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

Patent metadata

Field	Value
Publication number	US-11413294-B2
Application number	US-202016778526-A
Country	US
Kind code	B2
Filing date	Jan 31, 2020
Priority date	Feb 4, 2008
Publication date	Aug 16, 2022
Grant date	Aug 16, 2022

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.

First claim

What is claimed is:

1. A method of manufacturing a monolithic intravaginal progesterone ring, comprising:
(a) mixing progesterone, a polysiloxane elastomer composition, and a pharmaceutically acceptable hydrocarbon or glycerol esters of a fatty acid or pharmaceutically acceptable oil, to form a homogeneous mixture;
(b) placing the homogeneous mixture into a mold; and
(c) curing the homogeneous mixture in the mold to form a monolithic intravaginal progesterone ring comprising about 10% to about 30% by weight of the progesterone, about 60% to about 80% by weight of polysiloxane elastomer, and about 1% to about 8% by weight of the pharmaceutically acceptable hydrocarbon or glycerol esters of fatty acid or pharmaceutically acceptable oil, wherein the progesterone is homogeneously dispersed in the elastomer.

2. The method of claim 1 , wherein the polysiloxane elastomer is a diorganopolysiloxane elastomer.

3. The method of claim 2 , wherein the diorganopolysiloxane elastomer is a dimethylpolysiloxane elastomer.

4. The method of claim 3 , wherein the dimethylpolysiloxane elastomer is vinyl end blocked.

5. The method of claim 3 , wherein the dimethylpolysiloxane elastomer further comprises a dimethylmethylhydrogen polysiloxane crosslink.

6. The method of claim 1 , 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.

7. The method of claim 6 , wherein step (a) comprises:
(a1) mixing a first portion of the progesterone, the polysiloxane elastomer composition component (i), and a first portion of the pharmaceutically acceptable hydrocarbon or glycerol esters of fatty acid or pharmaceutically acceptable oil, to form a first homogenous mixture;
(a2) mixing a second portion of the progesterone, the polysiloxane elastomer composition component (ii), and a second portion of the pharmaceutically acceptable hydrocarbon or glycerol esters of fatty acid or pharmaceutically acceptable oil, to form a second homogenous mixture; and
(a3) mixing the first homogenous mixture with the second homogenous mixture.

8. The method of claim 1 , 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.

9. The method of claim 1 , wherein the pharmaceutically acceptable hydrocarbon or glycerol esters of fatty acid or pharmaceutically acceptable oil is mineral oil.

10. The method of claim 1 , 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.

11. The method of claim 1 , wherein step (b) comprises injecting the homogeneous mixture into the mold.

12. The method of claim 1 , wherein step (c) comprises curing at a temperature of from about 60° C. to about 180° C.

13. The method of claim 1 , wherein step (c) comprises curing at a temperature of from about 70° C. to about 150° C.

14. The method of claim 1 , wherein step (c) comprises curing at a temperature of from about 80° C. to about 120° C.

15. The method of claim 1 , wherein the intravaginal ring comprises:
(a) from about 15% to about 25% by weight of the progesterone;
(b) from about 70% to about 80% by weight of a dimethylpolysiloxane elastomer; and
(c) from about 1% to about 8% by weight of the pharmaceutically acceptable hydrocarbon or glycerol esters of a fatty acid or pharmaceutically acceptable oil.

Assignees

• Ferring Bv

Inventors

• Ahmed Salah U
• Tsao Jiaxiang
• Mahashabde Anu
• Harrison Diane D

Classifications

• B29L2031/753

  Medical equipment; Accessories therefor (bloodbags, medical bags B29L2031/7148; artificial eyes B29L2011/0008) · CPC title

• A61K31/57 Primary

  substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone · CPC title

• A61F6/08

  Pessaries, i.e. devices worn in the vagina to support the uterus, remedy a malposition or prevent conception {, e.g. combined with devices protecting against contagion} · CPC title

• A61K9/0036

  Devices retained in the vagina or cervix for a prolonged period, e.g. intravaginal rings, medicated tampons, medicated diaphragms · CPC title

• A61P15/06

  Antiabortive agents; Labour repressants · CPC title