Administration of serine protease inhibitors to the stomach

Patent metadata

Field	Value
Publication number	US-10137100-B2
Application number	US-201615335242-A
Country	US
Kind code	B2
Filing date	Oct 26, 2016
Priority date	Sep 23, 2010
Publication date	Nov 27, 2018
Grant date	Nov 27, 2018

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.

First claim

What is claimed is:

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.

Assignees

• Schmid Schonbein Geert W
• Lee Yung Tsai Andrew
• Wei Jeng
• Univ California
• Inflammagen Llc

Inventors

• Schmid-Schonbein Geert W
• Lee Yung-Tsai (Andrew)
• Wei Jeng

Classifications

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title

• A61P1/00

  Drugs for disorders of the alimentary tract or the digestive system · CPC title

• A61K38/57

  from animals; from humans {(A61K38/553, A61K38/556 take precedence)} · CPC title

• A61K9/0053

  Mouth and digestive tract, i.e. intraoral and peroral administration · CPC title