BIOTECHNOLOGY - V. H. Gerasymenko - 2006

Part II. Special Biotechnologies

CHAPTER 8. THE MEDICAL USE OF IMMOBILIZED PREPARATIONS

8.3. THERAPY WITH IMMOBILIZED ENZYMES

Due to the advantages that immobilized Enzymes possess over native ones—such as enhanced stability, non-immunogenicity, resistance to proteolysis and microbial degradation, and The ability to target and concentrate in desired Organs—they hold immense promise for clinical application. The greatest success has been achieved in two main areas: the Treatment of acute Heart Failure and wound therapy.

Proteolytic Enzymes are the most widely used in clinical practice. Immobilized proteases obtained to date include subtilisin, Trypsin, α-Chymotrypsin, terilytin, and others.

In the former Soviet Union, streptokinase immobilized on a polysaccharide carrier was introduced into clinical practice for the first time globally and continues to be successfully used today for treating various thromboembolic disorders. The preparation known as Streptodekynaza exhibits no antigenic properties, is non-toxic, and remains stable.

It is well known that proteinases break down denatured Proteins, thereby facilitating wound cleansing and subsequent healing. Fibrous Materials based on Cellulose, polyvinyl alcohol, alginate salts, as well as polyamide and Collagen fibers, are most commonly used as carriers for immobilizing proteolytic enzymes for this purpose. Preparations immobilized on granular carriers—such as cellulose beads and dextrin granules—are also prepared. Furthermore, threads incorporating the enzyme during formation are manufactured and used as suturing material.

A comparative Analysis of the effects of native versus immobilized proteinases (primarily α-chymotrypsin, trypsin, terilytin, subtilisin, and collagenase) has demonstrated that wounds are cleared of necrotic tissue as early as the 2nd to 4th day, with granulation occurring twice as fast. Immobilized proteolytic enzymes have been used with great success in treating purulent lung and pleural diseases. The natural polymer collagen has proven to be an effective carrier when administering proteinases into the Abdominal cavity AND for treating empyema and abscesses.

To fabricate vascular grafts with a reduced or eliminated potential for thrombosis, biocompatible polymer tubes are utilized, with proteinases immobilized on their inner surface.

Immobilized proteolytic enzymes are effectively employed for the treatment of purulent infections and Burns in both humans and animals (Aniulis E. et al., 1989; Shchetinin V.V., 1991).

Proteolytic enzymes such as profenzyme and procel, immobilized on hemocellulose via covalent bonding, are used to treat purulent endometritis, purulent mastitis, and purulent limb wounds in animals (Aniulis E. et al., 1989). An additional advantage of these enzymes is that they are not absorbed into the bloodstream and do not affect product quality.

Enzyme-inhibiting proteins play a crucial role in treating various pathologies, particularly the principal polyvalent proteinase inhibitor. It has been immobilized on the polysaccharide CM-dextran (carboxymethyldextran), which was further modified with galactose residues. Proteinase inhibitors are used to treat Sepsis, bacterial (endotoxic) Shock, allergic conditions, arthrosis and Arthritis, among other disorders. In myocardial infarction, proteinase inhibitors exert an anti-ischemic effect, reducing the necrotic zone and improving collateral Circulation.

Biospecific sorbents have been synthesized based on immobilized protein inhibitor proteins and are used to treat such conditions as sepsis, purulent Peritonitis, burn disease, and hepatorenal failure (Valueva T.A. et al., 1988).

Another development is protosubtilin, a proteolytic enzyme immobilized on an organic polyethylene oxide carrier, which is utilized in The production of biological preparations as well as in human and veterinary medicine (Salganik R.I. et al., 1988). This preparation exhibits enhanced activity and thermal stability, along with activity across a broader pH range.

A complex vitamin preparation immobilized on collagen has also been developed for the Prevention of Metabolic Disorders. The immobilization of vitamin complexes (ascorbic acid, thiamine, pyridoxine bromide) onto a collagen carrier was carried out by entrapment within a gel. Experiments on laboratory animals have established that the administration of the immobilized vitamin complex has a significantly greater positive effect on metabolic disorders than the aqueous solution of the same Vitamins administered individually.