IE61005B1 - Active substance-containing plaster for the controlled administration of active substances to the skin, the use thereof and a process for the controlled administration of active substances 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 invention relates to an active substance-containing plaster for the controlled administration of active substances onto the skin, which has a backing side and a skin side, with a backing layer, with an active substance reservoir which is divided essentially at right angles to the skin contact area of the plaster and has one or more active substances, with an adhesive device on the skin side, and, where appropriate, with a covering layer which can be detached before application of the plaster, where the active substance delivery area of the plaster can be reduced in size by a predetermined area by removing a part of the active substance reservoir, and to the use thereof and to a process for the controlled administration of one or more active substances onto the skin by means of a plaster, excepting, however, the therapeutic treatment of the human or animal body or diagnostic methods in human or veterinary medicine.

The invention particularly relates to those plasters which are employed as transdermal therapeutic systems for the controlled administration of medicinal active substances or else cosmetically active substances onto the human or animal skin. A therapeutic system is a medicinal agent- or active substance-containing device or administration form which delivers one or more active substances at a predetermined rate continuously over a fixed time period to a fixed site of use, These plaster-like systems are therapeutic precision instruments whose construction, requires exceptional measures in order to ensure continuous release of active substance.

Plaster-like therapeutic systems have already been developed for a wide variety of uses, it being possible also to achieve systemic action besides topical action. The wide variety of active substances which can be administered in this way, and their different chemical, physical and pharmacological properties, make it impossible to cover all therapeutic requirements with only one system.

A large number of plaster-like therapeutic systems for the administration of medicinal active substances onto the skin have already been disclosed, and a compilation is to be found, for example, in Klaus Heilmann Therapeutische Systems (Therapeutic Systems) published by Ferdinand Enke, Stuttgart, 1977. It has not been possible in all cases to achieve a completely satisfactory action by the systems according to the state of the art.

In the usual design of a transdermal plaster-like therapeutic system there is an active substance reservoir in which the active substance is present in solid, liquid or dissolved form, and a pressure-sensitive adhesion layer (adhesive) by which the system is tightly bonded to the skin. It is important that full-area contact of the active substance delivery areas with the skin is continuously guaranteed during the administration of the plaster-like system in order to ensure the kinetics of active substance delivery, it being possible to achieve this not only by an uninterrupted adhesion layer but also by demarcated adhesive areas in the skin contact layer of the plaster.

The plaster-like therapeutic systems to date do allow uniform or continuously decreasing administration of an active substance over a predetermined time period but not a defined kinetics of active substance delivery, such as a specific reduction in the active substance delivery after a - 4 predetermined time period, such as to adjust a graded amount of active substance delivered per unit time.

This measure is necessary, for example, when the active substance dose must be specifically reduced for therapeutic reasons during the period of administration. The same problem arises on administration of a combination product when one active substance of the combination is to be discontinued after a predetermined time period. It is true that a remedy which is possible in principle in these cases is to use two transdermal plasters, one of which is pulled off at the appropriate time. This entails great problems for the patient, especially elderly patients. Thus, it is easy to forget to attach the second plaster. In the case of a combination of two plasters with different active substance delivery areas, there is the additional risk that the wrong combination is chosen (two identical plasters) or the incorrect plaster is pulled off again. The same complications occur when plasters with different active substances have to be combined. An additional factor in this case is the double storage. This means that the use of two plasters is associated with very many disadvantages, and the avoidance of these is one aim of the invention.

The proposal to combine two plasters together in such a way that it is possible, with the aid of an intended breakage line, to detach a part thereof, does, it is true, improve compliance but leads to difficulties in manipulation. Thus, the part to be detached can be manipulated only after lifting from the skin, when there is unintended lifting of at least a part section of the plaster residue remaining on the skin, so that the latter must be held fixed during the detachment. This entails the exertion of pressure on the sensitive plaster-like transdermal system, which may have an adverse effect on the rate of release of the active substance.

