NO172278B - DEVICE FOR CONTROLLED RELEASE OF AN ACTIVE SUBSTANCE TO THE SKIN - Google Patents

Abstract

A plaster containing active ingredients for controlled administration of active ingredients to the skin and possessing a rear side and a skin side, has a rear layer, an active ingredient reservoir containing one or more active ingredients arranged essentially perpendicular to the surface of the plaster in contact with the skin, and an adhesive device on the skin side and possibly a covering layer which is detached before application of the plaster. At least one active ingredient reservoir part (12) can be detached on to the skin while one or more active ingredient reservoir parts remain. For this purpose, the part (13) of the active ingredient reservoir remaining on the skin adheres more strongly to the skin than to the rear side (11).

Description

The present invention relates to a device for the controlled delivery of an active substance to the skin of the type specified in the introduction to claim 1.

In TJS-PS 4 297 995, a patch for active substances that can be manipulated is described, whereby the reservoir for active substances is divided, but integrated into a single patch. The reservoir parts are arranged in concentric rings around a disk-shaped middle piece. The overall construction of the patch with a mechanical attachment of the reservoir to the back layer only allows changing the release surface for the active substances only before the application of the patch, so it can be chosen by the doctor/patient before the application of the patch which dose is to be released. However, for a change in the release of the active substance during the application of the patch, the patch must be removed from the skin during interruption of the therapy, which can lead to damage and contamination of the patch installation fleets. For the associated problems of reapplication and persistent reattachment of the system to the skin, no satisfactory solution has been found.

It is therefore the task of the present invention to provide a device for the controlled release of an active substance to the skin which can realize complicated changes in the release of the active substance, than was previously possible.

According to the present invention, the task is solved by means of a device of the type mentioned at the outset, the characteristic features of which appear in claim 1. Further features of the invention appear in the other non-independent claims.

By the fact that the reservoir for the active substances according to the invention is partially removable, as the non-removable parts of the reservoir have a greater adhesiveness to the skin than the back layer, means that after the removal of a pre-determined patch part with the reservoir parts adhered to it remains a specific reservoir share with active substance on the skin, such as e.g. after the desired period of use alone can be removed.

It is advantageous that the reservoir according to the invention is two-part. Fig. 1 shows a cross-section through a first embodiment of a patch according to the invention with two-part reservoir for active substances. Fig. 2 shows a second embodiment of the plaster according to the invention without a protective layer seen from above against the skin.

Fig. 3 shows a cross-section along the line I-1 in fig. 2.

Fig. 4 shows a third embodiment according to the invention without a protective layer seen from above against the skin. Fig. 5 shows a cross-section through the embodiment of fig. 4 along line II-II on an enlarged scale. Fig. 6 shows a fourth embodiment of the invention without a protective layer seen from above against the skin. Fig. 7 shows a cross-section through the embodiment of fig. 6 along the line III-III. Fig. 8 shows a cross section through a fifth embodiment of the invention. Fig. 9 shows a cross section through a sixth embodiment according to the invention. Fig. 10 shows a further embodiment of the patch according to the invention with a three-part reservoir for active substances without a protective layer and seen from above towards the skin. Fig. 11 shows an enlarged cross-section along the line IV-IV in fig. 10.

In what follows, the individual embodiments of the inventions shown in the individual figures will be described in more detail. Here, the last remaining reservoir part for active substances on the skin is called the first reservoir part for active substances, as the second and third reservoir parts for active substances respectively are those that are removed with the dorsal layer.

In fig. 1 shows a preferred embodiment of a possibly round or square plaster according to the invention with a two-part contact adhesive reservoir for active substance. The second reservoir part for active substances immediately adheres to the backing layer 11 and is separated by means of a reservoir separation layer 14, which can be formed as a gap/space between the reservoir part for active substances or can also be filled with the help of an inert separation material, from the first contact adhesive Reservoir part 13 for active substance, which in turn adheres via a remote layer 15, which realizes a staggered adhesion of both reservoir parts 12, 13 for active substances on the back, to the backing layer 11. The remote layer 15 can e.g. be a polymer or metal foil, a textile surface structure or a laminate of the same and form after removal from the back layer 11 with the second reservoir part 12 for active substances for the first reservoir part 13 for active substances remaining on the skin a protective layer for the protection of the other first reservoir parts 13 Thereby, the adhesion of the first reservoir part 13 to the skin must be greater than the adhesion between the remote layer 15 and the back layer 11. The protective layer 16 is removed before the application of the patch. Thereby, at the same puncture of the plates in fig. 1 which make up the reservoir parts 12, 13 made clear that here at both reservoir parts 12, 13 the same active substances or active substance combinations are present, with the patch in fig. 1 can thus be provided with a stepwise reduction of the delivery of the active substances to the skin.

