MECHANOCHEMICAL MODIFICATION OF TRIKLABENDAZOL TO OBTAIN AN EFFECTIVE DRUG AGAINST FACTIOLESIS

To study the possibility of increasing the solubility of the substance triclabendazole (TCB), we used the technology of mechanochemical modification of TCB using water-soluble polymers, polyvinylpyrrolidone (PVP) and arabinogalactan (AG) from Siberian larch Larix sibirica in particular. After joint machining of TCB with polymers (PVP, AG) in a LE-101 ball mill (made in Hungary), free flowing powder dispersions with an increased solubility (more than 50 times as compared to the original substance TCB) were obtained. This result was explained by the formation of intermolecular complexes of the type of hydrogen bond between the characteristic groups of TCB and polymers, which was confirmed by the data of IR-spectral studies. Tests of intermolecular complexes on spontaneously fasciola-infected sheep have shown high efficiency. As a result of the research, it was found that the complex of TCB: AG composition (1:9), which we named “triclafascid”, possesses a number of positive attributes in comparison with the substance of TCB and provides high fasciolocid and economic efficacy, and safety of use by reducing the therapeutic dose. Inclusion of arabinogalactan, which has hepatoprotective, antimutagenic, mitogenic, gastroprotective properties, in the preparation, made it possible to reduce the toxicity of the preparation proposed for practice. It was shown that residual amounts of TCB and its metabolites were not detected in tissues and organs on the 14th day of the experiment with triclafascid, which indicates the possibility of slaughtering an animal and using meat 14 days after using the drug. The drug has good solubility, bioavailability to helminthes, is non-toxic, and increases antihelminthic and economic efficiency. The obtained results confirmed the previously obtained data on the prospects of an innovative approach to improve the quality indicators of anthelmintic drugs and to obtain effective drugs for veterinary medicine.

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THE SOLVING OF PERSISTENCE PROBLEMS OF DRUGS ON THE BASIS OF IVERMEKTIN

10.31016/978-5-9902340-8-6.2019.20.671-677 ◽

2019 ◽

pp. 671-677

Author(s):

Khalikov ◽

Marchenko ◽

Khalikov

Keyword(s):

Siberian Larch ◽

Biological Properties ◽

Water Soluble ◽

Water Soluble Polymers ◽

Soluble Polymers ◽

Development Of Resistance ◽

Variable Voltage ◽

Three Samples ◽

Mechanochemical Modification ◽

Alternative Sources

Ivermectin-based preparations that have been intensively used in veterinary practice for more than 30 years have contributed to the development of resistance to drugs based on it, and this problem is very relevant in modern parasitology. One of the ways to solve this problem is the development of combined preparations based both on new ivermectin derivatives and the inclusion of preparations from other class-es of chemical compounds in their composition. We have proposed an alternative method, i.e. the mechanochemical modification of the substance ivermectin using water-soluble polymers. This paper presents the results of modifying the substance of ivermectin with arabinogalactan polysaccharide (AG), isolated from Siberian larch Larix sibirica by joint machining of components in a variable-voltage shred-der activator. During jointly machining ivermectin with samples of arabinogalactan from three alternative sources, compositions of "Ivermectin: AG" (1:10), which have increased solubility (more than 10 times as compared with the original substance of ivermectin), were obtained. The study of the parasiticidal efficacy of the obtained compositions of ivermectin in intestinal helminthiases was carried out on sheep. As a result of the experiments to evaluate the compositions of ivermectin with three samples of AG, it was found that their use of helminthic efficacy did not show the advantage of any of the batches of polysaccharide. To a greater extent, the effective-ness of the compositions of ivermectin was influenced by the dosage of the drug. Biological testing of the obtained compositions of ivermectin showed the possibility of reducing the dosage of ivermectin by 2 or more times while maintaining high ef-ficiency. The obtained data indicate the promising outlook for a mechanochemical approach for modifying the physicochemical and biological properties of prepara-tions based on ivermectin in solving problems of resistance.