US Patent 4,297,995 describes a manipulatafale active substance plaster in which the active substance reservoir is divided but is integrated in a single plaster. The active substance reservoir parts are arranged in concentric rings around a central piece in the form of a small disc. The overall construction of the plaster with a mechanical fixing of the reservoir to the backing layer allows the active substance delivery area to be changed only before application of the plaster - that is to say it is possible for the physician\patient to choose before application of the plaster which dose is to be delivered, while to change the active substance delivery during the application of the plaster it is necessary for the plaster to be lifted from the skin, with interruption of the therapy, which may also lead to damage and contamination of the plaster contact area. No satisfactory solution has yet been found for the problems, associated therewith, of repositioning and. of permanent re fixing of the system on the skin.

If is therefore an object of the invention to produce an improved plaster-like therapeutic transdermal system which is able to effect more complicated changes in active substance delivery than hitherto possible.

The object is achieved by a generic plaster which is characterised in that at least one part of the active substance reservoir can be detached while leaving one or more parts of the active substance reservoir on the skin, where the part of the active substance reservoir remaining on the skin has better adhesion to the skin than to the backing layer.

Because for the first time according to the invention partial detachment of the active substance reservoir is possible, with the portion of the active substance reservoir which is not to be detached having a greater adhesion to the skin than to the backing layer, after a predetermined part of the plaster, with active substance reservoir part adherent thereto, has been detached, there remains a predetermined active substance reservoir portion on the skin# which can be detached alone# for example# after the required administration period.

It is advantageous for the active substance reservoir in the plaster according to the invention to be in two parts.

It may also be advantageous# in certain therapies with active substance doses which differ or vary greatly in concentration# for the active substance reservoir to be in three parts. The active substance delivery areas of the active substance reservoir parts can be geometrically identical or different. The active substance delivery areas can be arranged side by side# or it is possible for one active substance reservoir part completely to surround one other or several active substance reservoir parts# viewed in terms of surface. The division of the part areas depends in this connection on the therapeutic requirements. Thus# for example# it is possible for an active substance reservoir part to surround in the form of a ring one or more other active substance reservoir part(s).

The delivery area/size ratio of one active substance reservoir part to another is preferably between about lsl and 1:10.

It is possible for the same active substance or the same active substance combination to be present in all active substance reservoir parts.

Particularly preferred products are plasters with the following active substances# but it is also possible to incorporate any other active substance combinations which are familiar to clinicians and can be administered transdermallys asthma/bronchodilators such as, for example, clenbuterol, procaterol and salbutamol and vasodilators such as, for example, bencyclane and cinnarisine.

Thus, in these cases it is possible with the aid of the 5 plaster according to the invention to reduce the dose administered during the application in a specific and, controlled manner.

The active substance reservoir parts can, however, also contain different active substances or different active substance combinations so that one active substance or one active substance combination can be discontinued during the application. Mention may be made as example of different active substances in the active substance reservoir parts.

Oestrogen/gestagsn (contraceptives), dexamethasone/ prednisolone (for inflammatory rheumatic muscle and joint disorders), nitroglycerin/|3~blockers (for heart diseases) phenytoin/phenobarbitone/caffeine (for epilepsy) and amitriptyline/chlordiazepoxide (psychopharmaceuticals).

All suitable active substances belong to the groups which display either topical or systemic effect.

It is possible in this connection for the active substance/active substance combination present in at least one active substance reservoir part to differ from that in the other active substance reservoir part(s).

The use of the plasters according to the invention is for the local and systemic transdermal administration of active substances in cosmetics.

The invention furthermore relates to a method for the controlled administration of one or more active substances onto the skin by means of a plaster according to any of the preceding Claims [sic], but excepting the therapeutic treatment of the human or animal body or diagnostic methods in human or veterinary medicine, characterised bys adhesion onto the skin of a plaster which, where appropriate, has a plurality of active substances and/or the same active substance in different or identical concentrations in different active substance reservoir parts which can be separated from one another; pulling off of one or more plaster parts with in each case one or more active substance reservoir parts after a predetermined period with retention of a plaster residue with, at least one active substance reservoir part on the skin, and, where appropriate, repetition of the last step after a predetermined period.

