Method for improving the oxygen-releasing ability of hemoglobin to organs or peripheral tissues in human bodies and a medication thereof

Patent metadata

Field	Value
Publication number	US-10047063-B2
Application number	US-201715411637-A
Country	US
Kind code	B2
Filing date	Jan 20, 2017
Priority date	Sep 1, 2014
Publication date	Aug 14, 2018
Grant date	Aug 14, 2018

Abstract

A method for improving the oxygen-releasing ability of hemoglobin, hemoglobin variants, recombinant hemoglobin or hemoglobin-based blood substitutes to organs or peripheral tissues in human bodies is disclosed by administering a compound of phthalides to a subject in need thereof. The compound of phthalides is characterized by a phthalide functional group which is represented as Formula I, and forms at least one hydrogen bond with αArg141 of hemoglobin, hemoglobin variants, recombinant hemoglobin or hemoglobin-based blood substitutes, stabilizing the α1/α2 interface of hemoglobin, further stabilizing the oxygenated hemoglobin, hemoglobin variants, recombinant hemoglobin or hemoglobin-based blood substitutes in the low oxygen affinity “T” state and facilitating the oxygen release to the organs or the peripheral tissues. A medication for improving the oxygen-releasing ability of hemoglobin, hemoglobin variants, recombinant hemoglobin, or hemoglobin-based blood substitutes to organs or peripheral tissues in human bodies is also disclosed.

First claim

What is claimed is:

1. A method for improving the oxygen-releasing ability of hemoglobin, hemoglobin variants, recombinant hemoglobin or hemoglobin-based blood substitutes to organs or peripheral tissues in human bodies, by administering a compound of Formula I to a subject in need thereof, wherein the compound of Formula I forms at least one hydrogen bond with αArg141 of hemoglobin, strengthening the α1/α2 interface of hemoglobin, further stabilizing the oxygenated hemoglobin in the low oxygen affinity “T” state and facilitating the oxygen release to the organs or the peripheral tissues,

wherein R 1 is C 2 -C 6 alkyl, C 2 -C 6 alkenyl or C 2 -C 6 alkenol group;
R 2 is one or more H or OH; and
R 3 and R 4 are each independent H or OH or both of them combine together to form a epoxy group.

2. The method of claim 1 , wherein the compound of Formula I is Z-butylidenephthalide.

3. The method of claim 1 , wherein the compound of Formula I is Z-ligustilide.

4. The method of claim 1 , wherein the compound of Formula I is senkyunolide A.

5. The method of claim 1 , wherein the compound of Formula I is senkyunolide H.

6. The method of claim 1 , wherein the compound of Formula I is senkyunolide I.

7. The method of claim 1 , wherein the compound of Formula I is senkyunolide F.

8. The method of claim 1 , wherein the compound of Formula I is E-butylidenephthalide.

9. The method of claim 1 , wherein the compound of Formula I is E-ligustilide.

10. The method of claim 1 , wherein the compound of Formula I is 3-butylphthalide.

11. The method of claim 1 , wherein the compound of Formula I is 3-butylidene-4-hydrophthalide.

12. The method of claim 1 , wherein the compound of Formula I is 6,7-dihydroxyligustilide.

13. The method of claim 1 , wherein the compound of Formula I is 6,7-epoxyligustilide.

Assignees

• National Sun Yat Sen University

Inventors

• Wang Chia-Chen
• Zulfajri Muhammad
• Yu You-Qing

Classifications

• C07D493/04

  Ortho-condensed systems · CPC title

• A61K31/6615

  Compounds having two or more esterified phosphorus acid groups, e.g. inositol triphosphate, phytic acid · CPC title

• C07D307/77

  ortho- or peri-condensed with carbocyclic rings or ring systems · CPC title

• C07D307/87 Primary

  Benzo [c] furans; Hydrogenated benzo [c] furans · CPC title

• A61K31/365

  Lactones · CPC title