In fig. 2 shows a square plaster according to the invention seen from above towards the skin side with two-part non-contact adhesive reservoirs for active substances, the protective layer having already been removed. According to this, the patch on the skin side has contact adhesive layers 21, 22, which can also be separated from each other by means of the inert reservoir separation layer 23, which again can be a single space or an inert material.

In fig. 3 shows a cross-section through it in fig. 2 showed embodiment along the line I-1 in fig. 3. The non-adhesive reservoir parts 24, 25 for active substances are attached on the back with a contact adhesive layer 27 to the back layer 28, with the first reservoir part 24 for active substances sticking to the back layer via a distance layer arranged between the contact adhesive layer 27 and the first reservoir part 24 with active substances 26. The remote layer 26 is thereby designed so that it sticks more strongly to the first reservoir part 24 than to the contact adhesive layer 27. Thereby, when the back layer 28 is removed, the remote layer 26 and the second reservoir part 25 remain attached via the contact adhesive layer 27 to the back layer 28 together with the first reservoir part 24 on the skin and takes over the function of a protective layer for this residual reservoir part 24, which protects against contamination and damage of the reservoir material and also against the escape of any volatile, active substance components.

The contact adhesive layers 21 and 22 on the outside are set on non-adhesive reservoir parts 24, 25 for the active substances so that the adhesion of the contact adhesive layer 22 to the first reservoir part 24 on the skin is greater than the adhesion between the removal layer 26 and the contact adhesive layer 27. The different applied surfaces of the drawing suggests that different active substances or active substance combinations are present at both reservoir parts 24, 25.

In fig. 4 shows a further preferred embodiment of a patch according to the invention seen from above against the skin. The oval plaster has a two-part reservoir for active substances, as a contact adhesive layer 41, which provides for fixing the reservoir parts 42, 43 on the back layer 45, also forms the attachment of the therapeutic system to the skin.

In fig. 5 shows an enlarged cross-section along the line II-II in fig. 4. The contact-adhesive reservoir parts 42 and 43 for active substances, which are separated from each other by means of inert reservoir-separation layer 46 designed here as spaces, are pocket-like surrounded by the back layer 45 coated with a contact-adhesive layer 41. Here, too, a separation layer 44 provides so that the adhesion of the first reservoir part 42 is greater on the skin than the adhesion between the removal layer 44 and the contact adhesive layer 41 and the first reservoir part 42 which is back on the skin after the removal of the second reservoir part 43 and the back layer 45 is protected by a layer. The two reservoir parts 42 and 43 contain, as indicated by the construction of the surfaces, different active substances or active substance combinations.

In fig. 6 shows a further patch according to the invention with a two-part reservoir for active substances, whereby a reservoir part 61 concentrically surrounds the other reservoir part 63 and where it is shown seen from the outside with the protective layer removed. The contact adhesive first circular reservoir 63 is surrounded by an annular second reservoir 61, separated by means of an inert reservoir separation layer 62, which may be designed as a space. This embodiment has the advantage that reduction of the release floats of the active substance by removing a part of the patch with the second reservoir part 61 together with the backing layer 65, the pull-off direction of the patch can be chosen freely.

In fig. 7 shows a cross-section through it in fig. 6 showed an embodiment along the line III-III of fig. 6. The annular second reservoir part 61 borders immediately on the back layer 65, while the remote layer 64 is arranged between the circular first reservoir part 63 and the back layer 65. The adhesion of the first reservoir part 63 to the skin and that between the remote layer 64 and the back layer 65 is greater than the adhesion between the remote layer 64 and the reservoir part 63 so that when the back layer 65 is pulled off, the second reservoir part 61 is removed while the first reservoir part 63 remains on the skin, which is now covered by the remote layer 64. The inert reservoir-separation layer 62 separates the reservoir part 61 and 63 from each other. In this embodiment, the active substance is the same in the two reservoir parts 61, 63.

In fig. 8 shows a further preferred embodiment of the invention in cross-section, in which both parts of a non-adhesive reservoir are again designed as a circular disk 82 with a surrounding ring 81. They are separated from each other by means of an inert reservoir separation layer 83. The back layer 88 is coated with a contact adhesive layer 87, which is in direct contact with the second reservoir part 81.

