NEUROSTEROID COMPOSITIONS AND METHODS OF USE THEREOF

• US 20180050107A1
• Filed: 08/15/2017
• Published: 02/22/2018
• Est. Priority Date: 08/16/2016
• Status: Abandoned Application

• Current Assignee: Janssen Pharmaceutica NV (Johnson & Johnson)
• Original Assignee: Janssen Pharmaceutica NV (Johnson & Johnson)
• Inventors: DiMauro, Thomas M, Wildenhaus, Kevin, Fevola, Michael J, Fuetterer, Tobias Johannes
• Application Number:
  US15/677,623
• Publication Number:
  US 20180050107A1
• Time in Patent Office: Days
• CPC Class Codes: A61K 31/57 substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 9/107 Emulsions ; Emulsion preconcentrates; Micelles composition of emulsions A61K47/00
• CPC Class Codes: A61K 9/1075 Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers A61K9/0026 takes precedence

Abstract

Provided herein are compositions comprising neurosteroids and saponins, methods of making said compositions, and methods of utilizing said compositions to treat or prevent perinatal depression (PND) in a subject in need thereof.

Claims

1. A composition comprising:

a. a neurosteroid; and

b. a saponin in an amount effective to form a self-assembled structure incorporating the neurosteroid.

2. The composition of claim 1, wherein the self-assembled structure is selected from the group consisting of a micelle, a gel, a liposome, a lamellar phase, and a multi-lamellar vesicle.

3. The composition of claim 2, wherein the self-assembled structure is a micelle.

4. The composition of claim 3, wherein the saponin is selected from the group consisting of a soyasaponin, a quillaja saponin, and a ginsenoside saponin.

5. The composition of claim 4, wherein the neurosteroid is selected from the group consisting of an allopregnanolone, a tetrahydrodeoxycorticosterone (THDOC), and a progesterone.

6. The composition of claim 5, wherein the neurosteroid is an allopregnanolone.

7. The composition of claim 6, wherein the saponin is at least about 0.1 wt % relative to the total weight of the composition.

8. The composition of claim 7, wherein the composition comprises at least about 100 parts per million of the neurosteroid.

9. The composition of claim 8, wherein the composition further comprises a pharmaceutically acceptable carrier.

10. The composition claim 9, wherein the composition further comprises an adjuvant.

11. The composition of claim 10, wherein the composition has a permeation coefficient P of about 0.01 per hour to about 0.05 per hour.

12. The composition of claim 11, wherein the composition has a permeation coefficient P of about 0.01 per hour.

13. A method of treating a perinatal depression (PND) in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the composition of claim 12.

14. The method of claim 13, wherein the therapeutically effective amount of the composition is administered topically, orally, mucosally, intravenously or by inhalation.

15. The method of claim 14, wherein the therapeutically effective amount of the composition is administered in a single dose.

16. The method of claim 15, wherein the therapeutically effective amount of the composition has a permeation coefficient P of about 0.01 per hour to about 0.05 per hour.

17. The method of claim 16, wherein the therapeutically effective amount of the composition has a permeation coefficient P of about 0.01 per hour.

18. The method of claim 17, wherein the therapeutically effective amount of the composition has a permeation coefficient P at least two times lower than a permeation coefficient P of a composition comprising a monomolecular neurosteroid or a cyclodextrin neurosteroid complex.

19. A method of producing the composition of claim 12, the method comprising adding a solution of the neurosteroid dissolved in an organic solvent to a saponin solution under flow, wherein the neurosteroid is incorporated into the self-assembled structure.

20. The method of claim 19, wherein the organic solvent dissolves at least 0.1 wt % of the neurosteroid.

21. The method of claim 20, wherein at least 1 wt % of the organic solvent is soluble in water.

22. The method of claim 21, wherein the organic solvent is selected from the group consisting of ethanol, methanol, propanol, butanol, glycol, ethylene glycol, propylene glycol, butylene glycol, diethyl ether, and mixtures thereof.

23. The method of claim 22, wherein the organic solvent is ethanol.