15, 16-methylene-17-(1′-propenyl)-17,3′-oxidoestra-4-en-3-one derivative, use thereof, and medicament containing said derivative

1. A 15,16-Methylene-17-(1′-propenyl)-17-3′-oxidoestra-4-en-3-one derivative with the general chemical formula I

in which

Z is oxygen, two hydrogen atoms, NOR′, or NNHSO 2 R′,

where R′ is hydrogen, C 1 -C 10 alkyl, aryl or C 7 -C 20 aralkyl, and

R 4 is hydrogen or halogen,

and further, either:

R 6a , R 6b are each mutually independently hydrogen, C 1 -C 10 alkyl, C 2 -C 10 alkenyl, or C 2 -C 10 alkynyl, or together form methylene or 1,2-ethanediyl and R 7 is hydrogen, C 1 -C 10 alkyl, C 3 -C 6 -cycloalkyl, C 2 -C 10 alkenyl or C 2 -C 10 alkynyl,

or:

R 6a , R 7 together comprise oxygen or a methylene group or are omitted, with the formation of a double bond between C 6 and C 7 and

R 6b is hydrogen, C 1 -C 10 alkyl, C 2 -C 10 alkenyl or C 2 -C 10 alkynyl and

R 18 is hydrogen or C 1 -C 3 alkyl,

and solvates, hydrates and salts thereof and including all crystal modifications and all stereoisomers.

2. The 15,16-Methylene-17-(1′-propenyl)-17-3′-oxidoestra-4-en-3-one derivative as claimed in claim 1 , characterized in that Z is oxygen, NOR′ or NNHSO 2 R′.

3. The 15,16-Methylene-17-(1′-propenyl)-17-3′-oxidoestra-4-en-3-one derivative as claimed in claim 1 , characterized in that Z is oxygen.

4. The 15,16-Methylene-17-(1′-propenyl)-17-3′-oxidoestra-4-en-3-one derivative as claimed in claim 1 , characterized in that R 4 is hydrogen or chlorine.

5. The 15,16-Methylene-17-(1′-propenyl)-17-3′-oxidoestra-4-en-3-one derivative as claimed in claim 1 , characterized in that R 6a and R 6b together form 1,2-ethanediyl or are each hydrogen.

6. The 15,16-Methylene-17-(1′-propenyl)-17-3′-oxidoestra-4-en-3-one derivative as claimed in claim 1 , characterized in that R 7 is hydrogen, methyl, ethyl, or vinyl.

7. The 15,16-Methylene-17-(1′-propenyl)-17-3′-oxidoestra-4-en-3-one derivative as claimed in claim 1 , characterized in that R 6a and R 7 together form a methylene group.

8. The 15,16-Methylene-17-(1′-propenyl)-17-3′-oxidoestra-4-en-3-one derivative as claimed in claim 1 , characterized in that R 6a and R 7 are omitted, with the formation of a double bond between C 6 and C 7 .

9. The 15,16-Methylene-17-(1′-propenyl)-17-3′-oxidoestra-4-en-3-one derivative as claimed in claim 1 , characterized in that R 18 is hydrogen or methyl.

10. The 15,16-Methylene-17-(1′-propenyl)-17-3′-oxidoestra-4-en-3-one derivative as claimed in claim 1 , that is

17α-(1′-propenyl)-15α,16α-methylene-17β-3′-oxidoestra-4-en-3-one;

17α-(1′-propenyl)-15β,16β-methylene-17β-3′-oxidoestra-4-en-3-one;

7α-methyl-15α,16α-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-en-3-one;

7β-methyl-15α,16α-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-en-3-one;

7α-methyl-15β,16β-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-en-3-one;

7β-methyl-15β,16β-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-en-3-one;

7α-ethyl-15α,16α-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-en-3-one;

7β-ethyl-15α,16α-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-en-3-one;

7α-ethyl-15β,16β-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-en-3-one;

7β-ethyl-15β,16β-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-en-3-one;

