Liquid spreading composition with ectoparasiticidal activity, a method and use thereof for combating ectoparasites in human and veterinary medicine, as well as in agricultural, horticultural and/or garden environments

Abstract

The present invention relates to a liquid spreading composition with ectoparasiticidal activity. The invention also relates to a method and use of such a liquid spreading composition for combating ectoparasites in human and veterinary medicine, as well as in agricultural, horticultural and/or garden environments. The composition comprises at least one emollient ester and isohexadecane, wherein the weight ratio of said at least one emollient ester to isohexadecane is within 1:9 to 7:3. The invention improves the spreading properties of a composition enabling it for an efficient delivery of an active substance or substances over the surface of the host on which it is applied. The spreading composition may also be used alone for an efficient ectoparasiticidal treatment in human and veterinary medicine, as well as for combating ectoparasites in agricultural, horticultural and/or garden environments. With at least one additional agent the spreading composition may also be used in cosmetic, as well as for pest control, including insect and rodent control.

Claims

1. An insecticidal composition for combating ectoparasites comprising: an ectoparasiticidal liquid spreading composition comprising between 3.5% and 50% by weight isopropyl myristate and between 1.5% and 68% by weight isohexadecane, and a spraying agent; wherein the ectoparasiticidal liquid spreading composition does not comprise silicones.

2. The composition according to claim 1, wherein the ectoparasiticidal liquid spreading composition further comprises at least one surfactant in an amount of up to 10% by weight.

3. The composition according to claim 1, wherein the ectoparasiticidal liquid spreading composition further comprises at least one additional agent selected from the group consisting of an inert pharmaceutically or cosmetically acceptable carrier, fragrance, insecticide, or insect growth regulator.

4. The composition according to claim 1, wherein the ectoparasiticidal liquid spreading composition further comprises at least one additional agent selected from the group consisting of an insecticide and an insect growth regulator.

Description

DETAILED DESCRIPTION OF THE INVENTION

(1) Without further elaboration, it is believed that one skilled in the art can, using the preceding description, utilize the present invention to its fullest extent. The following preferred specific embodiments and tests are, therefore, to be construed as merely illustrative, and not limitative of the remainder of the disclosure in any way whatsoever.

Example 1

(2) A composition of the present invention has been prepared containing: isopropyl myristate (IPM) in the amount of 50% by weight; isohexadecane in the amount of 48% by weight; polyoxyethylene (40) sorbitol oleate in the amount of 1.8% by weight; and fragrance in the amount of 0.2% by weight.
Spreading Tests

(3) The following tests have been performed to measure and compare spreading properties of the composition prepared according to Example 1 (N) with Isopropyl Myristate (IPM) and Diethylene Glycol Monoethyl Ether (DGME), known from the state of art as spreading agents. All compositions acted as a carrier of an active insecticidal substance: clove oil (an insect repellent), S-Methoprene (biochemical pesticide interfering with an insect's lifecycle and preventing it from reaching maturity or reproducing) or Etofenprox (neurotoxic insecticide, which disturbs insect nervous systems).

(4) Table I shows the results of these tests were performed by applying 5 μl drop of the composition in the middle of a glass plate at 25° C. Area (S) of the surface (cm.sup.2) covered by the composition has been measured after 30 min. As an alternative spreading indicator one might also employ Emollient Skin Spreading Factor as defined by Croda (Croda DS-128, Emollient Skin Spreading Factor (1998)).

(5) TABLE-US-00001 TABLE I Spreading properties of compositions acting as active substance carriers Main ingredients S [cm.sup.2] Comp. (volume fraction [%] or mass 5 μl/30 min No. fraction [% by weight]) glass surface 1. Clove oil (20%) + IPM (80%) 0.6 2. Clove oil (20%) + DGME (80%) 0.6 3. Clove oil (20%) + N (80%) 12.0 4. S-Methoprene (10%) + IPM (90%) 0.6 5. S-Methoprene (10%) + DGME (90%) 0.7 6. S-Methoprene (10%) + N (90%) 22.0 7. Etofenprox (40% by weight) + 0.6 IPM (60% by weight) 8. Etofenprox (40% by weight) + 0.5 DGME (60% by weight) 9. Etofenprox (40% by weight) + 7.0 N (60% by weight) 10. IPM (100% by weight) 0.6 11. DGME (100% by weight) 0.6

(6) Test results in Table I clearly indicate excellent spreading features of the composition of the present invention which in each case significantly increased the area available for delivery of an active substance.

