Administration of serine protease inhibitors to the stomach

Patent metadata

Field	Value
Publication number	US-2020246291-A9
Application number	US-201816197956-A
Country	US
Kind code	A9
Filing date	Nov 21, 2018
Priority date	Sep 23, 2010
Publication date	Aug 6, 2020
Grant date	—

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

1 . (canceled)

2 . 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 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, (vii) damage from a mechanical ventilator, or (viii) dialysis.

3 . The method of claim 2 , wherein the shock is caused by surgical intervention.

4 . The method of claim 2 , wherein the composition comprises about 2 grams to about 20 grams of tranexamic acid.

5 . The method of claim 2 , wherein composition comprises about 0.16 wt % to about 1.80 wt % of tranexamic acid.

6 . The method of claim 2 , wherein the liquid carrier is an isotonic saline solution.

7 . The method of claim 2 , wherein the liquid carrier is an isotonic polyethylene glycol solution.

8 . 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 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, (vii) damage from a mechanical ventilator, or (viii) dialysis.

9 . The method of claim 8 , wherein the shock is caused by surgical intervention.

10 . The method of claim 8 , wherein the composition comprises about 2 grams to about 20 grams of tranexamic acid.

11 . The method of claim 8 , wherein the composition comprises about 0.16 wt % to about 1.80 wt % of tranexamic acid.

12 . The method of claim 8 , wherein the liquid carrier is an isotonic saline solution.

13 . The method of claim 8 , wherein the liquid carrier is an isotonic polyethylene glycol solution.

14 . 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, (vii) damage from a mechanical ventilator, or (viii) dialysis.

15 . The method of claim 14 , wherein the shock is caused by surgical intervention.

16 . The method of claim 14 , 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.

17 . The method of claim 14 , wherein the protease inhibitor is a serine protease inhibitor.

18 . The method of claim 14 , 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.

19 . The method of claim 14 , wherein the composition comprises about 2 grams to about 20 grams of the protease inhibitor.

20 . The method of claim 14 , wherein the composition comprises 0.16 wt % to 1.80 wt % of the protease inhibitor.

21 . The method of claim 14 , wherein the composition has a volume of about 500 ml to about 1000 ml.

Assignees

• Inflammagen Llc
• Univ California

Inventors

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

Classifications

• A61K9/0053

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

• A61K9/08

  Solutions {(composition of solutions A61K47/00)} · CPC title

• A61K38/57

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

• A61K31/24

  having an amino or nitro group · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title