Hexagonal self-adhesive layer structure

Abstract

The present invention relates to a self-adhesive layer structure for a medical patch having a hexagonal shape comprising at least one hexagon, a medical patch and a medical patch sheet comprising one or more such self-adhesive layer structures, as well as such medical patches for use in methods of treatment and a method of manufacturing such medical patches.

Description

[0001] TECHNICAL FIELD

[0002] The present invention relates to a self-adhesive layer structure for a medical patch having a hexagonal shape comprising at least one hexagon. Further, the present invention relates to a medical patch comprising a self-adhesive layer structure and to a medical patch sheet comprising two or more self-adhesive layer structures. BACKGROUND

[0004] Medical patches are adhesive patches placed on the skin of a patient to deliver a specific dose of a medicament through the skin.

[0005] For thousands of years, topical application of medicaments to the skin has been the usual treatment for local ailments. Recently, transdermal delivery techniques have been developed to treat a range of ailments beyond the site of topical application. While topical delivery of compounds and / or drugs involves only minimal penetration of the skin layers and thus avoids systemic effects, transdermal medicaments refer to drug compounds that are applied on the skin but penetrate through the outermost layer of the skin (skin barrier) into the bloodstream and / or are used for targeting effects on more distant tissues or organs.

[0006] Therefore, the body location where a medical patch is applied can vary with the therapeutic class of the drug contained therein. Sites where systemic effective transdermal medical patches are placed typically include large and flat surfaces such as the upper arm, chest or back of a patient. In contrast, topical medical patches have to be applied at the site of the ailment to be treated, e.g. the hand or foot of a patient. Due to the surface unevenness and complexity, such application sites are particularly challenging and require considerations depending on the shape and size of the medical patch.

[0007] However, medical patches and in particular topical medical patches are usually only available as large size patches which require cutting according to the application site and / or cannot be applied without wrinkles in order to provide a seamless full coverage of the application site. This is time consuming and requires the application personnel to improve their sticking skills. Wrinkles not only affect the wear comfort and aesthetics of the application site, but the loss of contact area can result in less active agent being utilized and also leads to a reduced adhesion of the patch and is therefore undesirable. Furthermore, cutting the patch bears the risk of contamination as the active agent containing adhesive layer can come into contact with the cutting tool and / or the hand of the person handling the patch.

[0008] For example, the 8% capsaicin patch skin delivery system applied under the trademark QUTENZA® (Grünenthal) suggests to be cut to match the size and shape of the treatment area. QUTENZA® initially covers a rectangular area of 14 cm x 20 cm. The surface system is indicated for the treatment of neuropathic pain associated with postherpetic neuralgia (PHN) and diabetic peripheral neuropathy (DPN) in adults and is currently approved for the treatment of post-surgical neuropathic pain (PSNP) in adults. Thus, it is often applied on the hand and fingers or the lower leg and foot and thus has to be trimmed for small and uneven application surfaces.

[0009] Therefore, it is desirable to provide a self-adhesive layer structure for a medical patch which simplifies the coverage of the skin area to be treated, in particular of challenging and uneven surfaces.

[0010] Invention purposes and contents

[0011] It is an object of the present invention to provide a self-adhesive layer structure for a medical patch which is improved compared to the patches described in the prior art.

[0012] It is a further object of the present invention to provide a self-adhesive layer structure for a medical patch which provides an easy and time-saving handling.

[0013] It is a further object of the present invention to provide a self-adhesive layer structure for a medical patch which allows to simplify the coverage of the application site. In particular, it is an object to provide a self-adhesive layer structure for a medical patch which enables to simplify the coverage of uneven application sites without the need to cut the medical patch before application. In particular, it is an object to provide a self-adhesive layer structure for a medical patch which is improved in promoting a seamless and complete coverage of the application site.

[0014] It is a further object of the present invention to provide a self-adhesive layer structure for a medical patch which reduces wrinkles during application. In particular, it is an object to provide a self-adhesive layer structure for a medical patch which provides sufficient adhesion even on complex skin areas.

[0015] It is a further object of the present invention to provide a self-adhesive layer structure for a medical patch which simplifies the encircling of fingers or toes.

[0016] It is a further object of the present invention to provide a self-adhesive layer structure for a medical patch which allows to cover larger skin areas without leaving gaps.

[0017] These and other objects are achieved by the present invention, according to one aspect, the present invention relates to a self-adhesive layer structure for a medical patch, the self-adhesive layer structure having a hexagonal shape and comprising:

[0018] A) a backing layer; and

[0019] B) an active layer, the active layer comprising a polymer I and an active agent;

[0020] wherein

[0021] the backing layer and the active layer are coextensive and provide the hexagonal shape of the self-adhesive layer structure, and

[0022] the hexagonal shape comprises at least one hexagon, wherein

[0023] each pair of opposite sides of the hexagon is parallel, and

[0024] the sides of the hexagon have a length of 0.2 to 10 cm.

[0025] It has surprisingly been found that the self-adhesive layer structure according to the present invention having a hexagonal shape comprising at least one hexagon with a length of 0.2 to 10 cm has advantageous properties with respect to improved coverage of small and / or uneven application sites of the human body. In particular, it has been found that the hexagonal shape allows for simplified adhesion and reduced wrinkling without the need to cut the medical patch prior to application. Thus, the medical patch is even suitable for problematic application sites, such as hands or feet.

[0026] According to certain embodiments of the present invention, the present invention relates to a medical patch, the medical patch comprising

[0027] a self-adhesive layer structure as described herein and

[0028] a release liner,

[0029] wherein the release liner is coextensive with the self-adhesive layer structure or extends beyond the boundaries of the self-adhesive layer structure in all directions.

[0030] According to certain embodiments of the present invention, the present invention relates to a medical patch sheet, the medical patch sheet comprising

[0031] two or more self-adhesive layer structures as described herein and

[0032] a release liner,

[0033] wherein the release liner is coextensive with the self-adhesive layer structures or extends beyond the boundaries formed by all self-adhesive layer structures in all directions.

[0034] Definitions

[0035] Within the meaning of the present invention, the term "medical patch" refers to a skin delivery system by which an active agent is applied to a patient and which comprises an effective amount of the active agent in a self-adhesive layer structure on a detachable protective layer (release liner). In this context, the term "medical patch" is understood to mean an adhesive patch, which can be a topical medical patch or a transdermal therapeutic system (TTS). Even though topical medical patches as well as TTS are applied topically in the sense that they are attached to the skin of a patient, the term "topical" or "topical application" refers to the application of the active agent by passive diffusion into the skin itself, which leads to a local effect at the site of action. In contrast, the term "TTS" refers to a system which applies the active agent to the systemic circulation via transdermal delivery.

[0036] Within the meaning of the present invention, the term "self-adhesive layer structure" refers to an active agent-containing structure which provides the active agent release area during application. It is "self-adhesive" and thus provides adhesion to the skin, so that usually no further assistance is needed to be fixed on the skin. The self-adhesive layer structure comprises a backing layer and an active layer, and optionally a skin contact layer as described herein. Thus, the self-adhesive layer structure comprises an effective amount of the active agent.

[0037] As used herein, the expression "active agent" refers to any substance of interest to be delivered by the self-adhesive layer structure to provide a beneficial or desired effect on a condition of the body of a subject either systemically or locally at the site of delivery. Active agents specifically include biologically or pharmacologically active compounds, which can also be referred to as active substances, drug substances, drugs, active ingredients, active pharmaceutical ingredients (APIs), etc. In this context, the term "effective amount" or "therapeutically effective amount" refers to an amount of the active agent in the self-adhesive layer structure which is sufficient to provide the desired (therapeutic) effect, such as pain relief, if applied to a patient by the medical patch. TTS usually contain more active agent in the system than is actually provided to the skin and systemic circulation, which is often necessary to provide sufficient driving force to be delivered from the TTS to the systemic circulation.

[0038] Within the meaning of the present invention, the terms "active substance", "active agent" and the like refer to the respective active agent in any pharmaceutically acceptable chemical and morphological form and physical state. These forms include, but are not limited to, the active agent in free base / free acid form, protonated or partially protonated form, deprotonated or partially deprotonated form, salts, co-crystals, and in particular acid / base addition salts formed by the addition of inorganic or organic acids / bases, such as hydrochloride or tartrate, solvates, hydrates, clathrates, complexes, etc., as well as the active agent in particulate form, which can be micronized, crystalline and / or amorphous, and any mixture of the above-mentioned forms.

[0039] When contained in a medium such as a solvent, the active agent can be dissolved or dispersed or partially dissolved and partially dispersed.

[0040] When it is mentioned that the active agent is used in a specific form for the manufacture of the medical patch, this does not exclude an interaction between the active agent in this form and other components of the self-adhesive structure in the final medical patch, such as salt formation or complexation. This means that even if the active agent is included in its free base / acid form, it can be present in the final medical patch in protonated or partially protonated / or deprotonated or partially deprotonated form or in the form of an acid addition salt, or if it is included in the form of a salt, parts of it can be present in the final medical patch as free base. Unless otherwise indicated, the amount of active agent in the self-adhesive structure specifically refers to the amount of active agent included in the medical patch during manufacture of the medical patch and is calculated on the active agent itself and not on other forms. The active agent starting material included in the medical patch during manufacture of the medical patch can be in particulate form. The active agent can be present in the self-adhesive structure, for example, in particulate and / or dissolved form.

[0041] In this context, the term "particulate" refers to a solid particulate material comprising individual particles, which are negligible in size compared to the material. Specifically, the particles are solid, including plastic / deformable solids, including amorphous and crystalline materials. The term "dispersion" refers to a step or combination of steps in which the starting material (e.g. active agent) is not completely dissolved. Dispersion in the sense of the present invention comprises dissolution of a portion of the starting material (e.g. active agent particles), which depends on the solubility of the starting material (e.g. solubility of the active agent in the coating composition).

[0042] There are two main types of medical patches using (passive) active agent delivery, namely matrix-type medical patches and reservoir-type medical patches. The release of the active agent in matrix-type medical patches is mainly controlled by the matrix itself including the active agent. In contrast to this, reservoir-type medical patches usually require a rate controlling membrane to control the release of the active agent. In principle, matrix-type medical patches can also contain a rate controlling membrane. However, matrix-type medical patches are advantageous in that they usually do not require a rate determining membrane and no dose dumping can occur due to a rupture of the membrane. In summary, matrix-type medical patches are less complex to manufacture and easy and convenient to use compared to reservoir-type medical patches.

[0043] In this context, "matrix-type medical patch" is understood to mean a system or structure in which the active agent is uniformly dissolved and / or dispersed within a polymeric carrier, i.e. a matrix, which forms a matrix layer with the active agent and optional remaining ingredients. In such a system, the matrix layer controls the release of the active agent from the medical patch. Preferably, the matrix layer has sufficient cohesion to support so that no sealing between the other layers is required. Thus, the active layer can be an active matrix layer, in which the active agent is uniformly distributed within a polymeric matrix. The active matrix layer can comprise two active agent-containing matrix layers, which can be laminated together. The matrix-type medical patch can in particular be in the form of a "drug-in-adhesive" type medical patch, which means a system in which the active agent is uniformly dissolved and / or dispersed in a pressure-sensitive adhesive matrix. For this reason, the active matrix layer can also be an active pressure-sensitive adhesive layer or an active pressure-sensitive adhesive matrix layer. According to the present application, a medical patch comprising an active agent dissolved and / or dispersed within a polymeric gel, e.g. a hydrogel, is also considered to be matrix-type.

[0044] The term "reservoir-type medical patch" means a medical patch having a liquid active agent-containing reservoir. In such a system, the release of the active agent is preferably controlled by a rate-controlling membrane. In particular, the reservoir is sealed between the backing layer and the rate-controlling membrane. Thus, the active layer can be an active agent reservoir layer, which preferably comprises a liquid reservoir containing the active agent, and wherein the active agent reservoir layer and the skin contact layer can be separated by a rate-controlling membrane. In the active agent reservoir layer, the active agent is preferably dissolved in a solvent such as ethanol or water or in silicone oil.

[0045] Within the meaning of the present application, a reservoir-type medical patch is not to be understood as matrix-type. However, a microreservoir-type medical patch, which is a biphasic system having deposits (e.g. spheres, droplets) of an internal active agent-containing phase dispersed in an external polymeric phase, which is considered in the art as a hybrid form of matrix-type and reservoir-type medical patches, different from the homogeneous monophasic matrix-type and reservoir-type medical patches in the concept of drug transport and drug delivery, is considered to be matrix-type within the meaning of the present application.

[0046] Thus, a microreservoir type medical patch refers to a microreservoir system in which a liquid active agent formulation is dispersed in the adhesive matrix in the form of small droplets ("microreservoirs"). The size of the resulting droplets depends on the stirring conditions and the shear force applied during stirring. It can be determined by light microscopy (e.g. by a Leica MZ16 comprising a camera, e.g. a Leica DSC320) by taking pictures of the microreservoirs at different locations with an enhancement factor between 10 and 400 times according to the required detection limit. By using imaging analysis software, the size of the microreservoirs can be determined. Microreservoir systems are disclosed in U.S. Patent Nos. 3,946,106; 4,053,580; 4,814,184; and 5,145,682, each incorporated herein by reference. A particular microreservoir system is described in International Patent Publication WO 0101967, the disclosure of which is incorporated herein by reference. These microreservoir systems contain polysiloxane as base polymer and an amphiphilic solvent for the microreservoir droplets.

[0047] The self-adhesive layer structure can be a pressure sensitive adhesive layer structure.

[0048] Within the meaning of the present invention, the term "pressure sensitive adhesive" (also abbreviated as "PSA") refers to a material that adheres, in particular with finger pressure, is permanently tacky, exerts a strong holding force, and should be removable from a smooth surface without leaving a residue. It can be obtained after coating a film with a solvent-containing adhesive coating composition and evaporating the solvent (e.g. n-heptane or ethyl acetate). In this context, the term "solvent" is understood to mean any liquid substance, which is preferably a volatile organic liquid such as methanol, ethanol, isopropanol, acetone, ethyl acetate, dichloromethane, hexane, n-heptane, toluene and mixtures thereof. The pressure sensitive adhesive layer is self-adhesive when in contact with the skin. According to certain embodiments, the self-adhesive layer structure according to the present invention comprises a pressure sensitive adhesive layer for contacting the skin, which can be provided in the form of a pressure sensitive adhesive matrix or in the form of another layer, i.e. a pressure sensitive adhesive skin contact layer. An adhesive cover layer can still be used to improve adhesion.

[0049] Within the meaning of the present application, the term "active layer" refers to a layer containing an active agent (active agent-containing layer) and providing a release area. The term encompasses active agent-containing reservoir layers (active reservoir layers) and active agent-containing matrix layers (active matrix layers), and in particular active agent-containing microreservoir layers (active microreservoir layers). If the active layer is an active matrix layer, the layer is present in a matrix-type medical patch. As used herein, the active layer is preferably an active matrix layer, and it refers to the final solidified layer, e.g. the final solidified layer obtained after coating and drying a solvent-containing coating composition as described herein. Alternatively, the active matrix layer is obtained after melt coating and cooling. The active matrix layer can also be manufactured by laminating two or more such solidified layers (e.g. dried or cooled layers) of identical composition to provide the required area weight. According to certain embodiments, the matrix layer is a pressure sensitive adhesive matrix layer.

[0050] Within the meaning of the present application, the term "skin contact layer" refers to a layer that can be included in the self-adhesive layer structure to be in direct contact with the patient's skin during application. In this case, the other layers of the self-adhesive layer structure do not contact the skin and do not necessarily have self-adhesive properties. The skin contact layer is directly attached to the active layer, or a film is located between the active layer and the skin contact layer. In this context, the term "film" is understood to mean a layer provided between the active layer and the skin contact layer and is at least semi-permeable to the active agent. The film can be a microporous film or a non-porous barrier film. Preferred films can be selected from the group consisting of polyethylene films, polyurethane-coated polyethylene terephthalate / polyethylene films, polyurethane films and ethylene vinyl acetate films. Preferably, a further skin contact layer is present as an adhesive layer.

[0051] Within the meaning of the present application, the term "backing layer" refers to a layer that supports the active layer. At least one backing layer in the self-adhesive layer structure of the medical patch, and typically the backing layer of the active layer, is substantially impermeable to the active agent contained in the layer and, optionally, any additives during storage and application, and thus prevents active agent loss or cross-contamination as required by regulations. According to certain embodiments, the backing layer is also barrier, meaning substantially impermeable to water and water vapor. Suitable materials for the backing layer include polyethylene terephthalate (PET), polyethylene (PE), ethylene vinyl acetate copolymer (EVA), polyesters, polyurethanes and mixtures thereof. Suitable backing layers can be siliconized to improve the adhesion of the active layer to the backing layer.

[0052] Furthermore, an adhesive overlay can be present. In this context, the term "adhesive overlay" is understood to mean a self-adhesive layer structure which does not contain active agents and which has a larger area than the self-adhesive layer structure and which provides additional area for adhesion to the skin, but does not provide active agent release area. It thus enhances the overall adhesive properties of the self-adhesive layer structure or medical patch. The area of the adhesive overlay increases the overall size of the medical patch, but does not increase the release area. The adhesive overlay can comprise a self-adhesive polymer or self-adhesive polymer mixture selected from the group of acrylic polymers, polyisobutylenes, styrene-isoprene-styrene copolymers, polysiloxanes and mixtures thereof, which can be the same or different from any polymer or polymer mixture comprised in the self-adhesive layer structure. The adhesive overlay comprises a backing layer and an adhesive layer which can provide occlusive or non-occlusive properties. According to certain embodiments, the backing layer of the adhesive overlay provides non-occlusive properties.

[0053] Within the meaning of the present invention, the term "area weight" refers to the dry weight of a specific layer, e.g. the active layer, in g / m2. 2 Tolerances of the area weight values are ±10%, ±7.5% or ±5% due to manufacturing variability.

[0054] If not indicated otherwise, "%" means wt.% (weight %).

[0055] Within the meaning of the present invention, the term "polymer" (e.g. polymer I or II) refers to any substance which consists of so-called repeating units obtained by polymerization of one or more monomers and includes homo- and copolymers consisting of one type of monomer and copolymers consisting of two or more types of monomers. The polymer can have any architecture, such as linear polymers, star polymers, comb polymers, brush polymers, in case of copolymers with any monomer arrangement, e.g. alternating, statistical, block copolymers or graft polymers. The minimum molecular weight varies depending on the polymer type and is known to the skilled person. The polymer may, for example, have a molecular weight higher than 2000, higher than 5000 or higher than 10,000 Dalton. Correspondingly, compounds with a molecular weight lower than 2000, lower than 5000 or lower than 10,000 Dalton are generally referred to as oligomers.

