Claims for Patent: 10,668,082

Summary for Patent: 10,668,082

Title:	Vaginal inserted estradiol pharmaceutical compositions and methods
Abstract:	Disclosed herein is, among other things, a soft gel vaginal pharmaceutical composition and dosage form containing solubilized estradiol for the treatment of vulvovaginal atrophy (VVA) and female sexual dysfunction (FSD).
Inventor(s):	Mirkin; Sebastian (Boca Raton, FL), Amadio; Julia M. (Boca Raton, FL), Bernick; Brian A. (Boca Raton, FL)
Assignee:	TherapeuticsMD, Inc. (Boca Raton, FL)
Application Number:	15/975,723
Patent Claims:	1. A method of treating vulvovaginal atrophy (VVA), comprising vaginally administering to a subject in need thereof a liquid pharmaceutical composition comprising estradiol at a dosage of 4 mcg, wherein the composition has a viscosity in the range of about 50 cP to about 1000 cP at 25.degree. C., and increasing the dosage of estradiol if the subject does not exhibit an improvement in a clinical response for VVA. 2. The method of claim 1, wherein the composition comprising estradiol is administered once daily for two weeks, then twice weekly thereafter. 3. The method of claim 1, wherein the estradiol is solubilized. 4. The method of claim 1, wherein a dosage form comprising the composition is manually inserted about two inches into the vagina. 5. The method of claim 1, wherein the composition comprising estradiol is encapsulated in a soft gelatin capsule. 6. The method of claim 1, wherein the subject's clinical response is measured as an improvement in one or more clinical parameters 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, a decrease in the severity of moderate to severe dyspareunia, a decrease in vaginal dryness, a decrease in vulvar or vaginal itching or irritation, an increase of vaginal mucosa, an assessment of standard pK parameters, a change in the Female Sexual Function Index (FSFI), a visual vaginal assessment, and the subject's self-reported response. 7. The method of claim 1, wherein the subject's clinical response is measured by a decrease in the severity of moderate to severe dyspareunia. 8. The method of claim 1, wherein the subject's clinical response is measured by a visual vaginal assessment or by the subject's self-reported response. 9. The method of claim 1, comprising increasing the dosage of estradiol to 10 mcg if the subject does not exhibit an improvement in the clinical response. 10. The method of claim 1, comprising increasing the dosage of estradiol to 25 mcg if the subject does not exhibit an improvement in the clinical response. 11. The method of claim 1, comprising decreasing the dosage of estradiol if an improvement in the clinical response is achieved. 12. A method of treating vulvovaginal atrophy (VVA), comprising vaginally administering to a subject in need thereof a liquid pharmaceutical composition comprising estradiol once daily for two weeks, then twice weekly thereafter, wherein the composition comprises estradiol at a dosage of 4 mcg and wherein the composition has a viscosity in the range of about 50 cP to about 1000 cP at 25.degree. C. 13. The method of claim 12, wherein the estradiol is solubilized. 14. The method of claim 12, wherein a dosage form comprising the composition is manually inserted about two inches into the vagina. 15. The method of claim 12, wherein the composition comprising estradiol is encapsulated in a soft gelatin capsule. 16. A method of treating moderate to severe dyspareunia, comprising vaginally administering to a subject in need thereof a liquid pharmaceutical composition comprising estradiol at a dosage of 4 mcg, wherein the composition has a viscosity in the range of about 50 cP to about 1000 cP at 25.degree. C., and increasing the dosage of estradiol if the subject does not exhibit an improvement in the moderate to severe dyspareunia. 17. The method of claim 16, wherein the composition comprising estradiol is administered once daily for two weeks, then twice weekly thereafter. 18. The method of claim 16, wherein the estradiol is solubilized. 19. The method of claim 16, wherein the composition comprising estradiol is encapsulated in a soft gelatin capsule. 20. The method of claim 16, comprising increasing the dosage of estradiol to 10 mcg if the subject does not exhibit an improvement in the moderate to severe dyspareunia. 21. The method of claim 16, comprising increasing the dosage of estradiol to 25 mcg if the subject does not exhibit an improvement in the moderate to severe dyspareunia.