(7) The following tests have been performed to measure and compare spreading properties of the composition prepared according to Example 1 with ectoparasiticidal compositions known from the state of art. As in the previous tests 5 μl drop of the composition has been applied in the middle of a glass plate at 25° C. Area of the surface (cm.sup.2) covered by the composition has been measured after 30 min.

(8) TABLE-US-00002 TABLE II Spreading properties of the composition according to the invention compared to known ectoparasiticidal compositions (pediculosis treatment) Composition Main ingredients S [cm.sup.2] (Manufacturer/ (volume fraction [%] or mass 5 μl/30 min Distributor) fraction [% by weight]) glass surface Composition of the IPM (50% by weight) + 46.6 invention (Example 1) isohexadecane (48% by weight) Nyda spray (Siroscan) Dimethicone (92%) 3.5 Hedrin 4% lotion cyclomethicone D5 (96%) + 2.8 dimeticone (Thornton& dimethicone (4%) Ross) Hedrin Treat&Go lotion Octane-1,2-diol + PEG-6 caprylic/ 2.3 (Thornton& Ross) capric glycerides + H.sub.2O Hedrin Treat&Go spray Octane-1,2-diol + PEG-6 caprylic/ 2.0 (Thornton& Ross) capric glycerides + H.sub.2O Hedrin Once Spray Gel Dimethicone + PEG/PPG 1.3 (Solpharm) dimethicone-co-polymer + SiO.sub.2 Lyclear spray Mineral oil + dimethicone 1.3 (Chefaro) Paranit Mineral oil surfactant 0.3 (Medgenix)

(9) Test results in Table II clearly also indicate excellent spreading features of the composition according the present invention.

(10) Ectoparasiticidal Tests

(11) During further research the inventors tested ectoparasiticidal properties of the composition according the present invention alone (i.e. with no additional active ectoparasiticidal agent).

(12) Ectoparasiticidal Tests Against Body Louse Eggs

(13) Body louse eggs were obtained by providing actively laying adult lice with a close meshed nylon substrate, in place of the normal cotton corduroy substrate, over a 48 hour period. At the end of this period the insects were removed and the gauze cut into appropriately sized smaller pieces. The small gauze pieces were randomly allocated to plastic Petri dishes in advance of the test.

(14) Each square of gauze with eggs on (4 cm.sup.2) was then massaged with a close containing approximately 5 ml of the tested composition. This was performed on the dry gauze so that the products could be used neat and could be massaged in. Both the product and control were left on the gauze for the allotted exposure time of 60 minutes.

(15) Gauze squares bearing the eggs were then incubated under normal maintenance conditions (30±2° C. and 50±15% relative humidity) for the remainder of the test period. At the end of exposure period the insects and gauze for the composition according to the present invention were rinsed using 500 ml of warm (35° C.) tap water poured through and over the gauze squares. They were then blotted dry using medical wipe tissue and incubated under normal maintenance conditions in clean plastic Petri dishes of the appropriate size until the results were recorded. The same testing procedure was applied for the comparative example.

(16) Hedrin Once Spray Gel test gauzes bearing eggs were then shampooed off using a 1:14 frequent wash shampoo. They were then rinsed through using 500 ml of warm (35° C.) tap water poured through and over the gauze squares. They were then blotted dry using medical wipe tissue and incubated under normal maintenance conditions in clean plastic Petri dishes of the appropriate size until the results were recorded.

(17) After the treatments had been washed off, the eggs were incubated at 25° C. and 75% relative humidity (RH) until all unaffected eggs had hatched between 10-14 days after testing. The eggs were then observed for their state of development.

(18) Tests results are listed in Table III, wherein ectoparasiticidal has been calculated using the following egg development categories with regard to degree of penetration of the insecticide:

(19) “Hatched”: louse eggs that have not been penetrated by the insecticide so that the embryo inside the egg developed and hatched normally.

