A method to increase the thromboresistance of the biospecific antiproteinase hemosorbent was suggested based on simultaneous immobilization of duck egg ovomucoid and blood anticoagulant—heparin or hirudin—in the bulk of polyacrylamide hydrogel. It was demonstrated that modification of the hemosorbent with hirudin resulted in a significant increase of its compatibility with blood with simultaneous preservation of high capacity with regards to serine proteinases.

The effect of the structure of a mucoadhesive, insulin-containing, polymeric hydrogel on the rate of hormone release was studied. It has been shown that a decrease in the pore size of the hydrogel leads to an increase in the rate of insulin release, which contributes to a reduction in the time to achieve a positive effect upon oral administration of the drug while maintaining the physiological pathway of hormone penetration of the blood through the liver.

The possibility of creating acid-stable polymeric insulin carriers capable of swelling in a weakly alkaline medium and being adsorbed on the intestinal walls with insulin release has been studied. In vitro and in vivo experiments have shown that the optimal carrier is a gastric-insoluble polymer capsule containing a hydrogel based on a copolymer of acrylamide and acrylic acid modified by a compound that inhibits the enzymes of the small intestine and provides an enhanced mucoadhesive hydrogel.

Using the polymer model of small intestine, it is shown that the dependence of the efficiency of the preparation Ransulin on the size of an animal is due to a difference in the diameter of the small intestine and the enhanced enzymatic hydrolysis of insulin accompanying its diffusion from the intestine with a larger diameter. Unlike hypodermic injections, in the oral administration of preparations, insulin is initially accumulated in the liver and only then is transported into the bloodstream; that is, the physiological pathway of insulin secretion is realized.

Сополимеризацией акриламида с N-(2-D-глюкоз)акриламидом и N,N-метиленбисакриламидом в присутствии конканавалина А и меркаптоуксусной кислоты синтезированы гидрогели с повышенным содержанием мелких пор. При увеличении концентрации глюкозы в окружающей среде гидрогели самопроизвольно выделяют предварительно введенный в них инсулин аналогично поджелудочной железе по двустадийному механизму с максимальной скоростью на первом этапе.

Hydrogels with an increased content of fine pores are synthesized via the copolymerization of acrylamide with N-(2-D-glucose) acrylamide and N, N-methylenebis(acrylamide) in the presence of concanavalin A and mercaptoacetic acid. Insulin introduced into the hydrogels is spontaneously released in response to increase in the concentration of glucose in the environment via a two-step mechanism similar to that in the case of the pancreas and the maximum rate is observed at the first stage.

Используя полимерную модель тонкого кишечника, в работе показано, что зависимость эффективности действия препарата Рансулин от размеров животного обусловлена различным диаметром тонкого кишечника и повышенным ферментативным гидролизом инсулина в процессе его диффузии из кишечника с большим диаметром. В отличие от подкожных инъекций при пероральном введении препаратов инсулин первоначально накапливается в печени и только затем поступает в кровоток, т.е. реализуется физиологический путь секреции инсулина.

The reaction of the amino group of α-chymotrypsin with poly(N,N-diethylacrylamides) bearing terminal carboxyl groups which have the degree of polymerization ranging from 30 to 180 and which possess an LCST of 34–29°C affords polymer derivatives of the enzyme. It is found that, upon an increase in the temperature of the aqueous solution of the resulting derivatives to 40°C, the derivative with a degree of polymerization of 180 precipitates at 34°C, while the derivatives with a degree of polymerization of 30–80 remain in solution. The activity of α-chymotrypsin as a part of the derivatives with a degree of polymerization of 30 does not change with increasing temperature, whereas the activity of the enzyme as a part of the derivatives with degrees of polymerization of 60 and 80 decays almost to zero near the LCST of the initial polymers. Such a change in the enzyme activity is reversible (the activity fully recovers with a decrease in temperature).

How the activity of trypsin immobilized in a polyacrylamide hydrogel depends on the method of hydrogel preparation, the degree of swelling, and pore size is studied. It is shown that the measured activity of trypsin immobilized at the stage of hydrogel formation is always higher than the activity of trypsin immobilized by the reaction with the activated hydrogel. The higher the degree of swelling of the hydrogel and the lower the number of larger pores, the higher the activity of immobilized trypsin.

Исследована зависимость активности иммобилизованного в полиакриламидном гидрогеле трипсина от способа получения гидрогеля, степени его набухания и размеров пор. Показано, что измеряемая активность трипсина, иммобилизованного на стадии формирования гидрогеля, всегда выше, чем активность трипсина, иммобилизованного реакцией с активированным гидрогелем. Активность иммобилизованного трипсина тем выше, чем больше степень набухания гидрогеля и чем меньше количество пор большого размера. Определяющим фактором в проявлении активности являются размеры пор.

The copolymerization of a macromonomeric inhibitor of proteolytic enzymes with acrylamide and N,N′-methylenebis(acrylamide) in an aqueous solution in the presence of a redox catalyst has been studied. It has been shown that the addition of mercaptoacetic acid as a chain-transfer agent to the polymerization system results in a change in the structure of the forming hydrogel, i.e., a decrease in the number of large pores. Simultaneously, a substantial increase in the degree of the macromonomer incorporation into the hydrogel is attained and favorable conditions for the development of the biological activity of the macromonomer are created.

Изучена сополимеризация макромономера ингибитора протеолитических ферментов с акриламидом и N,N-метиленбисакриламидом в водном растворе под действием окислительно-восстановительного катализатора. Показано, что введение в полимеризующуюся систему передатчика цепи – меркаптоуксусной кислоты приводит к изменению структуры образующегося гидрогеля, т.е. снижению количества пор большого размера. При этом достигается существенное повышение степени вхождения макромономера в состав гидрогеля и создаются благоприятные условия для проявления макромономером его биологической активности.

New blood-contacting materials have been synthesized via graft copolymerization of a mixture of a hydrophilic monomer and the macromonomers hirudin and ovomucoid onto a synthetic polymer, either polyethylene, poly(ethylene terephthalate), or polydimethylsiloxane. It has been shown that the surface modification of the polymer via grafting of the hydrophilic monomer alone reduces the degree of denaturation of adsorbed proteins and that the introduction of hirudin and ovomucoid into the hydrophilic layer leads to a decrease in the amount of platelets adhering to the polymer surface and an increase in the clotting time on the polymer surface.

The thromboresistance of glucose-sensitive polymer hydrogels, modeling one of the functions of the pancreas, namely, the ability to secrete insulin in response to the introduction of glucose into the environment, has been studied. Hydrogels were synthesized by the copolymerization of hydroxyethyl methacrylate with N-acryloyl glucosamine in the presence of a cross-linking agent and subsequently treated with concanavalin A. Introduction of glucose residues into the hydrogel did not result in significant changes in either the number of trombocytes adhered to the hydrogel or the degree of denaturation of blood plasma proteins interacting with the hydrogel. Consequently, the biological activity of insulin did not change after release from the hydrogel. The use of glucose-sensitive hydrogels is supposed to contribute to the development of a novel strategy for the treatment of diabetes.