ЭФФЕКТИВНОСТЬ СУПРАМОЛЕКУЛЯРНЫХ КОМПЛЕКСОВ АНТИГЕЛЬМИНТИКОВ ПРИ ЖЕЛУДОЧНО-КИШЕЧНЫХ СТРОНГИЛЯТОЗАХ ОВЕЦ В ПРОИЗВОДСТВЕННЫХ УСЛОВИЯХ

Effectiveness of a supramolecular nanotech-based Albendazole – Fenbendazole complex has been tested using the Drug Delivery System. Tests for efficacy of new drugs Albendazole and Fenbendazole were conducted on 37 sheep spontaneously infected with Nematodirus sp. and other gastrointestinal strongylates in agricultural farm «Leninsky Put’» located in Pestravsky district of Samara region. The supra-molecular Albendazole – Arabinogalactan complex at a dose of 1,0 mg/kg of active ingredient and the base Albendazole at a dose of 10 mg/kg have shown a 100 % effectiveness. Albendazole – Chitosan complex has shown a 87,5 % extenseffectiveness and a 98,4 % reduction in number of nematode eggs in feces. The effectiveness of supramolecular Fenbendazole – polymer complex was lower. Испытана эффективность супрамолекулярных комплексов альбендазола и фенбендазола, приготовленных по нанотехнологии с использованием адресной доставки Drug Delivery System. Испытание новых лекарственных форм альбендазола и фенбендазола проводили в колхозе «Ленинский путь» Пестравского района Самарской области на 37 овцах, спонтанно инвазированных нематодирусами и другими видами желудочно-кишечных стронгилят. Супрамолекулярный комплекс альбендазола с арабиногалактаном в дозе 1,0 мг/кг по ДВ и базовый альбендазол в дозе 10 мг/кг показали 100%-ную эффективность. Комплекс альбендазола с хитозаном проявил 87,5%-ную экстенсэффективность и 98,4%-ное снижение числа яиц нематод в фекалиях. Эффективность супрамолекулярного комплекса фенбендазола с полимером была ниже

ЭФФЕКТИВНОСТЬ СУПРАМОЛЕКУЛЯРНОГО КОМПЛЕКСА ФЕНБЕНДАЗОЛА ПРИ НЕМАТОДОЗАХ ОВЕЦ

 Objective of research: to study the anthelmintic efficacy of the supramolecular complex of Fenbendazole used against different nematode species in sheep Materials and methods: Experiments were carried out on young sheep spontaneously infected with gastrointestinal strongylates (48 head), Dictyocaulus filaria (42 head), Strongyloides papillosus (21 head) и Trichocephalus ovis (24 head). In each helminthiasis, the supramolecular complex of Fenbendazole was given once orally to sheep from various groups at the dose of 3,0; 2,0 and 1,0 mg a.i./kg in comparison with the base preparation Fenbendazole at the doses of 1,0 and 3,0 mg/kg. Sheep which didn’t receive the drug served as controls. The efficacy of drugs was evaluated before and 18 days after dehelmintization according to the results of coprolarvoscopic examination by flotation and G. Baermann methods. The registration of drug activity was performed using the «control test». Results and discussion: Anthelmintic efficacy was studied and a therapeutic dose for the supramolecular complex of Fenbendazole produced by chemical mechanical technology using the Drug Delivery System was determined. In gastrointestinal strongylatoses the supramolecular complex against D. filaria. at the doses of 3,0; 2,0 and 1,0 mg a.i./kg showed the efficacy of 100; 93,4 and 78% , respectively. The efficacy of supramolecular complex at the dose of 3,0 mg/kg against S. papillosus was 100 %, and against T. ovis - 98,3 % at 10–13% efficacy of the base preparation Fenbendazole at the dose of 1,0 mg/kg. The therapeutic dose for the supramolecular complex at main nematodiasis in sheep was 3,0 mg a.i./kg. Цель исследования – изучение антигельминтной эффективности супрамолекулярного комплекса фенбендазола против разных видов нематод у овец. Материалы и методы. Опыты проводили на молодняке овец, спонтанно инвазированном желудочно-кишечными стронгилятами (48 гол.), Dictyocaulus filaria (42 гол.), Strongyloides papillosus (21 гол.) и Trichocephalus ovis (24 гол.). При каждом гельминтозе овцам разных групп задавали однократно перорально супрамолекулярный комплекс фенбендазола в дозе 3,0; 2,0 и 1,0 мг/кг по ДВ в сравнении с базовым препаратом фенбендазолом в дозах 1,0 и 3,0 мг/кг. Контролем служила группа овец, не получавшая препарат. Эффективность препаратов учитывали по результатам копрооволарвоскопических исследований методом флотации и Бермана до и через 18 сут после дегельминтизации. Учет активности препаратов проводили по типу «контрольный тест». Результаты и обсуждение. Изучена антигельминтная эффективность и установлена терапевтическая доза супрамолекулярного комплекса фенбендазола, полученного по механохимической технологии с адресной доставкой Drug Delivery System. Комплекс в дозах 3,0; 2,0 и 1,0 мг/кг по ДВ показал соответственно 100; 93,4 и 78%-ную эффективность при  стронгилятозах пищеварительного тракта, 100; 92,4 и 76,0%-ную – против D. filaria. Эффективность комплекса в дозе 3,0 мг/кг составила против S. papillosus 100 % и против T. ovis 98,3 % при 10–13%-ной эффективности базового препарата – фенбендазола в дозе 1,0 мг/кг. Терапевтическая доза супрамолекулярного комплекса при основных нематодозах овец составила 3,0 мг/кг по ДВ