(20) “Half-hatched”: eggs penetrated by a small amount of insecticide, yet amount insufficient to kill the emerging insect prior hatching; or the emerging insect absorbed sufficient amount of insecticide from the outside of the eggshell to be killed it but only after it has partially emerged from the shell.

(21) “Dead”: eggs in which the embryo apparently completed its development but has not emerged from the eggshell, as well as eggs in which sufficient amount of insecticide was absorbed within outer layers of the eggshell between the chorionic membranes that surround the embryo and the eggshell cap, so that the insect was killed during hatching but before it was capable of lifting the lid from the eggshell.

(22) “Undeveloped”: eggs that failed to develop correctly or at all. This could be identified because at the time of testing the young embryos appear amorphous inside the transparent eggshell. When the developing embryo is about 48 hours old it starts to develop a small pigmented spot at the cap end of the shell. This spot will develop to become the eye of the louse and is referred to as the “eyespot”. If a toxic material is capable of entering the eggshell and penetrating the chorionic membrane it can kill the young embryo before it has developed to the point of showing the eyespot. In some cases the embryo may develop only to the point of showing an eyespot but in these cases the spot is misshapen or may even be at the wrong end of the eggshell.

(23) Percentage mortality has been calculated using the formula:
Mortality=(Half-hatched+Dead+Undeveloped)/(No of eggs in a sample)

(24) TABLE-US-00003 TABLE III Ectoparasiticidal properties of the composition according to the invention against body louse eggs compared to Hedrin Once Spray Gel and water control Sample No of eggs Eggs Mortality Formulation No in a sample Hatched Half-hatched Dead Undeveloped [%] Water 1. 119 101 1 2 15 (control) 2. 118 114 1 1 2 3. 97 70 4 2 21 Total: 334 285 6 5 38 14.67 Composition of 1 115 0 0 8 107 the invention 2 99 0 0 1 98 (Example 1) 3 131 0 0 6 125 Total: 345 0 0 15 330 100.00 Hedrin Once 1 111 1 0 0 110 Spray Gel 2 106 1 0 0 105 (Solpharm) 3 106 2 0 0 104 Total: 323 4 0 0 319 98.76

(25) As illustrated in Table III, the composition according to the present invention alone was unexpectedly the most effective (100% mortality) at killing louse eggs after a 60 minute exposure compared with Hedrin Spray Gel (98.76% mortality) and a water control (14.67% mortality).

(26) Ectoparasiticidal Tests Against Adult Body Lice

(27) Head lice, Pediculus capitis, were obtained from individual volunteers. On each day of testing all of the samples were evaluated once. For each of the tests performed on the same day all of the lice were obtained from the same individual patient so there was an internal consistency within a batch of test replicates. As only one replicate test of formulation was performed on any one day there could have been some variation between tests conducted on different days. However, this would have represented the normal variation of head lice likely to be encountered in the community and any variation of response would be representative of the range of response likely to be encountered in consumer use.

(28) Lice were collected using plastic louse detection combs and transported to the laboratory within 2 hours. Lice were counted into batches that were provided with squares of nylon gauze, as a substrate upon which to stand, and each batch allocated to a marked 55 mm plastic Petri dish.

(29) For the test procedure an aliquot of approximately 5-10 ml of the formulation was poured into the base of a clean 55 mm plastic Petri dish. The gauze bearing the lice was immersed in the fluid for 10 seconds, during which time the gauze was turned at least twice to ensure removal of air bubbles. After removal from the fluid the gauze and insects were lightly blotted to remove excess fluid and returned to a 5.5 mm marked Petri dish. The same procedure was repeated for the other replicate gauze squares in that batch.

(30) Gauze squares bearing the lice were then incubated under normal maintenance conditions (30±2° C. and 50±15% relative humidity) for the remainder of the test period.

