ANTINECROTIC ACTIVITY OF ALPHA 1-ANTITRYPSIN

• US 20190307866A1
• Filed: 06/17/2019
• Published: 10/10/2019
• Est. Priority Date: 09/10/2008
• Status: Active Application

• Current Assignee: Ben Gurion University of The Negev
• Original Assignee: Ben Gurion University of The Negev
• Inventors: Nathan, Ilana, Lewis, Eli, Khalfin, Boris
• Application Number:
  US16/442,624
• Publication Number:
  US 20190307866A1
• Time in Patent Office: Days
• 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 31/70 Carbohydrates; Sugars; Derivatives thereof sorbitol A61K31/047
• 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 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system

Abstract

The present invention is related to the use of alpha-1-antitrypsin as an anti-necrotic agent. This invention provides a method for the treatment of tissue necrosis by administration of alpha-1-antitrypsin. This invention further provides methods for prophylactic treatment of tissue necrosis and for inhibition of tissue necrosis in culture by addition of alpha-1-antitrypsin.

Claims

1. A method of treating a subject suffering from a disease characterized by tissue necrosis, said method comprising administering to said subject a therapeutically effective amount of alpha-1-antitrypsin or a homologue or variant thereof, wherein said effective amount inhibits said tissue necrosis and said disease is characterized in that affected tissue in said subject is undergoing necrosis.

2. The method of claim 1 further comprising the step of monitoring a decrease in said tissue necrosis.

3. The method of claim 1 wherein said effective amount of said alpha-1-antitrypsin is between about 20 to 500 mg/kg/day of body weight.

4. The method of claim 1, further comprising monitoring alpha-1-antitrypsin levels.

5. The method of claim 1, wherein said subject is administered a pharmaceutical composition comprising said alpha-1-antitrypsin or a homologue or variant thereof

6. The method of claim 5, wherein said composition comprises a pharmaceutically acceptable carrier.

7. The method of claim 1, wherein said subject is a human.

8. The method of claim 1, wherein said subject suffers from a condition that is refractory to anti-inflammatory agent.

9. The method of claim 8, wherein said subject suffers from or is at risk for a cancer, neurodegenerative disease, myocardial infarction, stroke, sepsis, ischemia, liver disease, open wound, or gangrene.

10. The method of claim 9, further comprising the step of administering at least a second therapeutic compound to said subject.

11. The method of claim 1, wherein said at least a second therapeutic compound comprises an antibiotic, a beta blocker, an analgesic, or any combination thereof.

12. The method of claim 1, wherein said subject suffers from AIDS.

13. The method of claim 1, wherein said subject is immunocompromised.

14. The method of claim 1, wherein said tissue necrosis is a consequence of contact with venom.

15. The method of claim 1, wherein said administering is via a parenteral, oral, vaginal, rectal, nasal, buccal, intravenous, intramuscular, subcutaneous, intraperitoneal, intrathecal, epidural, transdermal, or intraccrebroventricular route, or combinations thereof.

16. A method of prophylactically treating a subject at risk for a pathological condition that is precipitated at least in part by tissue necrosis, said method comprising administering to said subject a therapeutically effective amount of alpha-1-antitrypsin such that said effective amount inhibits tissue necrosis in said subject.

17. A method for inhibiting necrosis in a cell or tissue culture, said method comprising contacting a cell or tissue in culture with an amount of alpha-1-antitrypsin sufficient to inhibit necrosis in said cell or tissue in culture.

18. The method of claim 17, wherein said tissue culture is an organ culture or a fragment thereof.

19. The method of claim 17, wherein cells in said cell culture are predisposed to or undergoing necrosis.

20. A method of preventing pancreatitis in a subject, comprising administering to said subject a therapeutically effective amount of alpha-1-antitrypsin prior to an abdominal surgical procedure in said subject, thereby preventing pancreatitis in a subject.

21. The method of claim 20, wherein said abdominal surgical procedure is endoscopic retrograde cholangiopancreatography (ERCP), pancreatic stenting, pancreaticoduodenectomy, pancreatectomy, or any combination thereof.

22. The method of claim 20, wherein said preventing pancreatitis in a subject further comprises reducing the risk or severity of pancreatitis.

23. The method of claim 20, wherein said administering is via a parenteral, oral, vaginal, rectal, nasal, buccal, intravenous, intramuscular, subcutaneous, intraperitoneal, intrathecal, epidural, transdermal, or intraccrebroventricular route, or combinations thereof.

24. The method of claim 20, wherein said effective amount of said alpha-1-antitrypsin is between about 20 to 100 mg/kg body weight/day.