Administration of serine protease inhibitors to the stomach
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.
1. 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 (i) a surgical intervention, (ii) a complication from radiation treatment, (iii) a complication from chemotherapy treatment, (iv) an organ perforation, (v) chylothorax, (vi) damage from a mechanical ventilator, or (vii) dialysis.
2. The method of claim 1 , wherein the shock is caused by surgical intervention.
3. The method of claim 1 , wherein the composition comprises about 2 grams to about 20 grams of tranexamic acid.
4. The method of claim 1 , wherein the composition comprises about 0.16 wt % to about 1.80 wt % of tranexamic acid.
5. The method of claim 1 , wherein the liquid carrier is an aqueous saline solution.
6. The method of claim 1 , wherein the liquid carrier is an isotonic polyethylene glycol solution.
7. 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 (i) a surgical intervention, (ii) a complication from radiation treatment, (iii) a complication from chemotherapy treatment, (iv) an organ perforation, (v) chylothorax, (vi) damage from a mechanical ventilator, or (vii) dialysis.
8. The method of claim 7 , wherein the shock is caused by surgical intervention.
9. The method of claim 7 , wherein the composition comprises about 2 grams to about 20 grams of tranexamic acid.
10. The method of claim 7 , wherein the composition comprises about 0.16 wt % to about 1.80 wt % of tranexamic acid.
11. The method of claim 7 , wherein the composition comprises an aqueous saline solution.
12. The method of claim 7 , wherein the composition comprises an isotonic polyethylene glycol solution.
13. 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 (i) a surgical intervention, (ii) a complication from radiation treatment, (iii) a complication from chemotherapy treatment, (iv) an organ perforation, (v) chylothorax, (vi) damage from a mechanical ventilator, or (vii) dialysis.
14. The method of claim 13 , wherein the shock is caused by surgical intervention.
15. The method of claim 13 , wherein the protease inhibitor is a serine protease inhibitor, a cysteine protease inhibitor, a threonine protease inhibitor, an aspartate protease inhibitor, a glutamate protease inhibitor, a matrix metalloprotease inhibitor, or a combination of two or more thereof.
16. The method of claim 13 , wherein the protease inhibitor is a serine protease inhibitor.
17. The method of claim 13 , wherein the protease inhibitor is a serpin, an alpha 1-antitrypsin, an alpha-2-macroglobulin, 6-amidino-2-naphthyl, p-guanidinobenzoate dimethanesulfate, gabexate monomethanesulfonate, diisopropylfluorophosphate, p-(amidinophenyl)methanesulfonyl fluoride, tranexamic acid, 4-(2-aminoethyl)benzenesulfonyl fluoride, or camostate.
18. The method of claim 13 , wherein the composition comprises about 2 grams to about 20 grams of the protease inhibitor.
19. The method of claim 13 , wherein the composition comprises 0.16 wt % to 1.80 wt % of the protease inhibitor.
20. The method of claim 13 , wherein the composition has a volume of about 500 ml to about 1000 ml.