Compositions for the treatment of autodigestion
Inventors
HALLAM, Thomas • JACKMAN, Robin • Rodenrys, John
Assignees
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Publication Number
US-9775821-B2
Publication Date
2017-10-03
Expiration Date
Abstract
Compositions for the treatment of shock, autodigestion, multi-organ failure, intestinal ischemia, or intestinal hypoperfusion are provided.
Core Innovation
The invention relates to compositions and methods for treating shock- and ischemia-associated autodigestion and multi-organ failure. The compositions are aqueous enteral formulations that include tranexamic acid and PEG, including PEG 3350, in a non-colonic cleansing amount, together with glucose and electrolytes including sodium sulfate, sodium bicarbonate, sodium chloride, and potassium chloride.
The background problem addressed by the invention is that shock and ischemia are associated with autodigestion and multi-organ failure, including intestinal ischemia and intestinal hypoperfusion. The documented approach targets intestinal integrity by increasing intact intestinal villi. The disclosed compositions combine tranexamic acid with a PEG 3350 component in a non-colonic cleansing amount and include glucose and the listed electrolytes within defined ranges.
Documented examples describe aqueous formulations at approximately 700 mL and approximately 1000 mL and compare formulations with and without components such as PEG or glucose in relevant animal models, including SMAO ischemia and hemorrhagic shock. Intestinal villus integrity is assessed using measurements including intact intestinal villi and Alcian blue staining, with reported improvements versus comparative formulations that lack PEG or glucose. The document also describes Phase 2 clinical study(s) in septic shock and post-cardiovascular surgery patients, with primary endpoints including days alive without organ support.
Claims Coverage
The independent claims are directed to two aqueous enteral compositions. Collectively, the claims recite a defined multi-component formulation centered on tranexamic acid plus PEG 3350 in a non-colonic cleansing amount, glucose, and specified electrolytes, and they optionally cover a biological effect in subjects with intestinal ischemia (increasing intact intestinal villi).
Tranexamic acid and PEG 3350 with glucose and defined electrolytes (aqueous composition)
A composition comprising about 7.5 g of tranexamic acid, about 32.5 g to about 50.3 g of PEG 3350, about 28 g to about 40 g of glucose, about 4.0 g to about 5.7 g of sodium sulfate, about 1.2 g to about 1.7 g of sodium bicarbonate, about 1.0 g to about 1.5 g of sodium chloride, and about 0.5 g to about 0.7 g of potassium chloride.
Tranexamic acid and PEG 3350 with glucose and defined electrolytes (aqueous wt% ranges)
An aqueous composition comprising about 1.1 wt % of tranexamic acid, about 4.2 wt % to about 5.1 wt % of PEG 3350, about 3.6 wt % to about 4.4 wt % of glucose, about 0.51 wt % to about 0.63 wt % of sodium sulfate, about 0.16 wt % to about 0.19 wt % of sodium bicarbonate, about 0.13 wt % to about 0.17 wt % of sodium chloride, and about 0.06 wt % to about 0.09 wt % of potassium chloride.
Increasing intact intestinal villi in intestinal ischemia
A method of increasing the number of intact intestinal villi in a subject suffering from intestinal ischemia by administering an effective amount of the composition of claim 1, relative to not administering it.
Increasing intact intestinal villi in intestinal ischemia using aqueous wt% composition
A method for treating intestinal ischemia by administering an effective amount of the composition of claim 5 to increase the number of intact intestinal villi in the subject compared with not administering the composition.
Across the independent claims, the core claim coverage is the specified multi-component aqueous formulation containing tranexamic acid, PEG 3350, glucose, and electrolytes in defined ranges, together with dependent claim features that relate administration of an effective amount to increasing the number of intact intestinal villi in subjects with intestinal ischemia.
Stated Advantages
Improved intestinal villus integrity by increasing the number of intact intestinal villi in intestinal ischemia compared with not administering the composition.
Reported trends toward improved outcomes in Phase 2 clinical study(s) in septic shock and post-cardiovascular surgery patients versus placebo, using days alive without organ support as a primary endpoint.
Documented Applications
Treating shock- and ischemia-associated autodigestion and multi-organ failure, including intestinal ischemia and intestinal hypoperfusion.
Increasing the number of intact intestinal villi in a subject suffering from intestinal ischemia.
Phase 2 clinical study(s) in septic shock patients.
Phase 2 clinical study(s) in post-cardiovascular surgery patients, with primary endpoints including days alive without cardiovascular/pulmonary/renal replacement therapy or organ support as described in the document.
Animal model evaluation in SMAO ischemia and hemorrhagic shock models, with assessment of intact intestinal villi and Alcian blue staining.
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