The invention is explained in more detail hereinafter by means of the drawing, in whose figures preferred embodiments of the invention are depicted diagrammatically and not true to scale. In this: Fig. 1 shows a cross-section through a first embodiment of a plaster according to the invention with active substance reservoir in two parts Fig. 2 shows a view of the skin side of a second embodiment of the plaster according to the invention without protective layer Fig. 3 shows the cross-section along line I-I in Fig. 2 Fig. 4 shows a view of the skin side of a third embodiment according to the invention without protective layer Fig. 5 shows a cross-section through the embodiment of Fig. 4 along line II-II on an enlarged scale Fig. S shows a view of the skin side of a fourth embodiment of the invention without protective layer Fig. 7 shows a cross-section through the embodiment in Fig. along 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 of the invention Fig. 10 shows a view of the skin side of another embodiment of a plaster according to the invention with active substance reservoir in three parts without protective layer, and Fig. 11 shows an enlarged cross-section along line XV-IV in Fig. 10.

The preferred embodiments of the invention which are depicted, in the individual figures are to be explained hereinafter. In this connection, the active substance reservoir part which remains as last on the skin is called the first active substance reservoir part, the second, and third active substance reservoir part [sic] in each case are those which are detached with the backing layer.

Fig. 1 shows a preferred embodiment of an optionally round or angular plaster according to the invention with an adhesive active substance reservoir in two parts, in crosssection. The second active substance reservoir part 12 adheres directly to the backing layer 11 and is separated by a reservoir separating layer 14 which can be designed as a cleft/space between the active substance reservoir parts, or else can be filled with an inert separating material, from the first adhesive active substance reservoir part 13 which, in its turn, adheres to the backing layer 11 via a detachment layer 15 which effects a graded adhesion of the two active substance reservoir parts 12, 13 to the backing layer. The detachment layer 15 can be, for example, a polymeric or metallic sheet, a textile sheet-like structure or a laminate thereof, and forms, after the backing layer 11 with the second active substance reservoir part 12 has been pulled off, a protective layer for the first active substance reservoir part 13, remaining on the skin to protect the remaining first active substance reservoir part 13. It is moreover necessary for the adhesion of the first active substance reservoir part 13 to the skin to be greater than the adhesion between detachment layer 15 and backing layer 11. The protective layer 16 is removed before application of the plaster. In this case, identical stippling of the areas in Fig. 1 representing the active substance reservoir parts 12, 13 makes it clear that the same active substance or active substance combination Is present here in both active substance reservoir parts 12, 13 - thus with the plaster of Fig. 1 it is possible to achieve a stepwise decrease In. the active substance delivery to the skin.

Fig. 2 depicts a view of the skin side ox another angular plaster according to the invention with a non-adhesive active substance reservoir in two parts, where the protective layer has already been detached. As a consequence, the plaster has adhesive layers 21, 22 on the skin side, which are also separated from one another by the inert reservoir separating layer 23 which in turn can be a simple space or an inert material» Fig. 3 depicts a cross-section through the embodiment depicted in Fig. 2 along the line ϊ ϊ of Fig. 3 [sic]. The non-adhesive active substance reservoir parts 24, 25 are fixed by an adhesive layer 27 on the back to the backing layer 28, with the first active substance reservoir part 24 adhering to the backing layer via. a second adhesive layer 27 and detachment layer 26, which is assigned, to the first active substance reservoir part 24. The detachment layer 26 in this case is designed, so that its adhesion to the first active substance reservoir part 24 is greater than to the adhesive layer 27. This means that the detachment layer 26 remains, when the backing layer 28 and the second active substance reservoir part 25 which is fixed to the backing layer 28 via the adhesive layer 27 are detached, together with the first active substance reservoir part 24 on the skin and assumes the function of a protective layer for this remaining active substance reservoir part 24 and protects from contamination and damage to the reservoir material from outside or else from the escape of volatile active substance components where appropriate.

