Vaginal inserted estradiol pharmaceutical compositions and methods

• US 10,258,630 B2
• Filed: 02/09/2018
• Issued: 04/16/2019
• Est. Priority Date: 10/22/2014
• Status: Active Grant

• Current Assignee: TherapeuticsMD Inc.
• Original Assignee: TherapeuticsMD Inc.
• Inventors: Mirkin, Sebastian, Amadio, Julia M., Bernick, Brian A.
• Primary Examiner(s): Parad, Dennis J
• Application Number:
  US15/893,546
• Publication Number:
  US 20180161344A1
• Time in Patent Office: 431 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 9/0034 Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
• 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 9/02 Suppositories; Bougies; Bases therefor; Ovulesapparatus for making A61J3/08; devices for introducing into the body A61M31/00
• CPC Class Codes: A61K 9/4825 Proteins, e.g. gelatin gelatin capsule shells with substantial amounts of other macromolecular substances A61K9/4816
• CPC Class Codes: A61K 9/4858 Organic compounds
• CPC Class Codes: A61K 9/4866 Organic macromolecular compounds

Abstract

In one aspect, compositions and methods for the treatment of vulvovaginal atrophy (VVA) are provided. In one embodiment, the method comprises administering an estrogen to a subject having VVA by inserting a dosage form comprising a liquid pharmaceutical composition.

Claims

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

intravaginally administering to the subject a dosage form comprising a liquid pharmaceutical composition, wherein the viscosity of the composition ranges from about 50 cP to about 1000 cP at 25°

C., wherein the dosage form is manually inserted into the vagina, wherein the composition comprises estrogen as the only active agent, wherein all of the estradiol is encapsulated in the capsule, wherein the composition comprises about 4 μ

g to about 25 μ

g of estradiol, wherein the administration comprises inserting the capsule once daily for two weeks and twice weekly thereafter, and wherein upon contact of the dosage form with the vaginal mucosa, the composition comprising the estrogen is released into the vaginal tissue.

2. The method of claim 1, wherein the dosage form is a capsule.

3. The method of claim 1, wherein the capsule is a soft gelatin capsule.

4. The method of claim 1, where the composition comprises about 4 μ

g to about 25 μ

g of estradiol.

5. The method of claim 1, wherein administration of the dosage form results in an increase in the percentage of vaginal superficial cells within about two to six weeks from the first administration.

6. The method of claim 1, wherein administration of the dosage form results in a decrease in the percentage of vaginal parabasal cells within about two to six weeks from the first administration.

7. The method of claim 1, wherein administration of the dosage form results in a decrease in vaginal pH within about two to six weeks from the first administration.

8. The method of claim 1, wherein administration of the dosage form results in a decrease in the severity of moderate to severe dyspareunia within about two to six weeks from the first administration.

9. The method of claim 4, wherein the composition contains 4 μ

g estradiol or 10 μ

g estradiol.