Inositol pyrophosphates, and methods of use thereof

• US 7,618,954 B2
• Filed: 01/09/2006
• Issued: 11/17/2009
• Est. Priority Date: 04/29/2002
• Status: Active Grant

• Current Assignee: NormOxys, Inc.
• Original Assignee: Universite De Strasbourg (Financière Meeschaert SA), NormOxys, Inc.
• Inventors: Fylaktakidou, Konstantina, Nicolau, Yves Claude, Greferath, Ruth, Lehn, Jean-Marie
• Primary Examiner(s): Saeed; Kamal A
• Application Number:
  US11/328,313
• Publication Number:
  US 20060116358A1
• Time in Patent Office: 1,408 Days
• Field of Search: None
• US Class Current: 514/102
• CPC Class Codes: A61K 31/66 Phosphorus compounds
• CPC Class Codes: A61K 31/6615 Compounds having two or more esterified phosphorus acid groups, e.g. inositol triphosphate, phytic acid
• CPC Class Codes: A61K 31/70 Carbohydrates; Sugars; Derivatives thereof sorbitol A61K31/047
• CPC Class Codes: A61K 31/715 Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
• CPC Class Codes: A61K 35/18 Erythrocytes haemoglobin A61K38/42
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 39/00 General protective or antinoxious agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/06 Antianaemics
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07F 9/117 with cycloaliphatic alcohols
• CPC Class Codes: C07F 9/65746 the molecule containing more than one cyclic phosphorus atom
• CPC Class Codes: C07H 15/207 Cyclohexane rings not substituted by nitrogen atoms, e.g. kasugamycins
• CPC Class Codes: C12N 5/0641 : Erythrocytes

Abstract

The present invention comprises compounds, compositions thereof, and methods capable of delivering modified inositol hexaphospahte (IHP) comprising an internal pyrophosphate ring to the cytoplasm of mammalian cells. In certain embodiments, the present invention relates to compounds, compositions thereof, and methods that enhance the ability of mammalian red blood cells to deliver oxygen, by delivering IHP to the cytoplasm of the red blood cells.

Claims

1. A method of enhancing oxygen delivery to a tissue or organ of a mammal, comprising the step of administering to a mammal a therapeutically effective amount of a compound represented by structure I:

2. The method of claim 1, wherein the composition is administered orally.

9. The method of claim 1, wherein A is represented by the compound of structure II.

10. The method of claim 9, wherein C is sodium and n is 6.

11. The method of claim 1, wherein the mammal is afflicted with a cardiovascular disease.

12. The method of claim 11, wherein the cardiovascular disease is a coronary infarction, a pulmonary disease, congestive heart failure, a myocardial infarction, a peripheral vascular disease, stroke, an intermittent claudication, or arteriosclerosis.

13. The method of claim 12, wherein the cardiovascular disease is congestive heart failure.

3. A method of enhancing oxygen delivery to a tissue or organ of a mammal, comprising the step of administering to a mammal red blood cells previously treated with a compound represented by structure I:

4. A method of treating a mammal afflicted with a cardiovascular disease, comprising the step of administering to said mammal a therapeutically effective amount of a compound represented by structure I:

5. The method of claim 4, wherein the composition is administered orally.

14. The method of claim 4, wherein A is represented by the compound of structure II:

15. The method of claim 14, wherein C is sodium and n is 6.

16. The method of claim 4, wherein the cardiovascular disease is a coronary infarction, a pulmonary disease, congestive heart failure, a myocardial infarction, a peripheral vascular disease, stroke, an intermittent claudication, or arteriosclerosis.

17. The method of claim 16, wherein the cardiovascular disease is congestive heart failure.

6. A method of treating a mammal afflicted with a cardiovascular disease comprising the step of administering to said mammal red blood cells previously treated with a compound represented by structure I:

18. The method of claim 6, wherein the cardiovascular disease is a coronary infarction, a pulmonary disease, congestive heart failure, a myocardial infarction, a peripheral vascular disease, stroke, an intermittent claudication, or arteriosclerosis.

19. The method of claim 18, wherein the cardiovascular disease is congestive heart failure.

7. A method of improving the oxygen delivering capability of mammalian blood, comprising the step of adding to a volume of mammalian blood a compound represented by structure I:

8. A method of incorporating a therapeutically useful substance into mammalian red blood cells, comprising the step of treating a sample of mammalian red blood cells with a compound represented by structure I: