Claims for Patent: 11,850,251

Summary for Patent: 11,850,251

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:	US17/188,857
Patent Claims:	1. A method of providing birth control over thirteen 28-day product-use cycles, the method comprising: (a) initially inserting into the vagina of a female of reproductive potential on either day 2, 3, 4, or 5 of the female's menstrual cycle, a reusable vaginal ring system comprising: i. a silicone elastomer ring body comprising a first silicone elastomer, the ring body having a platinum concentration of at least 2 ppm, wherein the silicone elastomer ring body further comprises: (1) a first channel comprising a first core, the first core comprising second and third silicone elastomers, dibutyltin dilaurate, and a viscosity agent; and (2) a second channel comprising a second core, the second core comprising a fourth silicone elastomer and dibutyltin dilaurate; and ii. approximately 103 mg of segesterone acetate and approximately 17.4 mg of ethinyl estradiol, wherein the segesterone acetate is contained within at least the first core, and the ethinyl estradiol is contained within at least the second core; further wherein the reusable vaginal ring 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, each day in a 21-day first period as measured across thirteen 28-day product-use cycles; and wherein the initial insertion on day 2, 3, 4, or 5 is the first day of the 21-day first period, and wherein the initial insertion results in a segesterone acetate Cmax of approximately 1,147 pg/mL+/−315 pg/mL of segesterone acetate over the 21-day first period during a first product-use cycle and an ethinyl estradiol Cmax of approximately 129 pg/mL+/−39 pg/mL of ethinyl estradiol over the 21-day first period during the first product-use cycle; (b) removing the reusable vaginal ring system on the day following the end of the 21-day first period; (c) storing the reusable vaginal ring system removed in step (b) for a second period of between five and seven days including the day the reusable vaginal ring system in step (b) is removed, wherein the 21-day first period and second period together comprise a product-use cycle; (d) reinserting the reusable vaginal ring system into the female's vagina after a preceding product-use cycle on either day 2, 3, 4, or 5 of the female's next menstrual cycle for a subsequent 21-day first period; and (e) repeating steps (b), (c), and (d) for a total of up to thirteen product-use cycles including the first product-use cycle, wherein each reinsertion of step (d) is performed at approximately the same time of day as in a previous product-use cycle in order to achieve at least one of the following segesterone acetate or ethinyl estradiol pharmacokinetic parameters: i. 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; ii. a segesterone acetate Cmax of approximately 294 pg/mL+/−116 pg/mL of segesterone acetate over a twenty-one day first period during a thirteenth product-use cycle; iii. 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; or iv. 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 method of claim 1, wherein a) the first core has a first end face and a second end face, wherein the first core is fully disposed within the first channel; b) the second core has a first end face and a second end face, wherein the second core is fully disposed within the second channel; and c) an end face of the first core is substantially coplanar with an end face of the second core. 3. The method of claim 1, wherein the first channel and the second channel each have lengths of approximately 27 mm. 4. The method of claim 1, wherein the first and second cores each have a diameter of approximately 3 mm. 5. The method of claim 1, wherein the first and second cores are secured in the first and second channels, respectively, with an adhesive. 6. The method of claim 1, wherein the silicone elastomer ring body has outer diameter, an inner diameter, and a cross-sectional diameter. 7. The method of claim 6, wherein the outer diameter is approximately 56 mm. 8. The method of claim 6, wherein the inner diameter is approximately 40 mm. 9. The method of claim 6, wherein the cross-sectional diameter is approximately 8.4 mm. 10. The method of claim 1, wherein the silicone elastomer ring body has a hydride/vinyl ratio from approximately 1:1 to approximately 1.3:1 before curing. 11. The method of claim 1, wherein the silicone elastomer ring body has a platinum concentration of approximately 5 ppm to approximately 8 ppm. 12. The method of claim 1 wherein at least one of the first or second cores contains greater than 95% solubilized segesterone acetate and segesterone acetate Polymorphic form I, wherein an XRPD of a cross section of the at least one 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. 13. The method of claim 1 wherein at least one of the first or second cores contains greater than 95% solubilized segesterone acetate and segesterone acetate Polymorphic form I, but contains no detectable amount of segesterone acetate Polymorphic form II. 14. The method of claim 12, wherein an XRPD of a cross section of the at least one 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. 15. The method of claim 12, wherein an XRPD of a cross section of the at least one 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. 16. The method of claim 1, wherein the second and third 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; and wherein the fourth 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. 17. The method of claim 1, wherein at least about 80% of the ethinyl estradiol is recoverable from the reusable vaginal ring system after approximately 18 months of storage at 25° C. and 60% relative humidity. 18. The method 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-0H-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. 19. A method of providing birth control over thirteen 28-day product-use cycles, the method comprising: (a) initially inserting into the vagina of a female of reproductive potential on either day 2, 3, 4, or 5 of the female's menstrual cycle, a reusable vaginal ring system comprising: i. a silicone elastomer ring body comprising a first silicone elastomer, the ring body having a platinum concentration of at least 2 ppm, wherein the silicone elastomer ring body has at least one feature selected from the group consisting of 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%; wherein the silicone elastomer ring body further comprises: (1) a first channel comprising a first core, the first core comprising second and third silicone elastomers, dibutyltin dilaurate, and a viscosity agent; and (2) a second channel comprising a second core, the second core comprising a fourth silicone elastomer and dibutyltin dilaurate; and ii. approximately 103 mg of segesterone acetate and approximately 17.4 mg of ethinyl estradiol, wherein the segesterone acetate is contained within at least the first core, and the ethinyl estradiol is contained within at least the second core; further wherein the reusable vaginal ring 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, each day in a 21-day first period as measured across thirteen 28-day product-use cycles; and wherein the initial insertion on day 2, 3, 4, or 5 is the first day of the 21-day first period, and wherein the initial insertion results in a segesterone acetate Cmax of approximately 1,147 pg/mL+/−315 pg/mL of segesterone acetate over the 21-day first period during a first product-use cycle and an ethinyl estradiol Cmax of approximately 129 pg/mL+/−39 pg/mL of ethinyl estradiol over the 21-day first period during the first product-use cycle; (b) removing the reusable vaginal ring system on the day following the end of the 21-day first period; (c) storing the reusable vaginal ring system removed in step (b) for a second period of between five and seven days including the day the reusable vaginal ring system in step (b) is removed, wherein the 21-day first period and second period together comprise a product-use cycle; (d) reinserting the reusable vaginal ring system into the female's vagina after a preceding product-use cycle on either day 2, 3, 4, or 5 of the female's next menstrual cycle for a subsequent 21-day first period; and (e) repeating steps (b), (c), and (d) for a total of up to thirteen product-use cycles including the first product-use cycle, wherein each reinsertion of step (d) is performed at approximately the same time of day as in a previous product-use cycle in order to achieve at least one of the following segesterone acetate or ethinyl estradiol pharmacokinetic parameters: i. 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; ii. a segesterone acetate Cmax of approximately 294 pg/mL+/−116 pg/mL of segesterone acetate over a twenty-one day first period during a thirteenth product-use cycle; iii. 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; or iv. 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. 20. The method of claim 19, 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%.