7α-vinyl-15α,16α-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-en-3-one;

7β-vinyl-15α,16α-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-en-3-one;

7α-vinyl-15β,16β-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-en-3-one;

7β-vinyl-15β,16β-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-en-3-one;

7α-cyclopropyl-15α,16α-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-en-3-one;

7β-cyclopropyl-15α,16α-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-en-3-one;

7α-cyclopropyl-15β,16β-ethylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-en-3-one;

7β-cyclopropyl-15β,16β-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-en-3-one;

6-methylene-15α,16α-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-en-3-one;

6-methylene-15β,16β-ethylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-en-3-one;

6α-hydroxymethylene-15α,16α-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-en-3-one;

6β-hydroxymethylene-15α,16α-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-en-3-one;

6α-hydroxymethylene-15β,16β-ethylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-en-3-one;

6β-hydroxymethylene-15β,16β-ethylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-en-3-one;

6,6-(1,2-ethanediyl)-15α,16α-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-en-3-one;

6,6-(1,2-ethanediyl)-15β,16β-ethylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-en-3-one;

6α,7α;15α,16α-bismethylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-en-3-one;

6β,7β;15α,16α-bismethylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-en-3-one;

6α,7α;15β,16β-bismethylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-en-3-one;

6β,7β;15β,16β-bismethylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-en-3-one;

17α-(1′-propenyl)-15α,16α-methylene-17β-3′-oxidoestra-4,6-dien-3-one;

17α-(1′-propenyl)-15β,16β-ethylene-17β-3′-oxidoestra-4,6-dien-3-one;

(E/Z)-3-(hydroxyimino)-17α-(1′-propenyl)-15α,16α-methylene-17β-3′-oxido-estra-4-ene;

(E/Z)-3-(hydroxyimino)-17α-(1′-propenyl)-15β,16β-methylene-17β-3′-oxido-estra-4-ene;

(E/Z)-3-(hydroxyimino)-7α-methyl-15α,16α-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-ene;

(E/Z)-3-(hydroxyimino)-7β-methyl-15α,16α-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-ene;

(E/Z)-3-(hydroxyimino)-7α-methyl-15β,16β-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-ene;

(E/Z)-3-(hydroxyimino)-7β-methyl-15β,16β-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-ene;

(E/Z)-3-(hydroxyimino)-7α-ethyl-15α,16α-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-ene;

(E/Z)-3-(hydroxyimino)-7β-ethyl-15α,16α-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-ene;

(E/Z)-3-(hydroxyimino)-7α-ethyl-15β,16β-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-ene;

(E/Z)-3-(hydroxyimino)-7β-ethyl-15β,16β-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-ene;

(E/Z)-3-(hydroxyimino)-7α-vinyl-15α,16α-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-ene;

(E/Z)-3-(hydroxyimino)-7β-vinyl-15α,16α-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-ene;

(E/Z)-3-(hydroxyimino)-7α-vinyl-15β,16β-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-ene;

(E/Z)-3-(hydroxyimino)-7β-vinyl-15β,16β-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-ene;

(E/Z)-3-(hydroxyimino)-7α-cyclopropyl-15α,16α-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-ene;

(E/Z)-3-(hydroxyimino)-7β-cyclopropyl-15α,16α-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-ene;

(E/Z)-3-(hydroxyimino)-7α-cyclopropyl-15β,16β-ethylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-ene;

(E/Z)-3-(hydroxyimino)-7β-cyclopropyl-15β,16β-ethylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-ene;

(E/Z)-3-(hydroxyimino)-6-methylene-17α-(1′-propenyl)-15α,16α-methylene-17β-3′-oxidoestra-4-ene;

(E/Z)-3-(hydroxyimino)-6-methylene-17α-(1′-propenyl)-15β,16β-ethylene-17β-3′-oxidoestra-4-ene;

(E/Z)-3-(hydroxyimino)-6α-hydroxymethylene-17α-(1′-propenyl)-15α,16α-methylene-17β-3′-oxidoestra-4-ene;

