VAGINAL INSERTED ESTRADIOL PHARMACEUTICAL COMPOSITIONS AND METHODS

• US 20180161344A1
• Filed: 02/09/2018
• Published: 06/14/2018
• 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.
• Granted Patent: US 10,258,630 B2
• Time in Patent Office: Days
• 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 VVA in a subject, the method comprising:

administering, by inserting into the vagina of the subject, a dosage form comprising a liquid pharmaceutical composition, wherein the composition comprises estrogen as the only active agent, and wherein the dosage form dissolves and at least 80% of the composition is absorbed by the vaginal tissue with no vaginal discharge of the composition.

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

3. The method of claim 2, 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 solubilized estradiol.

5. The method of claim 1, wherein at least about 85% by weight, at least about 90% by weight, at least about 95% by weight, at least about 97% by weight, at least about 98% by weight, or at least about 99% by weight of the composition is absorbed by the vaginal tissue.

6. The method of claim 1, wherein the composition is fully absorbed by the vaginal tissue.

7. The method of claim 1, wherein administering the dosage form results in an improvement in one or more clinical parameters in the subject within two weeks from the first administration, wherein the parameters are selected from the group consisting of an increase in the percentage of vaginal superficial cells, a decrease in the percentage of vaginal parabasal cells, a decrease in vaginal pH, and a decrease in the severity of moderate to severe symptoms of dyspareunia.

8. The method of claim 7, wherein administration of the composition results in an increase in the percentage of vaginal superficial cells within two weeks from the first administration.

9. The method of claim 7, wherein administration of the composition results in a decrease in the percentage of vaginal parabasal cells within two weeks from the first administration.

10. The method of claim 7, wherein administration of the composition results in a decrease in vaginal pH within two weeks from the first administration.

11. The method of claim 7, wherein administration of the composition results in a decrease in the severity of moderate to severe symptoms of dyspareunia within two weeks from the first administration.

12. The method of claim 1, wherein the administration is conducted daily for two weeks, and twice weekly thereafter.