Transdermal fertility control system and process

• US 4,818,540 A
• Filed: 08/29/1986
• Issued: 04/04/1989
• Est. Priority Date: 02/25/1985
• Status: Expired due to Term

• Current Assignee: Rutgers University
• Original Assignee: Rutgers University
• Inventors: Chien, Te-Yen, Chien, Yie W., Huang, Yih-Chain
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): HORNE, LEON
• Application Number:
  US06/902,440
• Time in Patent Office: 949 Days
• Field of Search: 424/448, 424/449
• US Class Current: 424/448
• CPC Class Codes: A61K 9/7069 obtained otherwise than by reactions only involving carbon to carbon unsaturated bonds, e.g. polysiloxane, polyesters, polyurethane, polyethylene oxide
• CPC Class Codes: A61K 9/7084 Transdermal patches having a drug layer or reservoir, and one or more separate drug-free skin-adhesive layers, e.g. between drug reservoir and skin, or surrounding the drug reservoir; Liquid-filled reservoir patches

Abstract

Transdermal fertility-controlling absorption polymer matrix dosage units have been developed which comprise a backing layer, an adjoining layer of a solid polymer matrix in which minimum effective daily doses of an estrogen and a progestin are microdispersed and released for transdermal absorption. Presently preferred is use of the natural estrogen, 17-beta-estradiol, and of the progestin, levonorgestrel. The units have a biologically acceptable adhesive polymer layer. The polymer matrix as well as the adhesive layer can have dispersed one or more skin permeation enhancers. Dosage units are provided which transdermally deliver at least minimum daily doses of the estrogen and progestin for multiple days, such as for one week. The invention also provides a process of fertility control using the novel polymer matrix dosage units for the first three weeks of consecutive menstrual cycles of the subject desiring fertility control.

Claims

1. A transdermal fertility-controlling polymer matrix dosage unit comprising:

(a) a backing layer which is substantially impervious to the fertility-controlling estrogen and progestin hormones to be delivered transdermally;

(b) a polymer matrix disc layer which is adhered to said backing layer and which has microdispersed therein effective dosage amounts of fertility-controlling estrogen and progestin hormones said estrogen being selected from the group consisting of 17-beta estradiol, ethinyl estradiol and biocompatible derivatives thereof convertible to said estradiols, progestin being selected from the group consisting of levonorgestrel and norethindrone, said polymer being bioacceptable and permitting said hormones to be transmitted for transdermal absorption, said hormones being stable in said polymer matrix and being transdermally absorbed simultaneously to provide at least minimum effective daily doses of said hormones to effect fertility control; and

(c) an adhesive means for securing the dosage unit for transdermal absorption to the subject treated.

2. A transdermal fertility-controlling polymer matrix dosage unit of claim 1 wherein said polymer matrix layer has dispersed therein an effective amount of one or more skin permeation enhancing agents.

3. A transdermal fertility-controlling dosage unit of claim 1 wherein the polymer matrix is a silicone polymer or copolymer.

4. A transdermal fertility-controlling polymer matrix dosage unit of claim 3 wherein the silicone polymer or copolymer is a methyl silicone polymer or copolymer or a methylvinyl silicone polymer or copolymer.

5. A. transdermal fertility-controlling polymer matrix dosage unit of claim 1 wherein the polymer matrix disc layer is a crosslinked polysiloxane polymer of the following formula:

##STR5## wherein R is selected from the group consisting of alkyl or alkoxy having 1-7 carbon atoms, vinyl, phenyl or a combination thereof; and

wherein n is about 100 to about 5,000.

6. A transdermal fertility-controlling polymer matrix dosage unit of claim 3 wherein the matrix is made up of microdispersed compartments having a cross-sectional dimension of from about 10 to about 200 microns.

7. A transdermal fertility-controlling polymer matrix dosage unit of claim 1 wherein the estrogen hormone is 17-beta-estradiol.

