Claims for Patent: 10,925,882

Summary for Patent: 10,925,882

Title:	System for providing birth control
Abstract:	The present disclosure relates to a vaginal system that prevents pregnancy comprised of segesterone acetate and ethinyl estradiol and is configured for thirteen 28-day product-use cycles.
Inventor(s):	Bruce Variano
Assignee:	Population Council Inc
Application Number:	US16/827,388
Patent Claims:	1. A reusable vaginal ring system for preventing pregnancy comprising: a) a silicone elastomer ring body having a platinum concentration of approximately 3 ppm to approximately 10 ppm and a hydride/vinyl ratio from approximately 1:1 to approximately 1.3:1 before curing, the ring body comprising i. a first cylindrical channel adapted to receive a first cylindrical core; ii. a second cylindrical channel adapted to receive a second cylindrical core; b) a first cylindrical core disposed within the first cylindrical channel, wherein the first cylindrical core comprises first and second condensation-cure silicone elastomers, dibutyltin dilaurate, and a viscosity agent; c) a second cylindrical core disposed within the second cylindrical channel, wherein the second cylindrical core comprises a third condensation-cure silicone elastomer and dibutyltin dilaurate; and d) approximately 103 mg of segesterone acetate and approximately 17.4 mg of ethinyl estradiol, wherein both the segesterone acetate and ethinyl estradiol are contained within the cores of the vaginal ring system; wherein at least one cylindrical core contains solubilized segesterone acetate and segesterone acetate Polymorphic form I and substantially no detectable amount of segesterone acetate Polymorphic form II; further wherein the system releases an approximate average of 0.15 mg/day of segesterone acetate and an approximate average of 0.013 mg/day of ethinyl estradiol, or bioequivalent amounts thereof, for up to 13 cycles of 21 days per cycle; further wherein the contraceptive ring system achieves in a plasma sample of a female patient: i. a segesterone acetate Cmax of approximately 1,147 pg/mL+/−315 pg/mL of segesterone acetate over a twenty-one day first period during a first product-use cycle; ii. a segesterone acetate Cmax of approximately 363 pg/mL+/−133 pg/mL of segesterone acetate over a twenty-one day first period during a third product-use cycle; iii. a segesterone acetate Cmax of approximately 294 pg/mL+/−116 pg/mL of segesterone acetate over a twenty-one days first period during a thirteenth product-use cycle; iv. an ethinyl estradiol Cmax of approximately 129 pg/mL+/−39 pg/mL of ethinyl estradiol over a twenty-one day first period during the first product-use cycle; v. an ethinyl estradiol Cmax of approximately 60 pg/mL+/−32 pg/mL of ethinyl estradiol over a twenty-one day first period during the third product-use cycle; and vi. an ethinyl estradiol Cmax of approximately 39 pg/mL+/−16 pg/mL of ethinyl estradiol over a twenty-one day first period during the thirteenth product-use cycle. 2. The vaginal system of claim 1, wherein the first cylindrical core has a length of approximately 11 mm. 3. The vaginal system of claim 1, wherein the second cylindrical core has a length of approximately 18 mm. 4. The vaginal system of claim 1, wherein the first and second cylindrical cores each have a diameter of approximately 3 mm. 5. The vaginal system of claim 1, wherein the first and second cylindrical channels each have a diameter of approximately 3 mm. 6. The vaginal system of claim 1, wherein the first and second cylindrical cores are secured in the first and second channels, respectively, with an adhesive. 7. The vaginal system of claim 1, wherein the first cylindrical core is substantially longitudinally centered in the first cylindrical channel, further wherein the second cylindrical core is substantially longitudinally centered within the second cylindrical channel. 8. The vaginal system of claim 1, wherein approximately 80% to approximately 90% of the ethinyl estradiol is recoverable from the system after approximately 18 months of storage at 25° C. and 60% relative humidity. 9. The vaginal system of claim 1, wherein a) the first cylindrical core has a first end face and a second end face, wherein the first cylindrical core is fully disposed within the first cylindrical channel; b) the second cylindrical core has a first end face and a second end face, wherein the second cylindrical core is fully disposed within the second cylindrical channel; and c) an end face of the first cylindrical core is substantially coplanar with an end face of the second cylindrical core. 10. The vaginal system of claim 1, wherein the first cylindrical channel and the second cylindrical channels each have lengths of approximately 27 mm. 11. The vaginal system of claim 1, wherein the ring body has outer diameter, an inner diameter, and a cross-sectional diameter. 12. The vaginal system of claim 11, wherein the outer diameter is approximately 56 mm. 13. The vaginal system of claim 12, wherein the inner diameter is approximately 40 mm. 14. The vaginal system of claim 13, wherein the cross-sectional diameter is approximately 8.4 mm. 15. The vaginal system of claim 1, wherein the silicone elastomer has a platinum concentration of approximately 4 ppm to approximately 9 ppm. 16. The vaginal system of claim 1, wherein the silicone elastomer has a platinum concentration of approximately 5 ppm to approximately 8 ppm. 17. The vaginal system of claim 1, wherein no more than approximately 10% to approximately 20% of the ethinyl estradiol undergoes hydrosilylation with unreacted hydrosilane in the ring body after approximately 18 months of storage at 25° C. and 60% relative humidity. 