Pharmaceutical preparation adapted for oral administration

• US 4,071,623 A
• Filed: 05/17/1976
• Issued: 01/31/1978
• Est. Priority Date: 05/30/1975
• Status: Expired due to Term

• Current Assignee: Akzona Incorporated (Nouryon BV)
• Original Assignee: Akzona Incorporated (Nouryon BV)
• Inventors: van der Vies, Johannes
• Primary Examiner(s): Roberts, Elbert L.
• Application Number:
  US05/687,267
• Time in Patent Office: 624 Days
• Field of Search: 260/397.5 A, 424/238, 424/239
• US Class Current: 514/170
• CPC Class Codes: A61K 31/565 not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/4858 Organic compounds
• CPC Class Codes: A61P 13/02 of urine or of the urinary tract, e.g. urine acidifiers
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 5/00 Drugs for disorders of the endocrine system
• CPC Class Codes: C07J 1/0074 Esters

Abstract

The invention relates to a novel pharmaceutical preparation with oestrogenic activity adapted for oral administration comprising an oestradiol-17β-ester, the ester group of which has been derived from aliphatic carboxylic acids having 9-16 carbon atoms, in combination with a non-steroidal lipoid. The preparation may additionally contain a progestational steroid or an androgen. The invention also relates to novel oestradiol-17β-esters.

Claims

1. A pharmaceutical preparation with oestrogenic activity adapted for oral administration comprising

an oestrogenically effective amount when orally administered of at least one 17β

-ester of oestradiol having the formula ##STR2## the ester group thereof being derived from an aliphatic carboxylic acid having 9 to 16 carbon atoms, and

a pharmaceutically acceptable non-steroid lipoid carrier, wherein said 17-β

ester of oestradiol constitutes from 0.01 to 50% by weight of said preparation and said non-steroid lipoid carrier is present in an amont of at least equal to the amount of said 17β

-ester of oestradiol.

2. Preparation according to claim 1 wherein said ester has been derived from an aliphatic carboxylic acid having 10-14 carbon atoms.

3. Preparation according to claim 1 wherein said lipoid is liquid at ambient temperarure.

4. Preparation according to claim 1 which comprises as an additional active ingredient an orally active androgen or gestagen.

5. Preparation according to claim 4 wherein said orally active androgen is an ester selected from the group consisting of esters of testosterone and 5α

-dihydrotestosterone, the ester group of which has been derived from an aliphatic carboxylic acid having 9-16 carbon atoms.

6. Preparation according to claim 1 wherein said ester of oestradiol constitutes 0.01-10% by weight, of said preparation.

7. Preparation according to claim 1, wherein said lipoid constitutes 25-95% by weight of said preparation, preferably 50-80% by weight.

8. Preparation according to claim 1 in unit dosage form comprising from 0.001 to 2 mg of said ester of oestradiol.

9. Preparation according to claim 1 in unit dosage form consisting of a soft gelatine capsule containing a solution of said oestradiol ester in said lipoid.

10. A process for conducting estrogen deficiency therapy in a female patient requiring such therapy comprising orally administering daily to said patient from 0.001 to 2 mg of the oestradiol-ester preparation of claim 1 together with a non-steroidal lipoid, the amount of said lipoid being equal to or higher than the amount of said ester or esters.

18. Preparation according to claim 1 in unit dosage form comprising from 0.005 to 1 mg of said ester of oestradiol.

19. The pharmaceutical preparation of claim 1 wherein said 17β

-ester of oestradiol is oestradiol-17β

-decanoate.

20. The pharmaceutical preparation of claim 1 wherein said 17β

ester of oestradiol is oestradiol-17α

'"'"'-methyl decanoate.

21. The pharmaceutical preparation of claim 1 wherein said 17β

-ester of oestradiol is oestradiol-17β

-β

'"'"'-methyl decanoate.

22. The pharmaceutical preparation of claim 1 wherein said 17β

-ester of oestradiol is oestradiol-17β

-undecanoate.

23. The pharmaceutical preparation of claim 1 wherein said 17β

-ester of oestradiol is oestradiol-17β

-dodecanoate.

24. The pharmaceutical preparation of claim 1 wherein said 17β

-ester of oestradiol is oestradiol-17β

-tetradecanoate.

25. The pharmaceutical preparation of claim 1 wherein said 17β

-ester of oestradiol is oestradiol-17β

-α

'"'"'-methyl-β

'"'"'-cyclohexyl-propionate.

11. A 17β

-ester of oestradiol having the formula;

##STR3## wherein n = 0, 1 or 2;

R₁ = alkyl having 1-10 carbon atoms;

R₂ = h or alkyl having 1-10 carbon atoms;

R₃ = an aliphatic group having 1-18 carbon atoms, which group may contain a ring having 5-12 carbon atoms;

or R₁ and R₃ form together with the carbon atom to which they are attached and a cycloaliphatic group having 7-12 carbon atoms, said cycloaliphatic group optionally being substituted by an aliphatic group having 1-6 carbon atoms, with the proviso that the total number of carbon atoms in the ester group is in the range of 8-20 carbon atoms.

12. A compound according to claim 11, wherein n = 0 and R₂ = H.

13. A compound according to claim 11, wherein n = 1 and R₂ = H.

14. A compound according to claim 12, wherein R₁ = methyl.

15. A compound according to claim 13, wherein R₁ = methyl.

16. A compound according to claim 12, wherein R₁ and R₃ form together with the carbon atom to which they are attached a cycloaliphatic group having 7-12 carbon atoms.

17. A compound according to claim 13, wherein R₁ and R₃ form together with the carbon atom to which they are attached a cycloaliphatic group having 7-12 carbon atoms.

26. The compound of claim 11 which is oestradiol-17β

-α

'"'"'-methyl decanoate.

27. The compound of claim 11 which is oestradiol-17β

-β

'"'"'-methyl decanoate.

28. The compound of claim 11 which is oestradiol-17β

-α

'"'"'-methyl-β

'"'"'-cyclohexyl propionate.

29. The compound of claim 11 which is oestradiol-17β

-β

'"'"'-cyclohexyl butyrate.

30. The compound of claim 11 which is oestradiol-17β

-cyclo-octyl acetage.

31. The compound of claim 11 which is oestradiol-17β

-α

'"'"'-ethyl hexanoate.

32. The compound of claim 11 which is oestradion-17β

-α

'"'"'-propylpentanoate.