Transdermal therapeutic systems that contain sex steroids and di

Details Transdermal therapeutic systems that contain sex steroids and di Transdermal therapeutic systems that contain sex steroids and di

1996-11-08

1999-05-18

Brouillette, D. Gabrielle

Drug, bio-affecting and body treating compositions

Preparations characterized by special physical form

Web, sheet or filament bases; compositions of bandages; or...

424447, 424448, A61F13/00

Patent

active

059049316

DESCRIPTION:

BRIEF SUMMARY
The invention relates to transdermal therapeutic systems that contain sex steroids and optionally penetration-enhancers and crystallization inhibitors, which are characterized in that they contain dimethyl isosorbide, with the exception of systems that contain active ingredient-containing, non-free-flowing gel phases or 3-keto-desogestrel.
According to the invention, sex steroids are to be defined preferably as gestagens and/or estrogens although, in principle, other sex steroids, such as androgens, antiestrogens or antigestagens, are suitable for the production of the agent according to the invention.
Suitable gestagens for the agent according to the invention are, for example, gestodene, levonorgestrel, desogestrel, norethisterone and norethisterone acetate. For the production of the agent according to the invention, 3-keto-desogestrel is also suitable, as indicated by PCT/EP93/02224, which had not yet been prepublished as of the time of priority of this application.
Estrogens that are suitable for the agent according to the invention are, for example, estradiol, estriol, ethinylestradiol, mestranol, 14.alpha.,17.alpha.-ethanoestra-1,3,5(10)-triene-3,17.beta.-diol (WO 88/01275), 14.alpha.,17.alpha.-ethanoestra-1,3,5(10)-triene-3.beta.,16.alpha.,17.alph a.-ethanoestra-1,3,5(10)-triene-3.beta.,16.alpha.,17.alpha.-triol (WO91/08219) and their esters (EP-A 163596), such as estradiol-dipropionate, estradiol-dihexanoate and estradiol-didecanoate. In addition to at least one gestagen, the combination preparations according to the invention preferably contain 1 to 3--especially 1 to 2--estrogen(s).
EP-B 0 137 278, which relates to transdermal therapeutic systems in which the active ingredient is embedded in a non-free-flowing gel phase, contains a general reference stating that dimethyl isosorbide can also be used in them as a solvent, but the patent specification does not indicate that the use of this agent could be of special benefit in the case of transdermal therapeutic systems.
As is generally known, therapeutic systems that are to be administered transdermally have the advantage that they make possible a more uniform release of the active ingredient over a longer period than is generally possible with other agents that are to be administered in other ways--such as, for example, perorally. These properties can be used advantageously in the case of a number of endocrine diseases. For sparingly water-soluble steroid hormones, such as, for example, gestagens, however, it is generally quite problematical to provide transdermal systems that ensure a level of penetration of the active ingredient through the skin that is sufficient for treatment.
With the aid of the agent according to the invention, which in addition to sex steroid(s) also contains dimethyl isosorbide, it has now been found that it is possible, surprisingly enough, to achieve a therapeutically adequate, very uniform rate of penetration of the steroid hormones through the skin, while this is only conditionally possible with the known steroid hormones that contain agents that are to be administered transdermally (EP-A 137278 and EP-A 275716), which makes it necessary to use comparatively large systems.
Dimethyl isosorbide is a substance of formula ##STR1##
As is generally known, it is a substance with good dissolving power for organic compounds (H. P. Fiedler, Lexikon der Hilfsstoffe fur Pharmazie, Pharmaceutics, Cosmetics and Related Fields!, Editio Cantor Aulendorf, 1989). This is used in, for example, U.S. Pat. No. 4,082,881 to keep high concentrations of organic pharmaceutical substances dissolved in various topical preparations, but not in transdermal systems. In U.S. Pat. No. 4,814,173, dimethyl isosorbide is used as a solvent for various pharmaceutical substances, but not for sex steroids, in solutions, emulsions as well as in complex synthesized transdermal therapeutic systems based on silicone skin contact adhesives.
It has now been found that dimethyl isosorbide is able to dissolve a number of sex steroids to a considerable extent. A selec

REFERENCES:
patent: 4082881 (1978-04-01), Chen et al.
patent: 5071657 (1991-12-01), Oloff et al.
patent: 5393529 (1995-02-01), Hoffmann et al.
patent: 5538736 (1996-07-01), Hoffmann et al.

Affiliated with

Also associated with

Rating

Transdermal therapeutic systems that contain sex steroids and di does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Transdermal therapeutic systems that contain sex steroids and di, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Transdermal therapeutic systems that contain sex steroids and di will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-1758592