(E/Z)-3-(hydroxyimino)-6β-hydroxymethylene-17α-(1′-propenyl)-15α,16α-methylene-17β-3′-oxidoestra-4-ene;

(E/Z)-3-(hydroxyimino)-6α-hydroxymethylene-17α-(1′-propenyl)-15β,16β-ethylene-17β-3′-oxidoestra-4-ene;

(E/Z)-3-(hydroxyimino)-6β-hydroxymethylene-17α-(1′-propenyl)-15β,16β-ethylene-17β-3′-oxidoestra-4-ene;

(E/Z)-3-(hydroxyimino)-6,6-(1,2-ethanediyl)-17α-(1′-propenyl)-15α,16α-methylene-17β-3′-oxidoestra-4-ene;

(E/Z)-3-(hydroxyimino)-6,6-(1,2-ethanediyl)-17α-(1′-propenyl)-15β,16β-methylene-17β-3′-oxidoestra-4-ene;

(E/Z)-3-(hydroxyimino)-6α,7α;15α,16α-bismethylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-ene;

(E/Z)-3-(hydroxyimino)-6β,7β;15α,16α-bismethylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-ene;

(E/Z)-3-(hydroxyimino)-6α,7α;15β,16β-bismethylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-ene;

(E/Z)-3-(hydroxyimino)-6β,7β;15β,16β-bismethylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-ene;

(E/Z)-3-(hydroxyimino)-17α-(1′-propenyl)-15β,16β-methylene-17β-3′-oxidoestra-4,6-diene;

(E/Z)-3-(hydroxyimino)-17α-(1′-propenyl)-15β,16β-methylene-17β-3′-oxidoestra-4,6-diene;

17α-(1′-propenyl)-18-methyl-15α,16α-methylene-17β-3′-oxidoestra-4-en-3-one;

17α-(1′-propenyl)-18-methyl-15β,16β-methylene-17β-3′-oxidoestra-4-en-3-one;

7α,18-dimethyl-15α,16α-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-en-3-one;

7β,18-dimethyl-15α,16α-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-en-3-one;

7α,18-dimethyl-15β,16β-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-en-3-one;

7β,18-dimethyl-15β,16β-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-en-3-one;

7α-ethyl-18-methyl-15α,16α-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-en-3-one;

7β-ethyl-18-methyl-15α,16α-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-en-3-one;

7α-ethyl-18-methyl-15β,16β-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-en-3-one;

7β-ethyl-18-methyl-15β,16β-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-en-3-one;

7α-vinyl-18-methyl-15α,16α-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-en-3-one;

7β-vinyl-18-methyl-15α,16α-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-en-3-one;

7α-vinyl-18-methyl-15β,16β-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-en-3-one;

7β-vinyl-18-methyl-15β,16β-methylene-17α-(1-propenyl)-17β-3′-oxidoestra-4-en-3-one;

7α-cyclopropyl-18-methyl-15α,16α-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-en-3-one;

7β-cyclopropyl-18-methyl-15α,16α-methylene-17α-(1-propenyl)-17β-3′-oxidoestra-4-en-3-one;

7α-cyclopropyl-18-methyl-15β,16β-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-en-3-one;

7β-cyclopropyl-18-methyl-15β,16β-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-en-3-one;

6-methylene-18-methyl-15α,16α-methylene-17α-(1′-propenyl)-17β-3-oxido-estra-4-en-3-one;

6-methylene-18-methyl-15β,16β-methylene-17α-(1′-propenyl)-17β-3′-oxido-estra-4-en-3-one;

6α-hydroxymethylene-18-methyl-15α,16α-methylene-17α-(1′-propenyl)-17β-3-oxidoestra-4-en-3-one;

6β-hydroxymethylene-18-methyl-15α,16α-methylene-17α-(1-propenyl)-17β-3′-oxidoestra-4-en-3-one;

6α-hydroxymethylene-18-methyl-15β,16β-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-en-3-one;