The adhesive layers 21 and 22 on the skin side on the non-adhesive active substance reservoir parts 24, 25 are adjusted so that the adhesion of the adhesive layer 22 of the first active substance reservoir part 24 to the skin is greater than the adhesion between detachment layer 26 and adhesive layer 27. The differently shaded areas in the drawing Is [sic] intended to indicate that different active substances or active substance combinations are present in the two active substance reservoir parts 24, 25.

Fig. 4 depicts another preferred embodiment of a plaster according to the invention as a view of the skin side thereof. The oval plaster has an active substance reservoir in two parts, with an adhesive layer 41 which ensures fixing of the active substance reservoir parts 42, 43 to the backing layer 45 also forming the attachment of the therapeutic system to the skin.

Fig. 5 depicts an enlarged cross-section along line IIII in Fig 4,. The adhesive active substance reservoir parts 42 and 43, which are separated from one another by an inert reservoir separating layer 46 which is depicted here as space, are enveloped in the form of a bag by the backing layer 45 which is coated with an adhesive layer 41. In this case too, a separating [sic] layer 44 ensures that the adhesion of the first active substance reservoir part 42 to the skin is greater than the adhesion between the detachment layer 44 and the adhesive layer 41 and that the first active substance reservoir part 42 which remains on the skin after the second active substance reservoir part 43 and the backing layer 45 have been detached is protected by a layer. The two active substance reservoir parts 42 and 43 contain# as is evident by the shading of the areas# different active substances or active substance combinations.

Fig. 6 depicts another plaster according to the invention with active substance reservoir in two parts# in which one active substance reservoir part SI surrounds the other active substance reservoir part 63 concentrically from the skin side# the protective layer having been detached, The adhesive first circular active substance reservoir 63 is surrounded by the annular second active substance reservoir 61# separated by an inert reservoir separating layer 62# which can also be designed as space. This embodiment has the advantage that# when the active substance delivery area is reduced by removing one part of the plaster with the second active substance reservoir part 61 together with the backing layer 65# the direction of pulling off the plaster can be chosen freely.

Fig. 7 depicts the cross-section through the embodiment depicted in Fig. 6 along line lll-III in Fig. 6. The annular second active substance reservoir part 61 is directly adjacent to the backing layer 65# whereas the detachment layer 64 is arranged between the circular first active substance reservoir part 63 and the backing layer 65. The adhesion of the first active substance reservoir part 63 to the skin and that between detachment layer 64 and backing layer 65 is greater than the adhesion between detachment layer 64 and active substance reservoir part 63# so that# when the backing layer 65 is pulled off# the second active substance reservoir part 61 is removed# while the first active substance reservoir part 63 remains on the skin and is now covered by the detachment layer 64. Th© inert reservoir separating layer 62 separates the active substance reservoir parts 61 and 63. In this embodiment the active substance is the same in both active substance reservoir parts SI, S3.

Fig. 8 depicts another preferred embodiment of the invention in cross-section, in which the two parts of a nonadhesive active substance reservoir are again designed as circular disc 82 with surrounding ring 81. They are separated from one another by an inert reservoir separating layer 83. The backing layer 88 is coated with an adhesive layer 87 which is directly in contact with the second active substance reservoir part 81.

An inert detachment layer 85 which is designed so that its adhesion to the adhesive layer 87 is less than that between the adhesive layer 85 and the skin is located between the adhesive layer 87 and the first active substance reservoir part 82. The other adhesions at the interfaces of this part of the plaster must, of course, be greater than the adhesion to the skin. The adhesive layers 84 and 85 on the skin side of the active substance reservoir parts 81, 82 ensure contact with the skin and are, before application of the plaster according fco fche invention, advantageously covered by a protective layer 89.

