Transdermal parasiticidal formulations

Abstract

Described herein are transdermal parasiticidal formulations and methods of treatment and use, wherein the formulation is not only able to deliver an agent or agents through the skin layer, but is able to do so through wool, dirt and/or a sebum layer on the skin if such layers are present. The transdermal parasiticidal formulation may be a solution including a therapeutically effective amount of levamisole anthelmintic agent dissolved in a solution including isopropyl myristate and D-limonene. This base formulation is highly compatible with other compounds and various other actives may be added to this formulation.

1 . A formulation comprising a therapeutically effective amount of levamisole anthelmintic agent dissolved in a solution comprising one or more fatty acid ester compounds and one or more terpene compounds, wherein the formulation is suitable for transdermal administration. 
     
     
         2 . The formulation of  claim 1 , wherein the formulation is anhydrous. 
     
     
         3 . The formulation of  claim 1 , wherein the levamisole anthelmintic agent is fully dissolved. 
     
     
         4 . The formulation of  claim 1 , wherein the levamisole is stable for at least 2 months in the solution, wherein there is no substantial change in levamisole activity, and wherein there is no substantial separation and/or sedimentation of the levamisole from the solution. 
     
     
         5 . The formulation of  claim 1 , wherein the one or more fatty acid ester compounds is a fatty acid ester with skin emollient and penetrating properties, and wherein the fatty acid ester enhances levamisole dissolution. 
     
     
         6 . The formulation of  claim 1 , wherein each of the one or more fatty acid ester compounds is independently selected from the group consisting of lauric fatty acid esters, palmitic fatty acid esters, stearic fatty acid esters, and myristic fatty acid esters. 
     
     
         7 . The formulation of  claim 1 , wherein the one or more fatty acid ester compounds is isopropyl myristate. 
     
     
         8 . The formulation of  claim 1 , wherein the one or more terpene compounds is independently selected from the group consisting of monoterpenes, sesquiterpenes, and diterpenes. 
     
     
         9 . The formulation of  claim 1 , wherein the one or more terpene compounds is independently selected from the group consisting of pinene, camphene, myrcene, cymene, eucaliptol, linalool, menthol, borneol, citrals, ocimene, sabinene, torpinolene, and D-limonene. 
     
     
         10 . The formulation of  claim 1 , wherein the one or more fatty acid ester compounds and the one or more terpene compounds, taken together, are 1-55% w/v of the formulation. 
     
     
         11 . The formulation of  claim 1 , wherein the molar ratio of the one or more fatty acid ester compounds to the one or more terpene compounds is from about 10:1 to about 15:1. 
     
     
         12 . The formulation of  claim 1 , further comprising one or more macrocyclic lactone compounds. 
     
     
         13 . The formulation of  claim 12 , wherein the one or more macrocyclic lactone compounds are independently selected from the group consisting of abamectin, moxidectin, eprinomectin, selamectin, ivermectin, and milbemycins. 
     
     
         14 . The formulation of  claim 12 , wherein the one or more macrocyclic lactone compounds, taken together, are 0.1 to 10% w/v of the composition. 
     
     
         15 . The formulation of  claim 1 , further comprising one or more solvents independently selected from the group consisting of diethylene glycol ether (DGE) compounds. 
     
     
         16 . The formulation of  claim 15 , wherein the one or more DGE compounds are independently selected from the group consisting of diethylene glycol monobutyl ether, diethylene glycol monoethyl ether, and diethylene glycol monomethyl ether. 
     
     
         17 . The formulation of  claim 15 , wherein the solvent is 30-70% w/v of the formulation. 
     
     
         18 . The formulation of  claim 1 , wherein the formulation further comprises one or more transdermal penetrating agents independently selected from the group consisting of non-ionic surfactants. 
     
     
         19 . The formulation of  claim 18 , wherein the one or more transdermal penetrating agents are independently selected from the group consisting of EO/PO block co-polymers, alcohol ethoxylates, and cocamide diethanolamine. 
     
