Granted Patent B2

US 12,409,141 · App. 18/021,165 · Granted Sep 9, 2025

Inventor: Enrico Colli (Madrid, ES)

Assignee: CHEMO RESEARCH, S.L.

A61K9/2054A61K31/567A61K47/26A61K47/32A61P15/18

Abstract

Claims (64)

1. An oral contraceptive composition, comprising:

(a) 2 mg of 17α-cyanomethyl-17-β-hydroxyestra-4,9-dien-3-one (dienogest, DNG);

(b) 0.02 mg of 17α-ethinylestradiol (ethynyl estradiol, EE); and

(c) 20% to 60% w/w of a polymeric matrix forming agent based on a total weight of the composition,

wherein:

the composition is in an extended-release form, such that at least the 0.02 mg of EE is formulated with a controlled release material comprising the polymeric matrix forming agent;

all of the EE in the contraceptive composition is subject to extended release;

the EE is formulated such that, when the composition is subjected to an in vitro dissolution test according to USP1 (baskets) method using 900 mL of water at 37° C. (±0.5° C.) at a stirring rate of 75 rpm, the EE exhibits a dissolution profile such that:

no more than 20% of the EE initially present in the composition is dissolved within 0.5 hour, and

between 30% and 60% of the EE initially present in the composition, is dissolved within 2 hours; and

the extended release of the EE occurs at a rate that is independent of pH.

2. The oral contraceptive composition of claim 1 , wherein all the content of the DNG and the EE are subject to the extended release.

3. The oral contraceptive composition according to claim 1 , wherein:

the extended-release form is a tablet, optionally coated, which comprises one or more release rate controlling excipients; and

the DNG and the EE are dispersed within an extended-release matrix comprising the polymeric matrix forming agent; and

the extended release of the DNG and the EE occur at rates that are independent of pH.

4. The oral contraceptive composition according to claim 3 , wherein the tablet is a film-coated tablet.

5. The oral contraceptive composition according to claim 1 , wherein the composition presents a pharmacokinetic profile further to oral administration under fasting conditions once daily for 7 days characterized by:

a) a Tmax of the DNG from 3.5 h to 4 h; and

b) a Tmax of the EE from 3.5 h to 4 h.

6. The contraceptive composition according to claim 1 , wherein when the composition is subjected to an in vitro dissolution test according to USP1 (baskets) method using 900 mL of water at 37° C. (±0.5° C.) at a stirring rate of 75 rpm, the DNG and the EE, respectively, exhibit a dissolution profile characterized in that:

(i) no more than 25% of an amount initially present in the composition is dissolved within 1 hour;

(ii) between 30% and 60% of the amount initially present in the composition is dissolved within 2 hours; and

(iii) at least 70%, of the amount initially present in the composition is dissolved within 8 hours.

7. The contraceptive composition according to claim 6 , wherein the DNG and the EE, respectively, exhibit a dissolution profile as determined by the USP1 (baskets) method characterized in that:

(i) no more than 25% of the amount initially present in the composition is dissolved within 1 hour;

(ii) between 35% and 55% of the amount initially present in the composition is dissolved within 2 hours, and

(iii) at least 80% of the amount initially present in the composition is dissolved within 5 hours.

8. The contraceptive composition according to claim 1 , wherein the composition is formulated for administration as a daily active oral form in a contraceptive regimen comprising administration of the daily active oral form for 21 to 24 consecutive days followed by a period of 4 to 7 days of daily administration of a placebo oral form or no oral form administration.

9. The contraceptive composition according to claim 8 , wherein the contraceptive regimen comprises administration of the daily active oral form for 24 consecutive days followed by a period of 4 days of daily administration of a placebo oral form.

10. The contraceptive composition according to claim 3 , wherein the polymeric matrix forming agent comprises a hydrophilic polymer.

11. The contraceptive composition according to claim 10 , wherein the hydrophilic polymer is a cellulosic derivative at a range from 25% to 60% w/w.

12. The contraceptive composition according to claim 10 , wherein the hydrophilic polymer is selected from the group consisting of a hydroxyethyl cellulose, a hydroxypropyl cellulose, a hydroxypropyl methylcellulose (HPMC) and a combination thereof.

13. The contraceptive composition according to claim 1 , further comprising:

a diluent;

a binder; and

a lubricant.

14. The contraceptive composition according to claim 1 , comprising:

2 mg of the DNG;

0.02 mg of the EE;

35-45% w/w of lactose;

45-55% w/w of HPMC;

2-7% w/w of povidone; and

1-3% w/w of magnesium stearate.

15. A process for obtaining the oral contraceptive composition according to claim 1 , the process comprising:

i) independently mixing each of the DNG and the EE with a diluent, and then mixing these together to obtain a mixture;

ii) granulating a diluent and the polymeric matrix forming agent;

iii) drying, optionally sieving, and mixing the granules obtained in step ii) with the mixture obtained in step i);

iv) blending the mixture obtained in step iii) with a lubricant, and then compressing into tablets;

v) optionally coating the tablets obtained in step iv) with a coating agent and dry.

16. A contraceptive kit comprising one or more packaging units wherein each packaging unit comprises at least 21 to 24 oral contraceptive compositions according to claim 1 as daily active dosage forms and at least 4 to 7 daily placebo dosage forms.

17. The contraceptive composition according to claim 11 , wherein the hydrophilic polymer is a hydroxyalkyl cellulose, and a content of the hydroxyalkyl cellulose in the contraceptive composition is 30% to 50% w/w.

18. The contraceptive composition according to claim 11 , wherein the hydrophilic polymer is a hydroxypropyl methylcellulose (HPMC), and a content of the hydroxypropyl methylcellulose (HPMC) in the contraceptive composition is 30% to 50% w/w.

19. The contraceptive composition according to claim 1 , further comprising:

30-60% w/w of a diluent;

1-10% w/w of a binder; and

0-5% w/w of a lubricant.

20. The contraceptive composition according to claim 1 , comprising:

2 mg of the DNG;

0.02 mg of the EE;

35-45% w/w of lactose monohydrate;

45-55% w/w of HPMC K100 low viscosity;

2-7% w/w of povidone K30; and

1-3% w/w of magnesium stearate.

Assignments (1)

Priority Claims (1)

Continuity (1)

References Cited (22)