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

Fig. 9 depicts a cross-section through another embodiment of the invention, where the backing layer 95 surrounds the concentric arrangement of the adhesive active substance reservoir parts 91 and 92 as far as the skin side. To attach the complete plaster and the active substance reservoir parts to the skin... the backing layer 95 is provided over the complete area with an adhesive layer 93. Ths second active substance reservoir part 91 adheres directly to th® latter, while the first active substance reservoir part 92 is attached via a detachment layer 94. The adhesion of the detachment layer 94 to the active substance reservoir part 92 is greater than, and the adhesion of the detachment layer 94 to the adhesive layer 93 is less than, the adhesion between the first active substance reservoir part 92 and the skin. This makes it possible for the backing layer 95 to be pulled off selectively together with the second active substance reservoir part 91. It is, of course, also possible by an appropriate alteration in the design for the first active substance reservoir part 92 to be selectively pulled off. The reference number 96 designates the inert reservoir separating layer or the space between the active substance reservoir parts 91 and 92. The entire arrangement is covered by a detachable protective layer 97 until applied. The active substances or active substance combinations in the two active substance reservoir parts 91, 92 in this embodiment are different.

Another preferred embodiment of the invention with active substance reservoir in three parts is given in Fig. 10. It shows a view of the skin side of a plaster according to the invention without protective layer. A first circular adhesive active substance reservoir part 105 is surrounded by a second annular adhesive active substance reservoir part 103 and separated from the latter by an inert reservoir separating layer 104, the third adhesive active substance reservoir part 101 surrounds the second active substance reservoir part 103 in the form of a concentric ring; another inert reservoir separating layer 102 being provided between the second and third active substance reservoir par 101, 103? an enlarged cross-section along line IV-IV is depicted in Fig. 11.

In this, the active substance reservoir part 101 adheres directly to the backing layer 108. A first detachment layer 106 which is bonded to the backing layer 108 covers the active substance reservoir parts 103 and 105. Their adhesion to the backing layer 108 is less than the adhesion of the active substance reservoir parts 103 and 105 to the skin, so that the active substance reservoir parts 103 and 105 remain on the skin when the backing layer 108 with active substance reservoir part 101 is pulled off. The first detachment layer 106 then forms a new protective layer for the remaining parts of the plaster. The adhesive active substance reservoir part 103 adheres directly to the first detachment layer 106 and can be removed together with the latter in another detachment step, leaving behind the first active substance reservoir part 105 on the skin, which is made possible by the second detachment layer 107 between the first active substance reservoir part 105 and the first detachment layer 106. The adhesion of the second detachment layer 107 to the first 106 is less than the adhesion of the first active substance reservoir part 105 to the skin. The inert reservoir separating layers 102 and 104, which can also be designed as spaces, are located between the active substance reservoir parts 101 and 103, and 102 and 105,, respectively. The selected example shows the same active substance or the same active substance combination for the active substance reservoir parts 103, 105 which is indicated by the same stippling in Fig. 11,, while the active substance reservoir part 101 has an active substance or active substance combination different therefrom.

The figures, which illustrate the invention merely by way of example, are not intended to restrict the invention either in terms of its geometric shape, the arrangement of particular single components with respect to one another or in terms of the size of the active substance delivery areas; all these parameters can, as is familiar to th® person skilled in ths relevant art, be adapted appropriate for the therapeutic requirements, it being necessary, of course, to take account of the aspects of economic fabrication. The part which is to IS be detached of the active substance reservoir part can also have a detachment layer which then has greater adhesion to the backing layer than does the detachment layer of the reservoir part remaining on the skin. This design is advantageous when the active substance reservoir parts have the same thickness. The adhesive layers, especially those on the skin side, can, in order to improve active substance permeability, have areas free of adhesive or be designed only as isolated adhesive areas, for example embedded in the active substance reservoir material. The release of the active substances from the active substance reservoir parts can, where appropriate, also be controlled by control membranes which are embedded in the reservoir composition in one or more active substance reservoir part(s) in a manner known per se or are located between active substance reservoir and the adhesive layer on the skin side or else within the adhesive layer on the skin side.

