Treatment of conditions related to shock

• US 9,272,034 B2
• Filed: 10/06/2008
• Issued: 03/01/2016
• Est. Priority Date: 10/04/2007
• Status: Active Grant

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Schmid-Schonbein, Geert W., DeLano, Frank A.
• Primary Examiner(s): Lankford, Blaine
• Assistant Examiner(s): Visone, Thomas J
• Application Number:
  US12/681,510
• Publication Number:
  US 20100303799A1
• Time in Patent Office: 2,703 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/195 having an amino group
• CPC Class Codes: A61K 31/197 the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid carnitine A61K31/205
• CPC Class Codes: A61K 31/201 having one or two double bonds, e.g. oleic, linoleic acids
• CPC Class Codes: A61K 31/24 having an amino or nitro group
• CPC Class Codes: A61K 31/337 having four-membered rings, e.g. taxol
• CPC Class Codes: A61K 31/407 condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
• CPC Class Codes: A61K 31/4164 1,3-Diazoles
• CPC Class Codes: A61K 31/424 condensed with heterocyclic ring systems, e.g. clavulanic acid
• CPC Class Codes: A61K 31/431 containing further heterocyclic rings, e.g. ticarcillin, azlocillin, oxacillin
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 31/546 containing further heterocyclic rings, e.g. cephalothin
• CPC Class Codes: A61K 31/65 Tetracyclines
• CPC Class Codes: A61K 38/38 Albumins
• CPC Class Codes: A61K 38/57 from animals; from humans A61K38/553, A61K38/556 take precedence
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/50 for increasing or potentiating the activity of insulin

Abstract

Techniques are disclosed for prevention or treatment of physiological shock by administering a specific therapeutic agent, which is able to use smaller volumes of reagent to achieve complete inhibition, than other previously described techniques.

Claims

1. A method for prevention or treatment of physiological shock in an individual comprising administering to the lumen of an intestine of the individual a therapeutic dose of a combination of a pancreatic digestive enzyme inhibitor, a cytotoxic mediator inhibitor, an MMP inhibitor, and an antibacterial agent.

2. The method of claim 1, wherein the MMP inhibitor comprises doxycycline.

3. The method of claim 1, further comprising:

administering to the lumen of the intestine of the individual a therapeutic dose of one or more of a serine protease inhibitor and a lipase inhibitor.

4. The method of claim 1, wherein the pancreatic digestive enzyme inhibitor comprises a serine protease inhibitor.

5. The method of claim 1, wherein the pancreatic digestive enzyme inhibitor comprises a lipase inhibitor.

6. The method of claim 1, wherein the cytotoxic mediator is lipid derived.

7. The method of claim 6, wherein the cytotoxic lipid derived mediator inhibitor comprises free fatty acid binding proteins.

8. The method of claim 7, wherein the free fatty acid binding protein comprises albumin.

9. The method of claim 1, wherein the antibacterial agent comprises an antibiotic agent.

10. The method of claim 9, wherein the antibiotic agent comprises one or more of ciprofloxacin, metronidazole, imipenem, cilastatin, ticarcillin, clavulanate, or cefuroxime.

12. The method of claim 1, wherein the administering to the lumen of the intestine is by oral administration.

13. The method of claim 1, wherein the administering to the lumen of the intestine is by esophageal catheter.

14. The method of claim 1, wherein the administering to the lumen of the intestine is by duodenal catheter.

15. The method of claim 1, wherein the administering to the lumen of the intestine is by direct injection into the intestine.

16. The method of claim 1, wherein the pancreatic digestive enzyme inhibitor is selected from the group consisting of 6-amidino-2-napthyl p-guanidobenzoate dimethane-sulfate (ANGD), gabexate mesilate, tranexamic acid, aprotinin, and orlistat.

17. The method of claim 5, wherein the lipase inhibitor is orlistat.

11. A method for prevention or treatment of physiological shock in an individual comprising administering to the lumen of an intestine of the individual a therapeutic dose of a combination of a pancreatic digestive enzyme inhibitor and a cytotoxic mediator inhibitor, and administering to the lumen of the intestine of the individual a therapeutic dose of an MMP inhibitor.

18. The method of claim 11, wherein the administering to the lumen of the intestine is by oral administration.

19. The method of claim 11, wherein the administering to the lumen of the intestine is by esophageal catheter.

20. The method of claim 11, wherein the administering to the lumen of the intestine is by duodenal catheter.

21. The method of claim 11, wherein the administering to the lumen of the intestine is by direct injection into the intestine.

22. The method of claim 11, wherein the pancreatic digestive enzyme inhibitor is selected from the group consisting of 6-amidino-2-napthyl p-guanidobenzoate dimethane-sulfate, nafamostat mesilate, gabexate mesilate, tranexamic acid, aprotinin, and orlistat.