Vol 52, No 2 (2018)

The therapy of Huatanjiangqi capsule (HTJQ) has been used in the treatment of chronic obstructive pulmonary disease (COPD) clinically, with remarkable benefits. A lower functional activity of MRP1 is related to COPD development. However, the mechanism that contributes to MRP1 up-regulation by HTJQ was unclear. This study aimed to investigate the effects of HTJQ on the expression of Nrf2 and MRP1 in COPD rats. Rats were exposed to cigarette smoke plus lipopolysaccharide tracheal instillation to induce a COPD model. Then, Nrf2, HO-1, and MRP1 mRNA expression and their protein production in lung tissues were examined. The model group showed significant changes in the above assessments as compared to those of the control group (p < 0.05). The lung function of model group treated with low/high dose of HTJQ was significantly strengthened (both p < 0.05), and the inflammatory cells and goblet cells were decreased in lung tissues. Treatment with low/high dose of HTJQ resulted in obvious increase in Nrf2, HO-1, and MRP1 mRNA and protein expression levels (p < 0.05). HTJQ could up-regulate Nrf2 and MRP1 expression in lung tissues of COPD model rats. The mechanism by which HTJQ up-regulates MRP1 expression may be associated with Nrf2.

New 5-hydroxyadamantan-2-one derivatives with heteroaromatic, aromatic, and aliphatic acids (nicotinic, succinic, p-chlorophenoxyacetic, 3,4,5-trimethoxybenzoic, and anisic) were synthesized. Their pharmacological properties were studied to discover compounds with cerebrovascular anti-ischemic activity and without hypotensive activity. Esters of succinic acid and 5-hydroxyadamantan-2-one (diester Ia and monoester Ib, 100 mg/kg, i.v.) exhibited the most potent effect on cerebral circulation under ischemic conditions. They did not lower arterial blood pressure. The monoester was less toxic with LD₅₀ 740.0 (676.0 – 804.0) mg/kg. Analysis of the cerebrovascular effects of the succinate esters of 5-hydroxyadamantan-2-one using bicuculline revealed a GABA-ergic mechanism of action on cerebral vessels. However, radioligand analysis in vitro using the specific ligand [³H]-SR 95531 found that these esters did not compete for rat-brain membrane GABA_A-receptors. Thus, the monoester of succinic acid and 5-hydroxyadamantan-2-one possessed pronounced cerebrovascular anti-ischemic activity and did not produce hypotensive effects. The latter circumstance differentiated it from well-known drugs used in neurology (picamilon, Mexidol, nimodipine, cinnarizine, and Cavinton).

A method for synthesizing new tricyclic heterocyclic 7-cyclohexyl-6,7,8,9-tetrahydro-3H-pyrazolo- [3,4-c]-2,7-naphthyridine-1,5-diamines from 1,3-dichloro-7-cyclohexyl-5,6, 7,8-tetrahydro-2,7-naphthyridine-4-carbonitrile was elaborated. Investigation of the biological activity of the synthesized compounds showed that several of them exhibited pronounced neurotropic properties.

Hydrogel particles containing up to 49 mass% imatinib methanesulfonate (mesylate) (IM) were prepared from the chitosan—folic-acid conjugate. The release kinetics of IM from the particles in solutions simulating physiological body media were studied. It was established that the release kinetics of IM from the chitosan—folic-acid conjugate particles obeyed the Korsmeyer—Peppas model and a reciprocal power function of time. It was shown that the release rate of IM from the hydrogel particles could be controlled by varying the folic-acid content in the conjugate.

In continuation of our previous work, we have studied controlled release of gallic acid – anhydride (GAAN) conjugate prodrug through crosslinked-PVAbased hydrogel. The GAAN conjugate prodrug was prepared and incorporated into PVA-based hydrogel in order to formulate a drug delivery system with controlled release properties. The loaded and unloaded hydrogels were investigated by FTIR spectroscopy. Their thermal stability was studied by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). The drug release was studied spectrophotometrically, and the obtained data were interpreted in the framework of zero-order, first-order, Higuchi and Korsmeyer – Peppas models.

A comparison of spectrophotometric and chromatographic (HPLC) procedures for determining 3-phenethylrhodanine (cyclo-2-phenethyldithiocarbanoylacetic acid, CPET) drug substance using experimental and computational statistical methods showed that both methods had good precision and accuracy and could be recommended as equivalent alternative methods for quantitative determination of CPET drug substance.

A method for anilocaine determination in rat blood plasma using HPLC with UV-detection was developed. Samples were prepared by liquid—liquid extraction with 1-BuOH—hexane (2:98, v/v) followed by stripping with aqueous formic acid (0.1%). Chromatographic analysis used a Nucleodur HILIC column eluted in isocratic mode by a mobile phase of MeCN and aqueous ammonium formate (25 mM) (85:15) and UV detection at 205 nm. The method was validated for selectivity, carry-over, calibration curve linearity, precision, accuracy, limit of quantitation, dilution integrity, and stability. The analytical range was 25 – 1,000 ng/mL. The proposed method could be applied to pharmacokinetic studies of anilocaine preparations.

In recent years, several studies have focused on antioxidant, anti-inflammatory, and anti-cancer activities of quercetin (3,3′,4′,5, -pentahydroxyflavone). The nanotization of quercetin was shown to enhance its therapeutic efficacy due to smaller particle size. In the present study, an additional step was added to simple extraction cum RP-HPLC method for the quantification of nanotized quercetin (nQ) in biological samples to understand the pharmacokinetics and biodistribution of nQ following intravenous administration. The proposed method involves extraction of nQ from blood serum and tissues of mice with 2N HCl in comparison to well-known DMSO:MeOH mix method. The HCl extraction was found to be 2 – 3 times more efficient than DMSO:MeOH mix method. Results showed that the amount of nQ at various time intervals in the serum and tissues was 2 – 3 fold greater for HCl extraction than for DMSO:MeOH mix method, suggesting that HCl extraction must take into account nQ bound with protein. The reversed-phase HPLC was used for nQ detection, which showed the nQ retention time of 3.2 min. The limit of detection of nQ in blood serum was found to be 0.1 μg/mL. The proposed method was also validated in terms of linearity, precision, and accuracy.

A polyextract consisting of the extracts of the five title plants shows a marked prostate-protective effect in experimental chronic prostatitis. The pharmacotherapeutic efficacy of the phytoextract gives a basis to recommend its use in complex treatment and prophylaxis of prostatitis.

Low-molecular-weight heparins (LMWHs) are widely used in medical practice. LMWHs are produced using various methods of controlled depolymerization of unfractionated heparin (UFH). Herein, a method for radiation-induced destruction of aqueous heparin solutions using a ⁶⁰Co gamma-irradiation source is presented. The optimal conditions for depolymerization of starting heparin were found. The anticoagulant activity of LMWHs was studied as a function of irradiation dose. The results allowed this LMWH production method to be recommended for development of new anticoagulants.

An inorganic film of ruthenium hexachloroplatinate (RuPtCl₆) deposited on the surface of a glassy-carbon electrode exhibited catalytic activity for oxidation of S-containing amino acids. Catalytic electrochemical oxidation of cysteine, cystine, and methionine occurred at various potentials. The optimum conditions for producing a RuPtCl₆ film that gave the greatest catalytic effect were found. A method for selective voltammetric determination of cysteine, methionine, and cystine at an RuPtCl₆-film electrode was developed. The lower limit of quantitation of cysteine and cystine was 5 × 10^–6 M; of methionine, 5 × 10^–7 M. The proposed voltammetric method was used to determine cysteine, cystine, and methionine in drugs and vitamin complexes.