Vol 50, No 3 (2016)

The influence of the melatonin-correcting drugs melaxen and Valdoxan on the gene-transcription level of superoxide dismutase (SOD, EC 1.15.1.1) and catalase (EC 1.11.1.6) in liver and heart of rats with hyperthyroidism has been investigated. Administration of these drugs to rats with model pathology leads to changes in SOD and catalase expression in their tissues toward the control values.

This study was aimed at the preparation of curcumin-loaded alginate/pectin microparticles (beads) in order to enhance the pharmaceutical effect of curcumin as a drug for colon related diseases. For this purpose, three types of curcumin-loaded beads were prepared with different alginate/pectin ratios (100/0, 75/25 and 50/50) and studied in various experiments including the release of curcumin from beads and swelling of beads in buffer solutions of simulated gastric, intestinal, and colon fluids. The results of curcumin releasing experiments under conditions mimicking stomach to colon transit showed that the beads with higher content of pectin exhibit stronger curcumin entrapment, slower release rate, and lower swelling. Thus, 50/50 alginate/pectin composition has minimum release in the upper parts of gastrointestinal tract (stomach and intestine). However, when these beads reached colonic buffer medium, the curcumin release suddenly increased. Therefore, beads with 50/50 alginate/pectin compositions could be useful as a suitable carrier for curcumin delivery to colon. Moreover, the stability and chemical protection of curcumin encapsulated in these beads was confirmed by high performance liquid chromatography measurements after a period of six months.

The physicochemical and biological properties of a new finely dispersed Si- and Al-containing sorbent are presented. Its modification using silver nanoclusters immobilized on the sorbent-particle surface is described. The parameters of the sorbent porous structure, its sorption activity, and the rate of silver release from the sorbent surface in contact with a liquid medium are determined. Both the sorbent matrix and the original silver-modified sorbent are well tolerated by experimental animals upon intramuscular administration and cause no changes in the behavior, weight, and appearance of the animals. Results from studies of the leukocyte, platelet, and red-blood-cell pools of peripheral blood also confirm that the sorbents are biocompatible with body tissues.

Ionization constants (pK_a and pK_b) of N-substituted mono(di)halo(H)anthranilic acids and their amides and hydrazides were studied as functions of their quantum-chemical parameters. The predicted pK_a and pK_b values calculated for 10 new compounds of this series were confirmed experimentally. An analysis of the ionization constants predicted using the proposed equations showed them to be advantageous over other computer programs.

Novel structural hybrids of pyrazolobenzothiazine and triazole ring systems have been prepared to observe a synergistic effect of the two ring systems. The methodology involves condensation of pyrazolobenzothiazine rings with methyl chloroacetate, followed by hydrazide formation. The hydrazides were converted to triazoles through the formation of intermediate potassium salts of dithiocarbazate. The final compounds as well as intermediates were screened for their antibacterial activity against a multidrug resistant strain of Staphylococcus aureus. It was interesting to observe that dithiocarbazates (7a, 7b) and target triazoles (8a, 8b) exhibited antibacterial activity.

An effective four-step synthesis of the tripeptide H-Pyr-His-Trp-OH that is used to produce synthetic gonadoliberin agonists was developed. The synthesis was carried out without adding and removing protecting groups and could produce the target compound with >98% purity.

A solid-state ion-selective electrode (ISE) for doxycycline hydrochloride determination is proposed. A construction feature is a plasticized membrane ion—electron transducer containing polyaniline. The transducer is situated between the current conductor and ion-selective membrane. The main metrological characteristics of the electrode are determined. It is established that the transducer increases the stability of the electrode potential during the measurements. It is demonstrated that the ISE can be used in practice for quantitative determination of doxycycline hydrochloride in dosage forms.

Reductive amination of the tetraene macrolide antibiotic lucensomycin by para-substituted benzaldehydes and cyanoborohydride formed its N-benzyl derivatives. The physicochemical, medical, and biological properties of the obtained pimaricin derivatives were studied. Biological tests showed that the N-benzyl lucensomycin derivatives possessed high antifungal and antiviral activity. Pharmacological tests showed that the acute toxicity (LD₅₀) of the synthesized lucensomycin derivatives was six times less than that of the starting antibiotic.

The presence of several generics on the pharmaceutical market makes it possible to create a competitive environment and helps to reduce the costs of drug therapy. RF Government Decree No. 1154 of October 28, 2015, “On the procedure for determining the interchangeability of drugs for medical use” determines largely the fate of generics in Russia. Quality assurance of generics and the creation of a competitive environment for the procurement of pharmaceutical products by regional public health institutions in order to reduce costs were the primary drivers of this decree. However, results from substitution of antiepileptic drugs indicate a number of problems in this field. The present review is devoted to an analysis of the interchangeability problems of antiepileptic drugs.

Oxidative bromination of o-xylene with liquid bromine or hydrobromic acid in aqueous solution in the presence of an alkali-metal bromate as the oxidizing agent was studied. The proposed method allowed the amount of wastes to be reduced while maintaining a high yield of bromo-o-xylene, which is used in the synthesis of vitamin B₂.

A selective and specific quantitative assay with HPLC/MS determination of the broad-spectrum antituberculosis antibiotic cycloserine in blood plasma with reserpine internal standard was developed and validated. It was shown that the method was accurate and precise and linear in the range 0.5 – 20.0 μg/mL. A calibration curve obeyed the equation Y = aX + b, where a = 0.0893 and b = –0.0134 with a correlation coefficient of 0.9994. The cycloserine limit of detection was 0.1 μg/mL; the limit of quantitation, 0.5 μg/mL. The recoveries of cycloserine from the matrix at low (0.5 μg/mL) and high (20.0 μg/mL) drug concentrations were 41.7 and 62.4%, respectively, with matrix factors of 0.28 and 0.34, respectively, normalized to the internal standard.