Between the contact adhesive layer 87 and the first reservoir part 82 is an inert spacer layer 86, which is designed so that the adhesion to the contact adhesive layer 87 is less than between the contact adhesive layer 85 and the skin. The other adhesive values at the boundary layer of this plaster part must of course be above the adhesive values of the skin. The contact adhesive layers 84, 85 of the reservoir parts 81, 82 against the skin form the contact with the skin and are preferably covered by a protective layer 89 before use.

In this embodiment, both reservoir parts 81, 82 have different active substances or different active substance combinations.

In fig. 9 shows a cross-section through a further embodiment of the invention, where the back layer 95 encloses the concentric arrangement of the contact adhesive reservoir parts 91, 92 up to the skin side. In order to attach the entire patch and the reservoir part to the skin, the back layer 95 is provided with a contact adhesive layer 93 on the entire surface. To this, the second reservoir part 91 adheres directly while its first reservoir part 92 is attached via a remote layer 94. The adhesion of the remote layer 94 to the reservoir part 92 lies above and the adhesion to the remote layer 94 for the contact adhesive layer 93 lies below the adhesion between the first reservoir part 92 and the skin. Thus, a selective withdrawal of the back layer 95 together with the second reservoir part 91 is made possible. Naturally, corresponding changes to the structure can also realize a selective withdrawal of the reservoir part 92. The inert reservoir separation layer or the space between the reservoir parts 91, 92 is denoted by the reference number 96. Before use, the overall device is covered by a removable protective layer 97. The active substance, or the active substance combination, is different in the embodiment at both reservoir parts 91, 92 for active substances.

A further preferred embodiment of the invention is made with a three-part reservoir and shown in fig. 10. A patch without a protective layer is shown here, viewed from above against the skin. A first circular contact adhesive reservoir part 105 is surrounded by a second annular contact adhesive reservoir part 103, which is separated by an inert reservoir separation layer 104, the third contact adhesive reservoir part 101 encloses the second reservoir part 103 in concentric ring form. Between the second and third reservoir parts 101, 103, a further inert reservoir separation layer 102 is arranged.

Fig. 11 shows an enlarged cross-section along the line IV-IV.

The reservoir part 101 for the active . the fabric thereby sticks immediately to the back layer 108. A first remote layer 106 connected to the back layer 108 covers the reservoir parts 103 and 105. The adhesion of the remote layer 106 to the back layer 108 is less than the adhesion of the reservoir parts 103 and 105 to the skin so that when pulling off the back layer 108 with reser the reservoir part 101 remains the reservoir parts 103, 105 on the skin. The first removal layer 106 thus forms a protective new layer for the remaining part of the patch. The adhesive reservoir part 103 immediately adheres to the first removal layer 106 and together with this can be removed in a further removal step while the first reservoir part 105 remains on the skin, which is made possible by the second removal layer 107 between the first reservoir part 105 and the first removal layer 106 The adhesion of the second remote layer 107 to the first remote layer 106 is less than the adhesion of the first reservoir part 105 to the skin. The inert reservoir separation layers 102 and 104, which can be designed as spaces, lie between the reservoir parts 101 and 103, respectively 102 and 105. The example shown has for the reservoir parts 103, 105 the same active substance or the same active substance combinations, which is indicated by the like the puncture in fig. 11, while the reservoir part 101 has another active substance or active substance combination.

The features shown in the figures with regard to the geometric shape of the present invention, arrangement of specific individual components with regard to size and release surface for active substances are not intended as limitations, as all these sizes can, as is known to the person skilled in the field, be adapted to corresponding therapeutic requirements, as of course considerations for rational presentation are taken into account. The parts of the reservoir to be removed can also have a tear-off layer, which then has a greater adhesion to the back layer than the removal layer of the reservoir part that remains on the skin. This construction is advantageous when the reservoir parts for the active substances are to have the same thickness. The contact adhesive layer, preferably the one facing the skin, can have a better permeability in the contact adhesive-free areas for active substances or be embedded as individual contact adhesive surfaces or reservoir material for active substances. The release of the active substance from the reservoir part can possibly also be regulated by means of a control membrane, which is embedded in one or more reservoir parts in a manner known per se in the reservoir mass or "located between the reservoir and the contact adhesive layer on the skin or also within the contact adhesive layer applied to the skin.

