15 28 30 35 45 50 35 601,604,853 % Mortality Viscosity in Pediculicidal Ovicidal Compound centistokes ub iG up c Phenyldimethicone 2s 100100 94 uw Dimethicone 100 100 = 1001002 350 10-100 10035 300 10 = 10010082 i 1,000 10010010038 Dimethicone 12,000 100 = 100100 0 “The pediculcidal activity of various polysiloxanes asa function of concentration in 25% isopropanol, 7% Polysorbate 80 emulsifier, and water Q-S. was studied and the results are shown below. Phenyldimethicone 22.5 centistokes % wiW % Mortality 15 10 B 100 i 95 9 80 7 8 5 0 3 0 1 0 Dimethicone, 100 centistokes Se wiW % Morality 15 100 B 95 a 95 3 100 7 90 5 10 3 5 1 5 Dimethicone, 350 centistokes ww % Morality 15 100 B 100 a 100 9 100 7 95 5 85 3 % 1 0 Dimethicone, 900 centistokes % WiW % Mortality 15 100 B 100 H 100 9 85 7 0 5 20 3 20 1 04 1,604,853 4 Dimethicone, 1000 centistokes % Morality 15 100 5 B 100 5 1 95 9 85 7 0 5 65 10 3 40 10 i 0 Dimethicone, 12,000 centistokes ww % Mortality 15 15 15 100 B 85 iL 40 9 10 20 7 75 20 5 0 3 0 1 0 25 _,As can be seen ftom the foregoing, the viscosity range of 100 100 centistokes forthe 25 dimethicones tested exhibit the highest pediculicidal activity below a. 15% W/W concentration. The one phenyldimethicone adivatve tested dpleysequalnt sti) tut at a much lower viscosity value. ‘As noted above, various end use formulations can be prepared. Some typical 30 formulations are sei forth below and the amounts recited are percentages by weight. 30 EXAMPLES Gel 35 35 Isopropanol 25.0 Dimethicone, 100 centistokes 15.0 Sorbitan monolaurate Ts Carbomer 940 30 40 Triethanolamine 40 40 Water 45.5 Aerosol Spray 45° Ethanol 70.0 45 Phenyldimethicone, 22.5 centistokes 15.0 Isobutane 15.0 Powder 50 50 Tale 90.0 Dimethicone, 900 centistokes 10.0 Quick breaking aerosol foam _— = ide . the elycerides of 7 fono and diglycerides from the glycerides of ilible fats — 8.0 Isopropanol 25.0 Dimethicone, 350 centistokes 1.0 60. Glycerine 3.0 60 Water 410 Isobutane 8010 15 20 25 30 35 40 45 30 55 60 1,604,853 Stick Sodium stearate Ethanol Phenyldimethicone, 22.5 centistokes Cream Beeswax Dimethicone, 100 centistokes Cetyl alcohol Mineral oil Glycerlymonostearate Sorbitan monoaurate Isopropanol Xanthan gum Sodium borate, pentahydrate Water 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. % ww % Pediculicide sopropanol 5 10 Dimethicone 100 cs Water Polysorbate 80 Isopropanol 100 Gleoy sarcosine Dimethicone 100 cs Water Isopropanol 5 Phenyldimethicone 25 es Polysorbate Water sm) R Ree Isopropanol 25 100 POE (4) lauryl ether Phenyldimethicone 25 cs Polysorbate Water Isopropanol 10 Dimethicone 100 es Polysorbate 80 Water BRR BwvR EWS Isopropanol POE (2) lauryl ether Dimethicone 100 cs Polysorbate 80 Water Isopropanol 15 Phenyldimethicone 5 es Polysorbate 80 Water wiv % Pediculicide cRavests tte 29.05 % Ovicide 8 100 o % Ovicide 10 20 25 30 35 40 45 50 35 604S. 6 1,604,853 6 % wiw — % Pediculicide % Ovicide Isopropanol 25 100 2Methyl2,4- pentanediol 15 Phenyldimethicone 25 3 5 s Polysorbate 80 7 Water 4 10 Ssopropanol 25 30 3 10 POE (2) lauryl ether 1s Water o Isopropanol 25 100 93 15. Dimethicone 100 es 5 1s POE (4) lauryl ether 1s Polysorbate T Water 8 20 Isopropanol 25 1s 9 20 2 ety ntandiol 13 ater Co 25 Isopropanol 5 100 0 28 Dimmethicone 100 es 5 2Methyl2.4- entanediol 15 lysorbate 80 7 30. Water 48 30 Various changes and mosfeatons ean be made: the various embodiments dcased 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 35 Centigrade and-all parts and percentages are by weight unless otherwise indicated. 35 IAT WE CLAIM IS: i i 1. A method of controlling ectoparasites or their ova which comprises applying to a substrate ‘at least one near ‘ioxane polymer having 4 wcosity Of les than 20.000 centistokes. 40 2.""A method according to Claim 1 wherein the polymer has a viscosity of less than 40 10,000 centistokes. 3A method according to Claim 2 wherein the polymer has a viscosity of 1,000 centistokes or less. 4.” A-method according to any one of Claims 1,2 or 3 wherein the polymer is 45 dimethicone or phenyldimethicone. 5. A method according to any one of Claims 1,2 or 3 wherein the polymer is contained in’simethicone. 6. A method according to any one preceding claims wherein the polymer is employed in combination with an inert pharmaceutically acceptable cartier. 50 7. A method according to Claim 6 wherein the carrier is aqueous. 50 & A method of controling ectoparasites or their ova by applying to a substrate an active toxicant in an inert pharmaceuticelly acceptable carrier, wheréin the active toxica applied with at least one linear siloxane polymer having a viscosity of less than 20,000 centistokes as an adjuvant toxicant. 35 “"9." A method according to Claim 8 wherein the polymer has a viscosity of less than 55 10,600 centistokes. 10. A method according to Claim 9 wherein the polymer has a viscosity of 1,000 centistokes or less. {L.A method according to any one of Claims 8 to 10 wherein the polymer is 60 dimethicone or phenyldimethicone 60 “TA method according to any one of Claims 8 to 10 wherein the polymer is contained in simethicone. 13. A method according to any one of Claims 8 to 13 wherein the carrier is aqueous, 14, A method of controlling ectoparasites of their ova substantially as herein described 65 and which uses a linear siloxane polymer having a viscosity of less than 20,000 centistokes. 65,1,604,853 MARKS & CLERK, Chartered Patent Agents, Agents for the Applicants td oe Maj Sy fb Cn Ping Copan mb Code, Say 18 ate Fs Oe tn Duly ans WEA TA be