[0056] Within the meaning of the present invention, the term "silicone-based polymer" refers to a non-hybrid polymer comprising polysiloxane (i.e. a polymer that does not include hybrid substances). Polysiloxanes can be made from a solventless two-component system or in solution in an organic solvent. They exist in two fundamentally different variants: polysiloxanes with free silanol groups and aminoresistant polysiloxanes, which differ in that the free silanol groups are derivatized by trimethylsilyl groups. The methyl groups can be replaced completely or partially by other alkyl groups or, alternatively, by phenyl groups. Polysiloxanes as used herein are synthesized from linear difunctional and branched multifunctional oligomers, the ratio of which determines their physical properties. More multifunctional oligomers result in adhesives with higher cohesion and reduced crosslinking degree of adhesion, less multifunctional oligomers result in higher adhesion and reduced cohesion. The silicone-based polymer is preferably a mixture of high-tack and medium-tack or high-tack and low-tack polysiloxanes. According to certain embodiments, at least one silicone-based polymer is a silicone-based pressure sensitive adhesive.

[0057] Within the meaning of the present invention, the term "acrylic polymer" refers to a non-hybrid polymer based on acrylates. It can be a polymer obtainable from one or more monomers selected from acrylic acid, butyl acrylate, 2-ethylhexyl acrylate, glycidyl methacrylate, 2-hydroxyethyl acrylate, methyl acrylate, methyl methacrylate, butyl methacrylate, t-octyl acrylamide, and vinyl acetate.

[0058] Within the meaning of the present invention, the term "silicone-acrylic hybrid polymer" refers to a hybrid polymer based on silicone and acrylate in the form of a pressure sensitive adhesive. Silicone acrylic hybrid pressure sensitive adhesives are described, for example, in EP 2 599 847 and WO 2016 / 130408. It has been found that depending on the solvent in which the silicone acrylic hybrid PSA is provided, the arrangement of the silicone phase and the acrylic phase providing a continuous outer phase of silicone or acrylic and the corresponding discontinuous inner phase of acrylic or silicone, respectively, is different. If the silicone acrylic hybrid PSA is provided in n-heptane, the composition contains a continuous silicone outer phase and a discontinuous acrylic inner phase. If the silicone acrylic hybrid PSA composition is provided in ethyl acetate, the composition contains a continuous acrylic outer phase and a discontinuous silicone inner phase.

[0059] Within the meaning of the present application, the term "natural or synthetic rubber" refers to elastomers that can be obtained by polymerization of unsaturated hydrocarbons such as isoprene (2-methyl-1,3-butadiene) or by copolymerization of such hydrocarbons with styrene, butadiene, etc. It includes natural and synthetic polyisoprene, polybutene and polyisobutylene, styrene / butadiene polymers, styrene-isoprene-styrene block copolymers, hydrocarbon polymers such as butyl rubber, halogen-containing polymers such as polyacrylonitrile, polytetrafluoroethylene, polyvinyl chloride, polyvinylidene chloride and polychlorodiolefin, and other copolymers thereof. In certain embodiments, the natural or synthetic rubber can be a styrene tri-block copolymer or a polyisobutylene.

[0060] Within the meaning of the present application, the term "polyisobutylene" refers to a polymer obtained by polymerization of isobutylene.

[0061] Within the meaning of the present application, the term "styrene-isoprene-styrene block copolymer" refers to a polymer obtained by active ion copolymerization by sequential introduction of styrene, 2-methyl-1,3-butadiene (isoprene) and styrene into a reactor. The styrene content typically varies between 15% and 40%.

[0062] Within the meaning of the present application, the term "silicone gel adhesive" refers to an elastic, jelly-like material formed by lightly crosslinking silicone polymers. It can be prepared from a gel-producing composition as further described below after curing. In particular, a silicone gel adhesive is formed after curing of a polysiloxane comprising reactive groups such as Si-H reactive groups and aliphatic unsaturated groups that react with each other in the presence of a hydrosilylation catalyst. According to certain embodiments, the silicone gel adhesive is based on a polydimethylsiloxane network that can be formed in an addition reaction (hydrosilylation) between a vinyl-functional polydimethylsiloxane group (polymer) and a hydrogen-functional siloxane (crosslinker). Thus, the silicone gel adhesive is typically applied by using a curable gel (2-component) composition that sets after curing.

[0063] Within the meaning of the present application, the term "saturated concentration" refers to the active agent concentration corresponding to an equilibrium state in which the solvent, i.e. the polymer II of the skin contact layer, cannot further dissolve the solute, i.e. the active agent, and thus, at a defined temperature (room temperature, the unaltered temperature found in the laboratory where the experiment is performed, and typically within 15 to 35 °C or about 18 to 25 °C), the solid solute is in equilibrium with the solid solution. The saturated concentration of the active agent can be expressed in weight % based on the total weight of the active agent layer or the skin contact layer, respectively. The saturated concentration can be determined, for example, using the method described by Liu, P., Gargiulo, P., Wong, J. and Novartis. Pharm. Research. Vol. 14, p. 317 (1997), herein referred to as the "sandwich method", wherein a multi-layered laminate is prepared comprising an upper and a lower protective layer sandwiched between a donor layer and an acceptor layer, which are separated by a barrier film permeable to the active agent. As the donor layer contains an excess of the active agent and the acceptor layer is essentially free of the active agent, the active agent diffuses from the donor layer through the barrier film into the acceptor layer until the saturated concentration is achieved. The donor and acceptor layers are manufactured from the respective polymer II of the skin contact layer. The donor layer is supersaturated with the active agent, while the acceptor layer is prepared analogously to the donor layer, but does not comprise the active agent. The prepared sandwich system is stored at room temperature for a certain time, for example 7 days, to allow the active agent to diffuse from the donor layer into the acceptor layer. Then, the remaining active agent concentration of the donor layer is determined by means of HPLC (high performance liquid chromatography) to finally obtain the saturated concentration of the active agent in the respective polymer II of the skin contact layer.

[0064] As used herein, the solubility parameter (SP) is defined as the sum of all intermolecular attractions as a numerical estimate related empirically to the degree of mutual solubility of chemical substances. The most convenient method of determining the solubility parameter is the Hildebrand method, which calculates the solubility parameter from molecular weight, boiling point, and density data, which are generally available for many materials: SP = (ΔE v / V) 1 / 2 where V = molecular weight / density, and ΔE v = energy of evaporation. For materials, such as high molecular weight polymers, for which the vapor pressure is too low to be measured, several methods have been developed which use a summation of the contributions of atoms and groups to the energy of evaporation. Such methods of calculating the solubility parameter of materials have been described, for example, by Small, J. Applied Chem. Vol. 3, p. 71 (1953). Some solubility parameters (calculated by the Small method) of exemplary polymers useful in the practice of the present application are as follows: polydimethylsiloxane 14.9 MPa 1 / 2, polyisobutylene 15.7 MPa 1 / 2 , polyethylene / butene 16.2 MPa 1 / 2 , polyisoprene 16.6 MPa 1 / 2 , polyethylene 16.6 MPa 1 / 2 , polybutadiene 16.6 MPa 1 / 2 , polybutadiene-co-styrene (75 / 25 to 72 / 28) 17.4 MPa 1 / 2 , polystyrene 18.6MPa 1 / 2 , polymethyl methacrylate 19.0 MPa 1 / 2 , polymethyl acrylate 19.8 MPa 1 / 2 .

[0065] Within the meaning of the present invention, the term "soluble polyvinyl pyrrolidone" refers to polyvinyl pyrrolidone, also known as povidone, which is soluble in at least ethanol, preferably also in water, diethylene glycol, methanol, n-propanol, 2-propanol, n-butanol, chloroform, methylene chloride, 2-pyrrolidone, polyethylene glycol 400, 1,2 propylene glycol, 1,4 butylene glycol, glycerol, triethanolamine, propionic acid and acetic acid in an amount greater than 10%. Examples of commercially available polyvinyl pyrrolidone include Kollidon® 12PF, Kollidon® 17PF, Kollidon® 25, Kollidon® 30 and Kollidon® 90 F, or povidone K90F, supplied by BASF. The different grades of Kollidon® are determined by the K value, which reflects the average molecular weight of the polyvinyl pyrrolidone grade. Kollidon® 12 PF is characterized by a K value range of 10.2 to 13.8, corresponding to a nominal K value of 12. Kollidon® 17 PF is characterized by a K value range of 15.3 to 18.4, corresponding to a nominal K value of 17. Kollidon® 25 is characterized by a K value range of 22.5 to 27.0, corresponding to a nominal K value of 25, and Kollidon® 30 is characterized by a K value range of 27.0 to 32.4, corresponding to a nominal K value of 30. Kollidon® 90 F is characterized by a K value range of 81.0 to 97.2, corresponding to a nominal K value of 90. Preferred Kollidon® grades are Kollidon® 12 PF, Kollidon® 30, and Kollidon® 90 F. In this context, the term "K value" refers to the value calculated from the relative viscosity of polyvinylpyrrolidone in water according to the European Pharmacopoeia (Ph. Eur.) and the USP "Polyvidone" monograph. For all grades and types of polyvinylpyrrolidone, the amount of peroxide is preferably within certain limits, in particular, the amount of peroxide is equal to or less than 500 ppm, more preferably equal to or less than 150 ppm and most preferably equal to or less than 100 ppm.

[0066] Within the meaning of the present invention, the term "hexagonal shape" refers to the two-dimensional shape of the self-adhesive layer structure, which is provided by the backing layer and the active layer or by the backing layer, the active layer and the skin contact layer, respectively, and which can be seen when looking onto the self-adhesive layer structure from above the backing layer. In the sense of the present invention, a hexagonal shape is understood as any shape which can be formed by one hexagon or by an aggregation of two or more hexagons. This means that the hexagonal shape according to the present invention does not need to have the shape of a hexagon as a whole, but is composed of at least one hexagon. The vertices of the hexagonal shape can be pointed or rounded. If two or more hexagons compose the hexagonal shape, they can be integrally connected to each other, i.e. separable only by e.g. cutting the self-adhesive layer structure, or they can be separably connected to each other using e.g. perforation lines. The backing layer and the active layer or the backing layer, the active layer and the skin contact layer, respectively, and optionally the film are coextensive, i.e. they have the same planar extent and / or share the same boundaries. In other words, the backing layer and the active layer or the backing layer, the active layer and the skin contact layer, respectively, and optionally the film each provide a shape in the form of at least one congruent hexagon.

[0067] Within the meaning of the present invention, the term "hexagon" refers to a six-sided polygon. In a "convex hexagon", each of the six points (vertices) where pairs of sides intersect points outward. Two adjacent vertices are each connected by one of the six sides (a common side). Non-adjacent vertices can be connected by one of the nine diagonals that lie within the closed hexagonal chain (the boundary) of the convex hexagon. A convex hexagon requires the least total length of boundary compared to other polygons of the same area.

[0068] A convex hexagon can also be described as a six-sided polygon with each interior angle (apex angle) less than 180°. The sum of the interior angles of any simple (non-self-intersecting) hexagon is 720°. Thus, a (convex) hexagon with each apex angle equal to 120° is also called an equiangular hexagon. A (convex) hexagon with all sides equal is also called an equilateral hexagon. If a (convex) hexagon is equilateral and equiangular, it is also called a regular hexagon.

[0069] A (convex) hexagon can be symmetric, in particular mirror-symmetric or rotationally symmetric. Mirror-symmetry (also called reflection-symmetry) is understood in this context to mean symmetry with respect to reflection. This symmetry function of a two-dimensional shape is that if the shape is folded in half over a mirror axis, the two halves will be identical: the halves are mirror images of each other. Thus, a regular hexagon has six axes of symmetry, because there are six different ways to fold it and have all the sides match up. An n-fold rotational symmetry (also called n-fold rotational symmetry) of a two-dimensional shape with respect to a particular point is understood in this context to mean that a rotation by an angle of 360° / n (180°, 120°, 90°, 72°, 60°, etc.) does not change the shape. Thus, a regular hexagon has 6-fold rotational symmetry, because it looks the same after each partial rotation by an angle of 60°.

[0070] Within the meaning of the present invention, the term “parallelogon” refers to a (convex) hexagon, wherein each pair of opposite edges (two edges are separated from each other by the same number of edges in both boundary directions, i.e. in a hexagon by two edges) are parallel, and the two edges of each pair of parallel opposite edges are of equal length. This includes parallelogons having in total three different edge lengths or in total only two different edge lengths, as well as parallelogons in which all edges are of equal length. The term “parallelogon” includes shapes obtained, for example, by elongating a parallelogram, or by elongating a rhombus, and in particular shapes obtained by splitting a parallelogram or a rhombus, respectively, at two non-adjacent vertices thereof and introducing a pair of parallel opposite edges of equal length. Within this context, the term “parallelogram” is understood to mean a simple four-sided polygon having two pairs of parallel edges. A parallelogram is also called a “rhombus” if the four edges are of equal length.

[0071] Within the meaning of the present invention, the term “aspect ratio” refers to the height-to-width ratio, wherein the width and the length are the distances between two points on the boundary of the (convex) hexagon, and the longer of the two distances is considered to be the width. Within this context, the width of the (convex) hexagon is understood to mean the length of the longest distance between any two points on the boundary, which is typically the length of the longest diagonal between two opposite vertices of the (convex) hexagon. The height of the (convex) hexagon is understood to mean the longest distance obtainable between any two points on the boundary of the (convex) hexagon such that the line formed by connecting these two points is perpendicular to the line formed by connecting the two points defining the width (see above). The aspect ratio corresponds to the ratio of the radius of the inscribed circle (radius of the incircle) to the radius of the circumscribed circle (radius of the circumcircle), if obtainable. The aspect ratio of a regular hexagon is √3:2.

[0072] Hexagons fit together to tile a plane in a honeycomb pattern. The honeycomb pattern consists of hexagons arranged side by side that tile the plane, i.e. completely fill the entire surface they span, without any holes between them. This is because the 120° angle is the angle at which the edges of the hexagons meet when arranged side by side, so that exactly three hexagons meet at each vertex. The honeycomb pattern occurs not only in honeycombs, but also in many other places in nature, for example in organic compounds (benzyl rings, proteins).

[0073] Hexagonal tiling (also known as hexagonal tessellation) is a regular tiling of the Euclidean plane by congruent convex hexagons. In addition to using regular hexagons ( Figure 1a ), hexagonal tiling can also be done with other (hexagonal) parallelogons, in particular parallelogons obtained by elongating rhombi ( Figure 1b ) or parallelograms ( Figure 1c ). Such hexagonal shapes can tile the Euclidean plane by translation. Other hexagonal shapes can tile the plane in different orientations. In this context, the term "tile a plane" is understood to mean cover a particular plane (flat surface or curved surface) without leaving any gaps. According to the present invention, tiling a plane can be done with overlapping or non-overlapping adjacent self-adhesive layer structures. Preferably, overlapping is avoided as much as possible.

[0074] Within the meaning of the present invention, the term "patch of medical patches" refers to a plurality of medical patches sharing one common release liner. Each medical patch represents an individual dosage unit that can be applied to the skin of a patient after peeling off from the release liner. The amount of active agent contained in a medical patch refers to the amount of active agent contained in the self-adhesive layer structure of the medical patch. The amount of active agent contained in a patch of medical patches refers to the total amount of active agent contained in all self-adhesive layer structures of the medical patches that make up the patch of medical patches. Thus, the release area of a medical patch refers to the area provided by the self-adhesive layer structure of the medical patch, and the release area of a patch of medical patches refers to the area provided by all self-adhesive layer structures of the medical patches that make up the patch of medical patches.

[0075] Within the meaning of the present application, the term "release liner" refers to a detachable protective layer attached to the active layer or skin contact layer of one or more self-adhesive layer structures. The release liner can have any suitable two-dimensional geometry and is preferably of polygonal shape, in particular rectangular or square shape. According to certain embodiments, the area of the release liner encompasses the total area of all self-adhesive layer structures of the medicated patch constituting the medicated patch sheet. According to the present application, the release liner is coextensive with the self-adhesive layer structures or extends beyond the boundary formed by all self-adhesive layer structures in all directions, i.e. the polygonal chain formed by the outer sides of the hexagons of the self-adhesive layer structures is completely located within or on the polygonal chain formed by the sides of the release liner. Suitable release liners can be polyethylene terephthalate (PET) or polypropylene (PP) films, optionally provided with a silicone or a fluorescent polymer coating. This includes, for example, commercially available release liners such as Scotchpak® 9741 / 9742 / 9744 from 3M. ® Release liner 9741 / 9742 / 9744.

[0076] Within the meaning of the present application, the term "weakened" refers to the result of any action (weakening) that makes two portions of a self-adhesive layer structure or two different self-adhesive layer structures more easily separable, although the two portions / self-adhesive layer structures are still connected to each other. Such weakening can include, but is not limited to, folding, scratching, perforating, puncturing, piercing, punching or cutting. According to certain embodiments, weakening is performed by perforation. In this context, the term "perforation" is understood to mean the making of small holes therein. Perforation can be obtained by, for example, needle pricking or laser cutting.

[0077] Within the meaning of the present application, the term "linking bridge" refers to a single point between two or three self-adhesive layer structures, in particular between two or three hexagonal shapes (such as two or three convex hexagons or two or three convex double hexagons), at which they are still connected, while a major portion of the common side is cut or weakened. It is preferably obtained by remaining connected during the separation process, which can be performed by, for example, punching or cutting. One or more linking bridges enable the self-adhesive layer structures connected in this way to be peeled off jointly from the release liner. Furthermore, one or more linking bridges are preferably so thin that they can easily be untied, for example by pulling a portion of the self-adhesive layer structure, in order to separate some self-adhesive layer structures from other active agent-containing layer structures.

[0078] Within the meaning of the present application, the term "patient" refers to a subject who has shown clinical manifestations of one or more specific symptoms indicating a need for treatment, who is treated prophylactically or preventively against a disorder or who has been diagnosed with a disorder to be treated. Preferably, the patient suffers from neuropathic or mixed neuropathic and / or nociceptive pain, such as joint pain or cancer pain.