18. The vaginal system of claim 1, wherein the silicone elastomer ring body has a shore A hardness of approximately 25 to approximately 30, a mean fatigue parallel to the cores of approximately 95% and a mean fatigue perpendicular to the cores of approximately 98%. 19. The vaginal system of claim 1, wherein the first and second condensation-cure silicone elastomers are impregnated with a first amount of segesterone acetate particles having a particle size distribution: D90 of not more than 10 microns and a D50 of not more than 5 microns; further wherein the third condensation-cure silicone elastomer is impregnated with a second amount of segesterone acetate particles and an amount of ethinyl estradiol particles, wherein the ethinyl estradiol particles have a particle size distribution of 100% max 15 microns, 99% max 12.5 microns, 95% max 10 microns and max 40% less than or equal to 1.3 microns. 20. The vaginal system of claim 6, wherein any void spaces in the first and second cylindrical channels not occupied by the first and second cylindrical cores are filled with adhesive. 21. The vaginal system of claim 7, wherein any void spaces in the first and second cylindrical channels not occupied by the first and second cylindrical cores are filled with adhesive. 22. The vaginal system of claim 1, wherein after 18 months of storage, at least one degradation product selected from the group consisting of 6α-OH-EE, 6β-OH-EE, 6α-OH-NES, 6β-OH-NES, 17β-estradiol, NES ST-alcohol, NES iso-ST-alcohol, 6,7-didehydro-EE & 9,11-didehydro-EE, estrone, Δ6-NES, Iso-NES, 3-enolacetate-NES, 3-methoxy-NES, and combinations thereof, is detectable but does not account for more than 5% of ring extractables as measured by HPLC. 23. The vaginal system of claim 22, wherein the at least one degradation product is detectable but does not account for more than 1% of ring extractables as measured by HPLC. 24. The vaginal system of claim 1, wherein the first and second cylindrical channels are substantially parallel to each other. 25. The vaginal system of claim 1, wherein an XRPD of a cross section of the at least one cylindrical core containing segesterone acetate Polymorphic Form I has a diffraction pattern having peaks (° 2θ) selected from the group consisting of approximately 10.4, approximately 13.4, approximately 14.3, approximately 14.8, approximately 16.1, approximately 16.6, approximately 20, approximately 20.1, approximately 23.6, and combinations thereof. 26. The vaginal system of claim 1, wherein an XRPD of a cross section of the at least one cylindrical core containing segesterone acetate Polymorphic Form I has an XRPD diffraction pattern comprising peaks (° 2θ) at: approximately 10.4, approximately 13.4, approximately, 14.3, approximately 14.8, approximately 16.1, approximately 16.6, approximately 20, approximately 20.1, and approximately 23.6. 27. The vaginal system of claim 1, wherein an XRPD of a cross section of the at least one cylindrical core containing segesterone acetate Polymorphic Form I is substantially free of peaks (° 2θ) at approximately 8.5, approximately 15.5, approximately 17.7, and approximately 21.3. 28. A reusable vaginal ring system for preventing pregnancy comprising: a) a silicone elastomer ring body having a platinum concentration of approximately 3 ppm to approximately 10 ppm and a hydride/vinyl ratio from approximately 1:1 to approximately 1.3:1 before curing, the ring body comprising i. a first cylindrical channel adapted to receive a first cylindrical core; ii. a second cylindrical channel adapted to receive a second cylindrical core; b) a first cylindrical core disposed within the first cylindrical channel wherein the first cylindrical core comprises first and second condensation-cure silicone elastomers, dibutyltin dilaurate, and a viscosity agent; c) a second cylindrical core disposed within the second cylindrical channel, wherein the second cylindrical core comprises a third condensation-cure silicone elastomer and dibutyltin dilaurate; and d) approximately 103 mg of segesterone acetate and approximately 17.4 mg of ethinyl estradiol, wherein both the segesterone acetate and ethinyl estradiol are contained within the cores of the vaginal ring system; wherein at least one cylindrical core contains a single polymorphic form of segesterone acetate, the polymorphic form being Polymorphic form I; further wherein the system releases an approximate average of 0.15 mg/day of segesterone acetate and an approximate average of 0.013 mg/day of ethinyl estradiol, or bioequivalent amounts thereof, for up to 13 cycles of 21 days per cycle; further wherein the contraceptive ring system achieves in a plasma sample of a female patient: i. a segesterone acetate Cmax of approximately 1,147 pg/mL+/−315 pg/mL of segesterone acetate over a twenty-one day first period during a first product-use cycle; ii. a segesterone acetate Cmax of approximately 363 pg/mL+/−133 pg/mL of segesterone acetate over a twenty-one day first period during a third product-use cycle; iii. a segesterone acetate Cmax of approximately 294 pg/mL+/−116 pg/mL of segesterone acetate over a twenty-one days first period during a thirteenth product-use cycle; iv. an ethinyl estradiol Cmax of approximately 129 pg/mL+/−39 pg/mL of ethinyl estradiol over a twenty-one day first period during the first product-use cycle; v. an ethinyl estradiol Cmax of approximately 60 pg/mL+/−32 pg/mL of ethinyl estradiol over a twenty-one day first period during the third product-use cycle; and vi. an ethinyl estradiol Cmax of approximately 39 pg/mL+/−16 pg/mL of ethinyl estradiol over a twenty-one day first period during the thirteenth product-use cycle.