Monolithic intravaginal rings comprising progesterone and methods of making and uses thereof

Abstract

The present invention relates to monolithic intravaginal rings comprising progesterone, methods of making, and uses thereof. The intravaginal rings comprise progesterone, a polysiloxane elastomer, and a pharmaceutically acceptable hydrocarbon or glycerol esters of a fatty acid.

1 - 52 . (canceled) 
     
     
         53 . A monolithic intravaginal ring for treating a luteal phase defect in a patient in need thereof, comprising:
 (a) about 15% to about 30% by weight of progesterone;   (b) about 55% to about 90% by weight of polysiloxane elastomer; and   (c) about 1% to about 10% by weight of a pharmaceutically acceptable hydrocarbon or glycerol esters of a fatty acid or pharmaceutically acceptable oil, wherein the progesterone is homogeneously dispersed in the elastomer.   
     
     
         54 . The monolithic intravaginal ring of  claim 53 , wherein the polysiloxane elastomer is a diorganopolysiloxane elastomer. 
     
     
         55 . The monolithic intravaginal ring of  claim 54 , wherein the diorganopolysiloxane elastomer is a dimethylpolysiloxane elastomer. 
     
     
         56 . The monolithic intravaginal ring of  claim 55 , wherein the dimethylpolysiloxane elastomer is vinyl end blocked. 
     
     
         57 . The monolithic intravaginal ring of  claim 55 , wherein the dimethylpolysiloxane elastomer further comprises a dimethylmethylhydrogen polysiloxane crosslink. 
     
     
         58 . The monolithic intravaginal ring of  claim 53 , wherein the polysiloxane elastomer composition comprises, as separate components, (i) dimethylpolysiloxane vinyl end-blocked polymer, non-crystalline trimethylsilyl treated fumed silica, and a platinum silicone complex and (ii) dimethylpolysiloxane vinyl end-blocked polymer, non-crystalline trimethylsilyl treated fumed silica, dimethylmethylhydrogen polysiloxane, and 2-methyl-3-butyn-2-ol. 
     
     
         59 . The monolithic intravaginal ring of  claim 53 , wherein the pharmaceutically acceptable hydrocarbon or glycerol esters of fatty acid or pharmaceutically acceptable oil is selected from mineral oil, silicone oil, and combinations thereof. 
     
     
         60 . The monolithic intravaginal ring of  claim 53 , wherein the pharmaceutically acceptable hydrocarbon or glycerol esters of fatty acid or pharmaceutically acceptable oil is mineral oil. 
     
     
         61 . The monolithic intravaginal ring of  claim 53 , wherein the polysiloxane elastomer is a dimethylpolysiloxane elastomer, and wherein the ratio of progesterone to dimethylpolysiloxane elastomer to pharmaceutically acceptable hydrocarbon or glycerol esters of fatty acid in the ring is about 4:15:1. 
     
     
         62 . The monolithic intravaginal ring of  claim 53 , wherein the intravaginal ring comprises:
 (a) from about 15% to about 25% by weight of the progesterone;   (b) from about 55% to about 90% by weight of a dimethylpolysiloxane elastomer; and   (c) from about 1% to about 10% by weight of the pharmaceutically acceptable hydrocarbon or glycerol esters of a fatty acid or pharmaceutically acceptable oil.   
     
     
         63 . The monolithic intravaginal ring of  claim 53 , wherein the ring is constructed to release the progesterone at a steady rate for about 1 day to about 14 days. 
     
     
         64 . The monolithic intravaginal ring of  claim 53 , wherein the ring is constructed to release the progesterone at a steady rate for about 1 day to about 10 days. 
     
     
         65 . The monolithic intravaginal ring of  claim 53 , wherein the ring is constructed to release the progesterone at a steady rate for about 1 day to about 7 days. 
     
     
         66 . The monolithic intravaginal ring of  claim 53 , wherein ring is constructed to release the progesterone at about 10 mg/day to about 40 mg/day in vivo. 
     
     
         67 . The monolithic intravaginal ring of  claim 53 , wherein ring is constructed to release the progesterone at about 10 mg/day to about 30 mg/day in vivo. 
     
     
         68 . The monolithic intravaginal ring of  claim 53 , wherein ring is constructed to release the progesterone at about 15 mg/day to about 25 mg/day in vivo. 
     
     
         69 . The monolithic intravaginal ring of  claim 53 , wherein the ring is constructed to release about 11 mg to about 15 mg progesterone per day at a steady rate for 7 days. 
     
     
         70 . The monolithic intravaginal ring of  claim 53 , wherein the ring is effective to maintain a relatively constant serum progesterone level of from about 6 ng/mL to about 10 ng/ml over a 7-day period of use after administration to subject.