Reduced oxygen carriers and their use for the treatment of carboxyhemoglobinemia

Patent metadata

Field	Value
Publication number	US-10973883-B2
Application number	US-201716302324-A
Country	US
Kind code	B2
Filing date	May 19, 2017
Priority date	May 19, 2016
Publication date	Apr 13, 2021
Grant date	Apr 13, 2021

Abstract

In vitro and in vivo methods of removing carbon monoxide from hemoglobin in blood or animal tissue are described. Methods of treating carboxyhemoglobinemia (carbon monoxide poisoning) in a subject are also described. The methods include administering natural or artificial oxygen carriers that are in their reduced form. Methods of producing a reduced oxygen carrier are further described. Methods of treating cyanide poisoning or hydrogen sulfide poisoning with oxygen carriers are also described.

First claim

The invention claimed is:

1. A method of treating carboxyhemoglobinemia in a subject, comprising:
selecting a subject with carboxyhemoglobinemia, wherein the subject has at least 5% carboxyhemoglobin in their blood;
administering to the subject a therapeutically effective amount of a composition comprising a natural oxygen carrier, wherein the oxygen carrier is in the reduced form, and wherein the oxygen carrier is hemoglobin; and
wherein the therapeutically effective amount of the composition is an amount sufficient to scavenge carbon monoxide in the blood or tissues of the subject, thereby reducing the level of carboxyhemoglobin in the blood of the subject.

2. The method of claim 1 , wherein the composition further comprises a pharmaceutically acceptable reducing agent.

3. The method of claim 2 , wherein the reducing agent comprises sodium dithionite, ascorbic acid, N-acetylcysteine, methylene blue, glutathione, cytochrome b5/b5-reductase, hydralazine or any combination thereof.

4. The method of claim 1 , wherein the hemoglobin is human hemoglobin.

5. The method of claim 1 , wherein the hemoglobin is non-human animal hemoglobin.

6. A method of scavenging carbon monoxide from hemoglobin in blood or tissue of a subject, wherein the subject has at least 5% carboxyhemoglobin in their blood, comprising contacting the blood or tissue with a composition comprising a natural oxygen carrier, wherein the oxygen carrier is in the reduced form, and wherein the oxygen carrier is hemoglobin;
thereby scavenging carbon monoxide from hemoglobin in the blood or tissue.

7. The method of claim 6 , wherein contacting the blood or tissue with a composition comprising a natural oxygen carrier comprises administering a therapeutically effective amount of the composition comprising the natural oxygen carrier, wherein the oxygen carrier is in the reduced form, and wherein the oxygen carrier is hemoglobin to the subject;
wherein the therapeutically effective amount is an amount sufficient to scavenge carbon monoxide in the blood or tissue of the subject, thereby reducing the level of carboxyhemoglobin in the blood of the subject.

8. The method of claim 7 , comprising selecting a subject with carboxyhemoglobinemia prior to administering the composition to the subject.

9. The method of claim 7 , wherein the subject has at least 10% carboxyhemoglobin in their blood.

10. The method of claim 6 , wherein the composition further comprises a reducing agent.

11. The method of claim 10 , wherein the reducing agent comprises sodium dithionite, ascorbic acid, N-acetylcysteine, methylene blue, glutathione, cytochrome b5/b5-reductase, hydralazine, or any combination thereof.

12. The method of claim 6 , wherein the hemoglobin is human hemoglobin.

13. The method of claim 6 , wherein the hemoglobin is non-human animal hemoglobin.

Assignees

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

Inventors

• Rose Jason Joseph
• Xu Qinzi
• Gladwin Mark T
• Tejero Bravo Jesus

Classifications

• C01C3/08

  Simple or complex cyanides of metals {(C01C3/001, C01C3/002 take precedence)} · CPC title

• A61K35/14

  Blood; Artificial blood (perfluorocarbons A61K31/02; umbilical cord blood A61K35/51; haemoglobin A61K38/42) · CPC title

• C07K14/795

  Porphyrin- or corrin-ring-containing peptides · CPC title

• A61K33/00

  Medicinal preparations containing inorganic active ingredients · CPC title

• A61K31/409 Primary

  having four such rings, e.g. porphine derivatives, bilirubin, biliverdine (hemin, hematin A61K31/555) · CPC title