[0079] The term "neuropathic pain" refers to pain caused by lesions or diseases of the somatosensory nervous system. In this context, the term "chronic neuropathic pain" is to be understood to mean neuropathic pain lasting for at least three months. When suffering from neuropathic pain, most patients complain of spontaneous pain of continuous or intermittent, e.g. burning, shooting, squeezing nature, which can be accompanied by evoked pain, in particular to light touch and cold. E.g. neuromas of nerve endings, compressed nerves or nerve roots, dorsal root ganglia and ectopic activity in the thalamus can constitute the basis for spontaneous pain in different conditions. Neuropathic pain includes peripheral neuropathic pain, which particularly affects peripheral nerves, meaning nerves outside the brain and spinal cord. In particular, neuropathic pain within the meaning of the present invention relates to postoperative neuropathic pain as well as neuropathic pain associated with post-herpetic neuralgia or diabetic peripheral neuropathy of the hand or foot.

[0080] In this context, the term "postoperative neuropathic pain" is to be understood to mean chronic pain that develops after a surgical procedure and persists beyond the healing process, i.e. for at least three months after surgery. The pain is localized to the surgical or injury area, projects to the innervation area located in this area, or involves a dermatome (after surgery / injury of deep somatic or visceral tissue). Chronic postoperative pain is a result of nerve damage and can be attributed to the surgery itself or other pain causes, including infections, malignancies, etc.

[0081] In this context, the term "post-herpetic neuralgia" (also called post-herpetic neuralgia) is to be understood to mean pain that occurs if nerves are damaged due to a previous herpes zoster infection, commonly known as shingles. Symptoms of post-herpetic neuralgia are often confined to or localized in the area of skin where the first outbreak of shingles occurred in a band around the torso, usually on one side of the body. Less common symptoms of post-herpetic neuralgia include itching, numbness, or a "pins and needles" sensation.

[0082] In this context, the term "diabetic peripheral neuropathy" (also called "diabetic neuralgia") is to be understood to mean pain that occurs if nerves are damaged due to diabetes. While diabetic neuropathic pain can affect any nerve, it is most commonly seen in the extremities, such as the hands or feet.

[0083] Within the meaning of the present application, the term "joint pain" refers to discomfort, pain or soreness of any joint of the patient's body, including the spine, the shoulders, the hips, the elbows and the knees. This includes in particular joint pain caused by arthritis, such as osteoarthritis. In this context, the term "osteoarthritis" is understood to mean a degenerative disease characterized by erosion of the cartilage, bone hypertrophy, subchondral sclerosis and synovial and bursal changes. Its clinical features are joint pain, stiffness and limited function. While the pain of osteoarthritis is traditionally considered nociceptive, some patients also have neuropathic pain. Joint pain can be in particular knee pain, elbow pain, hip pain, shoulder pain, hand or foot pain or (lower) back pain.

[0084] Within the meaning of the present application, the term "cancer pain" relates to neuropathic cancer pain caused by nerve injury attributable to the cancer itself and / or treatment including chemotherapy, radiotherapy and surgery. Cancer pain caused by the tumor itself usually involves both nociceptive and neuropathic components, and mixed pain is more common than neuropathic cancer pain caused by cancer treatment. Most cancer pain caused by chemotherapy is purely neuropathic in nature. Neuropathic cancer pain is nerve-related (usually neuron-related) pain characterized by a burning or electric shock sensation; however, it is sometimes manifested as a decrease in sensation or actual muscle weakness.

[0085] Within the meaning of the present application, the term "coating composition" refers to a composition comprising all components of the active layer or the skin contact layer, respectively, which can be coated onto the backing layer or release liner to form the active layer and the skin contact layer upon drying.

[0086] Within the meaning of the present application, the term "dissolution" refers to the process of obtaining a solution which is clear and free of any visible particles.

[0087] Within the meaning of the present application, the term "crosslinking" refers to the process of crosslinking the functional groups contained within the coating composition not containing active agents.

[0088] Within the meaning of the present application and unless indicated otherwise, the term "about" refers to an amount ± 10% of the amount disclosed. In some embodiments, the term "about" refers to an amount ± 5% of the amount disclosed. In some embodiments, the term "about" refers to an amount ± 2% of the amount disclosed. BRIEF DESCRIPTION OF DRAWINGS

[0089] Figure 1a A hexagonal tiling of regular hexagons is shown.

[0090] Figure 1b A hexagonal tiling of parallelograms obtained by elongating rhombi is shown.

[0091] Figure 1cA hexagonal tiling of parallelogons obtained by elongating parallelograms is shown.

[0092] Figure 2a An exemplary pattern of a medical patch sheet according to the present application is shown, wherein the self-adhesive layer structure is a regular hexagon.

[0093] Figure 2b An exemplary pattern of a medical patch sheet according to the present application is shown, wherein the self-adhesive layer structure is a double hexagon formed by two identical regular hexagons sharing two adjacent vertices and their common edge.

[0094] Figure 2c An exemplary pattern of a medical patch sheet according to the present application is shown, wherein the self-adhesive layer structure is selected from a regular hexagon and a double hexagon formed by two identical regular hexagons sharing two adjacent vertices and their common edge.

[0095] Figure 3 An exemplary pattern of a medical patch sheet according to the present application is shown, wherein the self-adhesive layer structure is a regular hexagon, said regular hexagons being connected to each other by common junctional bridges, wherein adjacent self-adhesive layer structures are all connected to each other in groups of three by common junctional bridges provided at common vertices. DETAILED DESCRIPTION

[0096] Self-adhesive layer structure

[0097] The present application relates to a self-adhesive layer structure for a medical patch, in particular for the administration of an active agent contained therein. In certain embodiments, the self-adhesive layer structure is a pressure sensitive adhesive layer structure.

[0098] The self-adhesive layer structure, in particular the pressure sensitive adhesive layer structure, according to the present application has a hexagonal shape and comprises:

[0099] A) a backing layer; and

[0100] B) an active layer, said active layer comprising a polymer I and an active agent;

[0101] wherein the backing layer and the active layer jointly extend and provide the hexagonal shape of the self-adhesive layer structure.

[0102] In certain embodiments, the self-adhesive layer structure comprises

[0103] A) a backing layer;

[0104] B) an active layer, said active layer comprising a polymer I and an active agent; and

[0105] C) a skin contact layer;

[0106] wherein the backing layer, the active layer and the skin contact layer collectively extend and provide the hexagonal shape of the self-adhesive layer structure.

[0107] In such embodiments, the self-adhesive layer structure can or can not comprise a film located between the active layer and the skin contact layer. The film is preferably a rate controlling film.

[0108] In certain embodiments, the above-mentioned layers of the self-adhesive layer structure according to the present application are directly attached to each other, i.e. the backing layer is directly attached to the active layer, and optionally the active layer is directly attached to another skin contact layer. Alternatively, the active layer is directly attached to a film, which is directly attached on the other side to another skin contact layer. In other words, the self-adhesive layer structure according to the present application comprises its layers in the following order: (1) backing layer, (2) active layer, and optionally (3) skin contact layer, or (1) backing layer, (2) active layer, optionally (3) film, and optionally (4) skin contact layer.

[0109] The optional further skin contact layer preferably provides adhesion between the self-adhesive layer structure and the patient's skin during application. If the self-adhesive layer structure according to the present application does not comprise a further skin contact layer, sufficient adhesion between the self-adhesive layer structure and the patient's skin during application is provided by other means, e.g. the active layer and / or an adhesive cover layer.

[0110] In particular, the backing layer is substantially impermeable to the active agent. It can consist of a polyester film, preferably having a thickness of 10-20 μm, or of an ethylene-vinyl acetate copolymer.

[0111] In certain embodiments, the self-adhesive layer structure is used for transdermal or topical delivery of the active agent. In particular embodiments, the self-adhesive layer structure is used for topical delivery of the active agent.

[0112] The self-adhesive layer structure according to the present application can be used in a matrix-type medical patch or a reservoir-type medical patch, and is preferably a matrix-type medical patch. In certain embodiments, the self-adhesive layer structure according to the present application is used in a matrix-type medical patch, wherein the active agent is uniformly dissolved and / or dispersed within a polymeric carrier, i.e. matrix, which together with the active agent and optionally other additives forms the matrix layer. Thus, the active layer is preferably an active matrix layer. Accordingly, in certain embodiments of the self-adhesive layer structure according to the present application, the active layer is an active matrix layer, which comprises

[0113] (i) a polymer I, and

[0114] (ii) an active agent.

[0115] In particular embodiments, the self-adhesive layer structure according to the present application is used in a microreservoir-type medical patch. Thus, the active layer is preferably a microreservoir active layer, in particular a dry biphasic layer, which has

[0116] (i) an outer phase comprising polymer I, and

[0117] (ii) an inner phase comprising an active agent,

[0118] wherein the inner phase forms a dispersed deposit in the outer phase.

[0119] The self-adhesive layer structure according to the present application is typically located on a separable protective layer (release liner), which is removed from the active agent-containing layer structure immediately prior to application to the skin surface of a patient. Thus, the self-adhesive layer structure or medical patch can further comprise a release liner. The self-adhesive layer structure or medical patch thus protected is typically stored in a seam-sealed pouch. The packaging can be child-resistant and / or senior-friendly.

[0120] Active layer

[0121] As outlined in more detail above, the self-adhesive layer structure according to the present application comprises, inter alia, an active layer, which comprises

[0122] (i) polymer I, and

[0123] (ii) an active agent.

[0124] The active agent is preferably homogeneously distributed within the active layer. In particular embodiments, the active layer is an active matrix layer, in particular a microreservoir active layer.

[0125] Thus, in certain embodiments of the self-adhesive layer structure, the active layer is a dry biphasic layer, which has

[0126] (i) an outer phase comprising polymer I, and

[0127] (ii) an inner phase comprising an active agent,

[0128] wherein the inner phase forms a dispersed deposit in the outer phase.

[0129] In certain embodiments, the outer phase is hydrophobic and the inner phase is hydrophilic.

[0130] The outer phase of the dry biphasic layer preferably has a composition comprising 75% to 100% of polymer I. The inner phase preferably has a composition comprising an active agent and a hydrophilic agent forming a solution with the active agent. The hydrophilic agent can be a hydrophilic polymer or polymer mixture, which is in particular selected from the group consisting of polyvinylpyrrolidone having a K value of 10 to 200; copolymers of vinylcaprolactam, vinyl acetate and ethylene glycol; copolymers of vinylpyrrolidone and vinyl acetate; copolymers of ethylene and vinyl acetate; polyethylene glycol; polypropylene glycol; acrylic polymers; and modified celluloses.

[0131] The dry biphasic layer can further comprise an interfacial medium, in particular having a dynamic viscosity of 10 cSt to 100 000 cSt at 25 °C. The interfacial medium can be present in the dry biphasic layer in an amount of 0.1 % to 3.5 % and serves to reduce the maximum droplet size of the dispersed sediment of the inner phase in the outer phase in the dry biphasic layer. Without wishing to be bound by any theory, it is believed that this effect is achieved by filling cavities between the dispersed inner phase and the outer phase at the interface and thereby enhancing the compatibility of the two separate phases and facilitating the maximum separation / dispersion of the inner phase in the outer phase. Suitable interfacial media include, for example, silicone oil.

[0132] The polymer I contained in the active layer provides sufficient cohesion within the active layer. According to certain embodiments, the polymer I can also provide sufficient adhesion of the self-adhesive layer structure to the patient's skin during application. In these embodiments, the polymer I is selected from pressure sensitive adhesive polymers. Thus, in certain embodiments, the polymer I is a pressure sensitive adhesive polymer.

[0133] Polymers suitable as polymer I according to the present application can be selected from silicone-based polymers, acrylic polymers, silicone-acrylic hybrid polymers and polymers based on natural or synthetic rubbers, such as polyisobutylene or styrene-isoprene-styrene block copolymers, which are described in more detail below. In certain embodiments, the polymer is selected from silicone-based polymers. In particular embodiments, the polymer is a silicone-based polymer obtainable by polycondensation of a silanol-terminated polydimethylsiloxane with a silicate resin.

[0134] Further, in certain embodiments, the area weight of the active layer is in the range of 20 to 400 g / m 2 , 30 to 200 g / m 2 or 50 to 120 g / m 2 .

[0135] Active agent

[0136] According to the present application, the self-adhesive layer structure comprises an active layer, which comprises an active agent.

[0137] The active agent can be any compound responsible for one or more therapeutic effects of a medical patch comprising the self-adhesive layer structure. In particular, the active agent can be a topical or a systemic active agent. In certain embodiments, the active agent is at least one analgesic agent. Suitable analgesic agents include, for example, buprenorphine, capsaicin, diclophenac, fentanyl, ibuprofen or lidocaine.

[0138] According to certain embodiments, the active agent is a TRPV1 agonist, such as capsaicin.

[0139] In one embodiment, the active agent is capsaicin. Thus, the self-adhesive layer structure can comprise

[0140] A) a backing layer; and

[0141] B) an active layer, the active layer comprising

[0142] (i) a polymer I, and

[0143] (ii) capsaicin.

[0144] In particular, the self-adhesive layer structure comprises a therapeutically effective amount of capsaicin. In certain embodiments, the self-adhesive layer structure comprises capsaicin in an amount of 0.5 to 180 mg, 1.2 to 90 mg, or 19 to 45 mg. In some embodiments, the self-adhesive layer structure comprises capsaicin in an amount of about 179 mg. In other embodiments, the self-adhesive layer structure comprises capsaicin in an amount of about 60 mg, about 45 mg, about 30 mg, about 25 mg, about 10 mg, or about 1 mg.

[0145] Thus, the specific active layer according to the present application comprises

[0146] (i) a polymer I, and

[0147] (ii) capsaicin.

[0148] The active layer can contain at least 0.30 mg, at least 0.50 mg, or at least 0.60 mg capsaicin per cm2of release area, and / or less than 1.0 mg, less than 0.8 mg, or less than 0.7 mg capsaicin per cm2of release area. In particular, the active layer contains 0.30 mg to 1.0 mg, 0.30 mg to 8.0 mg, 0.50 mg to 8.0 mg, 0.60 mg to 0.8 mg, or 0.60 mg to 0.7 mg capsaicin per cm2of release area.

[0149] In certain embodiments, the active layer comprises capsaicin in an amount of 2 to 20 wt%, 5 to 15 wt%, or 5 to 10 wt%. In particular embodiments, the active layer comprises capsaicin in an amount of about 8 wt%.

[0150] Additionally, the active layer can comprise at least one silicone-based polymer in an amount of 20 to 90 weight percent or 60 to 90 weight percent, based on the total weight of the active layer. It will be appreciated that the above weight percent amounts refer to the total amount of at least one silicone-based polymer. For example, if there are two silicone-based polymers, the total amount in the active layer is 20 to 90 weight percent or 60 to 90 weight percent, based on the total weight of the active layer.

[0151] Thus, in one embodiment, the self-adhesive layer structure is used for transdermal or topical delivery of capsaicin, in particular for topical delivery of capsaicin.

[0152] Capsaicin ((6E)-N-[(4-hydroxy-3-methoxyphenyl)methyl]-8-methylnon-6- enamide) is the major biologically active component of chili peppers and is an alkaloid found in the Capsicum family. It is a potent agonist of the transient receptor potential cation channel subfamily V member 1 (TRPV1), better known as the vanilloid receptor. By binding to the TRPV1 receptor, the capsaicin molecule creates a sensation similar to over-heating or chafing. Capsaicin has an effect as a non-narcotic analgesic and is currently used to treat several pain syndromes, such as neuropathic pain. This pain is believed to be caused by sensitization in the peripheral and central nervous system and can occur as a result of peripheral injury or as a result of systemic disease, such as HIV, shingles, syphilis, autoimmune diseases, and diabetes. In addition, capsaicin also shows beneficial effects on pain relief in osteoarthritis due to its strong ability to inhibit the release of substance P, a potent neuropeptide pain modulator from sensory nerves to the central nervous system. Furthermore, capsaicin is believed to be able to kill cancer cells by subjecting them to apoptosis.

[0153] The active agent, in particular capsaicin, can be present in the active layer in an amount of 1 to 25 weight percent, 2 to 20 weight percent, or 5 to 10 weight percent.

[0154] Skin contact layer

[0155] As outlined in more detail above, the self-adhesive layer structure according to the present application can additionally comprise a skin contact layer. In this case, the backing layer and the active layer as well as the skin contact layer jointly extend and provide the hexagonal shape of the self-adhesive layer structure. In certain embodiments, the skin contact layer is an adhesive, in particular a pressure sensitive adhesive, and provides adhesion between the self-adhesive layer structure and the skin of the patient during application.

[0156] It has surprisingly been found that a self-adhesive layer structure comprising a skin contact layer in which the active agent is sparingly soluble and preferably directly attached to the active layer has advantageous properties with respect to reducing skin irritation, but at the same time has improved drug delivery behavior and adhesive properties. In particular, since the active agent is sparingly soluble, e.g. has a saturation concentration in the skin contact layer of less than 0.1 %, only insignificant amounts of the active agent are present on the surface of the skin contact layer, such that the medical patch has advantageous properties with respect to unwanted skin reactions and can thus be applied and / or removed safely. Thus, such a self-adhesive layer structure with a skin contact layer in which the saturation concentration of the active agent is negligible and a separate active layer (not in contact with the skin) prevents the release of the active agent before and / or after the self-adhesive layer structure is applied to the patient's skin and remains on the patient's skin. On the other hand, it has been found that such a self-adhesive layer structure with a skin contact layer is still able to provide sufficient drug delivery and even allows a faster release of the active agent.

[0157] Thus, such a self-adhesive layer structure comprising a skin contact layer is characterized, inter alia, by a low solubility of the active agent in the skin contact layer, and in certain embodiments, the saturation concentration of capsaicin in the skin contact layer is preferably less than 0.1 wt.%, as determined by the "sandwich method". In certain embodiments, the saturation concentration of the active agent in the skin contact layer is less than 0.05 wt.%, less than 0.02 wt.% or less than 0.01 wt.%. Preferably, the saturation concentration of the active agent in the skin contact layer is about 0 wt.%. The saturation concentration relates to the amount of active agent present in the skin contact layer, based on the total weight of the skin contact layer.

