Compositions and methods for drug sensitization of parasites

Patent metadata

Field	Value
Publication number	US-11083717-B2
Application number	US-201916720160-A
Country	US
Kind code	B2
Filing date	Dec 19, 2019
Priority date	Aug 26, 2015
Publication date	Aug 10, 2021
Grant date	Aug 10, 2021

Abstract

Compositions and methods for inhibiting and/or sensitizing or re-sensitizing a parasite to an antiparasitic drug are provided. The compositions can comprise a an arylphenoxypropionate derivative, an aryloxyphenoxyacetate derivative, an aryloxyphenylacetate derivative, one or more substituted quinols, or a pharmaceutically acceptable salt, hydrate, or prodrug thereof, or a combination thereof in an amount and formulation sufficient to sensitize the parasite to the drug, treating infection of a patient by a parasite with a drug, or to prevent symptomatic infection of a patient by a parasite with a drug.

First claim

The invention claimed is:

1. A method of inhibiting a parasite, comprising administering an arylphenoxypropionate derivative, an aryloxyphenoxyacetate derivative, an aryloxyphenylacetate derivative, one or more substituted quinols, or a pharmaceutically acceptable salt, hydrate, or prodrug thereof, or a combination thereof directly to the parasite in an amount and for a time sufficient to inhibit the parasite in an animal.

2. The method of claim 1 , further comprising administering an arylphenoxypropionate derivative, an aryloxyphenoxyacetate derivative, an aryloxyphenylacetate derivative, one or more substituted quinols, or a pharmaceutically acceptable salt, hydrate, or prodrug thereof, or a combination thereof directly to the parasite a second or greater time.

3. The method of claim 2 , wherein the parasite is a species of the genus Plasmodium , a species of the genus Ascaris , a species of the genus Enterobius , a species of the genus Trichinella , a species of the genus Haemonchus , a species of the genus Aphelenchoides , a species of the genus Ditylenchus , a species of the genus Globodera , a species of the genus Heterodera , a species of the genus Longidorus , a species of the genus Meloidogyne , a species of the genus Nacobbus , a species of the genus Pratylenchus , a species of the genus Trichodorus , a species of the genus Xiphinema , a species of the genus Bursaphelenchus , a species of the genus Fasciola , a species of the genus Coccidoides , or a species of the genus Onchocerca.

4. The method of claim 2 , wherein the parasite is selected from the group consisting of Pedicululs humanus, Phthiriasis pubis, Sarcoptes scabiei, Schistosoma mansoni, Schistosoma japonicum, Schistosoma haemotobium, Trichobilharzia regenti, Clonorchis simensis, Fasciola hepatica, Fasciola gigantica, Opisthorchis viverrinil, Paragonimus westermani, Paragonimus kellicotti, Fasciolopsis buski, Metagonimus yokagawai, Heterophyes heterophyes, Echinococcus granulosus, Echinococcus multilocularis, Taenia saginata, Taenia solium, Taenia asiatica, Hymenolpeis nana, Hymenolpeis diminuta, Diphyllobotrium latum, Diphyllobotrium mansonoides, Spirometra erinaceieuropaei, Dracunculus medinensis, Onchocerca volvulus, Lo vaginalis a loa, Mansonella perstans, Mansonella ozzardi, Mansonella streptocera, Wucheria bancrofti, Brugia malayi, Brugia timori, Gnathostoma spinigerum, Gnathostoma hispidium, Ancylostoma duodenale, Ancylostoma brazilienes, Necator americanus, Angiostrongylus cantonensis, Ascaris lumbricoides, Toxocara canis, Toxocara cati, Strongyloides stercoralis, Enterobius vermicularis, Trichinella spiralis, Trichuris trichiura, Cryptosporidium hominis, Cryptosporidium parvum, Isosporiasis befii, Cyclospora cayetanesis, Toxoplasma gondii, Balantidium coli, Entamoeba histolytica, dispar, Giardia lamblia, Trichmonas vaginalis, Dientamoeba fragilis, Blastocystis hominis, Plasmodium falciparum, Plasmodium vivax, Plasmodium ovate, Plasmodium malariea, Babesia divergens, Babesia microfti, Trypanosoma brucei, Trypanosoma cruzi, Leishomania mexicana, Leishomania aethiopica, Leishomania tropic, Leishomania braziliensis, Leishomania donovani , and Leishomania infantum, Eimeria vermiformis, Eimeria brunett, Eimeria praecox, Eimeria maxima, Eimeria mitis, Eimeria necatrix and Eimeria tenefla.

5. The method of claim 1 , wherein the arylphenoxypropionate derivative is NZ-369.

6. The method of claim 5 , wherein the parasite is a species of the genus Plasmodium , a species of the genus Ascaris , a species of the genus Enterobius , a species of the genus Trichinella , a species of the genus Haemonchus , a species of the genus Aphelenchoides , a species of the genus Ditylenchus , a species of the genus Globodera , a species of the genus Heterodera , a species of the genus Longidorus , a species of the genus Meloidogyne , a species of the genus Nacobbus , a species of the genus Pratylenchus , a species of the genus Trichodorus , a species of the genus Xiphinema , a species of the genus Bursaphelenchus , a species of the genus Fasciola , a species of the genus Coccidoides , or a species of the genus Onchocerca.

