Befloxatone, a novel oxazolidinone derivative, inhibited selectively and competitively monoamine oxidase (MAO)-A in human and rat brain, heart, liver and duodenum homogenates with Ki values ranging from 1.9 to 3.6 nM for MAO-A and from 270 to 900 nM for MAO-B. In vitro, befloxatone was more potent at inhibiting MAO-A activity than reference compounds (befloxatone > harmaline > brofaromine > BW 137OU87 > RS 8359 > toloxatone > moclobemide). The inhibition of MAO-A by befloxatone was time-dependent and fully reversible after dilution. After p.o. administration, befloxatone induced a dose-dependent and selective inhibition of rat brain and duodenum MAO-A activities ex vivo with ED50 values of 0.06 and 0.025 mg/kg, respectively. Befloxatone (0.5 mg/kg p.o.) decreased MAO-B activity by only 20% in both tissues. In the brain, liver and duodenum, the inhibition of MAO-A activity by befloxatone was short lasting. Twenty-four hours after administration of befloxatone (0.75 mg/kg p.o.), a full recovery of MAO-A activity was observed in the brain, but the enzyme activity was still decreased by 38 and 56% in the duodenum and liver, respectively. In the rat brain, befloxatone (0.75 mg/kg p.o.) increased levels of norepinephrine, dopamine and 5-hydroxytryptamine and decreased levels of their respective deaminated metabolites. These variations were dose-dependent and reversed 24 hr after administration. In addition, befloxatone (0.75 mg/kg p.o.) decreased free 3,4-dihydroxyphenylethylene glycol levels in the brain and plasma. Befloxatone (10 microM) did not modify the activities of diamine or benzylamine oxidase and did not interact with monoamine uptake mechanisms or with a variety of neurotransmitter or drug receptor sites. In conclusion, the neurochemical profile of befloxatone demonstrates that this compound is a selective, competitive, potent and reversible MAO-A inhibitor.

The data reported here for native and immobilized enzymes show that the stabilization (or destabilization) effect changes as a function of the temperature, so that the term "stabilization" only has meaning for the concrete temperature conditions and the concrete enzyme [compare lysoamidase (LA) and trypsin (TR)]. For this reason, there are always two temperature regions in the general case -where the native or the modified enzyme is more stable [21]. The analysis of the times for cleansing wounds of suppurative-necrotic masses and complete healing showed that the immobilized forms of the enzymes were much more effective than the corresponding native preparations. This is because native (unmodified) enzymes are rapidly inactivated and washed out in wound discharges, while the immobilized preparations are more stable and have a lasting action. In addition, the therapeutic effect of the materials containing an enzyme complex (collitin -CL -or crab hepatopancreas -CP) is higher in comparison to monoenzymatic preparations (Tr, for example) [22,23].Proteolytic enzymes (trypsin, chymotrypsin, collagenase, etc.) are widely used in medicine [1][2][3][4]. In application on a suppurative-necrotic wound, proteolytic enzymes (PE) split, bringing nonviable tissues which must usually be removed with a scalpel to the soluble state [4]. The possibility of intracavitary, intramuscular, and in many cases also local administration is low due to the irritating effect of proteinases, their immunogenic and allergenic properties, hemolytic action in intravenous administration, poor bioavailability, and other factors manifested together or separately, but relatively frequently. Clinical use is limited by the high cost, low availability, rapid elimination from the body, and impossibility of creating a high local concentration of the preparation without increasing its systemic concentration. These drawbacks can be eliminated to a significant degree by chemical modification of the proteins with high-molecular-weight compounds, which allows reducing the total dose of the preparation used, increasing its time in the body, and simultaneously attenuating undesirable side effects -i.e., a high local concentration of the preparation can be attained with chemical modification, while the total dose will be negligibly small in comparison to use of the native protein [5].Relatively cheap proteinase complexes are preferred for industrial use in comparison to monoenzymatic preparations for many reasons; first, lower loss of overall activity during production; second, the most expensive and laborious stages of purification are eliminated (gel filtration and ion-exchange chromatography, etc.); third, the complexes have a broader spectrum of action both with respect to the pH range and with respect to substrate specificity [6].The Textile Materials Research Institute is the basic developer and manufacturer of textile materials containing various enzymes. These materials are used as applications, cotton wool, lint or powder, and as dressings for treatment...

The properties of unmodified crab hepatopancreas proteolytic complex and the complex immobilized on chitosan-containing cellulose substrates were investigated. The kinetics of immobilization and storage of dried preparations was investigated. Three stages of inactivation of the immobilized sample were established: in immobilization, during drying and storage. It was shown that immobilization of the complex on a textile substrate protects enzymes from thermal inactivation in model buffer solutions at different pH.The Scientific-Research Institute of Textile Materials is manufacturing various biologically active substances (BAS), including enzymes immobilized on insoluble textile substrates, on the industrial scale. These materials are used for medical purposes as applications, lints, or powders, as dressings for treating purulent and necrotic, burn, and other wounds [1].Incorporation of hydrocarbons in the structure of drugs significantly reduces their harmful side effects on the body and increases bioavailability [2,3]. Chitosan (more precisely, the products of its degradation in the wound by endogenous enzymes) has a powerful wound-healing property [2] and as the literature indicates, antiseptic activity with respect to the most frequently encountered pathogens of purulent complications [4]. The strength of its effect is inferior to antibiotics, but it retains its bacteriostatic activity for 2-2.5 days on contact with microbial flora in liquid medium. It is especially active in the acid medium characteristic of the initial stages of any wound process, and this is characteristic of antibiotics and Furacin solution to a lesser degree [4,5].The proteolytic complex from crab hepatopancreas (CP) is widely used in medicine, cosmetology, the food industry, and other sectors due to the content of unique proteases (including true collagenase), availability, and low cost [5][6][7]. One problem in obtaining insoluble derivatives of CP on oxidized or unmodified cellulose is the rapid desorption of CP from the textile substrate due to the unusually low isoelectric point of the enzymes it contains (pI < 3.5) [6,7].We synthesized substrates made from cellulose, oxidized cellulose, and chitosan with a positive charge on which CP was also immobilized [8,9].

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