[0158] In certain embodiments, the saturation concentration of the active agent in the skin contact layer is less than the concentration of the active agent that leads to any unintended harmful effects, such as skin irritation after short contact. Such a concentration can be determined empirically by observing whether harmful effects, such as any form of skin irritation (redness, erythema, itching or other skin reactions), occur or do not occur after short (e.g. 5 seconds, 10 seconds, 30 seconds or 1 minute) application of a model adhesive layer with a defined concentration of capsaicin on the skin. In particular, different model layers representing a range of concentrations of the active agent can be tested to determine the highest acceptable saturation concentration that does not cause any unintended harmful effects, such as skin irritation reactions. On the other hand, whether a medical patch with a certain set of active agents and a skin contact layer produces a saturation concentration that does not lead to any harmful effects can simply be determined by testing a model adhesive layer saturated with the active agent or the medical patch, i.e. by application to the skin as outlined above (without a range of different concentrations).

[0159] Before and / or after applying the medical patch, the skin contact layer can shield the active agent contained in the active layer from the skin of the patient or other application / removal personnel. Therefore, the skin contact layer needs to be substantially free of active agent. This means that the skin contact layer is usually made into a layer that does not contain active agent. However, due to the concentration gradient, the active agent can usually migrate from the active layer to the skin contact layer over time until equilibrium is reached. However, this migration is limited by the saturation concentration of the active agent in the skin contact layer. In certain embodiments, the skin contact layer does not allow the active agent to be present at a concentration greater than 0.1% by weight.

[0160] Thus, in certain embodiments, the skin contact layer comprises an amount of less than 0.1 wt% active agent based on the total weight of the skin contact layer. In specific embodiments, the skin contact layer comprises an amount of less than 0.01 wt% active agent based on the total weight of the skin contact layer.

[0161] According to certain embodiments, the skin contact layer comprises polymer II. Polymer II in the skin contact layer determines the adhesive properties and, due to its elasticity, can further reduce skin irritation. In certain embodiments, the skin contact layer comprises polymer II in an amount of at least 95% by weight, at least 99% by weight, or about 100% by weight, based on the total weight of the skin contact layer. In particular, the skin contact layer may consist essentially of polymer II. It should be understood that the above-mentioned % by weight amounts refer to the total amount of polymer II. For example, if polymer II is a mixture of polymers, the total amount in the skin contact layer is 50% to 100% by weight, based on the total weight of the skin contact layer.

[0162] In particular, polymers suitable as polymer II according to the present invention are polymers that allow the active agent to be concentrated to no more than 0.1% by weight, no more than 0.05% by weight, no more than 0.02% by weight, or no more than 0.01% by weight, i.e., polymers in which the active agent is substantially insoluble. Thus, according to certain embodiments, polymer II may be a polymer or a mixture of polymers in which the active agent is substantially insoluble.

[0163] Thus, the solubility parameter of polymer II may be different from the solubility parameter of the active agent, in particular may be at least 5.0 MPa lower than the solubility parameter of the active agent. 1 / 2 , at least 6.0 MPa 1 / 2 , at least 8.0 MPa 1 / 2 or at least 10.0 MPa 1 / 2 In particular, the solubility parameter of polymer II may preferably be less than 18.5 MPa as calculated by the method of Small. 1 / 2 , less than 18.0MPa 1 / 2 , less than 17.5 MPa 1 / 2 , less than 17.0 MPa1 / 2 less than 16.0 MPa 1 / 2 or less than 15.0 MPa 1 / 2 .

[0164] Polymer II can be selected from pressure sensitive adhesive polymers. Thus, in certain embodiments, Polymer II can be a pressure sensitive adhesive or a mixture of pressure sensitive adhesives.

[0165] In certain embodiments, Polymer II can be a polymer or a mixture of polymers selected from silicone acrylic hybrid polymers, silicone based polymers, silicone gel adhesives and polymers based on natural or synthetic rubbers, which are described in more detail below. In particular, Polymer II can be a polymer or a mixture of polymers selected from silicone based polymers and silicone gel adhesives.

[0166] In particular embodiments, Polymer II can be a silicone gel adhesive. Such self-adhesive layer structures comprising a further skin contact layer of a silicone gel adhesive provide improved wearability as well as clean and painless removal when applied to the skin of a patient. If necessary, e.g. in case of repositioning, the self-adhesive layer structure can be removed and applied again without loss of adhesion.

[0167] Further, Polymer II can be a polymer or a mixture of polymers selected from silicone based polymers, in particular polysiloxane based polymers, such as amine compatible polysiloxanes, or Polymer II can be a polymer or a mixture of polymers selected from natural or synthetic rubbers, in particular styrene triblock copolymers and / or polyisobutylenes, such as SIS block copolymers and / or polyisobutylenes.

[0168] Polymers suitable as Polymer II are commercially available, for example, under the trade designation Soft skin adhesives (two-component silicone adhesives which cure after mixing of the two components). Alternatively, polymers suitable as Polymer II are commercially available, for example, under the trade designation BIO-PSA (polysiloxane based pressure sensitive adhesives) JSR-SIS (SIS block copolymer based pressure sensitive adhesives) and Oppanol™ (polyisobutylene).

[0169] Further polymers can be added to enhance the adhesion of the skin contact layer.

[0170] According to some embodiments, Polymer II contained in the skin contact layer is different from Polymer I contained in the active layer. According to other embodiments, Polymer II contained in the skin contact layer is the same as Polymer I contained in the active layer.

[0171] According to certain embodiments, the area weight of the skin contact layer can be in the range of 80 to 500 g / m2, in particular in the range of 100 to 400 g / m2, more in particular in the range of 120 to 300 g / m2.2 In certain embodiments, the skin contact layer can have an area weight of 100 to 350 g / m2. 2 In certain embodiments, the skin contact layer can have an area weight of 150 to 320 g / m2. 2 In certain embodiments, the skin contact layer can have an area weight of 180 to 280 g / m2. 2

[0172] Silicone-based polymer

[0173] Suitable silicone-based polymers are non-curable polymers, which are typically applied by hot melt or solvent-based processes, and which preferably do not undergo further curing to solidify.

[0174] The silicone-based polymer is based on polysiloxane. It can thus also be referred to as a polysiloxane-based polymer. The silicone-based polymer can typically be obtained by polycondensation of a silanol-terminated polydimethylsiloxane with a silicate resin. An amine-compatible silicone-based polymer can be obtained by reacting the silicone-based polymer with a trimethylsilyl group, such as hexamethyldisilazane, to reduce the silanol content of the polymer and thus provide enhanced stability in the presence of amines. Thus, the residual silanol functionality is at least partially, preferably mostly or completely end-capped with trimethylsiloxy groups.

[0175] Thus, in certain embodiments, the silicone-based polymer is an amine-compatible polysiloxane, and preferably can be obtained by polycondensation of a silanol-terminated polydimethylsiloxane with a silicate resin followed by at least partial trimethylsilylation of the residual silanol functionality.

[0176] In certain embodiments, the silicone-based polymer is a pressure sensitive adhesive or a mixture of pressure sensitive adhesives, i.e. a polysiloxane-based pressure sensitive adhesive or a mixture of polysiloxane-based pressure sensitive adhesives.

[0177] Polysiloxane-based pressure sensitive adhesives provide suitable adhesion and fast bonding to a variety of skin types, including wet skin, suitable adhesion and cohesion, durable stickiness to skin, high flexibility, moisture permeability, and compatibility with many active agents and film substrates. Such pressure sensitive adhesives are based on the concept of a polymer package resin, wherein the polysiloxane-based pressure sensitive adhesive is prepared by condensation reaction of a silanol-terminated polydimethylsiloxane with a silica resin, also referred to as a silicate resin. For amine stability, the residual silanol functionality is additionally capped with trimethylsiloxy groups. The silanol-terminated polydimethylsiloxane content contributes to the viscous component with viscoelasticity and influences the wettability and spreadability of the adhesive. The resin acts as tackifier and reinforcing agent and participates in the elastic component. A proper balance between the silanol-terminated polydimethylsiloxane and the resin provides proper adhesion properties.

[0178] ​As previously mentioned, the tack of the silicone-based polymer can be adjusted by the ratio of resin to polymer, i.e. the ratio of silanol terminated polydimethylsiloxane to silicate resin, which is preferably in the range of 50:50 to 70:30 or 55:45 to 65:35. The tack will increase with increasing amounts of polydimethylsiloxane relative to the resin. A high tack silicone-based polymer preferably has a resin to polymer ratio of 55:45, a medium tack silicone-based polymer preferably has a resin to polymer ratio of 60:40, and a low tack silicone-based polymer preferably has a resin to polymer ratio of 65:35.

[0179] According to certain embodiments, the pressure sensitive adhesive can be obtained by polycondensation of silanol terminated polydimethylsiloxane with a silicate resin, preferably with a resin to polymer ratio of 50:50 to 70:30 or 55:45, 60:40 or 65:35. Thus, in one embodiment, the silicone-based polymer is a mixture of pressure sensitive adhesives obtainable by polycondensation of silanol terminated polydimethylsiloxane with a silicate resin, with a resin to polymer ratio of 55:45 or 60:40.

[0180] Further, according to certain embodiments, the silicone-based polymer is a mixture of pressure sensitive adhesives, wherein

[0181] has a solution viscosity of 450 mPa s at 25 °C and about 60% solid content in heptane and / or a complex viscosity of 1 x 10 8 Poise at 0.01 rad / s at 30 °C, and

[0182] has a solution viscosity of 500 mPa s at 25 °C and about 60% solid content in heptane and / or a complex viscosity of 5 x 10 6 Poise at 0.01 rad / s at 30 °C.

[0183] The polysiloxane-based pressure sensitive adhesives are supplied and used in solvents such as n-heptane, ethyl acetate or other volatile silicone oils. The solid content of the polysiloxane-based pressure sensitive adhesives in the solvent is typically between 60% and 85%, between 70% and 80% or between 60% and 75%. The skilled person knows that the solid content can be changed by adding a suitable amount of solvent.

[0184] The high tack silicone-based polymer preferably has a complex viscosity of about 5 x 10 6 Poise at 0.01 rad / s and 30 °C, the medium tack silicone-based polymer preferably has a complex viscosity of about 5 x 10 7 Poise at 0.01 rad / s and 30 °C, and the low tack silicone-based polymer preferably has a complex viscosity of about 5 x 10 8about 5 x 10 6 about 5 x 10 8 about 5 x 10 9 about 5 x 10 9 about 1 x 10 5 about 1 x 10 8 about 9 x 10

[0185] Suitable silicone-based polymers are commercially available under the trade name BIO-PSA. Examples of commercially available silicone-based PSA compositions include the standard Liveo™ BIO-PSA series (7-4400, 7-4500, and 7-4600 series) and the amine-compatible (capped) Liveo™ BIO-PSA series (7-4100, 7-4200, and 7-4300 series), which are manufactured in and typically supplied in either n-heptane or ethyl acetate. For example, BIO-PSA 7-4201 is characterized by a solution viscosity in heptane at 25°C and about 60% solids content of 450 mPa s, and a complex viscosity at 30°C at 0.01 rad / s of 1 x 10 8 -4. BIO-PSA 7-4301 has a solution viscosity in heptane at 25°C and about 60% solids content of 500 mPa s, and a complex viscosity at 30°C at 0.01 rad / s of 5 x 10 6 -4.

[0186] The polysiloxane-based pressure sensitive adhesives can be obtained according to the following protocol:

[0187]

[0188] Such silicone-based pressure sensitive adhesives are available under the trade name Liveo™ BIO-PSA 7-4401, BIO-PSA-7-4501, or BIO-PSA 7-4601, which are provided in the solvent n-Heptane (indicated by the code "01"), or under the trade name Liveo™ BIO-PSA 7-4402, BIO-PSA 7-4502, and BIO 7-4602, which are provided in the solvent ethyl acetate (indicated by the code "02"). Typical solid content in the solvent is in the range of 60% to 75%. The code "44" indicates a resin to polymer ratio of 65:35, resulting in low tack, the code "45" indicates a resin to polymer ratio of 60:40, resulting in medium tack, and the code "46" indicates a resin to polymer ratio of 55:45, resulting in high tack.

[0189] Silicone-based amine compatible pressure sensitive adhesives are available according to the following protocol:

[0190]

[0191] Such silicone-based pressure sensitive adhesives are available under the trade name Liveo™ BIO-PSA 7-4101, BIO-PSA-7-4201, or BIO-PSA 7-4301, which are provided in the solvent n-Heptane (indicated by the code "01"), or under the trade name Liveo™ BIO-PSA 7-4102, BIO-PSA 7-4202, and BIO 7-4302, which are provided in the solvent ethyl acetate (indicated by the code "02"). Typical solid content in the solvent is in the range of 60% to 75%. The code "41" indicates a resin to polymer ratio of 65:35, resulting in low tack, the code "42" indicates a resin to polymer ratio of 60:40, resulting in medium tack, and the code "43" indicates a resin to polymer ratio of 55:45, resulting in high tack.

[0192] Acrylic polymers

[0193] As used herein, the terms acrylic polymer and acrylate polymer are used synonymously to refer to acrylate-based polymers. According to certain embodiments, the acrylic polymer is an acrylate-based pressure sensitive adhesive. An acrylate-based pressure sensitive adhesive can also be referred to as an acrylate-based pressure sensitive adhesive or an acrylate pressure sensitive adhesive.

[0194] Acrylate-based pressure sensitive adhesives can be provided in the form of solutions with a solids content preferably between 30 and 60 %. Acrylate-based pressure sensitive adhesives can or can not comprise functional groups such as hydroxyl groups, carboxylic acid groups, neutralized carboxylic acid groups and mixtures thereof. Corresponding commercial products are available for example from Henkel under the trademark name Duro Tak®. Such acrylate-based pressure sensitive adhesives are based on monomers selected from one or more of the following: acrylic acid, 2-ethylhexyl acrylate, glycidyl methacrylate, 2-hydroxyethyl acrylate, methyl acrylate, methyl methacrylate, butyl acrylate, butyl methacrylate, t-octyl acrylamide and vinyl acetate and are provided in the form of ethyl acetate, heptane, n-heptane, hexane, methanol, ethanol, isopropanol, 2,4-pentanedione, toluene or xylene or mixtures thereof.

[0195] Particular acrylate-based pressure sensitive adhesives are commercially available in the following forms:

[0196] - Duro-Tak™ 387-2287 or Duro-Tak™ 87-2287 (a copolymer based on vinyl acetate, 2- ethylhexyl-acrylate, 2-hydroxyethyl-acrylate and glycidyl-methacrylate provided in the form of a solution in ethyl acetate without crosslinker),

[0197] - Duro-Tak™ 387-2516 or Duro-Tak™ 87-2516 (a copolymer based on vinyl acetate, 2- ethylhexyl-acrylate, 2-hydroxyethyl-acrylate and glycidyl-methacrylate provided in the form of a solution in ethyl acetate, ethanol, n-heptane and methanol with titanium crosslinker),

[0198] - Duro-Tak™ 387-2051 or Duro-Tak™ 87-2051 (a copolymer based on acrylic acid, butyl acrylate, 2-ethylhexyl acrylate and vinyl acetate provided in the form of a solution in ethyl acetate and heptane),

[0199] - Duro-Tak™ 387-2353 or Duro-Tak™ 87-2353 (a copolymer based on vinyl acetate, 2- ethylhexyl acrylate, glycidyl methacrylate and methyl acrylate provided in the form of a solution in ethyl acetate and hexane),

[0200] - Duro-Tak™ 87-4098 (a copolymer based on 2-ethylhexyl-acrylate and vinyl acetate provided in the form of a solution in ethyl acetate).

[0201] - Duro-Tak™ 387-9301 (a copolymer based on methyl acrylate, 2-ethylhexyl acrylate and t-octyl acrylamide, provided as a solution in ethyl acetate).

[0202] Thus, the acrylic polymer can be selected from acrylic polymers comprising functional groups, wherein the functional groups are selected from the group consisting of hydroxyl groups, carboxylic acid groups, neutralized carboxylic acid groups, and mixtures thereof. In certain embodiments, the functional groups are limited to hydroxyl groups. The acrylic polymer can not comprise carboxylic acid groups or neutralized carboxylic acid groups or both, or can not comprise acidic groups, or can not comprise functional groups.

[0203] Depending on the type of commercially available acrylic polymer used and depending on whether a crosslinker is added to the coating composition or not, the polymer in the final active or skin contact layer is crosslinked (and preferably crosslinked by aluminum and / or titanium crosslinkers) or not crosslinked by a crosslinker.

[0204] Silicone acrylic hybrid polymers

[0205] As used herein, a silicone acrylic hybrid polymer comprises a polymeric hybrid substance comprising silicone-based sub-stuff and acrylate-based sub-stuff that have been polymerized together. Thus, a silicone acrylic hybrid polymer comprises a silicone phase and an acrylic phase. According to certain embodiments, the silicone acrylic hybrid polymer is a silicone acrylic hybrid pressure sensitive adhesive.

[0206] Silicone acrylic hybrid pressure sensitive adhesives are typically supplied and used in solvents such as n-heptane and ethyl acetate. The solids content of the pressure sensitive adhesive is typically between 30% and 80%. The skilled person knows that the solids content can be varied by adding a suitable amount of solvent.

[0207] In certain embodiments, the weight ratio of silicone to acrylate in the silicone acrylate hybrid pressure sensitive adhesive is 5:95 to 95:5 or 20:80 to 80:20 or 40:60 to 60:40, or the ratio of silicone to acrylate is about 50:50. Suitable commercially available silicone acrylate hybrid pressure sensitive adhesives include the PSA Series 7-6100 and 7-6300 manufactured by Dupont and supplied in n-heptane or ethyl acetate (7-610X and 7-630X; X=l n-heptane based / X=2 ethyl acetate based). For example, the 7-6102 silicone acrylate hybrid PSA with a 50 / 50 silicone / acrylate ratio features a solution viscosity in ethyl acetate at 25°C and about 50% solids content of 2,500 cP, and a complex viscosity at 0.1 rad / s at 30°C of 1.0e7 Poise. The 7-6302 silicone acrylate hybrid PSA with a 50 / 50 silicone / acrylate ratio features a solution viscosity in ethyl acetate at 25°C and about 50% solids content of 1,500 cP, and a complex viscosity at 0.1 rad / s at 30°C of 4.0e6 Poise.

