Use of microperoxidases for the treatment of carboxyhemoglobinemia

Patent metadata

Field	Value
Publication number	US-10980864-B2
Application number	US-201515313231-A
Country	US
Kind code	B2
Filing date	May 19, 2015
Priority date	May 22, 2014
Publication date	Apr 20, 2021
Grant date	Apr 20, 2021

Abstract

It is disclosed herein that microperoxidases are capable of binding carbon monoxide (CO) with high affinity and displacing CO from hemoglobin, thereby acting as CO scavengers. The present disclosure provides methods of treating carboxyhemoglobinemia (or CO poisoning) in a subject by administering a therapeutically amount of an isolated or recombinant microperoxidase. Methods of removing CO from hemoglobin in blood or tissue by administering a therapeutically amount of an isolated or recombinant microperoxidase are also described. Methods of determining the effectiveness of a microperoxidase for removing CO from hemoglobin are further described.

First claim

The invention claimed is:

1. A method of treating carboxyhemoglobinemia in a subject by selecting a subject with carboxyhemoglobinemia and administering to the subject, via intravenous injection or infusion, a therapeutically effective amount of a pharmaceutical composition consisting of a pharmaceutically acceptable carrier and an isolated or recombinant microperoxidase, wherein the isolated or recombinant microperoxidase consists of a peptide covalently bound to a porphyrin moiety, and wherein the amino acid sequence of the peptide comprises any one of SEQ ID NOs: 4-10.

2. The method of claim 1 , wherein the amino acid sequence of the peptide consists of any one of SEQ ID NOs: 4-10.

3. The method of claim 1 , wherein the porphyrin moiety comprises a metal ion.

4. The method of claim 3 , wherein the metal is iron, zinc, palladium, manganese, cobalt, copper, nickel or cadmium.

5. The method of claim 1 , wherein the porphyrin moiety comprises protoporphyrin IX.

6. The method of claim 5 , wherein the porphyrin moiety further comprises iron.

7. The method of claim 1 , wherein the subject has at least 5%, at least 10%, at least 15%, at least 20%, at least 30%, at least 40% or at least 50% carboxyhemoglobin in blood relative to total hemoglobin.

8. The method of claim 1 , wherein the isolated or recombinant microperoxidase is administered by intravenous infusion.

9. The method of claim 1 , wherein the isolated or recombinant microperoxidase is administered in an amount required to decrease carboxyhemoglobin (HbCO) by at least 1% to at least 90% in blood or tissue of the subject.

10. The method of claim 9 , wherein the isolated or recombinant microperoxidase is administered in an amount required to decrease HbCO by at least 20% in blood or tissue of the subject.

11. The method of claim 9 , wherein the isolated or recombinant microperoxidase is administered in an amount required to decrease HbCO by at least 50% in blood or tissue of the subject.

Assignees

• Univ Of Pittsburgh—Of The Commonwealth System Of Higher Education

Inventors

• Gladwin Mark Thomas
• Tejero Bravo Jesus

Classifications

• A61K38/415

  Cytochromes · CPC title

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title

• C12Y111/01007

  Peroxidase (1.11.1.7), i.e. horseradish-peroxidase · CPC title

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• A61K38/44 Primary

  Oxidoreductases (1) · CPC title