For the construction of a reservoir for active substances which can be used in the present invention, measures and materials which should be known to the expert in the field are suitable. Low and high molecular weight natural and/or synthetic substances can be used as base materials, which choice depends on the properties of the active substances to be released and the therapeutic requirements. The reservoir may contain further suitable additions which should be known or close to the person skilled in the art as a result of his knowledge, as these additions can e.g. be dissolution promoters, plasticizers, agents that make the material sticky, stabilizers, fillers and reinforcers. The composition can be the same or different in the reservoir parts, which in turn depends on the active substances to be released and the desired release rate or kinetics. With the same reservoir composition and only one active substance to be released, a stepped-down concentration setting of the active substance in the different reservoir parts can be shown. As an active substance for plasters according to the invention, all are suitable in principle, which can penetrate the skin alone or with the aid of aids.

The backing covering the reservoir on the side facing away from the skin may be permeable or impermeable. It must be flexible and constitutes due to the mechanical stabilization of the plaster to the withdrawal of part of the reservoir for the active substance. If components of the reservoir or the incorporated active substance are volatile, then the backing layer for this substance must be impermeable. There can be one or more layers. The material which is suitable for the production includes e.g. polymeric substances, such as polyethylene, polypropylene, polyester and polyamide. A further material can also be metal foil, such as e.g. aluminum foil, alone or coated with a polymeric substrate. Permeable back layers are e.g. textile raft structures, such as layer fabrics and fleece fabrics, or also porous polymer materials. The back layer can optionally carry a marking to characterize the optimal tear-off direction of the patch. Optionally, a tear-off layer is arranged between the reservoir parts, instead of a space. For them, it is suitable to use the same material as described above for the separation layer between the reservoir part and the back layer. The protective layer that can be peeled off before use, which covers the contact adhesive layers against the skin side, can also be of the same material as used in the production of the back layer, provided that it can be made removable, e.g. by applying a silicone layer. Other removable protective layers that are available to the skilled person in the area of plasters and especially within plaster-like therapeutic systems, are e.g. polytetrafluoroethylene, treated paper, cellophane, polyvinyl chloride, etc. For easier removal, the protective layer can be provided with pull-off aids in a manner known per se. The protective layer can also be larger than the patch, e.g. when several plasters are arranged on an uninterrupted path of the protective material.

For the contact adhesive layer used in a patch according to the invention, all inert contact adhesives that are physiologically harmless with regard to the active substances and other reservoir components for the active substances are suitable, as these materials can be based on rubber, rubber-like synthetic homo-, co- or block polymers, polyacrylic acid esters and their copolymers, polyurethanes and silicones.

A preferred design example of the patch is shown in fig. 6 and can be structured as follows: On a contact adhesive layer (contact adhesive: DURATAC 80-2515; 30 g/m<2>dry) made back layer 65 is a ring-shaped protective layer material of siliconized, aluminum vaporized polyester foil. On this ring-shaped siliconized aluminum vapor-deposited polyester film there is one of the following materials contact adhesive first active substance containing reservoir part 61: 68.86 parts by weight of acrylate copolymer I (Durotac 280-2516 manufactured by the company National Starch & Chemical B.V. The Netherlands), 10.39 parts by weight of acrylate copolymer II, 5.20 parts by weight of POA" (10 )-oleyl alcohol (Brij97 to Fa. Atlas Chemical Industries, GB) and 15.56 parts by weight of active substances. In the annular recess of the polyester foil there is a disc-shaped second reservoir part (63) for active substances of the same material as the first reservoir part.

Claims (7)

1. Device for controlled delivery of an active substance to the skin, the device having a backing layer, a divided reservoir for one or more active substances, an adhesive device on the skin side and a covering layer removable from this, the device's contact surface with the skin can be reduced by a defined way, characterized in that at least one reservoir part (12, 25, 43, 61, 81, 91, 101, 103) can be removed together with the back layer (11, 28, 45, 65, 88, 95, 108), the rest of the reservoir (13, 24, 42, 63, 82, 92, 105) that remains on the skin adheres better to the skin than to the backing layer (11, 28, 45, 65, 88, 95, 108). 2. Device according to claim 1, characterized in that the reservoir for active substances is divided in two. 3. Device according to claim 1, characterized in that the reservoir is divided into three. 4. Device according to one of the preceding claims, characterized in that the release surface for the active substance of the reservoir part is geometrically similar or of a different shape. 5. Device according to one of the preceding claims, characterized in that a reservoir part (61, 81, 91, 101, 103) completely surrounds another or more reservoir parts (63, 82, 92, 103, 105) for active substances. Device according to claims 4 and 5, characterized in that a reservoir part (61, 81, 91, 101, 103) annularly surrounds one or more other reservoir parts (63, 82, 92, 103, 105). 7. Device according to one of claims 1 to 5, characterized in that the dispensing surface size ratio of one reservoir part in relation to another reservoir part is between 1:1 to 1:10.