[0208] The arrangement of the silicone and acrylic phases providing a continuous outer phase of silicone or acrylic and a corresponding discontinuous inner phase of acrylic or silicone, respectively, is different depending on the solvent in which the silicone acrylic hybrid pressure sensitive adhesive is provided. If the silicone acrylic hybrid pressure sensitive adhesive is provided in n-heptane, the composition contains a continuous silicone outer phase and a discontinuous acrylic inner phase. If the silicone acrylic hybrid pressure sensitive adhesive is provided in ethyl acetate, the composition contains a continuous acrylic outer phase and a discontinuous silicone inner phase. After evaporation of the solvent in which the silicone acrylic hybrid pressure sensitive adhesive is provided, the phase arrangement of the resulting pressure sensitive adhesive film or layer corresponds to the phase arrangement of the solvent containing adhesive coating composition. For example, in the absence of any substances that can cause a reversal of the phase arrangement in the silicone acrylic hybrid pressure sensitive adhesive composition, a pressure sensitive adhesive layer prepared from a silicone acrylic hybrid pressure sensitive adhesive in n-heptane provides a continuous silicone outer phase and a discontinuous acrylic inner phase, and a pressure sensitive adhesive layer prepared from a silicone acrylic hybrid pressure sensitive adhesive in ethyl acetate provides a continuous acrylic outer phase and a discontinuous silicone inner phase. The phase arrangement of the silicone acrylic hybrid PSA composition can be determined, for example, in a peel force test with a pressure sensitive adhesive film or layer prepared from the silicone acrylic hybrid PSA composition attached to a siliconized release liner. If the siliconized release liner cannot or hardly can be removed from the pressure sensitive adhesive film (laminated to a backing film) due to the blocking of two silicone surfaces, the pressure sensitive adhesive film contains a continuous silicone outer phase. The blocking is caused by the attachment of two silicone layers comprising similar surface energies. Silicone adhesives show good spreading on siliconized liners and thus can generate good adhesion to the liner. If the siliconized release liner can be easily removed, the pressure sensitive adhesive film contains a continuous acrylic outer phase. Acrylic adhesives do not have good spreading due to different surface energies and thus have low or hardly any adhesion to siliconized liners.

[0209] The silicone acrylic hybrid polymer can be a silicone acrylic hybrid pressure sensitive adhesive obtainable from a silicone-containing pressure sensitive adhesive composition comprising acrylate or methacrylate functional groups. It is to be understood that a silicone-containing pressure sensitive adhesive composition comprising acrylate or methacrylate functional groups can include only acrylate functional groups, only methacrylate functional groups, or both acrylate and methacrylate functional groups.

[0210] The silicone acrylic hybrid pressure-sensitive adhesive may comprise the reaction product of (a) a silicone-containing pressure-sensitive adhesive composition comprising acrylate or methacrylate functional groups, (b) an ethylenically unsaturated monomer, and (c) an initiator. In other words, the silicone acrylic hybrid pressure-sensitive adhesive is the product of a chemical reaction between these reactants ((a), (b), and (c)). In particular, the silicone acrylic hybrid pressure-sensitive adhesive may comprise the reaction product of (a) a silicone-containing pressure-sensitive adhesive composition comprising acrylate or methacrylate functional groups, (b) a (meth)acrylate monomer, and (c) an initiator (i.e., in the presence of an initiator). In other words, the silicone acrylic hybrid pressure-sensitive adhesive may comprise the product of a chemical reaction between these reactants ((a), (b), and (c)).

[0211] The reaction product of (a) a silicone-containing pressure-sensitive adhesive composition comprising acrylate or methacrylate functional groups, (b) an ethylenically unsaturated monomer, and (c) an initiator may contain a continuous silicone outer phase and a discontinuous acrylic inner phase, or the reaction product of (a), (b), and (c) may contain a continuous acrylic outer phase and a discontinuous silicone inner phase.

[0212] The silicone acrylic hybrid polymer may comprise the reaction product of a silicone polymer, a silicone resin, and an acrylic polymer, wherein the acrylic polymer is covalently self-crosslinked and covalently bonded to the silicone polymer and / or the silicone resin.

[0213] The silicone acrylic hybrid polymer may comprise the reaction product of a silicone polymer, a silicone resin, and an acrylic polymer, wherein the silicone resin contains triorganosiloxy units R3SiO 1 / 2 (where R is an organic group) and a tetrafunctional siloxy unit SiO 4 / 2 , the molar ratio of each SiO 4 / 2 0.1 to 0.9 R3SiO units 1 / 2 unit.

[0214] The acrylic polymer may comprise at least an alkoxysilyl functional monomer, a polysiloxane-containing monomer, a halosilyl functional monomer, or an alkoxyhalosilyl functional monomer. In certain embodiments, the acrylic polymer is prepared from an alkoxysilyl functional monomer selected from the group consisting of trialkoxysilyl (meth)acrylates, dialkoxyalkylsilyl (meth)acrylates, and mixtures thereof, or comprises a capped alkoxysilyl functional group. The alkoxysilyl functional group may preferably be selected from the group consisting of trimethoxysilyl, dimethoxymethylsilyl, triethoxysilyl, diethoxymethylsilyl, and mixtures thereof.

[0215] The acrylic polymers can also be prepared from a mixture comprising a polysiloxane monomer, preferably from a mixture comprising a polydimethylsiloxane mono(meth)acrylate.

[0216] The silicone acrylic hybrid polymer can be prepared by a) reacting a silicone polymer with a silicone resin to form a resulting product, b) reacting the resulting product of a) with an acrylic polymer comprising a reactive functional group, wherein the components are reacted in an organic solvent.

[0217] The silicone acrylic hybrid polymer can be prepared by a) reacting a silicone resin with an acrylic polymer comprising a reactive functional group to form a resulting product, b) reacting the resulting product of a) with a silicone polymer, wherein the components are reacted in an organic solvent.

[0218] The silicone acrylic hybrid polymer can be prepared by a) reacting a silicone polymer with an acrylic polymer comprising a reactive functional group to form a resulting product, b) reacting the resulting product of a) with a silicone resin, wherein the components are reacted in an organic solvent.

[0219] Other suitable acrylic polymers, silicone resins, and silicone polymers that can be used to chemically react the silicone polymer, silicone resin, and acrylic polymer together to provide a silicone acrylic hybrid polymer according to the preceding paragraphs are detailed in WO 2010 / 124187.

[0220] Natural or synthetic rubber based polymers

[0221] Natural or synthetic rubber based polymers include hydrocarbon polymers such as (natural and synthetic) polyisoprene, polybutene and polyisobutylene, styrene / butadiene polymers, styrene-isoprene-styrene block copolymers, butyl rubber, halogen containing polymers such as polyacrylonitrile, polytetrafluoroethylene, polyvinyl chloride, polyvinylidene chloride and polychloroprene, other copolymers thereof. The polymers can be used in particular in combination with the adhesives as defined hereinafter.

[0222] According to certain embodiments, the polymer can be a styrene triblock copolymer selected from the group consisting of styrene-ethylene-styrene (SES) block copolymer, styrene-butadiene-styrene (SBS) block copolymer, styrene-isoprene-styrene (SIS) block copolymer, styrene-ethylene / butylene-styrene (S-EB-S) block copolymer, styrene-ethylene / butylene / propylene-styrene (s-EBS-S) block copolymer, styrene-isoprene / butadiene-styrene (S-IB-S) block copolymer, and mixtures thereof.

[0223] In certain embodiments, the polymer can be at least one SIS block copolymer. The at least one SIS block copolymer can consist of three blocks of polystyrene, polyisoprene, and polystyrene, and in particular have a molecular weight of about 100,000 to 200,000. In particular embodiments, the SIS block copolymer can comprise polystyrene blocks and polyisoprene blocks in a ratio of about 10:90 (%) to about 30:70 (%) or a ratio of about 15:85 (%) or about 22:78 (%).

[0224] In other embodiments, the polymer is at least one polyisobutylene and can be a combination of two different types of polyisobutylene, in particular a combination of a low molecular weight polyisobutylene and a high molecular weight polyisobutylene. In particular embodiments, the ratio of low molecular weight polyisobutylene to high molecular weight polyisobutylene is in the range of 75:25 to 90:10.

[0225] Suitable styrene-isoprene-styrene (SIS) block copolymers according to the present application are commercially available, for example, under the trade name JSR-SIS. Particular SIS block copolymer based pressure sensitive adhesives are available under the trade names JSR-SIS 5229 and JSR-SIS 5002.

[0226] Suitable polyisobutylenes as used herein are available under the trade name Oppanol®. A combination of high molecular weight polyisobutylenes (B100, B80) and low molecular weight polyisobutylenes (B10, B11, B12, B13) can be used. Suitable ratios of low molecular weight polyisobutylenes to high molecular weight polyisobutylenes are in the range of 100:1 to 1:100, 95:5 to 40:60, or 90:10 to 75:25. Particular examples of polyisobutylene combinations are B10 / B100 in a ratio of 85 / 15 or B12 / B100 in a ratio of 80 / 20. Oppanol® B100 has a viscosity average molecular weight Mv of 1,110,000 and a weight average molecular weight Mw of 1,550,000 and an average molecular weight distribution Mw / Mn of 2.9. Oppanol® B80 has a viscosity average molecular weight Mv of 1,050,000 and a weight average molecular weight Mw of 1,400,000 and an average molecular weight distribution Mw / Mn of 2.9. Oppanol® B11 has a viscosity average molecular weight Mv of 40,000 and a weight average molecular weight Mw of 53,000 and an average molecular weight distribution Mw / Mn of 3.2. Oppanol® B12 has a viscosity average molecular weight Mv of 55,000 and a weight average molecular weight Mw of 70,000 and an average molecular weight distribution Mw / Mn of 3.2. Suitable polyisobutylene adhesives are also commercially available, for example, under the trade name Duro-Tak™ 87-6908. v and a weight average molecular weight Mw of 1,550,000. w and an average molecular weight distribution Mw / Mn of 2.9. w / M n . Oppanol® B10 has a viscosity average molecular weight Mv of 40,000 and a weight average molecular weight Mw of 53,000 and an average molecular weight distribution Mw / Mn of 3.2. Oppanol® B12 has a viscosity average molecular weight Mv of 55,000 and a weight average molecular weight Mw of 70,000 and an average molecular weight distribution Mw / Mn of 3.2. Suitable polyisobutylene adhesives are also commercially available, for example, under the trade name Duro-Tak™ 87-6908. v and a weight average molecular weight Mw of 1,550,000. w and an average molecular weight distribution Mw / Mn of 2.9. w / M n . Oppanol® B10 has a viscosity average molecular weight Mv of 40,000 and a weight average molecular weight Mw of 53,000 and an average molecular weight distribution Mw / Mn of 3.2. Oppanol® B12 has a viscosity average molecular weight Mv of 55,000 and a weight average molecular weight Mw of 70,000 and an average molecular weight distribution Mw / Mn of 3.2. Suitable polyisobutylene adhesives are also commercially available, for example, under the trade name Duro-Tak™ 87-6908.

[0227] Silicone gel adhesive

[0228] Silicone gel adhesives are elastomeric, glue-like materials formed from slightly cross-linked silicone polymers. Thus, in contrast to silicone-based polymers as used herein, silicone gel adhesives are based on compositions that yield a curable gel. When used in a skin contact layer, silicone gel adhesives provide adhesion of a medical patch to the skin while at the same time mitigating the problem of skin irritation. In addition, the drug delivery of the medical patch is not negatively affected, and surprisingly, the skin permeability is even improved.

[0229] Silicone gel adhesives are also referred to as silicone gels and are described, for example, in WO 2011 / 022199 A2.

[0230] Silicone gel adhesives are typically formed from linear or branched silicones having reactive groups thereon. Such reactive groups undergo cross-linking reactions during curing. Examples of cross-linking reactions include hydrosilylation reactions, in which silicones having Si-H reactive groups react with silicones having aliphatic unsaturated reactive groups in the presence of a hydrosilylation catalyst. These materials are described, for example, in US 5,656,279, US 5,891,076, EP 0 322 118, and US 4,991,574, which are incorporated herein by reference. An alternative reaction is condensation cure, in which alkoxyl- and / or hydroxyl-containing siloxanes cure in the presence of a catalyst as described in US 4,831,070, which is incorporated herein by reference.

[0231] Typically, silicone gel adhesives can be obtained by reacting a gel- yielding composition comprising (i) at least one alkenyl-substituted polydiorganosiloxane, (ii) at least one organosiloxane containing silicon-bonded hydrogen atoms, and (iii) at least one catalyst for the reaction of SiH groups with Si-alkenyl groups. These compositions cure at normal ambient temperatures, but the curing can be accelerated by heating to elevated temperatures (e.g., from 40 to 140 °C) or by applying UV light.

[0232] Suitable alkenyl groups contain 2 carbons to about 6 carbon atoms, and are exemplified by, but not limited to, vinyl, allyl, and hexenyl. The alkenyl groups in this component can be located at a terminal, pendant (non-terminal), or both terminal and pendant positions. The remaining silicon-bonded organic groups in the alkenyl-substituted polydiorganosiloxane are independently selected from the group consisting of monovalent hydrocarbon groups and monovalent halogenated hydrocarbon groups free of aliphatic unsaturation. These groups typically contain 1 carbon to about 20 carbon atoms, alternatively 1 carbon to 8 carbon atoms, and are exemplified by, but not limited to, alkyl groups such as methyl, ethyl, propyl, and butyl; aryl groups such as phenyl; and halogenated alkyl groups such as 3,3,3-trifluoropropyl. Typically, at least 50% of the organic groups in the alkenyl-substituted polydiorganosiloxane are methyl groups. The structure of the alkenyl-substituted polydiorganosiloxane is typically linear, however, it can contain some branching due to the presence of trifunctional siloxane units. The viscosity of the alkenyl-substituted polydiorganosiloxane can be any desired. For example, it can be > 0 mm 2 / s to 100,000 mm 2 / s, alternatively 50 mm 2 / s to 80,000 mm 2 / s, alternatively 300 mm 2 / s - 3,000 mm 2 / s.

[0233] Methods of making the alkenyl-substituted polydiorganosiloxanes (i) of the present invention, such as condensation of the corresponding halosilane or equilibration of a cyclic polydiorganosiloxane, are well known in the art.

[0234] The alkenyl-substituted polydiorganosiloxane can be used in the gel producing composition in an amount of 10 wt.% - 90 wt.% or 40 wt.% - 90 wt.% or 50 wt.% - 80 wt.% by weight of the composition. The amount of alkenyl groups present in the alkenyl-substituted polydiorganosiloxane is typically in the range of 0.05 wt.% - 1 wt.% or 0.05 wt.% to 1 wt.% by weight of the alkenyl-substituted polydiorganosiloxane.

[0235] Organosiloxanes containing silicon-bonded hydrogen atoms (ii) are also known in the art, as described, for example, in U.S. Patent No. 3,983,298. The hydrogen atoms in this component can be located at terminal, pendant (non-terminal), or both terminal and pendant positions. The remaining silicon-bonded organic groups in this component are independently selected from the group consisting of monovalent hydrocarbon groups and monovalent halogenated hydrocarbon groups free of aliphatic unsaturation. These groups typically contain from 1 carbon to about 20 carbon atoms or from 1 carbon to 8 carbon atoms, and are exemplified by, but not limited to, alkyl groups such as methyl, ethyl, propyl, and butyl; aryl groups such as phenyl; and halogenated alkyl groups such as 3,3,3-trifluoropropyl. In one embodiment of the present application, at least 50% of the organic groups in the organosiloxane containing silicon-bonded hydrogen atoms are methyl groups. However, the structure of the organosiloxane containing silicon-bonded hydrogen atoms is typically linear; it can contain some branching due to the presence of trifunctional siloxane units. The viscosity of the organosiloxane containing silicon-bonded hydrogen atoms can be any desired. For example, it can be > 0 mm 2 / s to 100,000 mm 2 / s, or 5 mm 2 / s to 500 mm 2 / s.

[0236] Methods for preparing the organosiloxane containing silicon-bonded hydrogen atoms of the present application by cohydrolysis of the appropriate chlorosilane are known in the art; U.S. Patent No. 2,877,255 to Clark; Japanese Laid-open Patent Application (KOKAI) SHO 62 (1987)-39660 to Mogi et al.; and U.S. Patent Nos. 5,446,185 and 5,493,040 to Cobb et al., all of which are incorporated herein by reference.

[0237] The organosiloxane containing silicon-bonded hydrogen atoms can be used in the gel producing composition in an amount of 1 wt.% - 30 wt.% or 5 wt.% - 20 wt.% or 5 wt.% - 15 wt.% by weight of the composition. In one embodiment, the amount of hydrogen groups present in the organosiloxane containing silicon-bonded hydrogen atoms is between 0.05 wt.% - 1.44 wt.% by weight of the organosiloxane containing silicon-bonded hydrogen atoms.

[0238] In the gel producing composition, preferably (i) and (ii) are present such that the ratio of (H as SiH):(alkyl as Si-alkenyl) is typically in the range of 0.1:1 to 10:1.

[0239] The hydrosilylation catalyst (iii) promotes the addition reaction of the alkenyl-substituted polydiorganosiloxane with the organosiloxane containing silicon-bonded hydrogen. The hydrosilylation catalyst can be any of the well-known hydrosilylation catalysts comprising a platinum group metal, a compound containing a platinum group metal, or a microencapsulated platinum group metal or compound containing the same. These platinum group metals include platinum, rhodium, ruthenium, palladium, osmium, and iridium. Platinum and platinum compounds are the preferred catalysts based on their high level of activity in hydrosilylation reactions. One class of platinum catalysts is the complex of chloroplatinic acid with certain vinyl-containing organosiloxane compounds disclosed by Willig in U.S. Patent No. 3,419,593, which is incorporated herein by reference. A specific catalyst of this type is the reaction product of chloroplatinic acid and 1,3-divinyl-1,1,3,3-tetramethyldisiloxane.

[0240] The hydrosilylation catalyst is present in an amount sufficient to cure the composition of the present invention. Typically, the concentration of the catalyst is sufficient to provide 0.1 ppm to 500 ppm (parts per million) or 1 ppm to 100 ppm or 1 ppm to 50 ppm of platinum group metal, based on the weight of (i) and (ii).

