Compositions, kits, and methods to induce acquired cytoresistance using stress protein inducers

• US 10,639,321 B2
• Filed: 09/28/2015
• Issued: 05/05/2020
• Est. Priority Date: 09/29/2014
• Status: Active Grant

• Current Assignee: Fred Hutchinson Cancer Center
• Original Assignee: Fred Hutchinson Cancer Research Center (Fred Hutchinson Cancer Research Center|Argus Genetics|Mars)
• Inventors: Zager, Richard, Johnson, Ali C M
• Primary Examiner(s): Yoo, Sun Jae
• Application Number:
  US15/030,008
• Publication Number:
  US 20160271164A1
• Time in Patent Office: 1,681 Days
• CPC Class Codes: A01N 1/0226 Physiologically active agents, i.e. substances affecting physiological processes of cells and tissue to be preserved, e.g. anti-oxidants or nutrients
• CPC Class Codes: A61K 31/194 having two or more carboxyl groups, e.g. succinic, maleic or phthalic acid
• CPC Class Codes: A61K 31/555 containing heavy metals, e.g. hemin, hematin, melarsoprol
• CPC Class Codes: A61K 31/714 Cobalamins, e.g. cyanocobalamin, i.e. vitamin B12
• CPC Class Codes: A61K 33/26 Iron; Compounds thereof
• CPC Class Codes: A61K 38/42 Haemoglobins; Myoglobins
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07H 23/00 Compounds containing boron, silicon, or a metal, e.g. chelates, vitamin B12 esters with inorganic acids C07H11/00; metal salts, see parent compounds

Abstract

The present disclosure provides compositions, kits, and methods to protect organs by inducing acquired cytoresistance without causing injury to the organ. The compositions, kits, and methods utilize heme proteins, iron and/or vitamin B12 and, optionally, agents that impact heme protein metabolism.

Claims

1. A method of protecting an organ of a human patient from injury based on a scheduled insult comprising administering to the organ a therapeutically effective amount of (i) iron or an iron complex;

and (ii) a heme protein degradation inhibitor, the therapeutically effective amount being administered before the scheduled insult to the organ occurs, wherein the heme protein degradation inhibitor is a metal protoporphyrin or a nitrited metal protoporphyrin, wherein the metal in the metal protoporphyrin or the nitrited metal protoporphyrin is Pt, Zn, Ni, Cu, Ag, Mn, Cr, or Sn.

2. The method of claim 1, wherein (i) is iron complex, the iron complex being a heme protein.

3. The method of claim 1, wherein (i) is iron complex, the iron complex being iron sucrose.

4. The method of claim 1, wherein the heme protein degradation inhibitor is a metal protoporphyrin.

5. The method of claim 4, wherein the metal-protoporphyrin is Sn-protoporphyrin.

6. The method of claim 1, wherein (i) is iron and (ii) is a metal protoporphyrin.

7. The method of claim 1, wherein (i) is iron sucrose and (ii) is Sn-protoporphyrin, the therapeutically effective amount being administered at least 2 hours before the scheduled insult to the organ occurs.

8. The method of claim 1, wherein the scheduled insult is surgery, chemotherapy, or radiocontrast toxicity.

9. The method of claim 1, wherein the organ is a heart, kidney, liver, or lung.

10. The method of claim 1, wherein the administration occurs at least 2 hours before the scheduled insult to the organ occurs.

11. The method of claim 1, wherein the administration occurs at least 4 hours before the scheduled insult to the organ occurs.

12. The method of claim 1, wherein the administration occurs at least 12 hours before the scheduled insult to the organ occurs.

13. The method of claim 1, wherein the administration occurs at least 18 hours before the scheduled insult to the organ occurs.

14. A method of protecting an organ of a human patient from injury based on a scheduled insult comprising administering to the organ a therapeutically effective amount of (i) iron or iron complex;

and (ii) a metal protoporphyrin, the therapeutically effective amount being administered at least 2 hours before the scheduled insult to the organ occurs, wherein the metal in the metal protoporphyrin is Pt, Zn, Ni, Cu, Ag, Mn, Cr, or Sn.

15. The method of claim 14, wherein (i) is iron.

16. The method of claim 14, wherein (i) is iron sucrose.

17. The method of claim 14, wherein the scheduled insult is surgery, chemotherapy, or radiocontrast toxicity.

18. The method of claim 14, wherein the organ is a heart, kidney, liver, or lung.

19. The method of claim 14, wherein the administration occurs at least 12 hours before the scheduled insult to the organ occurs.