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Background Information Serrazimes-I

Product Description
Serrazimes-I is a proteolytic enzyme system derived from Aspergillus oryzae and Aspergillus melleus that is designed as an alternative for Serrapeptidase (a.k.a. serratio-peptidase and serrapeptase) in dietary supplements used for cardiovascular, anti-inflammatory, respiratory, or immune support. Serrapeptidase is a 50-kDa, alkaline metalloprotease that works to activate the Hageman factor-kallikrein-kinin systems of mammals and directly degrades or inhibits IgG and IgA immune factors as well as the regulatory proteims a-2-macroglobulin, a-2-antiplasmin, and antithrombin III (Molla et al, 1989)(Maeda and Molla, 1989). While originally isolated from Serratia marcescens, a bacteria found in the gut of the Japanese silk worm, Serrapeptidase activity is found in fermentation extracts of Serratia E-15, Aspergillus oryzae, and Aspergillus melleus. (Salamone and Wodzinski, 1997). The Serrapeptidase activity of a proteolytic system can be determined using a spectrophotometric assay that measures the system's ability to hydrolyze a standard casein substrate. Using this tool, NEC has established that Serrazimes-I is a 1:1 enzymatic substitution for Serrapeptidase.

Serrapeptidase is a protease initally isolated from Serratia marcescens, a potentially pathogenic bacteria, found in the gut of the Japanese silkworm. Recognized as a pharmaceutical agent and sold under the names Danzen and Aniflazyme, Serrapeptidase has wide clinical use in Asia and Europe for the treatment of assorted inflammatory disorders (Rothschild, 1991). In recent years, recognition of the efficacy of this product has lead to growing interest in the US dietary supplement market. Despite international regulations, the product's efficacy and availability over the internet has fueled its popularity in the US dietary supplement industry where it is used for anti-inflammatory support, cardiovascular support, respiratory support, and as an adjunct to antibiotic therapy. Recognizing the potential for a "Serrapeptidase-type" enzyme in the U.S. dietary supplement market, National Enzyme Company set fourth to develop a protease system that has the same in vitro activity as Serrapeptidase, but that is from a source organism(s) that has a long history of safe use in dietary supplements. Serrazimes-I is the product of this research.

Serrapeptidase has been used in Europe and Asia to treat heart disease, inflammatory diseases, and bacterial infections for over 25 years. The proteolytic activities of Serrapeptidase explain these applications. Serrazimes-I exhibits these same proteolytic activities in vitro, demonstrating that Serrazimes-I is an excellent alternative for Serrapeptidase in supplements intended to provide cardiovascular, anti-inflammatory, respiratory, or immune support.

Since the 1960's plant and microbial proteases have been studied for their role in the treatment of inflammation and inflammatory disorders. In both animal and human trials, proteolytic enzymes, from a variety of sources, have repeatedly been shown to significantly reduce inflammation resulting from sickness or injury (Ryan, 1967)(Smyth et al, 1969)(Kumakura et al, 1988)(Lomax, 1999). Early research on the anti-inflammatory actions of proteases pointed entirely to their antithrombic and fibrinolytic aspects to explain this phenomenon. However, studies by Parmely and others indicate that, in addition to degrading fibrin, microbial proteases may actually inactivate pro-inflammatory cytokines to prevent or attenuate inflammatory cascades.

Evidence suggests this may be accomplished through hydrolysis of tumor necrosis factor alpha (TNFa) and/or interferon gamma (IFNy) Numerous human trials have shown Serrapeptidase to be highly effective for treating the inflammation resulting from carpal tunnel syndrome, surgery/injury, and breast engorgement (Mazzone et al, 1990)(Kee et al, 1989)(Esch et al, 1989)(Panagariya and Sharma, 1999)(Snowden et al, 2001)(Tachibana et al, 1984). Serrazimes-I shows in vitro activity similar to Serrapeptidase, but uses a protease system from Aspergillus melleus and Aspergillus oryzae. Like Serrapeptidase, protease from Aspergillus melleus has been shown both in vitro and in vivo to significantly inhibit inflammatory responses (Fossati, 2000). However, in a head to head in vivo trial between protease from Aspergillus melleus and Serrapeptidase, protease from Aspergillus melleus not only showed better anti-inflammatory results than Serrapeptidase, but it also showed fewer side effects (Bracale and Sevetella, 1997). For these reasons, it is clear that Serrazimes-I is not only an adequate substitution for Serrapeptidase in anti-inflammatory products, it may even be the better choice.

Cardiovascular Support
Proteases may play an important role in minimizing the effects of heart disease and in the prevention of heart attacks. In heart disease, blood flow to the heart is blocked, either by a blood clot or by aggregated arterial plaques (atherosclerosis). More and more, the medical community is coming to recognize that cardiovascular diseases like atherosclerosis and heart attack are actually symptoms of inflammatory venous disease. A clinical study of 40 patients suffering from inflammatory venous disease tested the efficacy of Serrapeptidase in the treatment of thrombophlebitis (Bracale and Selvetella, 1997). Serrapeptidase showed positive results in the treatment of this disorder for a majority of patients. However, this same study also tested the effectiveness of Aspergillus melleus protease for this condition. Aspergillus protease was shown to be superior to Serrapeptidase in both effectiveness and tolerability.

Antibacterial Support
Serrapeptidase has been shown to augment the activity of numerous antibiotic agents, including ampicillin, ciclacillin, cephalexin, minocylcine, and cefotiam (Selan et al, 1993)(Aratami et al, 1980)(Ishihara et al, 1983). A study of the interaction between proteases from Aspergillus melleus and erythromycin shows that this protease has similar capabilities. In one such study pharmacologic synergism between this protease and erythromycin allowed the antibiotic to better penetrate and sterilize bronchial mucosa (Braga et al, 1992).

Side Effects, Contraindications, and Drug Interactions
Systemically used proteases are known to have antithrombic properties. Persons who suffer from clotting disorders or who are on antithrombic medications, such as warfarin, coumadin, or aspirin therapy may experience increased clotting times when using systemic proteases. Such persons should consult a physician prior to taking systemic doses of any protease, including Serrazimes-I. Due to its effects on vascular permeability, the absorption and tissue distribution of antibiotics may be increased when administered concomitantly with Serrazimes-I (Braga et al, 1992). Persons on antibiotics should consult their physicians prior to taking Serrazimes-I.

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