The paper describes an improved single-stage method for obtaining betulonic acid from birch bark with recrystallization from ethanol. The structure and composition of the obtained betulonic acid were confirmed by FTIR, NMR spectroscopy and elemental analysis. Thermal studies of betulonic acid were carried out using differential scanning calorimeter (DSC). The antitumor activity of betulonic acid and betulin was studied on Ehrlich ascites carcinoma culture in vivo experiments. It was found that under the influence of betulin and betulonic acid the content of dead cells of Ehrlich ascites carcinoma increased. It was shown that betulonic acid has a protective effect on the hematopoiesis system and does not have a toxic effect on the body.

The purpose of this work was to develop a new one-step method for the synthesis of allobetulin 3-O-formate from birch bark, select optimal synthesis conditions and to studing its influence on blood/plasma coagulation. A new one-step method has been proposed for the synthesis of allobetulin 3-O-formate from birch bark Betula Pendula Roth., based on combining the extraction of betulin, its isomerization into allobetulin in the presence of a catalyst - orthophosphoric acid, and the esterification of allobetulin with formic acid. The influence of the duration of the process of treating birch bark with formic acid and the H3PO4 content on the yield of allobetulin 3-O-formate was established. The highest yield of crude allobetulin 3-O-formate (37% by weight of a.d.b.) is achieved at a process duration of 12 hours in the presence of 10% H3PO4, as well as with a duration of 16 hours in the presence of 8% H3PO4. The yield of recrystallized from ethanol allobetulin 3-O-formate is about 30% by weight of the a.d.b. The composition of the obtained samples of recrystallized allobetulin 3-O-formate was determined by elemental analysis, and its structure was confirmed by IR and NMR spectroscopy. In vitro experiments conducted using human donor blood showed that allobetulin 3-O-formate exhibits pronounced procoagulant properties and does not have a significant effect on the erythrocyte membrane. Allobetulin 3-O-formate can be used to create biomaterials with specified properties in relation to blood coagulation.

In order to improve bioavailability and expand the range of pharmacological properties of biologically active betulin, mechanocomposites of betulin with natural water- soluble polysaccharide arabinogalactan, with amino acid L-histidine and in the ternary system betulin- L-histidine- arabinogalactan were obtained. The formation of mechanocomposites was confirmed by X-ray phase analysis and IR-spectroscopy. It was found that when dissolving the obtained mechanocomposites in water, a higher concentration of betulin in solution was achieved compared to the solubility of the starting substance.

Changes in the morphology of betulin crystals during heating at selected temperatures corresponding to polymorphic transformations were investigated. It was shown that the prismatic crystals of starting betulin form III were converted into needles at 120 °C after water removal, followed by the III→II polymorphic transformation. During further heating up to 180 °C, the whiskers of betulin form I were grown. Experiments on betulin heating in the presence of dicarboxylic acids, adipic or suberic showed that the morphological changes can serve as a test for the formation of cocrystals. According to morphological changes, the formation of cocrystals of betulin with adipic acid under heating was identified. The interaction of adipic acid vapor with the surface of betulin crystals was suggested. In contrast, morphological changes in the mixture of betulin and suberic acid under heating provided only the evidence of polymorphic transformations of the components. The results on cocrystal formation by heating were compared with the preparation of cocrystals by the liquid-assistance grinding method. Despite the fact that polymorphic forms with a high surface area were formed when betulin was heated, dissolution studies showed that the starting betulin polymorph III exhibited the highest dissolution rate in comparison with betulin polymorphs obtained under heating.

The aim of this research was to obtain the grafted copolymer of chitosan with acrylamide using the electron beam irradiation. Radiation dose was varied from 6 to 160 kGy. The highest yield of the product was observed at radiation dose of 12–40 kGy. Further increase in the dose caused a decrease in the product yield as well as its solubility in water. Using gel permeation chromatography, it was confirmed that unreacted chitosan remained in the product. NMR study of the water-soluble part of the product obtained under the doses of 6, 12, and 20 kGy showed that the length of the side chains of grafted acrylamide was about 2 elementary units. Investigation of chitosan solutions by means of dynamic light scattering revealed the presence of chitosan agglomerates in the solution. The possibility of obtaining dense films was demonstrated. Mechanical treatment of the copolymer in the ball mill caused an increase in the solubility of the samples obtained even at radiation doses of 80 and 160 kGy. It was determined by means of chromatographic methods that there were no products with low molecular weight in the ball-milled product, and unreacted chitosan did not undergo mechanocracking during the mechanical treatment.

