[Oral insulin preparations for the regulation of the glucose level in the blood].

Oral administration of diluted solutions of insulin results in the absorption of the hormone into bloodstream. After oral administration of diluted insulin solutions to healthy volunteers and animals with experimental diabetes insulin does not undergo hydrolytic degradation under the action of proteolytic enzymes and its absorption is sufficient to produce the hypoglycemic effect. This approach gives a chance of creating of novel strategy for diabetes treatment.

[Biodegradable polymeric derivatives of polypeptide drugs for targeting].

Relatively short polymer chains with lower critical solution temperatures were immobilized on protein macromolecules to obtain biodegradable polymeric derivatives of proteins (including those for heat-inactivated targeting of polypeptide drugs). Addition of a derivative to a multicomponent biological system and heating of the target to a temperature in excess of the lower critical solution temperature was followed by the carrier release into a separate phase and the transportation of the bound protein to the target. The protein molecule served as a biodegradable region and was progressively hydrolyzed, with the formation of low-molecular-weight fragments. These fragments were readily eliminated from the organism. The physiological activity of immobilized serum albumin was independent of the number of attached chains in the polymer carrier (the constant of bilirubin binding equaled 10 M(-1)). The biodegradation of synthetic systems, caused by alpha-chymotrypsin, was also studied. The more polymer chains were attached to serum albumin, the greater was the resistance of the protein to enzymatic hydrolysis.

[Oral administration of protein solutions].

Experiments on animals showed that native proteins may diffuse into the blood flow after oral administration of diluted protein solutions. An in vitro study led us to hypothesize that treatment with diluted solutions is accompanied by a decrease in the rate of protein proteolysis and accelerated protein diffusion through the intestinal mucosa.

[To the question of the possibility of oral insulin administration]. / K voprosu o vozmozhnosti ispol'zovaniia peroral'noi formy insulina.

The influence of oral insulin upon carbohydrate exchange in healthy volunteers was evaluated. One of the two forms of insulin used in the study was insulin, immobilized in a volume of polyacrylamide gel, modified by ovomucoid (proteolytic enzyme inhibitor), isolated from duck eggs; the other form was enteric-coated tablets bases on hydrogel substance. The oral administration of the hydrogel substance or the tablets resulted in the fall of blood glucose concentration by 34.9 +/- 4.4% and 28.6 +/- 6.9%, respectively. The maximal effect of the hydrogel substance and the tablets was observed at the 90th and the 180th minutes.

Mucoadhesive polymers with immobilized proteinase inhibitors for oral administration of protein drugs.

A new approach to overcome the degradation of protein drugs by proteolytic enzymes and their targeting to the blood through the digestive apparatus was developed. The approach is based on the immobilization of drugs into the polymeric hydrogel containing glycoprotein--ovomucoid from duck egg whites. This glycoprotein inhibits the activity of proteolytic enzymes and acts as a biospecific ligand to lectins on the walls of the gastrointestinal tract.

[Stability of immobilized insulin preparation at various pH]. / Stabil'nost' preparata immobilizovannogo insulina pri razlichnykh pH.

The stability of polyacrylamide hydrogel, modified by ovomucoid with immobilized insulin was studied at different pH of external medium. At 3.8 < pH < 5.5 insulin binds to the gel, due to electrostatic interaction between ovomucoid and insulin molecules.

[Inhibitors of proteolytic enzymes in the treatment of diabetes mellitus]. / Ingibitory proteoliticheskikh fermentov v terapii sakharnogo diabeta.

A new approach to overcome the degradation of insulin by proteolytic enzymes and its targeting to the blood through the digestive apparatus was developed. The approach is based on the immobilization of insulin into the polymeric hydrogel which is modified by ovomucoid--glycoprotein, inhibitor of proteolytic enzymes. Oral administration of this system to rabbits and rats, (in contrast to the hydrogels modified by proteolytic enzymes inhibitors without polysaccharide part), statistically significantly lowered blood glucose level.

[Synthesis and study of immobilized insulin]. / Sintez i issledovanie immobilizovannogo insulina.

Conjugates of insulin with duck egg-white ovomucoid and soybean trypsin inhibitor were synthesized. The conjugates are highly stable to alpha-chymotrypsin treatment. Oral administration of insulin-ovomucoid conjugates in rabbits significantly lowered blood glucose level unlike administration of insulin-soybean trypsin conjugate.

[Problems in creating insulin preparations with increased stability against proteolysis]. / Problemy sozdaniia preparatov insulina s povyshennoi ustoichivost'iu k proteolizu.

Chemical methods that accelerate the transport of insulin and other polypeptides across biological membranes and increase their resistance to enzymatic hydrolysis are reviewed. These methods include chemical modification of insulin macromolecules, the use of compounds that increase the permeability of biological membranes or inhibit enzymatic proteolysis, the hormone immobilization in a polymer coat protecting it against the aggressive environment, the incorporation of insulin into liposomes, etc. The advantages and drawbacks of these methods are analyzed, and promising lines of research in this field of applied biochemistry are described.

[Oxidase activity of horseradish peroxidase in oxidation of the bilirubin-albumin complex]. / Oksidaznaia aktivnost' peroksidazy khrena v okislenii kompleksa bilirubin-al'bumin.

The catalytic activity of horseradish peroxidase was investigated upon oxidation of the bilirubin-albumin complex (10(-5)-10(-4) M; BR: SA = 1: 1.5 mol/mol) by dissolved oxygen to biliverdin and other components. The process can be described by the Michaelis-Menten equation with Km = 14.4 microM and Vmax = 0.12 microM/min, if HRP = 3.1 x 10(-8) M. Oxidation is supposed to proceed in the triple complex--peroxidase: albumin: bilirubin.