RESUMEN
The mechanochemical preparation of solid compositions of praziquantel with plant saponin (glycyrrhizic acid disodium salt) is described. The study of a number of physicochemical parameters showed that dissolving solid compositions in water is accompanied by the inclusion of praziquantel molecules into micelles, which are formed in the solution of the glycyrrhizic acid disodium salt. Using the opisthorchiasis model caused by Opisthorchis felineus, we found a 4- to 11-fold increase in the anthelmintic activity of praziquantel in the composition as compared to the official praziquantel. According to the pharmacokinetic data, the use of the composition increased the bioavailability of praziquantel 3 times.
Asunto(s)
Antiplatelmínticos/síntesis química , Antiplatelmínticos/farmacología , Ácido Glicirrínico/química , Fenómenos Mecánicos , Opistorquiasis/tratamiento farmacológico , Praziquantel/síntesis química , Praziquantel/farmacología , Animales , Antiplatelmínticos/farmacocinética , Antiplatelmínticos/uso terapéutico , Disponibilidad Biológica , Fenómenos Químicos , Técnicas de Química Sintética , Cricetinae , Praziquantel/farmacocinética , Praziquantel/uso terapéuticoRESUMEN
In an attempt to develop novel anthelmintic agents, our previously isolated osthol was used as lead structures for further optimization. In our research, a series of coumarin analogs, prepared from 7-hydroxy coumarin or 7-hydroxy-4-methyl coumarin, have been evaluated for their anthelmintic activities. In all of the compounds, 6 and 7 were first synthesized, and their structures were identified based on NMR and MS values. Among the candidates, 8-allyl-7-allyloxycoumarin showed better anthelmintic activity than other compounds against Dactylogyrus infestation with EC(50) value of 1.81 mg/L. The quantitative structure-activity relationship (QSAR) of 16 osthol analogs with anthelmintic activity expressed as pEC(50) and toxicity to goldfish expressed pLC(50), such results can offer useful theoretical references for future experimental works.
Asunto(s)
Antiplatelmínticos/síntesis química , Antiplatelmínticos/farmacología , Cumarinas/síntesis química , Cumarinas/farmacología , Carpa Dorada/parasitología , Platelmintos/efectos de los fármacos , Animales , Antiplatelmínticos/efectos adversos , Antiplatelmínticos/química , Técnicas de Química Sintética , Cumarinas/efectos adversos , Cumarinas/química , Platelmintos/fisiología , Relación Estructura-Actividad Cuantitativa , Seguridad , Pruebas de ToxicidadRESUMEN
The paper outlines a procedure for manufacturing the anthelminthic Azinox (biltricide) using the new interfacial transfer catalyst benzyl-di-propyl (beta-hydroxyethyl)ammonium chloride. Azinox has been shown to be identical to biltricide (praziquantel) in its properties. Azinox tests on models of Opisthorchis felineus in golden hamsters and of Hymenolepis nana in albino outbred mice have indicated that the agent is not inferior to biltricide in its antitrematodal and anticestodal activities. Azinox displayed a high activity at the preimaginal stages of O. felineus and H. nana and at the larval stage of H.nana.
Asunto(s)
Anticestodos/síntesis química , Antiplatelmínticos/síntesis química , Praziquantel/análogos & derivados , Animales , Anticestodos/uso terapéutico , Anticestodos/toxicidad , Antiplatelmínticos/uso terapéutico , Antiplatelmínticos/toxicidad , Cricetinae , Evaluación Preclínica de Medicamentos , Femenino , Himenolepiasis/tratamiento farmacológico , Himenolepiasis/parasitología , Dosificación Letal Mediana , Masculino , Mesocricetus , Ratones , Opistorquiasis/tratamiento farmacológico , Opistorquiasis/parasitología , Praziquantel/síntesis química , Praziquantel/uso terapéutico , Praziquantel/toxicidadRESUMEN
A manufacturing procedure has been developed to prepare the anthelmintic bromoxane as a finely divided dosage form. The maximum toxic dose of the drug was 1 g per kg mice body weight. Its therapeutic dose in sheep fascioliasis was 20 mg/kg.