6β-hydroxymethylene-18-methyl-15β,16β-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-en-3-one;

6,6-(1,2-ethanediyl)-18-methyl-15α,16α-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-en-3-one;

6,6-(1,2-ethanediyl)-18-methyl-15β,16β-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-en-3-one;

6α,7α; 15α,16α-bismethylene-18-methyl-17α-(1′-propenyl)-17β-3′-oxidoestra-4-en-3-one;

6β,7β;15α,16α-bismethylene-18-methyl-17α-(1′-propenyl)-17β-3′-oxidoestra-4-en-3-one;

6α,7α;15β,16β-bismethylene-18-methyl-17α-(1′-propenyl)-17β-3′-oxidoestra-4-en-3-one;

6β,7β;15β,16β-bismethylene-18-methyl-17α-(1′-propenyl)-17β-3′-oxidoestra-4-en-3-one;

17α-(1′-propenyl)-18-methyl-15α,16α-methylene-17β-3′-oxidoestra-4,6-dien-3-one;

17α-(1′-propenyl)-18-methyl-15β,16β-methylene-17β-3′-oxidoestra-4,6-dien-3-one;

(E/Z)-3-(hydroxyimino)-18-methyl-17α-(1′-propenyl)-15α,16α-methylene-17β-3′-oxidoestra-4-ene;

(E/Z)-3-(hydroxyimino)-18-methyl-17α-(1′-propenyl)-15β,16β-methylene-17β-3′-oxidoestra-4-ene;

(E/Z)-3-(hydroxyimino)-7α,18-bismethyl-15α,16α-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-ene;

(E/Z)-3-(hydroxyimino)-7β,18-bismethyl-15α,16α-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-ene;

(E/Z)-3-(hydroxyimino)-7α,18-bismethyl-15β,16β-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-ene;

(E/Z)-3-(hydroxyimino)-7β,18-bismethyl-15β,16β-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-ene;

(E/Z)-3-(hydroxyimino)-7α-ethyl-18-methyl-15α,16α-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-ene;

(E/Z)-3-(hydroxyimino)-7β-ethyl-18-methyl-15α,16α-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-ene;

(E/Z)-3-(hydroxyimino)-7α-ethyl-18-methyl-15β,16β-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-ene;

(E/Z)-3-(hydroxyimino)-7β-ethyl-18-methyl-15β,16β-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-ene;

(E/Z)-3-(hydroxyimino)-7α-vinyl-18-methyl-15α,16α-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-ene;

(E/Z)-3-(hydroxyimino)-7β-vinyl-18-methyl-15α,16α-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-ene;

(E/Z)-3-(hydroxyimino)-7α-vinyl-18-methyl-15β,16β-ethylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-ene;

(E/Z)-3-(hydroxyimino)-7β-vinyl-18-methyl-15β,16β-ethylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-ene;

(E/Z)-3-(hydroxyimino)-7α-cyclopropyl-18-methyl-15α,16α-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-ene;

(E/Z)-3-(hydroxyimino)-7β-cyclopropyl-18-methyl-15α,16α-methylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-ene;

(E/Z)-3-(hydroxyimino)-7α-cyclopropyl-18-methyl-15β,16β-ethylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-ene;

(E/Z)-3-(hydroxyimino)-7β-cyclopropyl-18-methyl-15β,16β-ethylene-17α-(1′-propenyl)-17β-3′-oxidoestra-4-ene;

(E/Z)-3-(hydroxyimino)-18-methyl-6-methylene-17α-(1′-propenyl)-15α,16α-methylene-17β-3′-oxidoestra-4-ene;

(E/Z)-3-(hydroxyimino)-18-methyl-6-methylene-17α-(1′-propenyl)-15β,16β-methylene-17β-3′-oxidoestra-4-ene;

(E/Z)-3-(hydroxyimino)-6α-hydroxymethylene-17α-(1′-propenyl)-18-methyl-15α,16α-methylene-17β-3′-oxidoestra-4-ene;

