Vol 53, No 1 (2019)

A comparative dissolution kinetics test was performed to model the actions of pathological duodenogastric reflux and therapeutic acid suppression on the stability of esomeprazole formulations from three different manufacturers. After exposure to solutions pH (1.2 ±0.05) or (4.0 ±0.05), formulations were transferred to medium pH (7.0 ±0.05), from which aliquots were collected at 0, 4, 10, 15, 20, 30, 45, and 60 min for estimation of esomeprazole concentrations. The duration of exposure of the medicinal formulation of esomeprazole to pathological duodenogastric refluxate was 4 min. In these test conditions, Generic-1 and Generic-2 were found not to be equivalent to the reference drug (RD); the medicinal formulation of the RD was probably influenced by pathological duodenogastric reflux in the stomach, while Generic-2 was completely degraded in moderately acidic medium pH 4.0, which is evidence of the possible adverse influence of its main antisecretory pharmacodynamic effect of the intragastric stability of the medicinal formulation and the active substance.

This review presents the main advances in the design of antitumor platinum complexes over the last five years. Particular attention is paid to unconventional antitumor platinum compounds (complexes in the trans configuration, Pt(IV) complexes with S and P donor ligands, multinuclear complexes).

A method for the synthesis of 1-amino-3,3-dimethyl-3,4-dihydronaphthaline-2-carbonitrile (β-aminonitrile) was developed and used to synthesize Schiff bases, thioureide and chloracetamide derivatives. This latter was cyclized to 5,5-dimethyl-2-chloromethyl-5,6-dihydrobenzo[h]quinazoline-4(3H)-one, which was used to synthesize a series of 2-sulfanylmethyl and 2-aminomethyl derivatives. 2-Chloromethylbenzo[h]quinazoline in the presence of a base was found to form condensed heterocyclic compounds with seven rings: 1,1,11,11-tetramethyl-1,2,11,12-tetrahydropyrazino[2,1-b:5,4-b′]di(benzo[h]quinazoline)-10,16(8H,18H)-di one. The antitumor properties of the compounds synthesized here were studied in an ascites carcinoma model and the antibacterial properties were studied using the agar diffusion method.

1-(6-Aminohexylamino)-1-phenylcyclohexyl dihydrochloride (IEM-2062) had significantly greater antihypoxic, anticonvulsant, antidepressant, and analgesic activity than memantine and similar antiparkinsonism activity as memantine; it had low toxicity and was safer for use. IEM-2062 produced significant pharmacological effects in the dose range 0.3 – 3 mg/kg.

The acute toxicity and analgesic activity of compounds of the ethyl-6-amino-4-aryl-5-cyano-2,4-dihydropyrano[2,3-c]pyrazole-3-carboxylate series were investigated. Study compounds were found to be essentially nontoxic and to have analgesic activity.

The paper presents the overlook on bismuth oxide nanoparticles as a potential material applied in medicine-related fields of science. First, the types of drug delivery systems are described. General properties of bismuth oxide are considered as well. The main part of article is devoted to bismuth oxide-based systems intended for drug delivery and medical imaging purposes. It has been confirmed by many scientists that bismuth oxide nanoparticles are a promising material for drug delivery systems and for enhancing the properties of other products in medical applications.

Studies at the V. V. Zakusov Science Research Institute of Pharmacology have worked on the basis of the β-pleated structure of loop 4 of brain-derived neurotrophic factor (BDNF) to construct its dimeric peptide mimetic - GSB-106, bis-(N-monosuccinyl-L-serine-L-lysine) hexamethylenediamide. GSB-106 is being developed as an antidepressant with a BDNF-ergic mechanism of action. We report here studies of the physicochemical properties of GSB-106 and development of a method for analysis of GSB-106 substance. The main pharmacopeia quality indicators were determined and IR and NMR spectra were obtained from samples of substance. A method was developed for detecting contaminants in substance using TLC and HPLC.

Escin-containing horse chestnut extracts and various medicinal formulations are widely used as venotonic agents whose mechanisms of action and intracellular targets remain unknown. Escin is used as an active substance to increase membrane permeability in experiments, and it has more recently been shown to have cytotoxic effects on a number of tumor cell lines. With the aim of increasing the percentage content of active pharmaceutical escin substance in medicinal formulations and studying its mechanism of action, we prepared a horse chestnut extract (HCE) with a 50% escin content. Comparison of the cytotoxic action on HeLa tumor cell cultures showed that at identical concentrations by weight, HCE and reference agent escin had identical cytotoxic effects. At a concentration of 0.003 mg/ml, both substances inhibited HeLa cell viability by more than 80% at 24 h. The cytotoxic effect was not seen when the concentration was reduced four-fold. At equivalent cytotoxic concentrations, the actions of escin in HCE were studied on isolated mitochondria. Both substances were found to increase mitochondrial membrane permeability, to induce mitochondrial swelling, to decrease mitochondrial calcium capacity, and to induce the opening of mitochondrial pores (MPTP). MPTP opening leads to cell death. Escin induced slow and irreversible swelling of mitochondria, while HCE produced rapid and reversible swelling. The MPTP inhibitor cyclosporin completely eliminated the actions of both substances, pointing to the involvement of mitochondria in the pharmacological actions of escin and HCE.

A chromatomass spectrometric method for assay of salicylic and acetylsalicylic acids in human plasma was developed and metrologically validated. The method measured salicylic and acetylsalicylic acid contents in plasma samples from 26 patients with cerebrovascular diseases (CVD) taking aspirin constantly at doses of 75 – 100 mg/day as antiaggregant therapy for primary or secondary prophylaxis of vascular events. Patients whose samples contained acetylsalicylic acid demonstrated more marked pharmacological responses to antiaggregant therapy.