Granted Patent B2

US 9,289,382 · App. 14/624,051 · Granted Mar 22, 2016

Abstract

Claims (41)

1. A pessary comprising about 25 μg of 17β-estradiol in a solubilizing agent comprising a medium chain oil, wherein after a single administration of the pessary to a patient provides, in a plasma sample from the patient:

1) a corrected geometric mean peak plasma concentration (C max ) of 17β-estradiol of about 19 pg*hr/ml to about 29 pg*hr/ml; and

2) a corrected geometric mean area under the curve (AUC) 0-24 of 17β-estradiol of about 75 pg*hr/ml to about 112 pg*hr/ml,

wherein 17β-estradiol is the only active hormone in the pessary.

2. The pessary of claim 1 , wherein administration of the pessary to a patient provides, in a plasma sample from the patient:

1) a corrected geometric mean peak plasma concentration (C max ) of estrone of about 9 pg*hr/ml to about 14 pg*hr/ml; and

2) a corrected geometric mean area under the curve (AUC) 0-24 of estrone of about 43 pg*hr/ml to about 65 pg*hr/ml.

3. The pessary of claim 1 , wherein administration of the pessary to a patient provides, in a plasma sample from the patient:

1) a corrected geometric mean peak plasma concentration (Cmax) of estrone sulfate of about 416 pg*hr/ml to about 613 pg*hr/ml; and

2) a corrected geometric mean area under the curve (AUC) 0-24 of estrone sulfate of about 3598 pg*hr/ml to about 5291 pg*hr/ml.

4. A pessary comprising about 10 μg of 17β-estradiol in a solubilizing agent comprising a medium chain oil, wherein after a single administration of the pessary to a patient provides, in a plasma sample from the patient:

1) a corrected geometric mean peak plasma concentration (C max ) of 17β-estradiol of about 12 pg*hr/ml to about 18 pg*hr/ml; and

2) a corrected geometric mean area under the curve (AUC) 0-24 of 17β-estradiol of about 42 pg*hr/ml to about 63 pg*hr/ml,

wherein 17β-estradiol is the only active hormone in the pessary.

5. The pessary of claim 4 , wherein the pessary further provides a corrected geometric mean time to peak plasma concentration (T max ) of 17β-estradiol of about 1 hrs to about 3 hrs.

6. The pessary of claim 4 , wherein administration of the pessary to a patient provides, in a plasma sample from the patient:

1) a corrected geometric mean peak plasma concentration (C max ) of estrone of about 4 pg*hr/ml to about 7 pg*hr/ml; and

2) a corrected geometric mean area under the curve (AUC) 0-24 of estrone of about 20 pg*hr/ml to about 31 pg*hr/ml.

7. The pessary of claim 6 , wherein the pessary further provides a corrected geometric mean time to peak plasma concentration (T max ) of estrone of about 4 hrs to about 8 hrs.

8. The pessary of claim 4 , wherein administration of the pessary to a patient provides, in a plasma sample from the patient:

1) a corrected geometric mean peak plasma concentration (C max ) of estrone sulfate of about 10 pg*hr/ml to about 16 pg*hr/ml; and

2) a corrected geometric mean area under the curve (AUC) 0-24 of estrone sulfate of about 56 pg*hr/ml to about 84 pg*hr/ml.

9. The pessary of claim 8 , wherein the pessary further provides a corrected geometric mean time to peak plasma concentration (T max ) of estrone sulfate of about 4 hrs to about 7 hrs.

10. A pessary comprising about 4 μg of 17β-estradiol in a solubilizing agent comprising a medium chain oil, wherein after a single administration of the pessary to a patient provides, in a plasma sample from the patient:

1) a corrected geometric mean peak plasma concentration (Cmax) of 17β-estradiol of about 4 pg*hr/ml to about 8 pg*hr/ml; and

2) a corrected geometric mean area under the curve (AUC) 0-24 of 17β-estradiol of about 16 pg*hr/ml to about 26 pg*hr/ml, wherein 17β-estradiol is the only active hormone in the pessary.

11. The pessary of claim 10 , wherein the pessary further provides a corrected geometric mean time to peak plasma concentration (T max ) of 17β-estradiol of about 0.25 hrs to about 2 hrs.

12. The pessary of claim 10 , wherein administration of the pessary to a patient provides, in a plasma sample from the patient:

1) a corrected geometric mean peak plasma concentration (C max ) of estrone of about 1 pg*hr/ml to about 3 pg*hr/ml; and

2) a corrected geometric mean area under the curve (AUC) 0-24 of estrone of about 8 pg*hr/ml to about 13 pg*hr/ml.

13. The pessary of claim 12 , wherein the pessary further provides a corrected geometric mean time to peak plasma concentration (T max ) of estrone of about 1 hrs to about 4 hrs.

14. The pessary of claim 10 , wherein administration of the pessary to a patient provides, in a plasma sample from the patient:

1) a corrected geometric mean peak plasma concentration (C max ) of estrone sulfate of about 4 pg*hr/ml to about 7 pg*hr/ml; and

2) a corrected geometric mean area under the curve (AUC) 0-24 of estrone sulfate of about 22 pg*hr/ml to about 34 pg*hr/ml.

15. The pessary of claim 14 , wherein the pessary further provides a corrected geometric mean time to peak plasma concentration (T max ) of estrone sulfate of about 1 hrs to about 3 hrs.

16. The pessary of claim 1 , wherein the medium chain oil comprises at least one C6-C12 fatty acid or a glycol, monoglyceride, diglyceride, or triglyceride ester thereof.

17. The pessary of claim 1 , wherein the medium chain oil comprises a monoglyceride, diglyceride, or triglyceride ester of the at least one C6-C12 fatty acid.

18. The pessary of claim 4 , wherein the medium chain oil comprises at least one C6-C12 fatty acid or a glycol, monoglyceride, diglyceride, or triglyceride ester thereof.

19. The pessary of claim 4 , wherein the medium chain oil comprises a monoglyceride, diglyceride, or triglyceride ester of the at least one C6-C12 fatty acid.

20. The pessary of claim 10 , wherein the medium chain oil comprises at least one C6-C12 fatty acid or a glycol, monoglyceride, diglyceride, or triglyceride ester thereof.

21. The pessary of claim 10 , wherein the medium chain oil comprises a monoglyceride, diglyceride, or triglyceride ester of the at least one C6-C12 fatty acid.

Assignments (9)