The pancreas is a vital gastrointestinal organ with both endocrine and exocrine functions. Acute pancreatitis is an inflammation of the pancreas that occurs when digestive enzymes leak out of the pancreatic ducts and damages the pancreas. Acute pancreatitis is a disease with significant morbidity and mortality affecting all groups. The incidence of acute pancreatitis is about 30 per 100,000, and the condition has a significant economic impact due to the need for hospitalization, including intensive care treatment.
Acute pancreatitis is a complex multi-step process consisting of early stages (trigger(s) followed by hypoperfusion, activation of proteases, lipases and amylase, and local production of inflammatory mediators) and late stages (recruitment of inflammatory cells, further tissue damage and ultimate repair or fibrosis/necrosis). Necrosis in the gland is strongly associated with a high morbidity and excruciating pain; if necrosis can be prevented or reduced, the mortality and morbidity associated with acute pancreatitis may be reduced.
Many patients also develop chronic pancreatitis with ongoing low-grade inflammation of the pancreas, progressive destruction of glandular tissue, anatomical deformities, loss of organ function and digestive capabilities, and chronic pain.
There are many putative causes of acute pancreatitis, but its typical course is reduced vascular perfusion, pancreatic ductal hypertension (often involving the bile duct) and/or hypersecretion of enzymes into the pancreatic tissue, leading to tissue autolysis. Approximately one-third of acute pancreatitis cases are associated with alcohol abuse, one-third with gallstones and one-third with other causes or lack concomitant medical conditions and are considered idiopathic. Episodes of acute pancreatitis tend to recur with resulting hospitalizations and morbidity.
Treatments for pancreatitis generally involve aggressive intravenous fluid administration to improve clinical outcomes by maintaining vascular perfusion to the gland. In addition, analgesia and antibiotics are also used in the treatment of the condition. Many studies have also concluded that ischaemia plays a major role in the development of necrosis, and so reducing ischemia may improve outcomes.
As will be appreciated, the existing treatments for acute pancreatitis are directed to maintaining vascular perfusion to the gland and the control of pain. However, pharmaceutical interventions for the treatment of acute pancreatitis remain limited. The present invention relates to methods and compositions for the prevention and/or treatment of pancreatitis.
A reference herein to a patent document or other matter which is given as prior art is not to be taken as an admission that that document or matter was, in Australia or any other country, known or that the information it contains was part of the common general knowledge as at the priority date of any of the claims.