Compositions and methods for treating parasitic infections

Abstract

Compositions for treating parasitic infections and methods of using the compositions to treat subjects with parasitic infections are provided. Methods of selecting compositions for use in treating parasitic infections are further provided.

1 . A composition for treating a parasitic infection in a subject, comprising two or more compounds selected from: trans-anethole, para-cymene, linalool, alpha-pinene, and thymol, wherein the composition demonstrates an anti-parasitic effect that exceeds that of any of its components. 
     
     
         2 . The composition of  claim 1 , comprising two more compounds selected from: para-cymene, linalool, alpha-pinene, and thymol. 
     
     
         3 . The composition of  claim 1 , comprising three or more compounds selected from: para-cymene, linalool, alpha-pinene, and thymol. 
     
     
         4 . The composition of  claim 1 , comprising para-cymene, linalool, alpha-pinene, and thymol. 
     
     
         5 . The composition of  claim 5 , and further comprising soy bean oil. 
     
     
         6 . The composition of  claim 5 , comprising: about 25-35% by weight para-cymene, about 1-10% by weight linalool, about 1-10% by weight alpha-pinene, about 35-45% by weight thymol, and about 20-30% by weight soy bean oil. 
     
     
         7 . The composition of  claim 6 , comprising: about 28.39% by weight para-cymene, about 6.6% by weight linalool, about 3.8% by weight alpha-pinene, about 37.2% by weight thymol, and about 24% by weight soy bean oil. 
     
     
         8 . The composition of  claim 5 , comprising: about 25-35% by volume para-cymene, about 1-10% by volume linalool, about 1-10% by volume alpha-pinene, about 35-45% by volume thymol and about 20-30% by volume soy bean oil. 
     
     
         9 . The composition of  claim 8 , comprising: about 30% by volume para-cymene, about 7% by volume linalool, about 4% by volume alpha-pinene, about 35% by volume thymol, and about 24% by volume soy bean oil. 
     
     
         10 . The composition of  claim 1 , comprising three or more compounds selected from: trans-anethole, para-cymene, linalool, alpha-pinene, and thymol. 
     
     
         11 . The composition of  claim 10 , comprising four or more compounds selected from: trans-anethole, para-cymene, linalool, alpha-pinene, and thymol. 
     
     
         12 . The composition of  claim 10 , comprising: trans-anethole, para-cymene, linalool, alpha-pinene, and thymol. 
     
     
         13 . The composition of  claim 12 , comprising: about 15-25% by weight trans-anethole, about 30-40% by weight para-cymene, about 1-10% by weight linalool, about 1-10% by weight alpha-pinene, and about 35-45% by weight thymol. 
     
     
         14 . The composition of  claim 13 , comprising: about 18.2% by weight trans-anethole, about 34.4% by weight para-cymene, about 4.7% by weight linalool, about 1.9% by weight alpha-pinene, and about 40.8% by weight thymol. 
     
     
         15 . The composition of  claim 12 , comprising: about 10-20% by volume trans-anethole, about 30-40% by volume para-cymene, about 1-10% by volume linalool, about 1-10% by volume alpha-pinene, and about 35-45% by volume thymol. 
     
     
         16 . The composition of  claim 15 , comprising: about 17% by volume trans-anethole, about 37% by volume para-cymene, about 5% by volume linalool, about 2% by volume alpha-pinene, and about 39% by volume thymol. 
     
     
         17 . The composition of  claim 12 , comprising: about 15-25% by weight trans-anethole, about 1-10% by weight para-cymene, about 35-45% by weight linalool, about 1-10% by weight alpha-pinene, and about 30-40% by weight thymol. 
     
     
         18 . The composition of  claim 17 , comprising: about 18.2% by weight trans-anethole, about 1.9% by weight para-cymene, about 40.8% by weight linalool, about 4.7% by weight alpha-pinene, and about 34.4% by weight thymol. 
     
     
         19 . The composition of  claim 12 , comprising: about 15-25% by volume trans-anethole, about 1-10% by volume para-cymene, about 35-45% by volume linalool, about 1-10% by volume alpha-pinene, and about 30-40% by volume thymol. 
     
     
         20 . The composition of  claim 19 , comprising: about 17% by volume trans-anethole, about 2% by volume para-cymene, about 39% by volume linalool, about 5% by volume alpha-pinene, and about 37% by volume thymol. 
     
     
         21 . The composition of  claim 1 , wherein the at least two compounds of the composition together demonstrate a synergistic anti-parasitic effect. 
     
     
         22 . The composition of  claim 21 , wherein the actual percent effect of the composition is greater than the expected percent effect of the composition. 
     
     
         23 . The composition of  claim 21 , wherein a coefficient of synergy relative to a component of the composition is greater than 5, 10, 25, 50, 75, or 100. 
     
     
         24 . The composition of  claim 1 , wherein the parasitic infection is by a parasite selected from:
 a protozoan parasite, and a helminthic parasite.   
     
