ESTROGEN PRODRUGS AND METHODS OF ADMINISTERING ESTROGEN PRODRUGS

• US 20190328658A1
• Filed: 04/26/2019
• Published: 10/31/2019
• Est. Priority Date: 04/27/2018
• Status: Abandoned Application

• Current Assignee: Evestra, Inc.
• Original Assignee: Evestra, Inc.
• Inventors: Nickisch, Klaus, Eggenreich, Karin, Eder, Simone, Witschnigg, Andreas
• Application Number:
  US16/395,349
• Publication Number:
  US 20190328658A1
• Time in Patent Office: Days
• CPC Class Codes: A61F 6/142 Wirelike structures, e.g. loops, rings, spirals
• CPC Class Codes: A61K 31/565 not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
• CPC Class Codes: A61K 31/567 substituted in position 17 alpha, e.g. mestranol, norethandrolone
• 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 31/575 substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 9/0036 Devices retained in the vagina or cervix for a prolonged period, e.g. intravaginal rings, medicated tampons, medicated diaphragms
• CPC Class Codes: A61K 9/025 characterised by shape or structure, e.g. hollow layered, coated
• CPC Class Codes: A61M 31/002 Devices for releasing a drug at a continuous and controlled rate for a prolonged period of time artificial gland structures or devices A61F2/022; intra-uterine contraceptive devices A61F6/14; tampons for introducing into the vagina A61F13/20, A61L15/00; suppositories or bougies for intra-vaginal or intra-uterine application A61K9/02; physical forms of medicinal preparations for sustained or differential drug release A61K9/20, A61K9/50
• CPC Class Codes: A61P 15/18 Feminine contraceptives

Abstract

Disclosed herein is an intravaginal drug delivery device that includes one or more compartments, each of the one or more compartments comprising an estrogen prodrug and/or a progestin dispersed in a thermoplastic polymeric matrix.

Claims

1. An intravaginal drug delivery device comprising:

one or more compartments, each of the one or more compartments comprising an estrogen prodrug and/or a progestin dispersed in a thermoplastic polymeric matrix.

2. The device of claim 1, wherein one or more of the compartments are uncoated compartments.

3. The device of claim 1, wherein one or more of the compartments are coated compartments comprising an estrogen prodrug and/or progestin dispersed in a coated thermoplastic polymeric matrix.

4. The device of claim 1, wherein the device comprises two or more compartments having different sizes.

5. The device of claim 1, wherein the estrogen prodrug is a mono or di ester of estriol.

6. The device of claim 1, wherein the estrogen prodrug is a prodrug of estriol having structure:

7. The device of claim 6, wherein R is methyl.

8. The device of claim 6, wherein R is cyclopropyl.

9. The device of claim 1, wherein the estrogen prodrug is a prodrug of estriol having the structure:

10. The device of claim 9, wherein R is methyl.

11. The device of claim 9, wherein R is cyclopropyl.

12. The device of claim 1, wherein the estrogen prodrug is a prodrug of estriol having the structure:

13. The device of claim 12, wherein R is cyclopropyl.

14. The device of claim 1, wherein the device comprises at least one compartment comprising a progestin, and wherein the progestin is released, during vaginal use, in an amount sufficient to inhibit ovulation in fertile women.

15. The device of claim 14, wherein the progestin is trimegestone.

16. The device of claim 1, wherein the device comprises at least one compartment comprising an estrogen prodrug and at least one compartment comprising a progestin, and wherein the estrogen prodrug and progestin are released, during vaginal use, in amounts sufficient to effect cycle control in fertile women.

17. The device of claim 1, wherein the intravaginal drug delivery device provides the estrogen prodrug and/or the progestin according to a non-zero order release profile.

18. The device of claim 1, wherein the thermoplastic polymeric matrix comprises an ethylene vinyl acetate copolymer.

19. The device of claim 1, wherein the thermoplastic polymeric matrix comprises a thermoplastic polyurethane.

20. The device of claim 1, wherein the compartment is a coated compartment comprising a thermoplastic polymeric matrix comprising an ethylene vinyl acetate (EVA) copolymer with a VA (vinyl acetate) content between 18% and 40% and wherein the coating comprises an EVA copolymer with a VA content between 6% and 18%.

21. The device of claim 1, wherein the thermoplastic polymeric matrix comprises an ethylene vinyl acetate (EVA) copolymer with a VA (vinyl acetate) content between 18% and 40% in the core and a low density polyethylene (LDPE).

26. The device of claim 1, wherein the amount of progestin and/or estrogen prodrug released by the device on the last day of treatment is at least 50% higher than on any day after the first day of use.

22-25. -25. (canceled)