[0241] In view of the foregoing, in one embodiment of the present invention, the silicone gel adhesive can be obtained by reacting a gel producing composition comprising (i) a copolymer of vinylmethylsiloxane and dimethylsiloxane in the presence of (iii) a platinum catalyst with (ii) a methylhydrosiloxane having trimethylsilyl end groups, wherein preferably (i) and (ii) are present such that the ratio of (H as SiH):(alkenyl as Si-alkenyl) is typically in the range of 0.1:1 to 10:1.

[0242] An optional ingredient is a hydroxyl-substituted silicone resin as described in U.S. Patent Application No. 2007-0202245, which is incorporated herein by reference. The resin typically comprises groups having the formula R 3 3SiO 1 / 2 ("M" groups) and groups having the formula SiO 4 / 2 ("Q" groups), wherein R 3 is an alkyl group having 1 carbon to 6 carbon atoms or an alkylene group having 1 carbon to 6 carbon atoms, typically methyl or vinyl. If alkenyl groups are present in the resin, the mol-% of R groups present as alkenyl groups is typically < 10 mol-% or 5 mol-%. The number ratio of M groups to Q groups is typically in the range of 0.6:1 to 4:1 or 0.6:1 to 1.0:1. The silicone resin typically contains 0.1 wt% to 5 wt% or 1.0 wt% to 5 wt% silicon-bonded hydroxyl groups.

[0243] The resin can be used in the gel-producing composition in an amount of 2 wt.% to 45 wt.% or 5 wt.% to 40 wt.% or 10 wt.% to 35 wt.% by weight of the gel-producing composition and the resin.

[0244] Thus, in one embodiment, the silicone gel adhesive is a silicate resin reinforced silicone gel adhesive comprising about 2 wt.% to about 45 wt.% of at least one hydroxyl-substituted silicate resin.

[0245] According to certain embodiments, the silicone gel adhesive is a 2-component silicone adhesive system that cures after mixing the two components. Examples of such commercially available two-part silicone adhesives include Liveo™ Soft Skin Adhesive provided in the form of a kit comprising components A and B (e.g., MG 7-9700, MG 7-9800, MG 7-9850, and MG 7-9900). It is a platinum-catalyzed soft, filler-free, elastic silicone adhesive for adhering medical devices to the skin with moderate adhesion and can be removed gently. The two components A and B are preferably mixed in a ratio of 1 : 1.

[0246] The silicone gel adhesive layer can be prepared by methods known in the art. For example, the gel can be preformed (e.g., preformed into a sheet) by molding, extruding, extruding, spraying, brushing, hand applying, casting, or coating on a substrate, such as a backing. Alternatively, the gel-producing composition can be applied to a substrate by spraying, coating, bar coating, or the like. After application to the substrate, the gel-producing composition is cured to produce the silicone gel adhesive on the substrate.

[0247] Other additives

[0248] The self-adhesive layer structure according to the present application and in particular the active layer can further comprise at least one additive or excipient. The additive or excipient is preferably selected from the group consisting of other polymers, crosslinking agents, crystallization inhibitors, solubilizers, fillers, adhesives, plasticizers, stabilizers, softeners, skin care substances, penetration enhancers, pH regulators, and preservatives. Such additives can be present in the active layer in an amount of 0.001 wt.% to 15 wt.% of the total weight of the active layer, for example 1 wt.% to 10 wt.% or 0.01 wt.% to 5 wt.%. In a certain embodiment, the total amount of all additives is 0.001% to 25% of the matrix layer composition. In the following, where a range of amounts of a particular additive is given, such range refers to the amount of each individual additive.

[0249] It should be noted that in pharmaceutical formulations, the formulation components are classified according to their physico-chemical and physiological properties and according to their function. In particular, this means that a substance or compound which belongs to one category can be a formulation component of another category. For example, a certain polymer can be a crystallization inhibitor, but also a adhesive. Some substances can for example be typical softening agents, but at the same time act as penetration enhancers. The skilled person is able to determine on the basis of his general knowledge to which category or categories of formulation components a certain substance or compound belongs. In the following, details are provided regarding excipients and additives, however, these details should not be understood as being exclusive. Other substances not explicitly listed in the present specification can also be used according to the present application and an explicitly listed substance and / or compound in one category of formulation components does not exclude use as another formulation component in the sense of the present application.

[0250] In certain embodiments, the active layer can further comprise another polymer, wherein preferably the other polymer is selected from dimethicone and ethyl cellulose. Dimethicone, such as dimethiconol, is preferably used to increase the tackiness of the active layer, while ethyl cellulose preferably acts as a tackifier. Another additional polymer of particular interest is a polymer with enhanced water absorption capacity, as higher water absorption and / or hygroscopicity helps to maintain / improve the tackiness properties of the self-adhesive layer structure. Thus, the active layer can further comprise at least one additional polymer selected from polymers providing improved water absorption and / or hygroscopicity of the matrix layer. Such polymers are well known in the art. Amongst others, particularly suitable and preferred is polyvinylpyrrolidone, and in particular soluble polyvinylpyrrolidone. Other polymers inter alia reduce cold flow and are thus also suitable as additional polymers. Polymer matrices can show cold flow, as such polymer compositions often exhibit the ability to flow very slowly, despite very high viscosity. Thus, during storage, the matrix can flow to some extent over the edges of the backing layer. This is a problem of storage stability and can be prevented by the addition of certain polymers. Basic acrylate polymers, for example Eudragit E100, which is a copolymer based on dimethylaminoethyl methacrylate, butyl methacrylate and methyl methacrylate, can for example be used to reduce cold flow. Thus, the active layer can additionally comprise a basic polymer, in particular an amine-functional acrylate, such as for example Eudragit E100. The additional polymer can for example be present in an amount of 0% to 20% of the active layer, preferably 0.5% to 5% or 5% to 15% of the active layer.

[0251] In certain embodiments, the active layer can further comprise a crosslinking agent. The crosslinking agent can be selected from the group consisting of an aluminum crosslinking agent and a titanium crosslinking agent, such as aluminum acetylacetonate, titanium acetylacetonate or polybutyl titanate, and is preferably a titanium crosslinking agent. The amount of crosslinking agent can range from 0.005% to 1% and preferably from 0.01% to 0.1% of the active layer. The active layer can further comprise a self-crosslinking polymer, i.e. comprising crosslinking functional groups that react upon heating, such as glycidyl groups. Thus, the active layer preferably comprises a crosslinking agent as described above and a self-crosslinking polymer.

[0252] In certain embodiments, the active layer can further comprise a crystallization inhibitor. Suitable examples of crystallization inhibitors include polyvinylpyrrolidone, vinyl acetate / vinyl pyrrolidone copolymer and cellulose derivatives. The crystallization inhibitor is preferably polyvinylpyrrolidone, more preferably soluble polyvinylpyrrolidone. The crystallization inhibitor can increase the solubility of the active agent or inhibit crystallization of the active agent. The crystallization inhibitor can be present in an amount of 0.5% to 10% by weight of the total weight of the active layer.

[0253] In certain embodiments, the active layer can further comprise a solubilizing agent. The solubilizing agent preferably improves the solubility of the active agent in the active layer. Preferred solubilizing agents include, for example: glycerol esters of medium-chain and / or long-chain fatty acids, polyglycerol esters, propylene glycol esters and polyoxyethylene esters, such as glyceryl monolinoleate, medium-chain glycerides and medium-chain triglycerides; non-ionic solubilizing agents prepared by reacting castor oil with ethylene oxide, and any mixtures thereof, which solubilizing agents can also contain fatty acids or fatty alcohols, cellulose and methylcellulose and derivatives thereof, such as hydroxypropyl cellulose and hypromellose acetate succinate; various cyclodextrins and derivatives thereof, non-ionic triblock copolymers with a central polyoxypropylene hydrophobic chain flanked by two polyoxyethylene hydrophilic chains, known as poloxamers, water-soluble derivatives of vitamin E, pharmaceutical grade or agglomerated spherical isomalt, polyethylene glycol, polyvinyl acetate and polyvinyl caprolactam-based graft copolymers (also abbreviated as PVAc-PVCap-PEG and known as Soluplus®), purified grade castor oil of natural origin, polyethylene glycol 400, polyoxyethylene sorbitan monooleate (such as polysorbate 80) or propylene glycol, diethylene glycol monoethyl ether, glucono-delta-lactone, corn and potato starch and any of the soluble polyvinylpyrrolidones mentioned below, but also insoluble / crosslinked polyvinylpyrrolidones, such as crosslinked povidone. However, the penetration enhancers mentioned below can also act as solubilizing agents. Furthermore, the crystallization inhibitors can also act as solubilizing agents.

[0254] Fillers such as silica gel, titanium dioxide and zinc oxide can be used in combination with the active layer in order to influence certain physical parameters, such as cohesion and bond strength, in a desired manner.

[0255] In cases where the active layer needs to have self-adhesion and one or more polymers that do not provide sufficient self-adhesion are selected, an adhesive is added. The adhesive can be selected from the group consisting of polyvinylpyrrolidone (polyvinylpyrrolidone is able to maintain the adhesiveness of the substrate layer due to its water absorption capacity, and thus can be considered an adhesive in a broad sense), triglyceride, polyethylene glycol, dipropylene glycol, resin, resin ester, terpene and its derivatives, ethylene vinyl acetate adhesive, dimethyl polysiloxane, and polybutene, preferably polyvinylpyrrolidone, and more preferably soluble polyvinylpyrrolidone. The adhesive can be present in an amount of 5% to 15% of the active layer.

[0256] In certain embodiments, the active layer can further comprise a softening agent / plasticizer. Exemplary softening agents / plasticizers include linear or branched, saturated or unsaturated alcohols having 6 to 20 carbon atoms, triglycerides, and polyethylene glycol.

[0257] In certain embodiments, the active layer can further comprise a stabilizer, wherein the stabilizer is preferably selected from the group consisting of tocopherol and ester derivatives thereof, and ascorbic acid and ester derivatives thereof. Preferred stabilizers include sodium metabisulfite, ascorbyl esters of fatty acids such as ascorbyl palmitate, ascorbic acid, butylated hydroxytoluene, tocopherol, tocopherol acetate, and tocopherol linoleate. Also particularly preferred is a combination of tocopherol and ascorbyl palmitate. In cases where the active layer comprises a stabilizer, the amount of stabilizer can be 0.001% to 2% of the active layer.

[0258] In certain embodiments, the active layer can further comprise a skin care material. Such materials can be detectable for avoiding or reducing skin irritation as by a skin reaction score. Suitable skin care materials include a sterol compound such as cholesterol, dexpanthenol, alpha-bisabolol, and an antihistamine.

[0259] In certain embodiments, the active layer may further comprise a penetration enhancer. A penetration enhancer is a substance that affects the barrier properties of the stratum corneum in the sense of increasing the permeability of capsaicin. Some examples of penetration enhancers are polyhydroxy alcohols such as dipropylene glycol, propylene glycol, and polyethylene glycol; oils such as olive oil, squalene, and lanolin; fatty ethers such as cetyl ether and oleyl ether; fatty acid esters such as isopropyl myristate; urea and urea derivatives such as allantoin; polar solvents such as dimethyldecylphosphine oxide, methyl hexadecyl sulfoxide, dimethylaurylamine, dodecyl pyrrolidone, isosorbide, dimethylacetonide, dimethyl sulfoxide, decyl methyl sulfoxide, and dimethylformamide, salicylic acid, amino acids, benzyl nicotinate, and higher molecular weight aliphatic surfactants such as lauryl sulfate. Other agents include oleic and linoleic acid, ascorbic acid, panthenol, butylated hydroxytoluene, tocopherol, tocopheryl acetate, tocopheryl linoleate, propyl oleate and isopropyl palmitate. If the active layer also contains a penetration enhancer, the penetration enhancer is preferably selected from diethylene glycol monoethyl ether (transcutol), diisopropyl adipate, isopropyl myristate, isopropyl palmitate, lauryl lactate and dimethylpropylene urea. Particularly preferably, the active layer contains a penetration enhancer selected from diethylene glycol monoethyl ether.

[0260] In certain embodiments, the active layer may further comprise a pH adjuster. Suitable pH adjusters include weak acids and weak bases, including amine derivatives, inorganic base derivatives, and polymers having basic or acidic functional groups.

[0261] In certain embodiments, the active layer may further comprise a preservative. Suitable preservatives include parabens, formaldehyde releasers, isothiazolinones, phenoxyethanol, and organic acids such as benzoic acid, sorbic acid, levulinic acid, and anisic acid.

[0262] Hexagonal shape

[0263] According to the present invention, the self-adhesive layer structure has a hexagonal shape, which is provided by the backing layer and the active layer, or the backing layer, the active layer and the other skin contact layer. The hexagonal shape comprises at least one hexagon, wherein

[0264] Each pair of opposite sides of a hexagon is parallel, and

[0265] The sides of the hexagon have a length of 0.2 to 10 cm.

[0266] The hexagonal shape may comprise one to ten (such as one, two, three, four or five) hexagons, wherein preferably the hexagons are adjacent to each other and / or do not overlap. Two or more hexagons are preferably integrally connected to each other. Preferred hexagonal shapes do not contain perforations.

[0267] In certain embodiments, the at least one hexagon is at least one convex hexagon, and the hexagonal shape comprises at least one convex hexagon, wherein each pair of opposite sides of the convex hexagon is parallel, and the sides of the convex hexagon have a length of 0.2 to 10 cm. In certain embodiments, the hexagonal shape comprises one or two convex hexagons, in particular integrally connected to each other. In particular embodiments, the hexagonal shape is a convex hexagon.

[0268] The hexagonal shape of the self-adhesive layer structure is decisive for easy and less time-consuming handling of the medical patch containing the self-adhesive layer structure. It allows for a simplified coverage of the skin area without cutting before application, thereby reducing the risk of contamination of the cutting tool or the fingers with the active agent and the risk of contamination of the patch at the cut. Furthermore, uneven or round skin surfaces can be covered without wrinkles, thereby providing a complete adhesion, and even complex areas, such as fingers or toes, can be easily surrounded using the self-adhesive layer structure. In particular, in case the hexagonal shape comprises at least one convex hexagon, the hexagonal shape only needs to have a short side length in relation to the area provided, thereby reducing the risk of detaching the edges of the medical patch.

[0269] In certain embodiments, the hexagonal shape is a double hexagon formed by two identical convex hexagons sharing two adjacent vertices of their common side. The double hexagon can be obtained by mirroring one convex hexagon over one of its sides (mirror axis), wherein the mirror axis then comprises the common side. In certain embodiments, the double hexagon can be split at the common side to obtain two equal convex hexagons, which can be applied together or separately. Thus, in one particular embodiment, the hexagonal shape is a double hexagon formed by two identical convex hexagons sharing two adjacent vertices of their common side, wherein the common side is perforated to facilitate tearing off.

[0270] In certain embodiments, the hexagonal shape is a hexagon or a double hexagon, in particular a convex hexagon or a double hexagon formed by two identical convex hexagons sharing two adjacent vertices of their common side, wherein preferably the hexagon or double hexagon has an area of more than 20 cm 2 , such as more than 24 cm 2 , more than 30 cm 2 , or more than 40 cm 2 , and preferably less than 150 cm 2 , such as less than 60 cm 2 , or less than 35 cm 2 .

[0271] Hexagonal shapes, in particular convex hexagons or double hexagons, can have mirror symmetry and / or rotational symmetry. Preferred hexagonal shapes are mirror symmetric and have at least one axis of symmetry, such as two, three or four axes of symmetry, in particular six axes of symmetry. Alternatively or additionally, preferred hexagonal shapes are rotationally symmetric and have at least 2-fold, such as 3- or 4-fold, in particular 6-fold rotational symmetry. Thus, particularly preferred hexagonal shapes are mirror symmetric and have at least four axes of symmetry and / or have at least 4-fold rotational symmetry, in particular are mirror symmetric and have six axes of symmetry and additionally have 6-fold rotational symmetry.

[0272] Hexagons, in particular convex hexagons, according to the present application have three pairs of parallel opposite sides, which can be of different or equal length. In certain embodiments, the two sides of each pair of parallel opposite sides are of equal length, i.e. the hexagon is a parallelogon. Parallelogons can be obtained by elongating a parallelogram having 2-fold rotational symmetry or by elongating a rhombus having 2-fold rotational symmetry and additionally being mirror symmetric and having two axes of symmetry.

[0273] In certain embodiments, the six sides of the hexagon, in particular the convex hexagon, are of equal length, i.e. the hexagon is equilateral. Alternatively, the hexagon is non-equilateral and has three sides of equal length and additionally three other sides of equal length. The three sides of equal length and the additionally three other sides of equal length are preferably present alternately. Such hexagons are preferably mirror symmetric and have three axes of symmetry. In another alternative, the hexagon is non-equilateral and has four sides of equal length and additionally two other sides of equal length. This includes in particular hexagons obtained by elongating a rhombus.

[0274] In certain embodiments, the hexagon is non-equilateral and the ratio of the shortest side to the longest side is 1 :4 or less, 1 :3 or less, 1 :2 or less, 1 :1.5 or less or is about 1 :1.

[0275] The sides of the hexagons according to the present application have a length of 0.2 to 10 cm. In certain embodiments, the sides of the hexagons have a length of 0.3 to 8 cm, 0.5 to 4 cm, 0.8 to 3.5 cm or 0.9 to 2.0 cm. In other embodiments, the sides of the hexagons have a length of 2.8 to 8 cm, 2.8 to 7.5 cm, 2.8 to 4 cm, 2.8 to 3.5 cm or 2.8 to 3.2 cm. In particular embodiments, two, three, four or six sides of the hexagons have a length of about 0.5 cm, about 0.9 cm, about 1.5 cm, about 1.8 cm, about 2.8 cm or about 3.2 cm. For example,

[0276] - two sides of the hexagon have a length of about 0.5 cm, about 0.9 cm, or about 1.5 cm, and four sides of the hexagon have a length of about 1.8 cm, about 2.8 cm, or about 3.2 cm, or

[0277] - three sides of the hexagon have a length of about 0.5 cm, about 0.9 cm, or about 1.5 cm, and three sides of the hexagon have a length of about 1.8 cm, about 2.8 cm, or about 3.2 cm, or

[0278] - four sides of the hexagon have a length of about 0.5 cm, about 0.9 cm, or about 1.5 cm, and two sides of the hexagon have a length of about 1.8 cm, about 2.8 cm, or about 3.2 cm.

