VAGINAL INSERTED ESTRADIOL PHARMACEUTICAL COMPOSITONS AND METHODS

• US 20150045335A1
• Filed: 10/22/2014
• Published: 02/12/2015
• Est. Priority Date: 12/21/2012
• Status: Active Grant

• Current Assignee: TherapeuticsMD Inc.
• Original Assignee: TherapeuticsMD Inc.
• Inventors: Bernick, Brian A., Persicaner, Peter H. R., Cacace, Janice Louise, Thorsteinsson, Thorsteinn, Sancilio, Frederick D.
• Granted Patent: US 10,537,581 B2
• Time in Patent Office: Days
• US Class Current: 514/182
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/565 not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
• CPC Class Codes: A61K 31/57 substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
• CPC Class Codes: A61K 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• 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 9/06 Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels composition of ointments, creams or gels A61K47/00
• CPC Class Codes: A61K 9/4858 Organic compounds
• CPC Class Codes: A61K 9/4866 Organic macromolecular compounds

Abstract

According to various embodiments of this disclosure, pharmaceutical compositions comprising solubilized estradiol are provided. In various embodiments, such compositions are encapsulated in soft capsules which may be vaginally inserted for the treatment of vulvovaginal atrophy.

Claims

1. A pessary comprising:

a) a therapeutically effective amount of estradiol; and

b) a solubilizing agent comprising a medium chain oil.

2. The pessary of claim 1, wherein the pessary comprises about 1 μ

g to about 25 μ

g of estradiol.

3. The pessary of claim 1, wherein the pessary comprises about 1 μ

g to about 10 μ

g of estradiol.

4. The pessary of claim 1, wherein the pessary comprises about 10 μ

g to about 25 μ

g of estradiol.

5. The pessary of claim 1, wherein the estradiol is solubilized.

6. The pessary of claim 1, wherein the medium chain oil comprises at least one C6-C12 fatty acid or a glycol, monoglyceride, diglyceride, or triglyceride ester thereof.

7. The pessary of claim 1, wherein the solubilizing agent comprises at least one ester selected from the group consisting of:

an ester of caproic fatty acid, an ester of caprylic fatty acid, an ester of capric fatty acid, and combinations thereof.

8. The pessary of claim 7, wherein the solubilizing agent comprises a caprylic/capric triglyceride.

9. The pessary of claim 1, wherein the pessary further comprises a capsule.

10. The pessary of claim 9, wherein the capsule is a soft gelatin capsule.

11. A pessary comprising:

a) a therapeutically effective amount of estradiol;

b) a caprylic/capric triglyceride;

c) a non-ionic surfactant comprising PEG-6 palmitostearate and ethylene glycol palmitostearate; and

d) a soft gelatin capsule.

12. A pessary comprising about 1 μ

g to about 25 μ

g of estradiol, wherein administration of the pessary to the proximal region of the vagina of a patient provides a therapeutically effective concentration of estradiol over 24 hours in the proximal region of the vagina.

13. A method of treating an estrogen-deficient state, the method comprising administering to a patient in need thereof, a pessary comprising:

a) a therapeutically effective amount of estradiol; and

b) a solubilizing agent comprising a medium chain oil.