Vaginal inserted estradiol pharmaceutical compositions and methods

• US 10,471,072 B2
• Filed: 02/09/2018
• Issued: 11/12/2019
• 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, Irani, Neda, Amadio, Julia M.
• Primary Examiner(s): Parad, Dennis J
• Application Number:
  US15/893,550
• Publication Number:
  US 20180161345A1
• Time in Patent Office: 641 Days
• Field of Search: None
• 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

Abstract

In one aspect, pharmaceutical compositions and methods for the treatment of vulvovaginal atrophy (VVA) are provided. In one embodiment, the method comprises digitally inserting into the lower third of the vagina of a subject having VVA a soft gelatin capsule containing a liquid pharmaceutical composition.

Claims

1. A method for treating moderate to severe dyspareunia in a human subject, the method comprising:

inserting about two inches into the vagina of the subject a soft gelatin capsule containing a liquid pharmaceutical composition, wherein the composition comprises about 4 μ

g to about 25 μ

g of estradiol and an excipient that increases the viscosity of the composition, wherein the composition has a viscosity from about 50 cP to about 1000 cP at 25°

C., and wherein the composition spreads over the vaginal tissue and the estradiol is absorbed by the vaginal tissue.

2. The method of claim 1, wherein the subject is in a reclined position while inserting the soft gelatin capsule.

3. The method of claim 1, wherein the subject is in a standing position while inserting the soft gelatin capsule.

4. The method of claim 1, wherein the viscosity of the composition is from about 50 cP to about 380 cP at 25°

C.

5. The method of claim 1, wherein the excipient that increases the viscosity comprises polyethylene glycol long chain saturated fatty acid esters, ethylene glycol long chain saturated fatty acid esters, or a mixture thereof.

6. The method of claim 1, wherein the composition comprises 4 μ

g estradiol or 10 μ

g estradiol.

7. The method of claim 1, wherein the soft gelatin capsule is inserted once daily for two weeks and twice weekly thereafter.