PHARMACEUTICAL COMPOSITIONS COMPRISING A HYDROXYETHYLQUERCETIN GLUCURONIDE METABOLITE

• US 20200101040A1
• Filed: 11/16/2018
• Published: 04/02/2020
• Est. Priority Date: 10/02/2018
• Status: Active Grant

• Current Assignee: Janssen Pharmaceutica NV (Johnson & Johnson)
• Original Assignee: Janssen Pharmaceutica NV (Johnson & Johnson)
• Inventors: DiMauro, Thomas M.
• Granted Patent: US 10,639,294 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 31/352 condensed with carbocyclic rings, e.g. methantheline cannabinoids A61K31/658
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61K 9/2009 Inorganic compounds
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/4866 Organic macromolecular compounds
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00

Abstract

Disclosed herein are metabolites of hydroxyethylrutoside (hydroxyethylquercetin-7-O-glucuronide), including compounds of Structural Formulas I, II, III and IV. The compounds disclosed are useful for inhibiting norepinephrine metabolism and in treating antenatal and postnatal depression in subjects in need thereof.

Claims

1. A pharmaceutical composition comprising from about 5% to about 95% weight/weight of a hydroxyethylquercetin-7-O-glucuronide, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent.

2. The composition of claim 1, wherein the composition is in the form of a capsule, a tablet, or a pill.

3. The composition of claim 1, wherein the composition is formulated for oral administration.

4. The composition of claim 1, further comprising a second acid.

5. The composition of claim 4, wherein the second acid is citric acid or hydrochloric acid or a combination thereof.

6. A method of inhibiting norepinephrine metabolism in a subject in need thereof, comprising:

administering to the subject an effective amount of the composition of claim 1.

7. The method of claim 6, wherein the administering is orally administering.

8. The method of claim 6, further comprising administering an acidifier.

9. The method of claim 8, wherein the acidifier is betaine or a pharmaceutically acceptable salt thereof.

10. The method of claim 8, wherein the acidifier is acidic liquid media.

11. The method of claim 10, wherein the acidic liquid media has a pH of less than about 3.

12. The method of claim 10, wherein the acidic liquid media comprises citric acid, acetic acid, or hydrochloric acid, or a combination of any of the foregoing.

13. The method of claim 10, wherein the acidic liquid media comprises vinegar or a citrus juice, or a combination of the foregoing.

14. A pharmaceutical composition comprising:

from about 5% to about 95% weight/weight of a compound represented by the following structural formula;

15. The composition of claim 14, wherein the composition is in the form of a capsule, a tablet, or a pill.

16. The composition of claim 14, wherein the composition is formulated for oral administration.

17. The composition of claim 14, further comprising a second acid.

18. The composition of claim 17, wherein the second acid is selected from citric acid, hydrochloric acid, and a combination thereof.

19. A method of inhibiting norepinephrine metabolism in a subject in need thereof, comprising:

administering to the subject an effective amount of the composition of claim 14.

20. The method of claim 19, wherein the administering is orally administering.

21. The method of claim 19, further comprising administering an acidic liquid media.

22. The method of claim 21, wherein the acidic liquid media is citric acid or hydrochloric acid or a combination thereof.

23. A pharmaceutical composition comprising:

a compound represented by the following structural formula;

24. The composition of claim 23, wherein the composition is in the form of a capsule, a tablet, or a pill.

25. The composition of claim 23, wherein the composition is formulated for oral administration.

26. The composition of claim 23, further comprising a second acid.

27. The composition of claim 26, wherein the second acid is selected from citric acid, hydrochloric acid, and a combination thereof.

28. A method of inhibiting norepinephrine metabolism in a subject in need thereof, comprising:

administering to the subject an effective amount of the composition of claim 23.

29. The method of claim 28, wherein the administering is orally administering.

30. The method of claim 28, further comprising administering an acidic liquid media.