For the first time, it was proposed to obtain carbon gels by carbonization of organic gels synthesized by sol-gel condensation of formaldehyde with larch bark tannins and pine cellulose. According to the BET method, the introduction of cellulose into the composition of an organic tannin- -formaldehyde gel changes such characteristics of the porous structure of the obtained carbon gels as specific surface area, total pore volume, micropore surface area, micro-and mesopore volume, and average pore diameter. The development of the porous structure of carbon gels obtained with the use of dissolved cellulose additives (10 and 20 wt%) occurs as a result of the formation of mesopores with an average diameter of 22.83 and 21.54 nm. The introduction of cellulose aerogel powder into the original organic gel promotes the formation of micropores in the resulting carbon gel. The most developed microporous structure has a carbon gel obtained by carbonization of an organic tannin-cellulose gel containing 20 wt% cellulose aerogel (specific surface 754 m2/g, of which 80 % (606 m2/g) relates to the surface of micropores). Using scanning electron microscopy, it was found that the surface morphology of carbon gels obtained by carbonization of organic tannin-cellulose gels may be controlled by varying both the concentration of cellulose and its state (cellulose solution or cellulose aerogel powder) during the synthesis of the initial organic gel.

Betulin dipropionate is a natural compound with high cytotoxicity toward many cancer cells. The one-step synthesis directly from the birch bark without a separate betulin isolation stage was developed to obtain betulin dipropionate. Due to its composition, betulin dipropionate is a promising drug for treating a wide range of diseases. However, the poor water solubility of this compound has limited its applications. We prepared the composites of betulin dipropionate using two methods: ball milling of the mixtures of betulin dipropionate with synthetic and natural polymers, such as polyvinylpyrrolidone polyethylene glycol, fumed silica, arabinogalactan, and preparation of thin films with arabinogalactan by evaporating the aqueous solutions. These composites showed higher water solubility and improved antitumor properties against ascites carcinoma cells and human lung adenocarcinoma cells compared with the initial substance. Furthermore, the cell viability studies based on Annexin V and Propidium iodide probes confirmed the high proapoptotic effect of betulin dipropionate against cancer cells.

Graft copolymers of chitosan with acrylamide were obtained by the radiation- thermal method using accelerated electrons. The formation of graft copolymers was confirmed by IR spectroscopy and gel permeation chromatography. It is shown that the efficiency and degree of grafting depend on the dose of ionizing radiation, and pass through a maximum with increasing dose. The conditions for obtaining copolymers with a high yield of the product were found. The resulting copolymers were used to obtain betulin composites using mechanochemical processing. It has been shown that the rate of release of betulin into an aqueous solution during the dissolution of the composite depends on the pH of the solution, which makes it possible to consider mechanocomposites based on copolymers of chitosan with acrylamide as promising means for controlled drug delivery.

Polysaccharides are important structural components of all plant species. Gel-like polysaccharides have found wide application in various fields, including medicine, construction, and the food industry. In the present work, galactomannan and galactoglucomannan gel-like polysaccharides were modified with sulfate groups and their anticoagulant activity was studied. Sulfation with chlorosulfonic acid in pyridine and with sulfamic acid in pyridine and a sulfamic acid–urea deep eutectic solvent were used as synthesis routes. The resulting gel-like polysaccharide sulfates were studied by elemental analysis, Fourier-transform infrared spectroscopy, and gel permeation chromatography. It was established that the anticoagulant effect of sulfated galactoglucomannan (SGGM) and galactomannan (SGM-1 and SGM-2) is related to an independent antithrombin-independent decrease in the amidolytic activity of thrombin and factor Xa. It is shown that the inhibitory activity of SGGM and SGM-2 against the collagen-induced platelet aggregation can be an additional factor in selecting compounds that are most promising for modifying polymer surfaces to ensure resistance to blood clotting.

In this work, the cocrystals of betulin with suberic acid were prepared by liquid-assisted grinding method using solvents of different polarity. The formation of cocrystals was confirmed by means of powder X-ray diffraction, IR spectroscopy and thermal analysis. It was shown that under heating, a structural transformation occurred after water removal, followed by cocrystal dissociation.

The cocrystal of betulin with adipic acid was prepared using a liquid-assisted grinding method. The formation of cocrystal was confirmed by powder X-ray diffraction and IR spectroscopy methods. In order to choose a liquid for preparing cocrystal, solvents of different polarity were compared. It was shown that cocrystal of betulin with adipic acid was formed if solvents were used during mechanical treatment, in which the increased solubility of adipic acid was observed

Arabinogalactan (AG) and sulphated arabinogalactans which are products of chemical modification of arabinogalactan polysaccharide with anticoagulant properties were studied by experimental infrared (IR) spectroscopy combined with density functional theory simulations. Mutual analysis of experimental and theoretical IR frequencies indicates that the discrepancies between experiment and theory is caused by the influence of –OH groups, which led to the energy shift and broadening of the absorption IR bands. It was found that theoretical and experimental spectra correspond well within the 3000–4000 cm −1 spectral region. Addition of sulphur group in AG structure causes hydroxyl group to become accessible for further sulphation. The difference between experimental and theoretical IR frequencies of sulphated AG derivatives is greater than that of the parent arabinogalactan due to the increase in the number of possible isomers and conformers.

The pharmaceutical cocrystals are nowdays intensively studied due to the improvements of solubility, stability, processability, etc. of the drugs. In this work, the cocrystals of betulin with terephthalic acid as a coformer were prepared by liquid-assisted grinding method. The formation of cocrystals was confirmed by powder X-ray diffraction, IR spectroscopy and thermal analysis methods. HPLC analysis showed that in the case of betulin – terephthalic acid cocrystals, solubility of betulin was significantly improved compared to the initial betulin as well as betulin from cocrystals with aliphatic dicarboxylic acids which were earlier prepared.

Methods have been developed for the preparation of enterosorbents by treating crushed abies bark with the 1.5% aqueous of NaOH solution or by extraction with hexane. It was found that all obtained enterosorbents have good sorption properties with respect to gelatin and methylene blue. The highest sorption activity for methylene blue was shown by a sample, obtained by extraction of abies bark with hexane (97.0 mg/g), and for gelatin sorption activity – a sample, obtained by treatment of abies bark with alkali (225.0 mg/g). It was found that the enterosorbent, obtained by treatment of abies bark with alkali solution both at a dose of 0.15 g per kg of animal weight (g/kg) and at a dose of 0.20 g/kg and the enterosorbent, obtained by extraction of abies bark with hexane at a dose of 0.20 g/kg, have the highest efficiency for the treatment and prevention of acute experimental Escherichiosis. From the considered methods of obtaining enterosorbents from abies bark for the treatment and prevention of gastrointestinal infections of animals, it is recomended to use a method based on treatment of abies bark with alkalai solution and apply the drug in a dose of 0.15 g/kg

The cocrystal formation potential of betulin with aliphatic dicarboxylic acids was investigated. Carboxylic acids of varying carbon chain length, namely: adipic, succinic and suberic acids, were selected to explore the effect of the coformer structure on cocrystal formation when liquid-assisted grinding was used. Cocrystal formation was characterized by powder XRD and IR studies. Betulin cocrystals with adipic acid were successfully synthesized and HPLC analysis showed that solubility of the betulin cocrystal was significantly improved compared to the initial betulin and its mechanocomposite with polymer

Betulin and betulin diacetate (BDA) composites with polyethylene glycol (PEG) were obtained by ball-milling. In case of betulin - PEG mixtures, there was almost complete amorphization under ball-milling. On the contrary, there were no significant changes in the intensity of the reflections in the powder X-ray diffraction patterns for ball-milled mixtures of BDA with PEG. Dissolution of BDA in PEG melts formed at the contacts of particles under collisions with milling bodies leading to crystallization of the drug was suggested. An opportunity to dissolve BDA crystals in PEG melt followed by their crystallization was proven by DSC and hot stage optical microscopic observation

It was carried out optimization of the process of water-ethanol extraction of ethanol-lignin from Siberian larch wood by calculation methods. A two-parameter mathematical model of the extrac-tion process based on the central second-order Kono composite plan was created. The influence of two parameters - the concentration of aqueous ethanol and temperature - on the degree of delignification of wood was studied. It was shown that the selected parameters are statistically independent of each other. The response surface is a parabolic cylinder. Optimal conditions for the process of the bark wood extraction which corresponds to the maximum yield of ethanollignin were determined: temperature 220 degrees C and ethanol concentration 70% vol.

A new method to obtain cellulose sulfates from available and inexpensive raw material—aspen wood was developed. This method integrates catalytic peroxide delignification and sulfamic acid sulfation stages. Solvents such as acetic acid and water were used for isolation of pure cellulose by wood peroxide delignification with TiO 2 catalyst. Low-aggressive and less-toxic sulfating agent—sulfamic acid–urea mixture was used to obtain cellulose sulfates.

It was found that the preparations for the prevention and treatment of the escherichiosis of animals, obtained from aspen bark have the good sorption properties in relation to gelatin and methylene blue. It was experimentally established that the all obtained preparations can be used for the prevention and treatment of the escherichiosis of animals. Good therapeutic and prophylactic properties have been proven for the sample of initial aspen bark at a dose of 0.15-0.20 g/kg and for the sample of aspen bark with supported arabinogalactan at a dose of 0.15 g/kg. The average level of therapeutic efficacy was established for the sample of extracted aspen bark at a dose of 0.15-0.20 g/kg. The highest efficacy in the treatment and prevention of acute experimental escherichiosis was established for the sample of "aspen fat" extracted by hexane from aspen bark, when administrated at optimal doses of 0/10-0.15 g/kg.