7. The method of claim 5 , wherein the parasite is selected from the group consisting of Pedicululs humanus, Phthiriasis pubis, Sarcoptes scabiei, Schistosoma mansoni, Schistosoma japonicum, Schistosoma haemotobium, Trichobilharzia regenti, Clonorchis simensis, Fasciola hepatica, Fasciola gigantica, Opisthorchis viverrinil, Paragonimus westermani, Paragonimus kellicotti, Fasciolopsis buski, Metagonimus yokagawai, Heterophyes heterophyes, Echinococcus granulosus, Echinococcus multilocularis, Taenia saginata, Taenia solium, Taenia asiatica, Hymenolpeis nana, Hymenolpeis diminuta, Diphyllobotrium latum, Diphyllobotrium mansonoides, Spirometra erinaceieuropaei, Dracunculus medinensis, Onchocerca volvulus, Lo vaginalis a boa, Mansonella perstans, Mansonella ozzardi, Mansonella streptocera, Wucheria bancrofti, Brugia malayi, Brugia timori, Gnathostoma spinigerum, Gnathostoma hispidium, Ancylostoma duodenale, Ancylostoma brazilienes, Necator americanus, Angiostrongylus cantonensis, Ascaris lumbricoides, Toxocara canis, Toxocara cati, Strongyloides stercoralis, Enterobius vermicularis, Trichinella spiralis, Trichuris trichiura, Cryptosporidium hominis, Cryptosporidium parvum, Isosporiasis befii, Cyclospora cayetanesis, Toxoplasma gondii, Balantidium coli, Entamoeba histolytica, dispar, Giardia lamblia, Trichmonas vaginalis, Dientamoeba fragilis, Blastocystis hominis, Plasmodium falciparum, Plasmodium vivax, Plasmodium ovate, Plasmodium malariea, Babesia divergens, Babesia microfti, Trypanosoma brucei, Trypanosoma cruzi, Leishomania mexicana, Leishomania aethiopica, Leishomania tropic, Leishomania braziliensis, Leishomania donovani , and Leishomania infantum, Eimeria vermiformis, Eimeria brunett, Eimeria praecox, Eimeria maxima, Eimeria mitis, Eimeria necatrix and Eimeria tenefla.

8. The method of claim 1 , wherein the parasite is a species of the genus Plasmodium , a species of the genus Ascaris , a species of the genus Enterobius , a species of the genus Trichinella , a species of the genus Haemonchus , a species of the genus Aphelenchoides , a species of the genus Ditylenchus , a species of the genus Globodera , a species of the genus Heterodera , a species of the genus Longidorus , a species of the genus Meloidogyne , a species of the genus Nacobbus , a species of the genus Pratylenchus , a species of the genus Trichodorus , a species of the genus Xiphinema , a species of the genus Bursaphelenchus , a species of the genus Fasciola , a species of the genus Coccidoides , or a species of the genus Onchocerca.

9. The method of claim 1 , wherein the parasite is selected from the group consisting of Pedicululs humanus, Phthiriasis pubis, Sarcoptes scabiei, Schistosoma mansoni, Schistosoma japonicum, Schistosoma haemotobium, Trichobilharzia regenti, Clonorchis simensis, Fasciola hepatica, Fasciola gigantica, Opisthorchis viverrinil, Paragonimus westermani, Paragonimus kellicotti, Fasciolopsis buski, Metagonimus yokagawai, Heterophyes heterophyes, Echinococcus granulosus, Echinococcus multilocularis, Taenia saginata, Taenia solium, Taenia asiatica, Hymenolpeis nana, Hymenolpeis diminuta, Diphyllobotrium latum, Diphyllobotrium mansonoides, Spirometra erinaceieuropaei, Dracunculus medinensis, Onchocerca volvulus, Lo vaginalis a boa, Mansonella perstans, Mansonella ozzardi, Mansonella streptocera, Wucheria bancrofti, Brugia malayi, Brugia timori, Gnathostoma spinigerum, Gnathostoma hispidium, Ancylostoma duodenale, Ancylostoma brazilienes, Necator americanus, Angiostrongylus cantonensis, Ascaris lumbricoides, Toxocara canis, Toxocara cati,

Assignees

• Texas A & M Univ Sys

Inventors

• Reddy Manchi C M
• Sacchettini James C
• Zhou Nian E
• Mccutchen Billy F

Classifications

• A61K31/423

  condensed with carbocyclic rings · CPC title

• A61K31/5377

  not condensed and containing further heterocyclic rings, e.g. timolol · CPC title

• A61K31/353

  3,4-Dihydrobenzopyrans, e.g. chroman, catechin · CPC title

• A61K31/4439

  containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465) · CPC title

• A61K31/7036

  having at least one amino group directly attached to the carbocyclic ring, e.g. streptomycin, gentamycin, amikacin, validamycin, fortimicins · CPC title