[0279] The height of the hexagon can be in the range of 0.3 to 17 cm, 0.8 to 12.5 cm, 1.3 to 6 cm, or 1.5 to 3.5 cm. The width of the hexagon can be in the range of 0.4 to 20 cm, 1 to 15 cm, 1.6 to 7 cm, or 1.8 to 4 cm.

[0280] In certain embodiments, the hexagon has an aspect ratio (height to width ratio) of 4:1 or less, 3:1 or less, 2:1 or less, 1.5:1 or less, or √3:2 or less. In particular embodiments, the hexagon has an aspect ratio of √3:2 or less.

[0281] In certain embodiments, the hexagon (in particular a convex hexagon) is an equiangular hexagon. Each internal angle of such a convex hexagon is equal to 120°. Alternatively, the hexagon is non-equiangular and the smallest angle is 60° or more, 80° or more, 90° or more, or 110° or more. In particular, the smallest angle is 60° or more, 80° or more, 90° or more, or 110° or more and less than 120°. In particular embodiments, the hexagon has two internal angles (smaller angles) of the same size and four further internal angles (larger angles) of another same size, wherein the smaller angles are about 90°.

[0282] In another embodiment, the hexagon (in particular a convex hexagon) is a regular hexagon. Such a regular hexagon is preferably mirror-symmetric and has six axes of symmetry and additionally has 6-fold rotational symmetry. In one embodiment, the hexagonal shape is a double hexagon formed by two identical convex hexagons sharing two adjacent vertices of their common sides, wherein the two identical convex hexagons are regular hexagons.

[0283] Further, according to certain embodiments, the hexagon has a perimeter of more than 20 cm 2 , such as more than 24 cm 2more than 30 cm 2 or more than 40 cm 2 and preferably less than 150 cm 2 such as less than 60 cm 2 or less than 35 cm 2 of area.

[0284] Medical patch and medical patch sheet

[0285] According to the present application, the self-adhesive layer structure as described above is used for a medical patch comprising the self-adhesive layer structure arranged on a release liner. The self-adhesive layer structure is also used for a medical patch sheet comprising a plurality of self-adhesive layer structures arranged on a release liner.

[0286] The one or more medical patches can be one or more surface medical patches or one or more transdermal therapeutic systems. In certain embodiments, the one or more medical patches is one or more surface medical patches, in particular for the topical application of capsaicin.

[0287] In one embodiment, the present application relates to a medical patch comprising

[0288] the self-adhesive layer structure as described above and

[0289] a release liner,

[0290] wherein the release liner is coextensive with the self-adhesive layer structure or extends beyond the boundaries of the self-adhesive layer structure in all directions.

[0291] In another embodiment, the present application relates to a medical patch sheet comprising

[0292] two or more self-adhesive layer structures as described above and

[0293] a release liner,

[0294] wherein the release liner is coextensive with the self-adhesive layer structures or extends beyond the boundaries of the self-adhesive layer structures in all directions.

[0295] The release liner protects the one or more self-adhesive layer structures and has to be removed prior to application. The one or more self-adhesive layer structures can be easily peeled off from the release liner and thus applied to the patient's skin individually or jointly. In certain embodiments, the release liner in the medical patch sheet is not intended to be detached jointly with the one or more self-adhesive layer structures, but remains intact after removal of the one or more self-adhesive layer structures from the patch sheet. This is advantageous because it is easier to peel off the self-adhesive layer structures from the release liner extending over the area of the border layer structure and because it is not necessary to remove the release liner separately for each self-adhesive layer structure. Thus, in such embodiments, the release liner does not comprise any means for jointly tearing off parts of the release liner.

[0296] In case the release liner extends beyond the borders of the self-adhesive layer structures, the release liner can be covered by a border layer structure having the same layer design (i.e. comprising a backing layer, an active layer comprising polymer I and an active agent and optionally a skin contact layer) and the same layer thicknesses and compositions as the self-adhesive layer structures and adjoining the one or more self-adhesive layer structures and jointly extending with the outer borders of the release liner. Such medical patch sheets can conveniently be prepared by first providing a sheet of the desired layer structure laminated with a release liner and then dividing the layer structure by means of a deep controlled punching, cutting or scoring through the backing layer, the active layer and optionally the skin contact layer, if present, but leaving at least a part of the release liner in order to obtain a plurality of self-adhesive layer structures arranged on the release liner surrounded by a border layer structure.

[0297] By using a plurality of self-adhesive layer structures, the surface of the skin area to be treated can be spanned by tiling the self-adhesive layer structures side by side without wrinkling. In doing so, the one or more hexagonal shapes of the self-adhesive layer structures allow to avoid gaps and / or overlaps.

[0298] The number of self-adhesive layer structures provided for peeling off from the release liner depends on the one or more dimensions of the self-adhesive layer structures. Suitable medical patch sheets comprise 2 to 400, 4 to 300, 6 to 120 or 8 to 30 self-adhesive layer structures. In certain embodiments, the medical patch sheet comprises 2 to 15 or 150 to 300 self-adhesive layer structures. In particular embodiments, the medical patch sheet comprises 3, 4, 5, 6, 7 or 8 self-adhesive layer structures. Alternatively, the medical patch sheet can comprise 150, 180, 200, 240 or 300 self-adhesive layer structures. The self-adhesive layer structures can be identical or different.

[0299] The self-adhesive layer structures can be arranged on the release liner in any pattern, adjoining each other (tiled plane) or providing small gaps to facilitate grasping the individual self-adhesive layer structures (e.g. as shown in Figure 2a , Figure 2b and Figure 2cIn certain embodiments, the self-adhesive layer structures are arranged on the release liner in a space-saving manner. In particular, the self-adhesive layer structures are arranged side-by-side on the release liner. Thus, the self-adhesive layer structures can be arranged in two or more parallel rows with respect to the longitudinal axis of the release liner, wherein preferably each row comprises 2 to 20, 3 to 12 or 4 to 8 self-adhesive layer structures. For example, the self-adhesive layer structures can be arranged in 20 rows, wherein each row comprises 15 self-adhesive layer structures, in particular 15 identical self-adhesive layer structures.

[0300] In certain embodiments, the self-adhesive layer structures are densely packed. Preferred self-adhesive layer structures of a densely packed plane are parallelograms, in particular regular hexagons. The self-adhesive layer structures can also have a hexagonal shape selected from the group consisting of regular hexagons and / or double hexagons formed by two identical regular hexagons sharing two adjacent vertices and their common edge. The self-adhesive layer structures can be separated from each other or connected to each other.

[0301] In certain embodiments, the self-adhesive layer structures are adjacent to each other by sharing two adjacent vertices and their common edge and separated from each other by the common edge which is cut in order to be peeled off the release liner independently. Alternatively, the self-adhesive layer structures are adjacent to each other by sharing two adjacent vertices and their common edge and connected to each other by the common edge which is weakened in order to be easily torn off. In particular, the common edge is perforated in order to be easily torn off. The medical patch sheet can also comprise self-adhesive layer structures which are adjacent to each other by sharing two adjacent vertices and their common edge, wherein some of the self-adhesive layer structures are separated from each other by the common edge which is cut in order to be peeled off the release liner independently and some are connected to each other by the common edge which is weakened in order to be easily torn off. For example, the self-adhesive layer structures can be arranged in two or more parallel rows with respect to the longitudinal axis of the release liner, wherein each row comprises 2 to 20 self-adhesive layer structures which are adjacent to each other by sharing two adjacent vertices and their common edge, wherein the rows are separated from each other in order to be peeled off independently and the self-adhesive layer structures within a row are connected to each other by the common edge which is perforated in order to be easily torn off. In a particular embodiment, all self-adhesive layer structures are separated from each other by the common edge which is cut in order to be peeled off the release liner independently.

[0302] In certain embodiments, the self-adhesive layer structures are connected to each other by at least one and preferably two or more common junction bridges for joint peeling from the release liner. The junction bridge(s) provide one or more single points at which the self-adhesive layer structures are connected to each other, even though they are separated from each other by at least partially cut common edges. This enables the self-adhesive layer structures thus connected to be joint peeled from the release liner to be applied to the patient's skin, which is particularly advantageous in the case of a large number and / or small area of self-adhesive layer structures. Alternatively, some of the junction bridges can be unfastened, e.g. torn off, to enable a lower number of self-adhesive layer structures thus connected to be joint peeled. In certain embodiments, the common junction bridges are provided at the apexes and connect at least two and preferably three self-adhesive layer structures. Alternatively, the common junction bridges can be provided at one edge and connect two self-adhesive layer structures. In one preferred medical patch sheet, adjacent self-adhesive layer structures are all pairwise connected to each other by at least two common junction bridges provided at two adjacent apexes or at their common edge, preferably at two adjacent apexes. In particular embodiments, adjacent self-adhesive layer structures are all connected to each other in groups of three by common junction bridges provided at the common apexes. This particularly relates to densely packed planar self-adhesive layer structures. Thus, in one embodiment of the medical patch sheet according to the present application, the self-adhesive layer structures are regular hexagons and connected to each other by at least one junction bridge for joint peeling from the release liner, wherein adjacent self-adhesive layer structures are all connected to each other in groups of three by common junction bridges provided at the common apexes (as shown in Figure 3 Fig. 2).

[0303] In certain embodiments, the self-adhesive layer structures have a hexagonal shape selected from a total of two or three different shapes. In particular embodiments, the self-adhesive layer structures have a hexagonal shape comprising a convex hexagon and a double hexagon formed from two identical convex hexagons sharing two adjacent apexes and a common edge, in particular a regular hexagon and a double hexagon formed from two identical regular hexagons. Alternatively, the self-adhesive layer structures all have the same hexagonal shape. In particular embodiments, the self-adhesive layer structures are double hexagons formed from two identical convex hexagons sharing two adjacent apexes and their common edge, in particular double hexagons formed from two identical regular hexagons. In this context, the (regular) convex hexagons or the double hexagons formed from two identical (regular) convex hexagons are congruent, respectively.

[0304] The self-adhesive layer structures of the medical patch sheet according to the present application can comprise one or more active agents, which can be the same or different.

[0305] In certain embodiments, a medical patch (a single medical patch) comprises capsaicin in an amount of about 179 mg or in an amount of about 60 mg, about 45 mg, about 30 mg, about 25.5 mg, about 10 mg, or about 1 mg. Likewise, a medical patch sheet (all medical patches in the patch sheet as a whole) can comprise capsaicin in an amount of about 179 mg or less. Preferred medical patch sheets comprise

[0306] - 3 self-adhesive layer structures each comprising capsaicin in an amount of about 60 mg, or

[0307] - 4 self-adhesive layer structures each comprising capsaicin in an amount of about 45 mg, or

[0308] - 6 self-adhesive layer structures each comprising capsaicin in an amount of about 30 mg, or

[0309] - 7 self-adhesive layer structures each comprising capsaicin in an amount of about 25.5 mg.

[0310] Alternatively, preferred medical patch sheets comprise up to 300 self-adhesive layer structures each comprising capsaicin in an amount of about 0.6 mg, wherein preferably the self-adhesive layer structures are regular hexagons and are connected to each other by common junctional bridges for joint peeling from the release liner, wherein adjacent self-adhesive layer structures are connected to each other in groups of three by common junctional bridges provided at common vertices.

[0311] In certain embodiments, a medical patch (a single medical patch) has a release area of 0.1 cm 2 to 280 cm 2 , 0.6 cm 2 to 150 cm 2 , or 1.5 cm 2 to 35 cm 2 . In particular embodiments, a medical patch has an area of greater than 20 cm 2 , such as greater than 24 cm 2 , greater than 30 cm 2 , or greater than 40 cm 2 , and preferably less than 150 cm 2 , such as less than 60 cm 2 , or less than 35 cm 2 . In certain embodiments, a medical patch sheet (all medical patches in the patch sheet as a whole) has a release area of 1 cm 2 to 300 cm 2 .

[0312] Method of treatment / medical use

[0313] The medical patch or medical patch sheet according to the present application can be suitable for use in a method of treatment, and in particular in a method of treating a human patient. The condition or disease to be treated depends on the active agent contained in the patch.

[0314] If the active agent is a capsaicin, the medical patch or medical patch sheet according to the present application is in particular suitable for use in a method of treating neuropathic pain, in particular chronic neuropathic pain, preferably including post-herpetic neuralgia, post-surgical neuralgia (such as post-herniorrhaphy pain, post-thoracotomy pain or post-mastectomy pain), post-traumatic neuropathy, polyneuropathy (such as painful diabetic neuropathy, chemotherapy-induced neuropathy, tumor-induced neuropathy, HIV-related neuropathy, alcohol-related neuropathy, small-fiber neuropathy) or complex regional pain syndrome, radiculopathy or crush injury syndrome (such as carpal tunnel syndrome), further preferably peripheral neuropathic pain, neuropathic pain of the hands and feet associated with post-herpetic neuralgia or diabetic peripheral neuropathy (DPN), post-surgical neuropathic pain, joint pain or cancer pain.

[0315] In connection with the above, the medical patch or (part of the medical patch sheet) according to the present application is preferably applied to at least one body surface of the patient, in particular selected from the back, the buttocks, the leg, the foot or the hand. The preferred application time of the medical patch or medical patch sheet according to the present application is less than or about 60 minutes on the back, the buttocks or the leg, and less than or about 30 minutes on the foot or the hand.

[0316] Manufacturing method

[0317] The one or more medical patches or the one or more medical patch sheets according to the present application can be manufactured by a conventional manufacturing method, such as a solvent casting method, which comprises the steps of preparing a coating composition comprising all components of the active layer, and coating and drying the coating composition.

[0318] In certain embodiments, in particular in case of a capsaicin-containing patch, the method for manufacturing the medical patch or medical patch sheet according to the present application comprises the following steps:

[0319] A. 1.1) coating an active agent-containing coating composition comprising

[0320] (i) a polymer I, and

[0321] (ii) an active agent;

[0322] 1.2) drying the coated coating composition to provide an active agent-containing self-adhesive layer structure;

[0323] 1.3) Laminating the active agent-containing self-adhesive layer structure with a backing layer.

[0324] Polymer I is in particular at least one silicone-based polymer, which is preferably non-curable and thus typically applied by a solvent-based process. Thus, the at least one silicone-based polymer is preferably provided in a solvent, wherein the solids content in the solvent is preferably from 40 to 75 wt.%. The solvent is preferably selected from alcoholic solvents, in particular methanol, ethanol, isopropanol and mixtures thereof, and non-alcoholic solvents, in particular ethyl acetate, hexane, heptane, petroleum ether, toluene and mixtures thereof, and more preferably from non-alcoholic solvents, and most preferably is ethyl acetate or n-heptane.

[0325] In particular, the active agent is capsaicin and is preferably uniformly dissolved or dispersed in the active agent-containing coating composition. In certain embodiments, the capsaicin is provided in an amphiphilic solvent, such as diethylene glycol monoethyl ether, 1,3-butanediol, dipropylene glycol or 2,2-dimethyl-4-hydroxymethyl-1,3-dioxolane, and the capsaicin formulation is dispersed in the capsaicin-containing coating composition in the form of small droplets (microreservoir system). The amphiphilic solvent cannot be mixed or can only be mixed to a small extent with the solvent used for the silicone-based polymer.

[0326] The coated active agent-containing coating composition is solidified by drying. Drying is preferably carried out at a temperature of from 20 to 60°C or from 30 to 40°C.

[0327] In the case of patches which additionally comprise a skin contact layer, these can be manufactured using a process comprising the following steps:

[0328] A. 1.1) Coating an active agent-containing coating composition comprising

[0329] (i) Polymer I, and

[0330] (ii) an active agent;

[0331] 1.2) Drying the coated coating composition to form an active layer;

[0332] 1.3) Laminating the active layer with a backing layer;

[0333] 2.1) Coating a non-active agent-containing coating composition comprising

[0334] (i) at least one alkenyl-substituted polydiorganosiloxane,

[0335] (ii) at least one organosiloxane, which contains silicon-bonded hydrogen atoms, and

[0336] (iii) at least one catalyst for the reaction of SiH groups with Si-alkenyl groups;

[0337] 2.2) crosslinking the active agent-free coating composition at a temperature of 50 °C to 150 °C or by applying UV light to form a skin contact layer;

[0338] 2.3) laminating the skin contact layer with a release liner.

[0339] After curing, i.e. crosslinking of the reactive groups of the silicone polymer, the active agent-free coating composition forms a silicone gel adhesive of the skin contact layer. Crosslinking is preferably carried out at a temperature of 40 °C to 140 °C.

[0340] The active layer and the skin contact layer are preferably prepared separately as indicated above and are then laminated together by removing the foil and then laminating the open sides of the two layers together in order to obtain a self-adhesive layer structure of a medical patch or two or more self-adhesive layer structures of a medical patch sheet constituting a medical patch sheet. Thus, the method can further comprise the following steps:

[0341] A. 3.1) removing the foil from the active layer and the skin contact layer;

[0342] 3.2) laminating the open side of the active layer to the open side of the skin contact layer to provide an active agent-containing self-adhesive layer structure.

[0343] Preparation of the active layer can be carried out before or after preparation of the skin contact layer or preparation of both layers can be carried out in parallel.

[0344] The active agent-containing self-adhesive layer structure is then preferably divided into one or more self-adhesive layer structures having a hexagonal shape according to the present application by, for example, punching or cutting through the backing layer and the active layer and optionally the skin contact layer and leaving the release liner. Thus, the method for manufacturing a medical patch or a medical patch sheet according to the present application can further comprise the following steps:

[0345] B. dividing at least one hexagonal shape from the active agent-containing self-adhesive layer structure to obtain a medical patch or a medical patch sheet.

[0346] In certain embodiments, the dividing is carried out by punching, in particular by punching using a steel rule die. In some embodiments, the punching tool can be discontinuous to provide a linking bridge.

[0347] The present application also relates to a medical patch or a medical patch sheet obtainable by the above described method.

[0348] Example

[0349] The present application will now be more fully described with reference to the accompanying examples. It is to be understood, however, that the following description is illustrative only and should not be considered limiting in any way. The numerical values provided in the examples with respect to the amounts of ingredients in the compositions or area weights can vary slightly due to manufacturing variability.

[0350] Example 1:

[0351] Preparation of capsaicin-containing medical patch

[0352] The medical patch according to Example 1 can or can not comprise another skin contact layer. Thus, the steps of preparing and coating a coating composition without active agent and laminating the resulting active agent-free layer with a previously prepared capsaicin-containing layer are optional.

