Vol 51, No 4 (2017)

Water-soluble random copolymers of N,N-(dimethylamino)ethyl methacrylate or N,N-(diethylamino)ethyl methacrylate with vinylsaccharides (N-methacryloyl aminoglucose, 3-O-methacryloyl glucose, 1-O-methacryloyl sorbose) were synthesized. The copolymers differed in composition, structure of the carbohydrate fragment, and type of carbohydrate–main-polymer-chain bonds. The immunomodulating activity and antitumor properties of the synthesized copolymers were established. Copolymers containing sorbose residues possessed the most pronounced immunodepressant properties.

The available oral forms of the antituberculosis drug ofloxacin do not ensure its long-term supply to the blood system. New polymeric complexes of ofloxacin based on copolymers of N-vinylpyrrolidone and 2-aminoethyl methacrylate hydrochloride with molecular masses of 25,000 – 87,000 were obtained with the purpose of creating effective prolonged release forms of ofloxacin. The polymeric complexes contained 25 – 35% ofloxacin, exhibited high activity against Mycobacterium tuberculosis H₃₇Rv, and ensured gradual release of ofloxacin (45 – 57% in 50 h) in pH 2.0 buffer at 37°C.

A series of new 7-bromo-5-(2′-chlorophenyl)-3-arylamino-1,2-dihydro-3H-1,4-benzodiazepine derivatives (II-VIII) were synthesized. The series of synthesized compounds included those that had a substantial effect on appetite in rats, exhibiting both orexigenic and anorexigenic effects at low doses (2.07 – 2.21 μM). Compound VI had anorexigenic activity comparable with that of the hormone leptin, which reduces the appetite and food intake. Co-administration of leptin and III, which exhibited a pronounced orexigenic effect, reduced appetite by 73%.

Compounds [Cu^II₂(benz)₄(Hbenz)₂] (1) and [Cu^II(ppa)₂(H₂O)₂]_n (2), where benz = benzoate and ppa = 3-pyridinepropionic acid, were synthesized and studied for their 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity and the inhibition of enzymes such as acetylcholinesterase (AChE), butyrylcholinesterase (BChE), lipoxygenase (LOX), urease, chymotrypsin and α-glucosidase. The synthesized compounds were also studied by hemolytic method for their cytotoxicity and found to be low-toxicity substances. For AChE inhibition, compound 2 showed IC₅₀ = 31.22 ± 0.45 μM, as compared to compound 1with IC₅₀ = 36.52 ± 0.44 μM. Both compounds showed comparably low activity against BChE and were also active against urease, but compound 1 exhibited selective anti-urease activity. The anti-α-glucosidase activity of both compounds was comparable with that of standard drug used.

Conversion of sugars into furans in acidic solution was used to quantify the carbohydrate contents in plant medicines using juice from fresh greater burdock (Arctium lappa L.) leaves as an example. Hexoses (fructose, glucose) and inulin degraded in acidic solution to form 5-hydroxymethylfurfurol (HMF) and other compounds. Fructose and sucrose could be quantified by spectrophotometry and HPLC and could also be determined spectrophotometrically after UV degradation by using the formation by acid hydrolysis of HMF and its derivatives with chromophores at 283 – 285 nm. It was found experimentally that furan derivatives (HMF) with absorption maximum at 283 nm, which was taken as the analytical wavelength, were formed via acid degradation of the juice and a solution of fructose. The carbohydrate contents in the test samples varied from 1.05 to 1.36%. The relative error of the mean of the result from the proposed method was 7.5%.

The biologically active melanin fraction was isolated from the mushroom chaga and investigated. Terpenic and phenolic compounds were found in it by using mass spectrometry. The total contents of lipids, phenols, and carbohydrates were determined. It was found that the isolated fraction possessed antioxidant, fungicidal, fungistatic, and prebiotic activity for several microorganism groups.

Problems hindering the implementation of modern technologies into pharmaceutical substance manufacturing are analyzed and classified according to the degree of negative impact. Proposals for their solution were developed considering the opportunities and constraints of implementing and scaling technologies presently in the pilot stage of development. A forecast of the emergence of new technologies at both the pilot and commercial development stages was presented.

An HPLC technique with UV spectrophotometric detection was developed for qualitative and quantitative determination of vitexin, rutin, hyperoside, and quercetin in Crataegus sanguinea hawthorn herbs (flowers and leaves). The separation used a Luna C18(2) column (4.6 × 150 mm, 5 μm) and a stepwise gradient. Calibration curves for the four flavonoids exhibited good linearity (r² > 0.995) in the studied ranges. The analytical recoveries over one day/week were 95.9-104.3%/95.6 – 102.9% for vitexin; 94.0 – 102.2%/93.5 – 101.5% for rutin; 98.0 – 102.2%/97.5 – 102.9% for hyperoside; and 96.0 – 109.8%/97.2 – 111.0% for quercetin. The intra- and interday coefficients of variation (RSD, %) were <3%. The relative error (ε, %) of a single determination at confidence level 95% was <3% for rutin, hyperoside, and vitexin and <4% for quercetin.

General information about the synthesis and properties of glatiramer acetate (GA) drug substance and the principles and methods for verifying the pharmaceutical identity of GA drug substance and Copaxone^® and generic Axoglatiran^® FS (INN) that are based on it was presented. Registration certificate No. LP-003572 dated Apr. 18, 2016, was issued by the RF for the first domestic GA-based generic drug Axoglatiran^® FS.

Lyophilization (freeze drying) is among the most effective methods used to stabilize drugs and increase their shelf life. It is influenced by many factors, the most important of which are the properties of the parent drug substance and the excipients and the freezing and drying conditions. This review considers in detail the excipients used in lyophilized dosage forms and gives examples of sublimation regimes used for the lyophilization of some antitumor drugs.

A sensor array composed of individual cylindrical cavities in a sheet of Plexiglas®, which served as tiny reaction compartments, has been developed previously by Abbaspour, et al. [39–41] based on holes created in the matrix sheet by laser beam. The cells containing sample solutions were scanned with a usual flatbed scanner, and then the obtained color image of each cell was analyzed with software written in Visual Basic (VB 6) media in red, green and blue (RGB) values. In this work, this simple, fast and inexpensive method has been used for determining free salicylic acid in aspirin tablets and urine in ferric nitrate solution. The results showed that Fe(III) forms a colored 1 : 1 complex with salicylic acid and the system response is linear in a concentration range of 2 – 280 μg/L of salicylic acid with a detection limit of 0.84 μg/L for pH in the range of 2.2 – 2.4. The scanner was used instead of a spectrophotometer and a series of interferences was examined.