Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Web – sheet or filament bases; compositions of bandages; or...
Reexamination Certificate
1998-06-08
2001-03-27
Page, Thurman K. (Department: 1615)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Web, sheet or filament bases; compositions of bandages; or...
C424S449000
Reexamination Certificate
active
06207183
ABSTRACT:
The present invention relates to a pharmaceutical preparation for the release of active substances through the skin into the human body.
Since the Middle Ages, it has been known that pharmaceutical active substances migrate through human skin, and that applying or spreading adequate pharmaceutical active substance preparations on the skin can therefore cause medicinal effects. These effects are not limited to the skin and the underlying tissue; they may reach distant organs when suitable substances are used, because the active substances are distributed via the blood circulation after absorption. For example, hormone-containing ointments and creams are on the market today. Moreover, antirheumatic semisolid preparations are commercially available; after spreading them onto the skin they develop a therapeutic action via local or systemic effects. In this connection, the degree of active substance absorption is determined not only by the active substance concentration, but also—among other things—by the difficultly controllable size of the treated skin area. Also, the user can hardly control the layer thickness of the applied preparation precisely, which is contributory to the therapeutic result. For this reason therapeutic measures using these forms involve unacceptable deficiencies.
Transdermal therapeutic systems (TTSs) which, in addition to the active substance concentration, also exactly define the application surface do not have this disadvantage. The currently known TTSs have several basic things in common:
1. A tack-free backing layer which is impermeable to the components of the TTS is used for protection from undesired release of volatile TTS components to the environment, for protection from disadvantageous effects on contact with other surfaces, and, not least, to ensure mechanical stability of the TTS.
2. Since TTSs are to adhere intimately to the skin, the layer which faces the skin is rendered self-adhesive, at least partially.
3. Because of these self-adhesive properties a removable protective layer which has been rendered anti-adherent is applied for storage purposes prior to use.
In general, the backing layer consists of suitable materials, such as plastic films; but papers, nonwovens, or textiles are also suitable.
Despite the progress achieved, the above-mentioned TTSs may also have some disadvantages. For example, a backing layer which is impermeable to active substances and whose surface has been stabilized impairs patients' feeling of wearing comfort. The rigidity of the films used may result in undesired area limitations. Since some pharmaceutical active substances may have a relatively low transport rate through the skin in relation to the surface, a larger system surface is desirable to provide sufficient effective TTSs also for these active substances.
There have been several attempts of improving the wearing comfort by using elastic materials for the backing layer (e.g., U.S. Pat. No. 5,246,705); however, a restriction to materials which are impermeable to the medicinal agents has expressly been made. Another disadvantage of prior art TTSs is their thickness which patients sometimes find disagreeable. In conventional designs only the matrix, adhesive layer, or optional reservoir layers are mainly used to store and release the active substance, for this reason a backing layer which, according to definition, is impermeable to active substances is of no function in this respect.
It is the object of the present invention to provide a pharmaceutical preparation adhering to the skin with a given size of contact surface, comprising a tack-free backing layer and an active substance-containing reservoir formed of a skin-adherent adhesive layer, and not having the drawbacks of the state of the art.
According to the present invention this object is achieved by the fact that the backing layer comprises at least a third of the total active substance amount contained in the preparation. Including the backing layer in the diffusion process, advantageously results in the fact that it has two functions in the system according to the present invention: On the one hand, it forms part of the active substance reservoir, and on the other hand it is a backing layer preventing the patch from sticking to textiles or other articles. Most surprisingly, it was found that the unavoidable active substance permeability is not disadvantageous in general, since only volatile active substances and/or auxiliary agents result in a noticeable loss via the backing layer to the environment.
Examples of such pharmaceutical active substances include nicotine and nitroglycerin. Ethanol, propanediol, and other low-molecular alcohols, menthol, eucalyptol, limonene, and many other terpenes, low-molecular fatty acids, such as, capric acid, dimethyl sulfoxide are examples of typical additives in such preparations which, to a greater or lesser extent, emerge from the preparation through the backing layer. Unexpectedly, a widespread reservation (e.g., EP 0 366 240, p. 3, I. 24; or EP 0 402 407, p. 5, I. 4) with respect to a backing layer that is permeable to active substances turned out to be essentially unfounded, since the active substance amount migrating from the backing layer via the adhesive layer to the skin is by far larger than that migrating to the outside.
Owing to the small thickness and the possibility of using very flexible materials as base materials for the backing layer, the preparations according to the present invention, in addition to their different functionality, clearly differ in appearance from other TTSs of classical design. Since the preparation follows fine skin wrinkles, there is the impression of a thin layer present on the skin as opposed to a rigid adhesive film. In this respect, the subject matter of the present invention is an intermediate between a TTS and an ointment applied to an area of the skin.
A production method wherein a substantial portion of the active substance is introduced into the backing layer already during manufacture avoids migration processes which probably result in fold formation owing to swelling.
Numerous materials are suitable for such a backing layer, some examples are: polyvinyl alcohol, styrene-diene block copolymers, polyurethanes, polyvinyl chloride, polymethacrylates, and many other substances are basically suitable.
In an advantageous embodiment, the backing layer is covered by a supporting layer which is removable after application; this adheres to the whole surface thereof and has been rendered anti-adherent. Pharmaceutical active substances which may advantageously be used include steroid hormones, active substances having an effect on the central nervous system or on the Alzheimer's disease, anti-rheumatics, or acetylsalicylic acid.
REFERENCES:
patent: 5536263 (1996-07-01), Rolf et al.
patent: 5770220 (1998-06-01), Meconi et al.
patent: 5820875 (1998-10-01), Fallon
patent: 0366244 (1993-03-01), None
patent: 0402407 (1994-03-01), None
Horstmann Michael
Laux Wolfgang
Hochberg D. Peter
Holt William H.
Howard S.
LTS Lohmann Therapie-Systeme AG
Page Thurman K.
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