Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Web – sheet or filament bases; compositions of bandages; or...
Patent
1996-02-12
1997-11-11
Phelan, Gabrielle
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Web, sheet or filament bases; compositions of bandages; or...
424449, 514946, 514947, A61F 1302
Patent
active
056860986
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/EP94/00670, filed Mar. 7, 1994.
The present invention relates to an active substance patch for the release of estradiol to the skin consisting essentially of a backing layer, an active substance reservoir which is connected to the backing layer, and which comprises a pressure sensitive adhesive and wherein the active substance is at least partially soluble, and a removable protective layer covering the adhesive film.
Estradiol is required to alleviate the symptoms of menopause, oophorectomy and primary pituitary failure. For this reason there is a significant need for an estradiol replacement therapy for alleviating both menopausal symptoms, such as hot flushes, nervous discomfort, or disturbed sleep, and osteoporosis (loss of bone mass) and atherosclerosis accompanying estradiol deficiency.
When estradiol, in particular 17-.beta.-estradiol, is administered orally, the absorption is unsatisfactory because of its low water-solubility after oral administration. Due to the rapid metabolism of 17-.beta.-estradiol through the liver high doses are required, frequently resulting in undesired side effects, such as sickness and thrombo-embolism. Therefore it is necessary to improve the means and methods of the estradiol therapy.
The transdermal route of parenteral administration allows the administration of lower doses of 17-.beta.-estradiol in order to avoid the first-pass-metabolism. With this administration form the metabolism of relatively large amounts of estradiol is avoided.
Thus, the transdermal route offers advantages over other routes. Transdermal systems for the administration of a large variety of different active substances or other medicinal agents are exemplified in U.S. Pat. Nos.: 4,906,169; 5,023,084; 4,818,540 and 4,746,515 and in WO 91/05529. With respect to their size, thickness and active substance utilization, the transdermal systems according to the state of the art are not satisfactory since only a small portion of the applied dose is utilized therapeutically. Despite the developments made in the modes of administration, there is a need for further improved techniques to provide the users of said drug with another constant estradiol level in a favorable, i.e. transdermally applicable, mode of dosage. In principle it is known to apply estradiol transdermally, however, for the above reasons it is desirable to develop improved transdermal processes for the administration of estradiol.
It is the object of the present invention to provide an active substance patch for releasing estradiol to the skin, which has a pressure sensitive adhesive-containing active substance reservoir in which the active substance is at least partially soluble and which delivers therapeutically effective estradiol rates at an increased bioavailability as compared to the oral or intramuscular administration of the active substance. The active substance patch is to provide a favorable therapy with an improved compliance, in particular owing to its advantageous mode of dosage.
In an active substance patch of the kind described herein this object is achieved according to the present invention by the fact that the active substance reservoir is a polymer matrix to which--in order to improve the bioavailability of the estradiol--a penetration enhancer of the general formula ##STR2## is added, in which R=--CH.sub.2 OH or --CH.sub.2 --O--CH.sub.2 --CHOH--CH.sub.2 OH, corresponding to the compounds monoisopropylidene glycerol (MIPG) or monoisopropylidene diglycerol (MIPD).
By adding the penetration enhancer according to the invention the bioavailability of the active substance is considerably improved to advantage, allowing the application of a lower active substance dose as compared to known systems. The active substance patch prepared according to the present invention provides the required estradiol dose from a transdermal system.
According to one embodiment of the present invention the active substance patch additionally comprises one or more other compounds further intensifying the action of t
REFERENCES:
patent: 4746515 (1988-05-01), Cheng et al.
patent: 4818540 (1989-04-01), Chien
patent: 4906169 (1990-03-01), Chien
patent: 5023084 (1991-06-01), Chien
patent: 5120546 (1992-06-01), Hansen
LTS Lohmann Therapie-Systeme GmbH
Phelan Gabrielle
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