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PROPERTIES OF ALBENDAZOLE SOLID DISPERSIONS OBTAINED BY MECHANOCHEMICAL MODIFICATION WITH POLYMERS

10.31016/978-5-9902341-5-4.2020.21.456-464 ◽

2020 ◽

pp. 456-464

Author(s):

S. Khalikov ◽

Oripov ◽

Isaev ◽

Ulashev

Keyword(s):

High Efficiency ◽

Solid Dispersions ◽

Anthelmintic Activity ◽

Water Soluble ◽

Water Soluble Polymers ◽

Natural Origin ◽

Soluble Polymers ◽

Stable Suspension ◽

Mechanochemical Modification ◽

Causative Agents

Given the potential for using methods of mechanochemical modification of difficultly soluble substances of drugs using water soluble polymers of synthetic and natural origin, we conducted studies to improve the solubility of the anthelmintic substance of albendazole (ABZ) by coprocessing ABZ with polymers chitosan and PVP. In this case, solid dispersions (SD) of the ABZ compositions – chitosan = 1:9 and ABZ : PVP = 1:9 – were obtained, which were easy loose powders that formed stable suspension concentrates suitable for the use on animals. Moreover, the solubility of ABZ in these SDs was 20 and 27 times higher respectively than that of the initial substance. When studying the anthelmintic activity of the obtained SDs against the causative agents of fascioliasis, monieziasis, marshallagiasis, nematodirosis and other gastrointestinal strongylatoses in sheep, their high efficiency was established. Thus, if before ABZ : chitosan = 1: 9 was used, sheep were infected with Marshallagia at 88.8%, Nematodirus at 58.0%, and other gastrointestinal strongylates (Ostertagia, Trychostrongilus, etc.) at 80.6%, Fasciola at 96.7%, Moniezia at 6.4%, and the total invasion rate was 96.7%, the prevalence (EI) of these helminths amounted to 58.0%, 3.2%, 9.6%, 5.8%, 0% and 83.8% respectively after 5 days following the use of the drug. When testing the drug composition ABZ : PVP = 1:9 on sheep infected with Marshallagia at 88.8%, Nematodirus at 66.6%, other gastrointestinal strongylates at 72.2%, Fasciola at 24.0%, Moniezia at 5.5%, and all helminths at 100%, decrease in the invasion was observed to 50.0%, 0%, 5.5%, 27.7%, 0% and 50.0% respectively. These experimental data allowed the authors to recommend the ABZ-based drugs for practical use.

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Development of Antihelminthics of Increased Efficiency on the Basis of Intermolecular Complexes of Active Substances with Water-Soluble Polymers Including Polysaccharides

Химия в интересах устойчивого развития ◽

10.15372/khur20150510 ◽

2015 ◽

Vol 23 (5) ◽

Keyword(s):

Water Soluble ◽

Water Soluble Polymers ◽

Soluble Polymers ◽

Intermolecular Complexes ◽

Active Substances

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New quenching media based on water-soluble polymers

Metal Science and Heat Treatment ◽

10.1007/bf01226357 ◽

1981 ◽

Vol 23 (2) ◽

pp. 104-106 ◽

Cited By ~ 1

Author(s):

A. V. Tolstousov ◽

O. A. Bannykh

Keyword(s):

Water Soluble ◽

Water Soluble Polymers ◽

Soluble Polymers ◽

Quenching Media

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SANS quantification of bound water in water-soluble polymers across multiple concentration regimes

Soft Matter ◽

10.1039/d0sm01962c ◽

2021 ◽

Author(s):

Helen Yao ◽

Bradley D. Olsen

Keyword(s):

Neutron Scattering ◽

Small Angle ◽

Small Angle Neutron Scattering ◽

Bound Water ◽

Water Soluble ◽

Wide Concentration Range ◽

Water Molecules ◽

Water Soluble Polymers ◽

Soluble Polymers

Small-angle neutron scattering is used to measure the number of bound water molecules associating with three polymers over a wide concentration range. Different fitting workflows are evaluated and recommended depending on the concentration regime.

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