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 an aqueous pharmaceutical composition comprising: (i) tranexamic acid, (ii) polyethylene glycol-3350, and (iii) electrolytes.
2. The method of claim 1 , wherein the composition comprises about 2 grams to about 20 grams of tranexamic acid.
3. The method of claim 1 , wherein the composition comprises 0.16 wt % to 1.80 wt % of tranexamic acid.
4. The method of claim 1 , wherein the shock is traumatic shock, septic shock, cardiogenic shock, or hypovolemic shock.
5. The method of claim 1 , wherein the shock is caused by (i) a surgical intervention, (ii) complications from radiation treatment, (iii) complications from chemotherapy treatment, (iv) organ perforation, (v) chylothorax, (vi) a bacterial infection, (vii) damage from a mechanical ventilator, or (viii) dialysis.
6. The method of claim 1 , wherein the shock is a developing shock or an acute shock.
7. The method of claim 1 , comprising orally administering the composition through a nasogastric tube.
8. The method of claim 1 , wherein the composition is administered as a single undivided dose.
9. The method of claim 1 , wherein the composition is administered as a divided dose.
10. The method of claim 1 , wherein the composition is administered daily for 2 days to 21 days.
11. 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: (i) a protease inhibitor, (ii) polyethylene glycol-3350, and (iii) electrolytes.
12. The method of claim 11 , wherein the shock is traumatic shock, septic shock, cardiogenic shock, or hypovolemic shock.
13. The method of claim 11 , wherein the shock is caused by (i) a surgical intervention, (ii) complications from radiation treatment, (iii) complications from chemotherapy treatment, (iv) organ perforation, (v) chylothorax, (vi) a bacterial infection, (vii) damage from a mechanical ventilator, or (viii) dialysis.
14. The method of claim 11 , 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.
15. The method of claim 14 , wherein the protease inhibitor is the serine protease inhibitor.
16. The method of claim 11 , 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.
17. The method of claim 11 , wherein the composition comprises about 2 grams to about 20 grams of the protease inhibitor.
18. The method of claim 11 , wherein the composition comprises 0.16 wt % to 1.80 wt % of the protease inhibitor.
19. The method of claim 1 , wherein the composition has a volume of about 500 ml to about 1000 ml.
20. The method of claim 11 , comprising orally administering the composition through a nasogastric tube.
21. The method of claim 11 , wherein the composition has a volume of about 500 ml to about 1000 ml.