Administration of serine protease inhibitors to the stomach
Inventors
Schmid-Schonbein, Geert W. • Lee, Yung-Tsai (Andrew) • Wei, Jeng
Assignees
Leading Biosciences LLC • University of California San Diego UCSD • Leading Biosciences Inc
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Publication Number
US-10772861-B2
Publication Date
2020-09-15
Expiration Date
Abstract
The inventors have unexpectedly discovered that shock and/or potential multi-organ failure due to shock can be effectively treated by administration of liquid high-dose protease inhibitor formulations to a location upstream of where pancreatic proteases are introduced into the gastrointestinal tract. Most preferably, administration is directly to the stomach, for example, via nasogastric tube under a protocol effective to treat shock by such administration without the need of providing significant quantities of the protease inhibitor to the jejunum and/or ileum.
Core Innovation
The invention relates to treating shock in a mammal by orally administering a therapeutically effective amount of a protease inhibitor pharmaceutical composition in a liquid carrier. The disclosure focuses on gastrointestinal delivery upstream of pancreatic protease release rather than delivery to downstream intestinal locations, including delivering to the stomach location.
The disclosed formulations include protease inhibitor agents and electrolytes in an aqueous pharmaceutical composition or related liquid formulations. In particular, the protease inhibitor includes tranexamic acid in a liquid carrier, and the liquid carrier comprises an aqueous saline solution or an isotonic polyethylene glycol solution in certain embodiments.
A further aspect of the disclosure includes optional co-therapy with intraluminal oxygen carriers to reduce organ damage and support intact mucosal barrier function. The patent describes a clinical case of Fournier’s gangrene with septic shock where switching to enteral gabexate mesilate infusion into the stomach correlated with stabilization of blood pressure and normalization of amylase, lipase, and WBC, with improved ileus.
Claims Coverage
The provided independent claims cover three inventive features. Across these claims, the core coverage centers on oral administration of therapeutically effective liquid or aqueous pharmaceutical compositions for treating shock, with composition requirements centered on tranexamic acid and a liquid carrier, tranexamic acid with polyethylene glycol and electrolytes, or a protease inhibitor with electrolytes.
Oral tranexamic acid liquid composition for listed shock causes
A method of treating shock in a mammal in need thereof comprising orally administering to the mammal a therapeutically effective amount of a pharmaceutical composition comprising tranexamic acid and a liquid carrier, wherein the shock is caused by a surgical intervention, a complication from radiation treatment, a complication from chemotherapy treatment, an organ perforation, chylothorax, damage from a mechanical ventilator, or dialysis.
Oral tranexamic acid, polyethylene glycol, and electrolytes liquid composition for listed shock causes
A method of treating shock in a mammal in need thereof comprising orally administering to the mammal a therapeutically effective amount of a liquid pharmaceutical composition comprising tranexamic acid, polyethylene glycol, and electrolytes, wherein the shock is caused by a surgical intervention, a complication from radiation treatment, a complication from chemotherapy treatment, an organ perforation, chylothorax, damage from a mechanical ventilator, or dialysis.
Oral aqueous protease inhibitor and electrolytes composition for listed shock causes
A method of treating shock in a mammal in need thereof comprising orally administering to the mammal a therapeutically effective amount of an aqueous pharmaceutical composition comprising a protease inhibitor and electrolytes, wherein the shock is caused by a surgical intervention, a complication from radiation treatment, a complication from chemotherapy treatment, an organ perforation, chylothorax, damage from a mechanical ventilator, or dialysis.
The independent claims cover oral treatment of shock in a mammal using liquid or aqueous protease-inhibitor-containing pharmaceutical compositions, with shock causation limited to the enumerated clinical events and with composition features centered on tranexamic acid or on an aqueous protease inhibitor plus electrolytes.
Stated Advantages
Stated clinical correlation with stabilization of blood pressure, normalization of amylase, lipase, and WBC, and improved ileus.
Oxygen carrier co-therapy is stated to reduce organ damage and support intact mucosal barrier function.
Documented Applications
Clinical case: human Fournier’s gangrene with septic shock, where switching to enteral gabexate mesilate infusion into the stomach correlated with stabilization of blood pressure and normalization of amylase, lipase, and WBC and improved ileus.
Feasibility data in an ischemic intestinal rat model using oxygen carrier administration.
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