Suitable for constructing an active substance reservoir which can be used according to the invention are the measures and materials familiar to the person skilled in the art; it is possible to use as base materials low and high molecular weight natural and/or synthetic substances chosen on the basis of the properties of the active substances to be administered and of the therapeutic requirements. The active substance reservoir can, besides the base material, also contain other suitable additives which are familiar or obvious to the person skilled in the art on the basis of his expert knowledge, such as, for example, solubilisers, plasticisers, tackifiers, stabilisers, fillers and enhancers. The composition in the reservoir parts can be identical or different, which in turn depends on the active substances to be administered and on the required release rates or the kinetics.

In the case of identical reservoir composition and only one active substance to be administered, a graded concentration level of the active substance in the different reservoir parts may be indicated. Suitable in principle as active substances for the plaster according to the invention are all those which are able, alone or with auxiliaries, to migrate into the skin.

The backing layer which covers the active substance reservoir on the side facing away from the skin can be permeable or impermeable. It must be flexible and serves, because of the mechanical stabilisation of the plaster, for pulling off one part of the active substance reservoir. If components of the reservoir or incorporated active substances are volatile, the backing layer must be impermeable fo these substances. It can be a single layer or a multilayer. Materials suitable for producing it comprise, for example, polymeric substances such as polyethylene, polypropylene, polyesters, and polyamides. Other materials which can be used are also metal foils such as, for example, aluminium foil, alone or coated with a polymeric substrate.

Permeable backing layers are, for example, textile sheetlike structures such as laid and nonwoven fabrics, or else porous polymeric materials. The backing layer can, where appropriate, be marked to Indicate the optimum direction for pulling off the plaster, where appropriate, detachment layers in place of & space are provided between the active substance reservoir parts.

Suitable for them are the same materials as described hereinbefore for the separating layers between active substance reservoir parts and backing layer. The protective layer, which can be detached before application and which covers the adhesive areas on the skin side, can be produced from the sam® materials as used to produce the backing layer, which covers the adhesive areas on the skin side, can be produced from the same materials as used to produce the backing layer, provided that they are made detachable, for exempl® by applying a silicone layer. Other detachable protective layers known to the person skilled in the relevant art of plasters and, in particular, plaster-like therapeutic systems are, for example, polytetrafluoroethylene, treated paper, cellophane, polyvinyl chloride and the like. To make detachment easier, the protective layer can be provided with aids, for pulling off in a manner known per se. The protective layer can also be larger than the plaster, for example when a plurality of plasters is arranged on a continuous web of the protective layer material.

Suitable for the adhesive layers used in the plaster according to the invention are all physiologically acceptable adhesives which are inert to active substances and other active substance reservoir constituents, for example based on rubber, rubber-like synthetic homopolymers, copolymers or block copolymers, polyacrylic esters and their copolymers, polyurethanes and silicones .