8. A transdermal fertility-controlling polymer matrix dosage unit of claim 1 wherein the progestin is levonorgestrel.

9. A transdermal fertility-controlling polymer matrix dosage unit of claim 1 wherein the estrogen is 17-beta-estradiol and the progestin is levonorgestrel.

10. A transdermal fertility-controlling polymer matrix dosage unit of claim 1 wherein an effective progestin dosage of at least about 20 mcg per day is transdermally delivered for at least for a term of more than one day to about one week and an effective dose of estrogen of at least 20 is transdermally delivered for at least for a term of more than one day to about one week.

11. A transdermal fertility-controlling polymer matrix dosage unit of claim 10 wherein the progestin is levonorgestrel and the estrogen is 17beta-estradiol.

12. A transdermal fertility-controlling polymer matrix dosage unit of claim 6 wherein the progestin is levonorgestrel and the estrogen is 17-beta-estradiol.

13. A transdermal fertility-controlling polymer matrix dosage unit of claim 1 wherein the progestin is norethindrone and the estrogen is ethinyl estradiol.

14. A transdermal fertility-controlling polymer matrix dosage unit of claim 12 wherein the silicone polymer is a cross-linked siloxane polymer levonorgestrel is transdermally delivered at a dosage of at least about 20 mcg per day for at least for a term of more than one day to about one week and 17-beta-estradiol is transdermally delivered at a dosage of at least about 20 mcg per day for at least for a term of more than one day to about one week, the microdispersed compartment having present aqueous polyethylene glycol dispersing agent and the matrix layer having present an enhancing amount of a skin permeation enhancing agent.

15. A transdermal fertility-controlling polymer matrix dosoage unit of claim 12 wherein the silicone polymer is a cross-linked siloxane polymer norethindrone, is transdermally delivered at an effective dose for at least for a term of more than one day to about one week and ethinyl estradiol is transdermally delivered at an effective dialy dose for at least for a term of more than one day to about one week, the microdispersed compartment having present aqueous polyethylene glycol dispersing agent and the matrix layer having present an enhancing amount of a skin permeation enhancing agent.

16. A transdermal fertility-controlling polymer matrix dosage unit of claim 13 wherein the daily dose amounts are transdermally delivered for at least one week.

17. A transdermal fertility-controlling polymer matrix dosage unit of claim 14 wherein the cross-linked silicone polymer is polydimethylsiloxane.

18. A transdermal fertility-controlling polymer matrix dosage unit of claim 4 wherein the cross-linked silicone polymer is a cross-linked methylvinyl silicone polymer.

19. A transdermal fertility-controlling polymer matrix dosage unit of claim 5 wherein the skin permeation enhancing agent is present in the matrix layer, the adhesive layer or both layers and is selected from isopropyl myristate, straight chain fatty acids having an alkyl groups having 4 to 18 carbon atoms or decyl methyl sulfoxide.

20. A transdermal fertility dosage unit of claim 16 wherein the skin permeation enhancing agent is present in the matrix layer, the adhesive layer or both layers and is selected from isopropyl myristate, straight chain fatty acids having an alkyl groups having 4 to 18 carbon atoms or decyl methyl sulfoxide.

21. A process of controlling fertility by applying to the skin of a subject desiring said treatment a dosage unit as described in claim 1 to provide at least the minimum effective dose amounts of progestin and estrogen for about the first three weeks of a menstrual cycle for successive menstrual cycles for a peroid extending as long as fertility control is desired.

22. A process of claim 19 wherein the dosage unit used is as described in claim 3.

23. A process of claim 19 wherein the dosage unit used is as described in claim 4.

24. A process of claim 19 wherein the dosage unit used is as described in claim 6.

25. A process of claim 19 wherein the dosage unit used is as described in claim 7.

26. A process of claim 19 wherein the dosage unit used is as described in claim 10.

27. A process of claim 19 wherein the dosage unit used is as described in claim 11.

28. A process of claim 19 wherein the dosage unit used is as described in claim 12.

29. A process of claim 19 wherein the dosage unit used is as described in claim 17.

30. A process of claim 19 wherein the dosage unit used is as described in claim 18.