(E/Z)-3-(hydroxyimino)-6β-hydroxymethylene-17α-(1′-propenyl)-18-methyl-15α,16α-methylene-17β-3′-oxidoestra-4-ene;

(E/Z)-3-(hydroxyimino)-6α-hydroxymethylene-17α-(1′-propenyl)-18-methyl-15β,16β-methylene-17β-3′-oxidoestra-4-ene;

(E/Z)-3-(hydroxyimino)-6β-hydroxymethylene-17α-(1′-propenyl)-18-methyl-15β,16β-methylene-17β-3′-oxidoestra-4-ene;

(E/Z)-3-(hydroxyimino)-6,6-(1,2-ethanediyl)-17α-(1′-propenyl)-18-methyl-15α,16α-methylene-17β-3′-oxidoestra-4-ene;

(E/Z)-3-(hydroxyimino)-6,6-(1,2-ethanediyl)-17α-(1′-propenyl)-18-methyl-15β,16β-ethylene-17β-3′-oxidoestra-4-ene;

(E/Z)-3-(hydroxyimino)-6α,7α;15α,16α-bismethylene-18-methyl-17α-(1′-propenyl)-17β-3′-oxidoestra-4-ene;

(E/Z)-3-(hydroxyimino)-6β,7β;15α,16α-bismethylene-18-methyl-17α-(1′-propenyl)-17β-3′-oxidoestra-4-ene;

(E/Z)-3-(hydroxyimino)-6α,7α;15β,16β-bismethylene-18-methyl-17α-(1′-propenyl)-17β-3′-oxidoestra-4-ene;

(E/Z)-3-(hydroxyimino)-6β,7β;15β,16β-bismethylene-18-methyl-17α-(1′-propenyl)-17β-3′-oxidoestra-4-ene;

(E/Z)-3-(hydroxyimino)-17α-(1′-propenyl)-18-methyl-15α,16α-methylene-17-oxidoestra-4,6-diene; or

(E/Z)-3-(hydroxyimino)-17α-(1′-propenyl)-18-methyl-15β,16β-methylene-17β-3′-oxidoestra-4,6-diene.

11. A method for providing oral contraception or for the treatment of pre-, peri- and postmenopausal problems, said method comprising administering to the patient an effective amount of a 15,16-methylene-17-(1′-propenyl)-17-3′-oxidoestra-4-en-3-one compound according to claim 1 .

12. The method as claimed in claim 11 , characterized in that the drug has progestational, antimineralcorticoid and neutral to slight androgenic activity.

13. A pharmaceutical composition comprising at least one 15,16-methylene-17-(1′-propenyl)-17-3′-oxidoestra-4-en-3-one derivative as claimed in claim 1 and at least one pharmaceutically acceptable excipient.

14. The pharmaceutical composition as claimed in claim 13 , further comprising at least one estrogen.

15. The pharmaceutical composition as claimed in claim 14 , characterized in that the estrogen is ethynylestradiol.

16. The pharmaceutical composition as claimed in claim 14 , characterized in that the estrogen is estradiol valerate.

17. The pharmaceutical composition as claimed in claim 14 , characterized in that the estrogen is a natural estrogen.

18. The pharmaceutical composition as claimed in claim 17 , characterized in that the natural estrogen is estradiol.

19. The pharmaceutical composition as claimed in claim 17 , characterized in that the natural estrogen is a conjugated estrogen.

20. The method according to claim 12 , wherein said 15,16-methylene-17-(1′-propenyl)-17-3′-oxidoestra-4-en-3-one compound is in a form suitable intrauterine administration.

21. The method as claimed in claim 20 , wherein said compound is administered in the form of an intrauterine system (IUS).

22. An medicinal product comprising at least one 15,16-methylene-17-(1′-propenyl)-17-3′-oxidoestra-4-en-3-one derivative according to claim 1 and at least one pharmaceutically acceptable excipient.

23. The medicinal product as claimed in claim 22 , that is an intrauterine system.