     
         25 . The composition of  claim 24 , wherein the parasite is a protozoa. 
     
     
         26 . The composition of  claim 25 , wherein the parasite is selected from an intestinal protozoa, a tissue protozoa, and a blood protozoa. 
     
     
         27 . The composition of  claim 26 , wherein the parasite is selected from:  Entamoeba hystolytica, Giardia lamblia, Cryptosporidium uris, Trypanosomatida gambiense, Trypanosomatida rhodesiense, Trypanosomatida crusi, Leishmania mexicana, Leishmania braziliensis, Leishmania tropica, Leishmania donovani, Toxoplasma gondii, Plasmodium vivax, Plasmodium ovale, Plasmodium malariae, Plasmodium falciparum, Trichomonas vaginalis , and  Histomonas meleagridis.    
     
     
         28 . The composition of  claim 24 , wherein the parasite is a helminth. 
     
     
         29 . The composition of  claim 28 , wherein the parasite is a nematode. 
     
     
         30 . The composition of  claim 29 , wherein the parasite is an Adenophorea. 
     
     
         31 . The composition of  claim 29 , wherein the parasite is a Secementea. 
     
     
         32 . The composition of  claim 29 , wherein the parasite is selected from:  Trichuris trichiura, Ascaris lumbricoides, Enterobius vermicularis, Ancylostoma duodenale, Necator americanus, Strongyloides stercoralis, Wuchereria bancrofti , and  Dracunculus medinensis.    
     
     
         33 . The composition of  claim 28 , wherein the parasite is a trematode. 
     
     
         34 . The composition of  claim 33 , wherein the parasite is selected from: blood flukes, liver flukes, intestinal flukes, and lung flukes. 
     
     
         35 . The composition of  claim 34 , wherein the parasite is selected from:  Schistosoma mansoni, Schistosoma haematobium, Schistosoma japonicum, Fasciola hepatica, Fasciola gigantica, Heterophyes heterophyes , and  Paragonimus westermani.    
     
     
         36 . The composition of  claim 28 , wherein the parasite is selected from cestodes. 
     
     
         37 . The composition of  claim 36 , wherein the parasite is selected from  Taenia solium, Taenia saginata, Hymenolepis nana, Echinococcus granulosus.    
     
     
         38 . The composition of  claim 1 , wherein the subject is a mammal. 
     
     
         39 . The composition of  claim 38 , wherein the subject is a human. 
     
     
         40 . A formulation comprising the composition of  claim 1  and a carrier. 
     
     
         41 . The formulation of  claim 40 , wherein the carrier is a food product. 
     
     
         42 . A formulation comprising the composition of  claim 1  encapsulated or microencapsulated with an outer shell material. 
     
     
         43 . A method of treating a parasitic infection in a subject, comprising administering an effective amount of the composition of  claim 1  to the subject. 
     
     
         44 . A method of treating a parasitic infection in a subject, comprising administering an effective amount of the composition of  claim 3  to the subject. 
     
     
         45 . A method of treating a parasitic infection in a subject, comprising administering an effective amount of the composition of  claim 4  to the subject. 
     
     
         46 . A method of treating a parasitic infection in a subject, comprising administering an effective amount of the composition of  claim 5  to the subject. 
     
     
         47 . A method of treating a parasitic infection in a subject, comprising administering an effective amount of the composition of  claim 10  to the subject. 
     
     
         48 . A method of treating a parasitic infection in a subject, comprising administering an effective amount of the composition of  claim 11  to the subject. 
     
     
         49 . A method of treating a parasitic infection in a subject, comprising administering an effective amount of the composition of  claim 12  to the subject. 
     
     
         50 . A method of selecting a composition for use in treating a parasitic infection, comprising:
 (a) providing a cell expressing a tyramine receptor;   (b) contacting test compounds to the cell;   (c) measuring the receptor binding affinity of the compounds;   (d) measuring at least one parameter selected from,
 (i) intracellular cAMP level; and 
 (ii) intracellular Ca 2+  level; 
   (e) identifying a first compound for the composition that is capable of altering at least one of said parameters, and which has a high receptor binding affinity for the tyramine receptor; and   (f) identifying a second compound for the composition that is capable of altering at least one of said parameters, and which has a low receptor binding affinity for the tyramine receptor; and   (g) selecting a composition including the first and second compounds.   
     
     
         51 . The method of  claim 50 , wherein the selected composition demonstrates an anti-parasitic effect that exceeds the anti-parasitic effect of any of the compounds when used alone. 
     
     
         52 . The method of  claim 50 , wherein the tyramine receptor is a Drosophila melanogaster tyramine receptor. 
     
     
         53 . The method of  claim 50 , wherein the at least one parameter is intracellular cAMP level. 
     
     
         54 . The method of  claim 50 , wherein the at least one parameter is intracellular Ca 2+  level.