Administration of serine protease inhibitors to the stomach
Inventors
Schmid-Schonbein, Geert W. • Lee, Yung-Tsai (Andrew) • Wei, Jeng
Assignees
University of California San Diego UCSD • Leading Biosciences Inc
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Publication Number
US-11439611-B2
Publication Date
2022-09-13
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 describes a shock-treatment approach using liquid, high-dose protease inhibitor formulations delivered upstream of pancreatic protease release in the gastrointestinal tract. The approach is preferably implemented by administering the formulation directly to the stomach via a nasogastric tube (NG tube). The stated intent is to treat developing or acute shock and potential multi-organ failure without substantial small-intestine dosing.
The disclosure describes a dosing and delivery concept in which an upstream enteral administration delivers a therapeutically effective amount of a protease inhibitor. It further describes use of an isotonic aqueous carrier, including electrolytes and polyethylene glycol (PEG), as part of the formulation concept. The provided illustrative description includes an illustrative human case in which enteral gabexate mesilate into the stomach via NG tube stabilized septic shock and improved pancreatic markers and ileus.
The disclosure also describes diagnosis markers used in connection with the shock treatment, including amylase and protease activity and/or blood protease activity. Additionally, the disclosure optionally describes co-administration of an oxygen carrier via the intestinal lumen, with the stated purpose of minimizing organ damage. The formulations and delivery are positioned as targeting the gastrointestinal release of pancreatic proteases upstream in the GI tract.
Claims Coverage
Only one independent claim is provided in the partial content. The claim specifies a liquid formulation with defined concentration components and an overall volume range, with inventive features focused on the formulation composition and isotonic aqueous solution characteristics.
Isotonic aqueous liquid formulation with tranexamic acid, polyethylene glycol, and electrolytes
A liquid formulation comprising from 0.16 wt % to 1.8 wt % of tranexamic acid, polyethylene glycol, and electrolytes, wherein the liquid formulation is an isotonic aqueous solution.
Defined formulation volume range
The isotonic aqueous liquid formulation has a volume of 250 ml to 1000 ml.
The provided independent claim coverage centers on an isotonic aqueous liquid formulation containing tranexamic acid, polyethylene glycol, and electrolytes, with specified component presence and an overall formulation volume of 250 ml to 1000 ml.
Stated Advantages
Treating developing or acute shock and potential multi-organ failure without substantial small-intestine dosing.
Documented Applications
An illustrative human case in which enteral gabexate mesilate into the stomach via NG tube stabilized septic shock and improved pancreatic markers and ileus.
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