Enzyme therapeutic

Theovent The 0x0 process Therapeutic agents Therapeutic enzymes Therapeutic lenses Therapeutic role Therbar Therm-8 Thermal analysis... 

Hydrolases represent a significant class of therapeutic enzymes [Enzyme Commission (EC) 3.1—3.11] (14) (Table 1). Another group of enzymes with pharmacological uses has budt-ia cofactors, eg, in the form of pyridoxal phosphate, flavin nucleotides, or zinc (15). The synthases, and other multisubstrate enzymes that require high energy phosphates, are seldom available for use as dmgs because the required co-substrates are either absent from the extracellular space or are present ia prohibitively low coaceatratioas. 

Therapeutic enzymes have a broad variety of specific uses, ie, as oncolytics, thrombolytics, or replacements for inherited deficiencies. Additionally, there is a growing group of miscellaneous enzymes of diverse function. 

Erythrocyte Entrapment of Enzymes. Erythrocytes have been used as carriers for therapeutic enzymes in the treatment of inborn errors (249). Exogenous enzymes encapsulated in erythrocytes may be useful both for dehvery of a given enzyme to the site of its intended function and for the degradation of pathologically elevated, diffusible substances in the plasma. In the use of this approach, it is important to determine that the enzyme is completely internalized without adsorption to the erythrocyte membrane. Since exposed protein on the erythrocyte surface may ehcit an immune response following repeated sensitization with enzyme loaded erythrocytes, an immunologic assessment of each potential system in animal models is required prior to human trials (250). 

There has been a steady growth ia the economic importance of therapeutic ensymes, with sales reaching hundreds of millions of dollars per year as of 1992. Table 2 Hsts the trade names and costs of some of the more commonly prescribed enzyme preparations. Despite the magnitude of use of these products, the manufacture and sale of therapeutic enzymes represents a comparatively small fraction of the production and profits of the pharmaceutical houses that market them. 

Since many therapeutic enzymes are still derived from bacterial sources, FDA requirements can serve to make the commercial preparations more expensive. However, toxicological examination of each lot may not be necessary when the purification procedures yield reproducible preparations. 

Currently, a common form of activated mPEG used for preparation of therapeutic enzymes is mPEG-succinate-N-hydroxysuccinimide ester (SS-PEG) (11). It reacts with proteins in short periods of time under mild conditions, producing extensively modified conjugates with well preserved biological activity. However, the ester linkage between the polymer and the succinic acid residue has limited stability in aqueous media (5,12). 

Source Business Communications Company, Inc. Report RC-202R New Developments in Therapeutic Enzyme Inhibitors and Receptor Blockers, www.bccresearch.com. 

Shuvaev, V., Dziubla, T. D., Rainer, W., and Muzykantov, V., Streptavidin-biotin cross-linking of therapeutic enzymes with carrier antibodies nanoconjugates for protection against endothelial oxidative stress, in Methods in Molecular biology , (C. Niemeyer, ed.), Humane Press, Louisville, KY (in press). 

Additional products Tumour necrosis factor (TNF), therapeutic enzymes 18 Various chapters... 

Monoclonal antibodies for in vivo use Cytokines (e.g. interferons and interleukins) Therapeutic enzymes Thrombolytic agents Hormones Growth factors Additional miscellaneous proteins Blood Blood proteins (e.g. albumin and blood factors) Vaccines Cell- and tissue-based products Gene therapy products Antitoxins, venoms and antivenins Allenergic extracts... 

CH12 RECOMBINANT BLOOD PRODUCTS AND THERAPEUTIC ENZYMES... 

Enzymes are used for a variety of therapeutic purposes, the most significant of which are listed in Table 12.8. A number of specific examples have already been discussed in detail within this chapter, including tPA, urokinase, and factor IXa. The additional therapeutic enzymes now become the focus of the remainder of the chapter. Although a limited number of polymer-degrading enzymes (used as digestive aids) are given orally, most enzymes are administered intravenously. 

Table 12.8 Enzymes used therapeutically Enzyme Application...

McGrath, B. and Walsh, G (eds). 2006. Directory of Therapeutic Enzymes. Taylor and Francis. Poller, H. 1996. Oral Anticoagulants. Arnold. 

---