MXPA99006419A - Transdermal, hormone-delivering therapeutic system - Google Patents

Abstract

An active substance-containing plaster for delivering oestradiol or its pharmaceutically tolerable derivatives in a controlled manner, either alone or in association with gestagens, to the human or animal skin, has an active substance-containing reservoir based on pressure sensitive adhesives which contain ethyl cellulose and adhesive resins, and is characterised by a pressure sensitive adhesive with a high plasticiser content.

Description

PERCUTANEOUS THERAPEUTIC SYSTEM FOR THE EMISSION OF HORMONES FIELD OF THE INVENTION The invention relates to a patch containing active compound for the controlled emission of Estradiol or its pharmaceutically acceptable derivatives, alone or in combination with progestins, to human or animal skin, with a deposit containing active compound, based on ethylcellulose and contact adhesives comprising adhesive resins.

BACKGROUND OF THE INVENTION Percutaneous therapeutic systems have been known for some time, in particular also for the percutaneous administration of hormones, in particular estrogens, possibly in combination with progestins.

DESCRIPTION OF THE INVENTION The active compounds are arranged for this purpose in a deposit based on contact adhesives, whose Ref .: 30742 adhesive power must guarantee a sufficient contact with the skin during application, without excessive softening or irritation occurring, corresponding to the absorption and emission of active compound through the skin at the desired systemic dose and continuous active compound.

As a basis for the layers of the deposits containing Estradiol, it is used, inter alia, to mass compounds based on rubber or polyacrylate, which contain in particular ethanol (for example DE-OS 32 05 258 and EP 0 275 716).

DE-OS 39 33 460 discloses active compound patches based on homopolymers and copolymers with at least one acrylic or methacrylic acid derivative, which must also contain substances that swell in water.

From DE-PS 40 20 144 a percutaneous system is known which optionally contains also hormones with at least one layer of self-adhesive active compound which, in addition to polyacrylate and a compatible smoke-forming agent, must contain a wide range of active compounds and additives. softeners.

A percutaneous therapeutic system described in reduced form (see DE-OS 195 00 662) consists of an estradiol and possibly a deposit of active compound containing gestagen based on ethylcellulose, with a high proportion of esters of colophony eventually hydrogenated as adhesive resin , with up to 20% by weight of lauric acid, which must counteract the recrystallization of the active compound and thus reduce its rate of release.

Surprisingly, it was found that it is possible to achieve the release of an unexpectedly high amount of Estradiol and in particular Norethindron acetate from a deposit of active compound based on ethyl cellulose and binder resin, which has an extraordinarily high proportion of plasticizers.

The patch according to the invention, of the aforementioned type, is characterized by the fact that the contact adhesive has a high proportion of plasticizers.

The contact adhesive contains in particular at least 15% by weight and preferably at least 20% by weight of plasticizers.

Otherwise, the patch containing active compound may contain emulsifiers, antioxidants and agents to improve absorption. A patch of this type can be used in particular to release large combined amounts of Estradiol and Norethindron acetate.

Preferred formulations of these contact adhesive masses, according to. the invention, which contain hormones, have the following composition (in ~ by weight): Ethylcellulose 5-25% Binding resins 10-70% plasticizers / Emulsifiers 20-40% Estradiol 1-10% Norethindron acetate and / or other progestins 1-15% It is known to add plasticizers to self-adhesive compositions containing active compound, such as those mentioned in DE-OS 40 20 144; However, the addition of softeners to the usual contact adhesives based on polyacrylates, block copolymers and polyisobutylenes is only possible in a limited way, since the cohesion of the contact adhesives decreases after a certain concentration, and is therefore unsuitable for a percutaneous application.

The fact that precisely masses based on ethylcellulose / adhesive resin with extraordinarily high additions of softeners provide particularly useful percutaneous therapeutic systems, with high skin penetration of the hormones and a particularly reduced tendency to recrystallization of the same, all together to good support properties of the percutaneous therapeutic system, it could not be foreseen at all as shown by the mentioned development of a percutaneous therapeutic system that has been known recently, with a deposit of active compound based on ethylcellulose / adhesive resin, which it presents as an additive, lauric acid and not as now high proportions of softener or plasticizer.

The composition of the active compound tank according to the invention, based on ethylcellulose / resin with a high proportion of fabric softener, but without lauric acid, has a considerably higher hormone release than the masses of DE-OS 195 00 662, particularly if incorporates a combination of Estradiol and Norethindron acetate.

This can be seen from the results indicated below (Tables 1 and 2), where Table 1 shows the composition of the analyzed masses and Table 2 shows the results of the test series for the release of active compound.

It will be appreciated that due to the softener content according to the invention considerable improvement in the release and penetration of the active compound is achieved.

Table 1 - Formulations Composition in% Where: Staybelite Ester 5E = Glycerinester of partially hydrogenated rosin NeA = Norethindronium Acetate IPM = Isopropylmiristase Renex 698 = Polyoxyethylene - (9) - nonylphenol Brij 92 = Polyoxyethylene - (2) - olylalcohol ol Brij 30 = Polyoxyethylene - (4) laurylalcohol Miglyol 812 = Caaena triglycerides medium Eutanol G = 2-octyldodecanol Table 2 - Release of active substance "3 It is noted that in relation to this date the best method known to the applicant, to carry out the aforementioned invention is that which is clear from the manufacture of the objects to which it relates.

Having described the invention as above, the content of the following is claimed as property.

Claims (6)

1. Patch that contains active compound for the controlled emission of Estradiol or its pharmaceutically acceptable derivatives, alone or in combination with progestins, to human or animal skin, which has a deposit containing active compound based on ethylcellulose and contact adhesives comprising resins adhesive, characterized by a contact adhesive that has a softener or a Dlastifier of at least 15% in this case.

2. Patch according to claim 1, characterized by a fabric softener or Dlastifirant of 40% in DTSO.

3. Patch according to claim 1 or 2, characterized by the rosin ester optionally hydrogenated as binder resin.

4. Patch according to one of the preceding claims, characterized by an emulsifier content in the contact adhesive of at least 15% by weight, particularly at least 20% by weight. Patch according to one of the preceding claims, characterized by the following composition of the contact adhesive containing active compound:

5-25% by weight of ethylcellulose 10-70% by weight of binding resins 20-40% by weight of softeners / emulsifiers 1-10% by weight of proportion of Estradiol 1-15% by weight of Norethindron acetate and / or Other gestagens

6. Patch according to one of the preceding claims, characterized by a content of antioxidants and / or agents that improve the absorption in the contact adhesive.