What is trypsin-chymotrypsin?

What is Trypsin-Chymotrypsin?

Trypsin-chymotrypsin is an oral proteolytic enzyme combination preparation used therapeutically since the 1960s to facilitate tissue repair and reduce inflammation following acute tissue injury, burns, and surgical trauma. 1

Biochemical Nature

• Trypsin and chymotrypsin are pancreatic serine proteases that are normally secreted as inactive precursors (trypsinogen and chymotrypsinogen) and activated in the digestive tract. 2
• Trypsin is considered the gold standard enzyme in proteomics and laboratory applications for protein digestion, while chymotrypsin serves as an alternative endoproteinase. 3
• Both enzymes can be inhibited by specific agents: Pefabloc inhibits both trypsin and chymotrypsin, while Bowman-Birk Inhibitors from plant sources effectively block both enzymes. 3
• Aprotinin is a serine protease inhibitor that blocks trypsin, chymotrypsin, plasmin, and kallikrein, though its clinical use is now highly restricted due to safety concerns including acute renal failure, myocardial infarction, and stroke. 3

Clinical Therapeutic Applications

• The International Association for the Study of Pain recognizes that trypsin-chymotrypsin combinations offer anti-edematous, anti-inflammatory, anti-thrombotic, and fibrinolytic therapeutic effects when used in conjunction with other proteases like papain and bromelain. 4
• The preparation provides better resolution of inflammatory symptoms and promotes speedier recovery from acute tissue injury compared to other enzyme preparations. 1
• In burn injury management, trypsin-chymotrypsin demonstrates anti-inflammatory activity by inhibiting the rise in C-reactive protein while enhancing alpha-1-antitrypsin and alpha-2-macroglobulin levels. 5
• The enzyme combination reduces oxidative damage during burn injury by decreasing lipid peroxidation products and maintaining higher levels of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase). 6

Diagnostic and Laboratory Uses

• Fecal chymotrypsin assays were previously used to diagnose pancreatic insufficiency, but the American Gastroenterological Association now considers them less reliable than newer tests. 4
• The European Society of Gastrointestinal Endoscopy recommends fecal elastase testing over chymotrypsin assays for pancreatic function testing due to elastase's greater stability and improved sensitivity. 4
• Chymotrypsin can be identified in acinar cell lesions through immunohistochemical labeling, which the American Association for Cancer Research uses to demonstrate pancreatic acinar differentiation. 4

Important Safety Considerations

• Trypsin and chymotrypsin are potential inhalable sensitizers that can cause immediate occupational hypersensitivities of the airways, with documented cases showing positive skin prick tests, challenge tests, and specific IgE antibodies. 2
• Immediate urticarial skin reactions are possible upon contact with these enzymes, though allergic cell-mediated delayed eczematous reactions lack clear evidence. 2
• The effectiveness of systemically administered proteolytic enzymes as anti-inflammatory agents remains incompletely established, primarily due to lack of precise measurement techniques in older studies. 7
• Topical use of trypsin-chymotrypsin (Biozyme) has demonstrated some value, though oral, buccal, or intramuscular administration has not been conclusively proven effective. 7

Mechanism of Action Limitations

• The exact mechanism of action for therapeutic trypsin-chymotrypsin remains vague, which may partly explain the uncertainty about their therapeutic value in some applications. 7
• Despite unclear mechanisms, clinical evidence supports anti-inflammatory effects through modulation of acute-phase proteins and reduction of oxidative stress markers. 5, 6