ECOLOGICALLY SAFE BENZIMIDAZOLE-BASED ANTHELMINTIC DRUGS: SYNTHESIS, PROPERTIES, MEDICATION

The aim is to study the process of mechanochemical modification of the physico-chemical and anthelmintic benzimidazole properties of drugs to change their water solubility and increase their efficiency.Methods. We have used the technology of solid phase mechanical processing of substances with polysaccharides to obtain the supramolecular complexes, which are characterized by a complex of physico-chemical methods (IR spectroscopy, DTA, XRF, solubility, etc.) as well as tested for anthelmintic effect in laboratory models and experiments on sheep.Results. The drug has a high efficiency in laboratory models of helminthes and in experiments on sheep infested spontaneously with nematodes of gastrointestinal tract lowering the dosages of substance.Conclusion. Solid phase mechanochemical processing of certain substances of benzimidazole anthelmintic drugs with polysaccharides shows the possibility of obtaining environmentally friendly products with improved solubility, bioavailability and increased biological activity against nematodes

Preparation of curcumin self-micelle solid dispersion with enhanced bioavailability and cytotoxic activity by mechanochemistry

An amorphous solid dispersion (SD) of curcumin (Cur) with disodium glycyrrhizin (Na2GA) was prepared by mechanical ball milling. Curcumin loaded micelles were self-formed by Na2GA when SD dissolved in water. The physical properties of Cur SD in solid state were characterized by differential scanning calorimetry, X-ray diffraction studies, and scanning electron microscope. The characteristics of the sample solutions were analyzed by reverse phase HPLC, UV–visible spectroscopy, 1H NMR spectroscopy, gel permeation LC, and transmission electron microscopy. In vitro cytotoxic tests demonstrated that Cur SD induced higher cytotoxicity against glioblastoma U-87 MG cells than free Cur. Besides, an improvement of membrane permeability of Cur SD was confirmed by parallel artificial membrane permeability assay. Further pharmacokinetic study of this SD formulation in rat showed a significant ∼19-fold increase of bioavailability as comparing to free Cur. Thus, Cur SD provide a more potent and efficacious formulation for Cur oral delivery

EFFECTIVENESS OF SUPRAMOLECULAR ANTHELMINTIC COMPLEXES APPLIED UNDER WORKING CONDITIONS FOR TREATMENT OF GASTROINTESTINAL STRONGYLATOSIS IN SHEEP

Effectiveness of a supramolecular nanotech-based Albendazole – Fenbendazole complex has been tested using the Drug Delivery System. Tests for efficacy of new drugs Albendazole and Fenbendazole were conducted on 37 sheep spontaneously infected with Nematodirus sp. and other gastrointestinal strongylates in agricultural farm «Leninsky Put’» located in Pestravsky district of Samara region. The supra-molecular Albendazole – Arabinogalactan complex at a dose of 1,0 mg/kg of active ingredient and the base Albendazole at a dose of 10 mg/kg have shown a 100 % effectiveness. Albendazole – Chitosan complex has shown a 87,5 % extenseffectiveness and a 98,4 % reduction in number of nematode eggs in feces. The effectiveness of supramolecular Fenbendazole – polymer complex was lower

EFFICACY OF THE SUPRAMOLECULAR COMPLEX OF FENBENDAZOLE AGAINST NEMATODIASIS IN SHEEP

Objective of research: to study the anthelmintic efficacy of the supramolecular complex of Fenbendazole used against different nematode species in sheep Materials and methods: Experiments were carried out on young sheep spontaneously infected with gastrointestinal strongylates (48 head), Dictyocaulus filaria (42 head), Strongyloides papillosus (21 head) и Trichocephalus ovis (24 head). In each helminthiasis, the supramolecular complex of Fenbendazole was given once orally to sheep from various groups at the dose of 3,0; 2,0 and 1,0 mg a.i./kg in comparison with the base preparation Fenbendazole at the doses of 1,0 and 3,0 mg/kg. Sheep which didn’t receive the drug served as controls. The efficacy of drugs was evaluated before and 18 days after dehelmintization according to the results of coprolarvoscopic examination by flotation and G. Baermann methods. The registration of drug activity was performed using the «control test». Results and discussion: Anthelmintic efficacy was studied and a therapeutic dose for the supramolecular complex of Fenbendazole produced by chemical mechanical technology using the Drug Delivery System was determined. In gastrointestinal strongylatoses the supramolecular complex against D. filaria. at the doses of 3,0; 2,0 and 1,0 mg a.i./kg showed the efficacy of 100; 93,4 and 78% , respectively. The efficacy of supramolecular complex at the dose of 3,0 mg/kg against S. papillosus was 100 %, and against T. ovis - 98,3 % at 10–13% efficacy of the base preparation Fenbendazole at the dose of 1,0 mg/kg. The therapeutic dose for the supramolecular complex at main nematodiasis in sheep was 3,0 mg a.i./kg