Processes of plaster technology known to the person skilled in the art can be used to produce the plasters according to the invention. This is demonstrated by the following example of the production of a plaster with active substance reservoir in two parts. gro^ctio&^exsmple In a roller-application process, an active substancecontaining reservoir material solution is applied to a film which has a repellent finish as intermediate cover and, adhesive layer of 55 g/m1 2. composition: 1. acrylate copolymer I 2. acrylate copolymer II owing to siliconisation and acts after drying at 65 °C, forms an This layer has the following 68.86 parts by weight .39 parts by weight 3. POE(10)oleyl alcohol 4. active substance where the meanings ares acrylate copolymer Is acrylate copolymer Ils POE(10)oleyl alcohols .20 parts by weight 15-56 parts by weight composed of Durotac 280-2516 supplied by National Starch & Chemical B.V.# The Netherlands composed of Eudragit E100 supplied by Rohm Pharma# Germany Brij 97 supplied by Atlas Chemical Industries# GB A non-siliconised polyester film (thickness 0.036 mm) is laminated onto one half of the active substance-containing adhesive layer# and the non-siliconised side of a polyester film siliconised on one side (thickness 0.036 mm) is laminated onto the other half» After the intermediate cover has been pulled off# the annular active substance reservoir parts are punched out of the first half and are placed with the adhesive side on a siliconised aluminium-metallised polyester film (protective layer). Active substance reservoir parts in the form of small discs# which have a diameter slightly smaller than the internal diameter of the rings into which they are inserted centrically with the adhesive side facing the protective layer# are punched out of the second half. The uncovered side of the composite obtained in this way is covered with a backing layer with an adhesive finish (Durotac 280-2516# 30 g/m2 dry) .

Claims (15)

Claras

1. „ Active substance-containing plaster for the controlled administration of active substances onto the skin, which has a backing side and a skin side, with a backing layer,

2. Active substance-containing plaster according to Claim 1, 20 characterised in that the active substance reservoir is in two parts.

3. Active substance-containing plaster according to Claim 1, characterised in that the active substance reservoir is in three parts. 25

4. Active substance-containing plaster according to any of the preceding claims, characterised in that the active substance delivery areas of the active substance reservoir parts are geometrically identical or different.

5. Active substance-containing plaster according to any of the preceding claims, characterised in that an active substance reservoir part completely surrounds one other or several other active substance reservoir part(s) viewed in terms of surface. y 5 with an active substance reservoir which is divided essentially at right angles to the skin contact area of the plaster and has one or more active substances, with an adhesive device on the skin side, and, where appropriate, with a covering layer which can be detached

6. Active substance-containing plaster according to Claim 4 or 5, characterised in that an active substance reservoir part surrounds in the form of a ring one or more other active substance reservoir part(s).

7. Active substance-containing plaster according to any of Claims 1 to 5, characterised in that the delivery area/size ratio of one active substance reservoir part to another is between about Isl to 1:10.

8. Active substance-containing plaster according to any of the preceding claims, characterised in that the same active substance or the same active substance combination is present in all active substance reservoir parts.

9. „ Active substance-containing plaster according to any of Claims 1 to 7,. characterised in that a different active substance/active substance combination is present in at least one active substance reservoir part than in the other active substance reservoir part.

10. » Active substance-containing plaster according to any of the preceding claims, characterised in that the active substances have a topical or systemic action. 10 before application of the plaster, where the active substance delivery area of the plaster can be reduced in sise by a predetermined area by removing a part of the active substance reservoir, characterised in that at least one active substance reservoir part can be detached 15 while leaving one or more active substance reservoir parts on the skin, where the part of the active substance reservoir part remaining on the skin has better adhesion to the skin than to the backing layer.

11. Method for the controlled administration of one or more active substances onto the skin by means of a plaster according to any of the preceding claims, but excepting the therapeutic treatment of the human or animal body or diagnostic methods in human or veterinary medicine. characterised bys adhesion onto the skin of a plaster which,, where appropriate, has a plurality of active substances and/or the same active substance in different or identical concentrations in different active substance reservoir parts which can be separated from one another; pulling off of one or more plaster parts with in each case one or more active substance reservoir parts after a predetermined period with retention of a plaster residue with at least one active substance reservoir part on the skin, and, where appropriate, repetition of the last step after a predetermined period.

12. Use of the active substance-containing plaster according to any of the preceding claims for local and/or systemic transdermal active substance administration In cosmetics.

13. 13. A plaster substantially as hereinbefore described with reference to the accompanying drawings.

14. A method substantially as hereinbefore described with reference to the accompanying drawings.

15. A use substantially as hereinbefore described with reference to the accompanying drawings. Dated this 22nd day of March 1988