     
         20 . The formulation of  claim 18 , wherein the one or more transdermal penetrating agents, taken together, are 0.1 to 20% w/v of the formulation. 
     
     
         21 . The formulation of  claim 1 , wherein the formulation further comprises one or more preservatives. 
     
     
         22 . The formulation of  claim 21 , wherein the one or more preservatives are independently selected from the group consisting of benzyl alcohol, chlorobutanol, phenylethyl alcohol, and ethyl alcohol. 
     
     
         23 . The formulation of  claim 21 , wherein the one or more preservatives, taken together, are about 0.1 to 5.0% w/v of the formulation. 
     
     
         24 . The formulation of  claim 1 , wherein the formulation further comprises one or more diluents. 
     
     
         25 . The formulation of  claim 24 , wherein the one or more diluents are independently selected from the group consisting of glycol compounds. 
     
     
         26 . The formulation of  claim 24 , wherein the one or more diluents are independently selected from the group consisting of propylene glycol and ethylene glycol. 
     
     
         27 . The formulation of  claim 24 , wherein the one or more diluents, taken together, are 5 to 50% w/v of the formulation. 
     
     
         28 . The formulation of  claim 1 , wherein the viscosity of the formulation is less than or equal to 5000 cps. 
     
     
         29 . The formulation of  claim 1 , wherein the formulation further comprises one or more additional active compounds. 
     
     
         30 . The formulation of  claim 29 , wherein the one or more additional active compounds are independently selected from the group consisting of an endo-parasiticide, ecto-parasiticide, or insecticide. 
     
     
         31 . The formulation of  claim 30 , wherein each insecticide is independently selected from the group consisting of triflumuron, diflubenzuron, cyromazine, and pyrethroid compounds. 
     
     
         32 . The formulation of  claim 29 , wherein the one or more additional active compounds, taken together, are equal to or less than 20% w/v of the formulation. 
     
     
         33 . A method of treating an endo-parasite or ecto-parasite infestation, comprising topically administering a therapeutically effective amount of the formulation of  claim 1  to a non-human animal in need thereof. 
     
     
         34 . The method of  claim 33 , wherein the non-human animal is selected from the group consisting of ovine, bovine, and cervine species. 
     
     
         35 . The method of  claim 34 , wherein the formulation is administered as a pour on stripe or stripes. 
     
     
         36 . The method of  claim 34 , wherein the formulation is administered as a spot or spots. 
     
     
         37 . The method of  claim 34 , wherein the non-human animal is a sheep. 
     
     
         38 . The method of  claim 34 , wherein the non-human animal is cattle or cows. 
     
     
         39 . The method of  claim 34 , wherein the non-human animal is deer. 
     
     
         40 . A method of treating an endo-parasite or ecto-parasite infestation, comprising topically administering a therapeutically effective amount of a dual active anthelmintic formulation to a non-human animal selected from the group consisting of ovine, bovine and cervine species in need thereof, the formulation comprising:
 a therapeutically effective amount of levamisole anthelmintic agent dissolved in a solution comprising one or more fatty acid ester compounds and one or more terpene compounds; and   a therapeutically effective amount of one or more macrocyclic lactone compounds dissolved in one or more diethylene glycol ether (DGE) compounds.   
     
     
         41 . The method of  claim 40  wherein the formulation further comprises:
 one or more penetrating agents independently selected from the group consisting of non-ionic surfactants; 
 one or more preservatives; and 
 one or more diluents. 
 
     
     
         42 . A method of manufacturing an anhydrous dual anthelmintic formulation comprising the steps:
 (a) preparing a solution of levamisole dissolved in one or more fatty acid ester compounds and one or more terpene compounds;   (b) adding to the solution of (a), a prepared solution of diethylene glycol ether and at least one macrocyclic lactone;   (c) mixing the combined formulation of step (b) until the macrocyclic lactone is dissolved;   (d) optionally, adding one or more preservatives and/or penetrating agents and adding one or more diluents.