(31) At the end of the 60 minutes exposure period, the insects and gauze were washed with water and then left for a further three minutes. They were then washed again using a bland toiletry shampoo diluted one part shampoo with fourteen parts water (FWS 1:15) after which they are rinsed using 500 ml of warm (35° C.) tap water poured through and over the gauze squares. They were then blotted dry using medical wipe tissue and incubated under normal maintenance conditions in clean plastic Petri dishes of the appropriate size until the results are recorded.

(32) Tests results are listed in Table IV, wherein ectoparasiticidal activity has been calculated using the following lice categories:

(33) “Immobile”: louse shows no signs of movement; it is presumably dead.

(34) “Moribund”: louse retains some movement at the time the results are scored; such movements can range from complete physical immobility, with just small observable gut movements, through minor twitches of limbs, antennae or other appendages, to insects that are nearly able to crawl but are sufficiently lacking coordination, so that they could considered as incapable of continued survival; lice in this category were also classified in the overall mortality as being no longer effectively alive.

(35) “Alive”: louse appears to crawl normally and it is expected, given the opportunity to feed, to be able to live normally.

(36) TABLE-US-00004 TABLE IV Ectoparasiticidal properties of the composition according to the invention against head lice adults Readings overnight after wash off Mortality Formulation Replicate Total Alive Moribund Immobile [%] Composition of 1 15 0 0 15 100 the invention 2 15 0 0 15 100 (Example 1) Water 1 15 15 0 0 0 (Control) 2 15 15 0 0 0

(37) As illustrated in Table IV, the composition according to the present invention alone produces 100% efficacy against lice of mixed development stages when compared to water control. The overnight reading after 60 minutes exposure shows 100% mortality for the two test replicates with the controls all still alive.

Example 2

(38) A composition of the present invention for combatting mammals ticks has been prepared containing: isopropyl myristate (IPM) in the amount of 3.5% by weight; isohexadecane in the amount of 1.5% by weight; and 1,1,1,2-tetrafluoroethane (HFC-134A) in the amount of 95% by weight as a spraying agent.

(39) The composition has been sprayed directly on ticks attached to dog's skin. Ticks were frozen by the composition and simultaneously covered by the film containing IPM and isohexadecane spread over their bodies. Frozen ticks were then removed from the skin with tweezers. Removed ticks were dead, with no recovery effect observed (100% mortality). Positive control composition prepared pursuant to teachings of publication U.S. Pat. No. 4,834,967 (Example 1, a halogenated hydrocarbon aerosol refrigerant) showed over 20% of recovery after the treatment.

Example 3

(40) A spot-on composition of the present invention with insect growth regulator (IGR) for controlling of fleas on cats has been prepared containing: isopropyl myristate (IPM) in the amount of 30.8% by weight; isohexadecane in the amount of 68% by weight; polyethylene glycol (30) hydroxystearate (as a surfactant) in the amount of 0.2% by weight; and pyriproxyfen (as an insect growth regulator) in the amount of 1% by weight.

(41) The composition was applied in a dosage of 0.5 ml on skin of a cat and provided no adverse reaction based on cooling or sticky effect (it spreads easily and do not leave the skin greasy and sticky).

(42) As shall be obvious to those skilled in the art all compositions of the present invention may be conveniently converted into a suitable dosage form together with at least one excipient or adjunct and, if appropriate, in combination with one or more additional active ingredients. The following dosage forms are therefore merely illustrative, and not limitative of the remainder of the disclosure in any way whatsoever.

Example A—Ampoules

(43) Composition prepared according to Example 1 is filled into ampoules and the ampoules are sealed under sterile conditions. Each ampoule contains 20 ml of the composition. Ampoules may be used for a spot-on or pour-on treatment of pediculosis.

Example B—Aerosol

(44) Composition prepared according to Example 1 is filed into a pressurised container with a suitable propellant (e.g. propane-butane dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide or other suitable gas). Such a dosage unit may be additionally provided with a valve to deliver a predetermined amount.

Example C—Sprayer

(45) Composition prepared according to Example 1 is filed into a container of a hand-pumped sprayer provided with a nozzle.

(46) All the above embodiments of the present invention are merely exemplary. These and other factors, however, should not be considered as limiting the spirit of the invention, the intended scope of protection of which is indicated in appended claims.