US 10,888,516 B2
Soluble estradiol capsule for vaginal insertion
Brian A. Bernick, Boca Raton, FL (US); Julia M. Amadio, Boca Raton, FL (US); Peter H. R. Persicaner, Boca Raton, FL (US); Thorsteinn Thorsteinsson, Boynton Beach, FL (US); Janice Louise Cacace, St. Petersburg, FL (US); Frederick D. Sancilio, Stuart, FL (US); and Neda Irani, Palm Beach Gardens, FL (US)
Assigned to TherapeuticsMD, Inc., Boca Raton, FL (US)
Filed by TherapeuticsMD, Inc., Boca Raton, FL (US)
Filed on Mar. 27, 2020, as Appl. No. 16/833,213.
Application 16/833,213 is a continuation of application No. 14/649,818, abandoned, previously published as PCT/US2013/046443, filed on Jun. 18, 2013.
Claims priority of provisional application 61/745,313, filed on Dec. 21, 2012.
Prior Publication US 2020/0289529 A1, Sep. 17, 2020
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 9/00 (2006.01); A61K 31/565 (2006.01); A61K 9/02 (2006.01); A61K 9/107 (2006.01); A61K 9/48 (2006.01); A61K 31/57 (2006.01); A61K 47/10 (2017.01); A61K 47/14 (2017.01); A61K 47/44 (2017.01)
CPC A61K 9/0034 (2013.01) [A61K 9/02 (2013.01); A61K 9/1075 (2013.01); A61K 9/48 (2013.01); A61K 9/4858 (2013.01); A61K 9/4866 (2013.01); A61K 31/565 (2013.01); A61K 31/57 (2013.01); A61K 47/10 (2013.01); A61K 47/14 (2013.01); A61K 47/44 (2013.01)] 19 Claims
 
1. A method of treating a symptom of vulvovaginal atrophy in a female human patient in need thereof, the method comprising administering to the female human an estradiol-containing soft gelatin capsule intravaginally once daily for 14 days and one capsule twice weekly thereafter, the estradiol-containing soft gelatin capsule comprising a gelatin shell surrounding an estradiol-containing liquid fill material, the estradiol-containing liquid fill material comprising one or more C6 to C14 fatty acid mono-, di-, or triesters of glycerol and 1 to 10 mcg of estradiol, wherein the estradiol-containing liquid fill material has a viscosity of between 50 to 1000 cP as measured at 25° C.
wherein:
administering the estradiol-containing soft gelatin capsule intravaginally to the female human in need thereof provides an estradiol AUC and estradiol Cmax that are each 80% to 125% of the estradiol AUC and estradiol Cmax obtained upon intravaginal administration of a reference soft gelatin capsule in a reference human female patient, the reference soft gelatin capsule consisting of a soft gelatin shell and a reference liquid fill material within the soft gelatin shell, wherein the reference liquid fill material consists of
approximately 270 mg of a C8 to C10 triglyceride composition containing at least about 80 percent by weight of a mixture of caprylic acid and capric acid;
approximately 30 mg of a surfactant containing a mixture of PEG-6 stearate, PEG-32 stearate, and ethylene glycol palmitostearate; and
1 to 10 mcg of estradiol
further wherein the reference liquid fill material has a viscosity of between 50 to 1000 cP as measured at 25° C.