Compositions for the treatment of autodigestion
Inventors
HALLAM, Thomas • JACKMAN, Robin • Rodenrys, John
Assignees
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Publication Number
US-9314442-B2
Publication Date
2016-04-19
Expiration Date
Abstract
Compositions for the treatment of shock, autodigestion, multi-organ failure, intestinal ischemia, or intestinal hypoperfusion are provided.
Core Innovation
The disclosed subject matter provides aqueous enteral compositions for treating shock-associated autodigestion. The compositions are formulated to preserve intestinal wall and villus integrity in the context of shock, including intestinal ischemia and intestinal hypoperfusion.
A core formulation includes tranexamic acid together with PEG 3350, glucose, and electrolytes including sodium sulfate, sodium bicarbonate, sodium chloride, and potassium chloride. The disclosure also includes aqueous solution formulations in representative pack sizes of 700 mL and 1000 mL, and a kit-based reconstitution concept in which components are provided in separate containers and reconstituted to form the aqueous enteral composition.
The document reports animal model evaluations using rat SMAO ischemia/hypoperfusion and a hemorrhagic shock model. Representative formulations are associated with higher percentages of structurally intact intestinal villi relative to comparative formulations lacking PEG or glucose, with intestinal structural outcomes described in terms of preservation of intact villi versus villi damage criteria.
The document also outlines Phase 2 clinical studies in septic shock and in post-cardiovascular surgery shock/multiorgan dysfunction. The described clinical endpoints include days alive without organ support and mortality endpoints such as mortality day 90, and the disclosure refers to tolerability and beneficial outcomes versus placebo.
Claims Coverage
The partial content includes two independent claims. Each independent claim defines an aqueous composition comprising tranexamic acid, PEG 3350, glucose, and specific electrolyte components, with claim-specific quantitative ranges or fixed concentrations; one family further grounds a therapeutic use tied to increasing intact intestinal villi in intestinal ischemia.
Fixed 700 mL aqueous tranexamic acid/PEG 3350/glucose/electrolytes composition
A composition formulated as a 700 mL aqueous solution comprising 7.5 g of tranexamic acid, 32.5 g of PEG 3350, 28 g of glucose, 4.0 g of sodium sulfate, 1.2 g of sodium bicarbonate, 1.0 g of sodium chloride, and 0.5 g of potassium chloride.
Concentration-defined aqueous tranexamic acid/PEG 3350/glucose/electrolytes composition
An aqueous composition comprising 1.1% w/v of tranexamic acid, 4.6% w/v of PEG 3350, 4.0% w/v of glucose, 0.6% w/v of sodium sulfate, 0.2% w/v of sodium bicarbonate, 0.1% w/v of sodium chloride, and 0.1% w/v of potassium chloride.
Administering to increase intact intestinal villi in intestinal ischemia
Administering an effective amount of the composition to a subject with intestinal ischemia to increase the number of intact intestinal villi, relative to no administration.
Overall, the independent claims define aqueous enteral compositions containing tranexamic acid, PEG 3350, glucose, and specified sodium/potassium salts and sodium bicarbonate. One independent claim additionally exemplifies a 700 mL formulation, and the partial content ties administration to increasing structurally intact intestinal villi in intestinal ischemia.
Stated Advantages
Preserves intestinal wall/villus integrity by increasing the number or percentage of intact intestinal villi relative to no administration or comparative formulations.
Provides beneficial outcomes in Phase 2 clinical studies versus placebo, including days alive without organ support and mortality-related endpoints such as mortality day 90.
Reported tolerability in Phase 2 clinical studies.
Documented Applications
Treating shock-associated autodigestion using an aqueous enteral composition in contexts involving intestinal ischemia and intestinal hypoperfusion.
Evaluating preservation of intestinal villi integrity in rat SMAO ischemia/hypoperfusion and in a hemorrhagic shock model.
Phase 2 clinical study use in septic shock and in post-cardiovascular surgery shock/multiorgan dysfunction.
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