[0353] Capsaicin-containing coating composition

[0354] The formulation of the capsaicin-containing coating composition is summarized in Table 1.1 below. The solid value refers to the amount (Amt) in weight %.

[0355] Table 1.1

[0356]

[0357] Preparation of capsaicin-containing coating composition

[0358] Transcutol was initially thickened in the presence of ethyl cellulose under stirring (100-300 rpm).

[0359] The silicone mixture and silicone oil were charged into a vessel and stirred (100-300 rpm) for at least 5 min, then the ethyl cellulose / Transcutol solution was added. After further stirring for 10 min (100-300 rpm), the capsaicin was added. The mixture was then stirred at about 250-300 rpm until a homogeneous mixture was obtained (at least 60 min).

[0360] Coating of the capsaicin-containing coating composition

[0361] The resulting capsaicin-containing coating composition was coated on a fluoropolymer coated polyester film (Scotchpak™ 1022). The solvent was removed at room temperature for about 20-30 min.

[0362] The coating thickness was chosen such that the removal of the solvent resulted in an area weight of the capsaicin-containing layer of about 80 g / m 2 .

[0363] The resulting capsaicin-containing microreservoir layer was then laminated with a backing layer (polyester film, 19 μm).

[0364] Optionally, the foil of the adhesive equipment used to coat and dry the capsaicin- containing layer is removed to obtain a capsaicin-containing self-adhesive layer structure comprising a backing layer and a capsaicin-containing layer, wherein the capsaicin- containing layer is attached to the backing layer.

[0365] Active agent-free coating composition

[0366] In Example 1, the formulation of the active agent-free coating composition is summarized in Table 1.2 below. The solid value refers to the amount (Amt) in weight %.

[0367] Table 1.2

[0368]

[0369] Preparation of the active agent-free coating composition

[0370] The two components are individually weighed and then the components A and B are added to a mixing vessel in sequence. Then, the mixture is mixed at about 200 rpm for about 5 min until a homogeneous mixture of components A and B is obtained.

[0371] Coating of the active agent-free coating composition

[0372] The resulting active agent-free coating composition is coated on the foil of the adhesive equipment within a time frame of about 30 min. The coating temperature is set to 120 °C. The resulting active agent-free layer is heated at this temperature for about 40 min.

[0373] The coating thickness is chosen such that the removal of the solvent results in a layer thickness of about 230 g / m2of the active agent-free (skin contact) layer. 2

[0374] The resulting active agent-free (skin contact) layer is laminated with a release liner (FEP, fluorinated ethylene propylene, 125 pm).

[0375] Lamination of the capsaicin-containing layer with the active agent-free (skin contact) layer

[0376] The active agent-free (skin contact) layer is then laminated with the capsaicin- containing layer. For this purpose, the foil of the adhesive equipment used to coat and dry the layer is removed and the resulting open side lamination of the capsaicin- containing layer and the active agent-free (skin contact) layer is brought together, resulting in a capsaicin-containing self-adhesive layer structure comprising a backing layer, a capsaicin-containing layer and an active agent-free (skin contact) layer, wherein the capsaicin-containing layer is attached to the backing layer and the active agent-free (skin contact) layer is attached to the capsaicin-containing layer, and wherein the structure is closed by a release liner attached to the active agent-free (skin contact) layer.

[0377] ​Preparation of medical patches and medical patch sheets

[0378] Without damaging the common release liner, individual medical patches are punched out from the capsaicin-containing self-adhesive layer structure as obtained, which comprises a backing layer and a capsaicin-containing layer or a backing layer, a capsaicin-containing layer and an active agent-free (skin contact) layer.

[0379] Then, the medical patch sheets are sealed into a primary packaging material pouch.

[0380] Examples 2A-M and reference example:

[0381] Evaluation of the performance of placebo medical patches and placebo medical patch sheets

[0382] Different medical patches and medical patch sheets according to the application are prepared based on an active agent-free adhesive layer (but not active agent-free) (Examples 2A-M). Medical patches having a rectangular shape of 20 cm x 14 cm are prepared in the same way (reference example).

[0383] Coating composition

[0384] The formulation of the coating composition is summarized in Table 2.1 below. The solid % value refers to the amount (Amt) in weight %.

[0385] Table 2.1

[0386]

[0387] Preparation of medical patches and medical patch sheets

[0388] Without damaging the common release liner, individual medical patches are punched out from the active agent-free self-adhesive layer structure as obtained as described above, which comprises a backing layer and an active agent-free layer, positioned on the release liner. In this way, medical patches and medical patch sheets having a hexagonal shape as shown in Table 2.2 are obtained.

[0389] Then, the performance of the medical patches and medical patch sheets is evaluated by applying one or more respective medical patches or medical patch sheets to different skin areas, in particular the ankle / finger, and the coverage of the skin area to be treated is evaluated (+: poor coverage to +++: good coverage) as well as the occurrence of wrinkles (*: no wrinkles / low degree of wrinkles to ***: high degree of wrinkles).

[0390] The results are shown in Table 2.2 below.

[0391] Table 2.2

[0392]

[0393] Overall, the medical patches / medical patch pieces with a hexagonal shape show improved coverage and a lower degree of wrinkling compared to medical patches with a rectangular shape. Different medical patches / medical patch pieces with a hexagonal shape perform similarly well on substantially planar or cylindrical surfaces such as the back, the thigh, the lower leg or the arm.

[0394] On uneven or curved surfaces, such as on the ankle or the fingers, the performance of the single hexagon is slightly better than that of the double hexagon. Smaller hexagonal shapes provide better coverage and a lower degree of wrinkling compared to larger hexagonal shapes. Hexagonal shapes with a side length of 1.55 cm or 1.8 cm achieve the best treatment results. Hexagonal shapes with a side length of 0.9 cm are less good in handling, but provide good coverage and a lower degree of wrinkling.

[0395] In the case of curved surfaces, gapless coverage is only possible by minimally overlapping the edges of the hexagonal shapes.

[0396] In addition, it has been proven that hexagonal shapes connected by a linking bridge are very good in handling. The single hexagonal shape or the hexagonal shape component can be separated (without using cutting tools), or all hexagonal shapes of the medical patch piece can be applied together.

[0397] The selection of one or more of the most useful medical patches / medical patch pieces depends on the respective skin area to be treated.

[0398] The present invention relates in particular to the following further items:

[0399] 1. A self-adhesive layer structure for a medical patch, the self-adhesive layer structure having a hexagonal shape and comprising:

[0400] A) a backing layer; and

[0401] B) an active layer, the active layer comprising a polymer I and an active agent;

[0402] wherein

[0403] the backing layer and the active layer jointly extend and provide the hexagonal shape of the self-adhesive layer structure,

[0404] the hexagonal shape comprises at least one hexagon, wherein

[0405] each pair of opposite sides of the hexagon is parallel, and

[0406] the sides of the hexagon have a length of 0.2 to 10 cm.

[0407] 2. The self-adhesive layer structure according to item 1, wherein

[0408] The self-adhesive layer structure is a pressure sensitive adhesive layer structure.

[0409] 3. The self-adhesive layer structure according to item 1 or 2, wherein

[0410] The at least one hexagon is at least one convex hexagon.

[0411] 4. The self-adhesive layer structure according to item 3, wherein

[0412] The hexagonal shape comprises one or two convex hexagons.

[0413] 5. The self-adhesive layer structure according to any one of items 1 to 4, wherein

[0414] The hexagonal shape is a convex hexagon.

[0415] 6. The self-adhesive layer structure according to any one of items 1 to 4, wherein

[0416] The hexagonal shape is a double hexagon formed by two identical convex hexagons sharing two adjacent vertices and a common edge.

[0417] 7. The self-adhesive layer structure according to item 6, wherein

[0418] The common edge is perforated for easy tearing.

[0419] 8. The self-adhesive layer structure according to any one of items 1 to 7, wherein

[0420] The hexagon is a parallelogon.

[0421] 9. The self-adhesive layer structure according to any one of items 1 to 8, wherein

[0422] The hexagon is equilateral, or

[0423] The hexagon is non-equilateral and has

[0424] three edges of equal length and three other edges of another equal length, or

[0425] four edges of equal length and two other edges of another equal length.

[0426] 10. The self-adhesive layer structure according to any one of items 1 to 9, wherein

[0427] The hexagon is non-equilateral and the ratio of the shortest side to the longest side is 1 :4 or less, 1 :3 or less, 1 :2 or less, 1 :1.5 or less, or about 1 :1.

[0428] 11. The self-adhesive layer structure according to any one of items 1 to 10, wherein

[0429] The sides of the hexagon have a length of 0.3 to 8 cm, 0.5 to 4 cm, 0.8 to 3.5 cm, or 0.9 to 2 cm.

[0430] 12. The self-adhesive layer structure according to any one of items 1 to 11, wherein

[0431] Two, three, four, or six sides of the hexagon have a length of about 0.5 cm, about 0.9 cm, about 1.5 cm, about 1.8 cm, about 2.8 cm, or about 3.2 cm.

[0432] 13. The self-adhesive layer structure according to any one of items 1 to 12, wherein

[0433] The hexagon has an aspect ratio of 4: 1 or less, 3: 1 or less, 2: 1 or less, 1.5: 1 or less, or √3: 2 or less.

[0434] 14. The self-adhesive layer structure according to any one of items 1 to 13, wherein

[0435] The hexagon is equiangular.

[0436] 15. The self-adhesive layer structure according to any one of items 1 to 13, wherein

[0437] The hexagon is non-equilateral, and

[0438] The smallest angle is 60° or greater, 80° or greater, 90° or greater, or 110° or greater.

[0439] 16. The self-adhesive layer structure according to any one of items 1 to 9 and 11 to 14, wherein

[0440] The hexagon is a regular hexagon.

[0441] 17. The self-adhesive layer structure according to any one of items 1 to 15, wherein

[0442] The active agent is at least one analgesic agent.

[0443] 18. The self-adhesive layer structure according to item 17, wherein

[0444] The active agent is selected from the group consisting of buprenorphine, capsaicin, diclofenac, fentanyl, ibuprofen, and lidocaine.

[0445] 19. The self-adhesive layer structure according to item 17 or 18, wherein

[0446] The active agent is capsaicin.

[0447] 20. The self-adhesive layer structure according to item 19, wherein

[0448] The active layer comprises the capsaicin in a concentration of 2 wt-% to 20 wt-%, 5 wt-% to 15 wt-%, 5 wt-% to 10 wt-%, or about 8 wt-%.

[0449] 21. The self-adhesive layer structure according to item 19 or 20, wherein

[0450] The self-adhesive layer structure comprises the capsaicin in an amount of 0.5 to 180 mg, 1.2 to 90 mg, or 19 to 45 mg.

[0451] 22. The self-adhesive layer structure according to any one of items 19 to 21, wherein

[0452] The self-adhesive layer structure comprises the capsaicin in an amount of about 179 mg, about 60 mg, about 45 mg, about 30 mg, about 25.5 mg, about 10 mg, or about 1 mg.

[0453] 23. The self-adhesive layer structure according to any one of items 1 to 22 for transdermal or topical delivery of the active agent.

[0454] 24. The self-adhesive layer structure according to any one of items 1 to 23, wherein

[0455] The polymer I is a pressure sensitive adhesive polymer.

[0456] 25. The self-adhesive layer structure according to any one of items 1 to 24, wherein

[0457] The polymer I is selected from silicone-based polymers, acrylic polymers, silicone-acrylic hybrid polymers, and polymers based on natural or synthetic rubbers.

[0458] 26. The self-adhesive layer structure according to any one of items 1 to 25, wherein

[0459] The polymer I is a silicone-based polymer obtainable by polycondensation of a silanol-terminated polydimethylsiloxane with a silicate resin.

[0460] 27. The self-adhesive layer structure according to any one of items 1 to 26, comprising

[0461] A) the backing layer;

[0462] B) the active layer; and

[0463] C) the skin contact layer;

[0464] wherein

[0465] the backing layer, the active layer and the skin contact layer collectively extend and provide the hexagonal shape of the self-adhesive layer structure.

[0466] 28. The self-adhesive layer structure according to item 27, wherein

[0467] the skin contact layer is an adhesive and preferably a pressure sensitive adhesive.

[0468] 29. The self-adhesive layer structure according to item 27 or 28, wherein

[0469] the skin contact layer comprises a polymer II.

[0470] 30. The self-adhesive layer structure according to item 29, wherein

[0471] the polymer II is a polymer or mixture of polymers, wherein the active agent is substantially insoluble.

[0472] 31. The self-adhesive layer structure according to item 29 or 30, wherein

[0473] the polymer II is a pressure sensitive adhesive or mixture of pressure sensitive adhesives.

[0474] 32. The self-adhesive layer structure according to any one of items 29 to 31, wherein

[0475] the polymer II is a polymer or mixture of polymers selected from the group consisting of silicone-acrylic hybrid polymers, silicone-based polymers, silicone gel adhesives and polymers based on natural or synthetic rubbers.

[0476] 33. The self-adhesive layer structure according to any one of items 29 to 32, wherein

[0477] the polymer II is a polymer or mixture of polymers selected from the group consisting of silicone-based polymers and silicone gel adhesives.

[0478] 34. The self-adhesive layer structure according to any one of items 29 to 33, wherein

[0479] the polymer II is a silicone gel adhesive.

[0480] 35. The self-adhesive layer structure according to item 27 or 28, wherein

[0481] The skin contact layer comprises a silicone gel adhesive.

[0482] 36. The self-adhesive layer structure according to item 34 or 35, wherein

[0483] The silicone gel adhesive can be obtained by reacting a gel producing composition comprising (i) at least one alkenyl-substituted polydiorganosiloxane, (ii) at least one organosiloxane containing silicon-bonded hydrogen atoms, and (iii) at least one catalyst for the reaction of SiH groups with Si-alkenyl groups.

[0484] 37. The self-adhesive layer structure according to any one of items 34 to 36, wherein

[0485] The silicone gel adhesive can be obtained by reacting a gel producing composition comprising (i) a copolymer of vinylmethylsiloxane and dimethylsiloxane and (ii) a methylhydrogenpolysiloxane having trimethylsilyl end groups in the presence of (iii) a platinum catalyst.

[0486] 38. The self-adhesive layer structure according to any one of items 34 to 37, wherein

[0487] The silicone gel adhesive is a silicate resin-reinforced silicone gel adhesive containing about 2 wt.% to about 45 wt.% or about 20 wt.% to about 30 wt.% of at least one hydroxyl-substituted silicate resin.

[0488] 39. The self-adhesive layer structure according to any one of items 1 to 38, wherein

[0489] The saturation concentration of the active agent in the skin contact layer is less than 0.1 wt.%, less than 0.05 wt.%, less than 0.02 wt.% or less than 0.01 wt.%.

[0490] 40. The self-adhesive layer structure according to any one of items 1 to 39, wherein

[0491] The active layer comprises a further excipient or additive selected from the group consisting of further polymers, crosslinking agents, crystallization inhibitors, solubilizers, fillers, adhesives, plasticizers, stabilizers, softeners, skin care substances, penetration enhancers, pH adjusting agents, and preservatives.

[0492] 41. The self-adhesive layer structure according to item 40, wherein

[0493] The active layer comprises a further polymer selected from dimethylpolysiloxane and ethyl cellulose.

[0494] 42. The self-adhesive structure according to item 40 or 41, wherein

[0495] The active layer comprises a permeation enhancer selected from diethylene glycol monoethyl ether.

[0496] 43. A medical patch comprising

[0497] The self-adhesive structure according to any one of items 1 to 42 and

[0498] a release liner,

[0499] wherein the release liner coextends or extends beyond the borders of the self-adhesive structure in all directions.

[0500] 44. A medical patch sheet comprising

[0501] two or more self-adhesive structures according to any one of items 1 to 42 and

[0502] a release liner,

[0503] wherein the release liner coextends or extends beyond the borders formed by all self-adhesive structures in all directions.

[0504] 45. The medical patch sheet according to item 44, comprising

[0505] 2 to 400, 4 to 300, 6 to 120 or 8 to 30 self-adhesive structures.

[0506] 46. The medical patch sheet according to item 45, comprising

[0507] 2 to 15 or 150 to 300 self-adhesive structures.

[0508] 47. The medical patch sheet according to item 45 or 46, comprising

[0509] 3, 4, 5, 6, 7 or 8 self-adhesive structures.

[0510] 48. The medical patch sheet according to any one of items 44 to 47, wherein

[0511] the self-adhesive structures are arranged in two or more parallel rows relative to the longitudinal axis of the release liner, wherein

[0512] each row preferably comprises 2 to 20, 3 to 12 or 4 to 8 self-adhesive structures.

[0513] 49. The medical patch according to any one of items 44 to 48, wherein

[0514] The self-adhesive layer structure is closely paved on a flat surface.

[0515] 50. The medical patch according to any one of items 44 to 49, wherein

[0516] The self-adhesive layer structures are adjacent to each other by sharing two adjacent vertices and their common edges and

[0517] separated from each other by the common edge, which is cut so as to be individually peeled from the release liner, or

[0518] By being connected to each other by the common edges, the common edges are weakened to facilitate tearing.

[0519] 51. The medical patch according to item 50, wherein

[0520] All self-adhesive layer structures are separated from each other by the common edge, which is cut so as to be individually peeled from the release liner.

[0521] 52. The medical patch according to item 51, wherein

[0522] The common edge is perforated to facilitate tearing.

[0523] 53. The medical patch according to any one of items 44 to 49, wherein

[0524] The self-adhesive layer structures are connected to each other by at least one and preferably two or more common bonding bridges for joint peeling from the release liner.

[0525] 54. The medical patch according to item 53, wherein

[0526] The public bridge provides

[0527] at a vertex and connecting at least two and preferably three self-adhesive layer structures, or

[0528] At one edge, two self-adhesive layer structures are connected.

[0529] 55. The medical patch according to item 53 or 54, wherein

[0530] Adjacent self-adhesive layer structures are all connected to each other in pairs by at least two common connecting bridges provided at two adjacent vertices or at their common sides, preferably at the two adjacent vertices.

[0531] 56. The medical patch according to items 53 to 55, wherein

[0532] The adjacent self-adhesive layer structures are all connected to each other in groups of three via a common junction bridge provided at a common vertex.

[0533] 57. The medical patch sheet according to any one of items 44 to 56, wherein

[0534] The self-adhesive layer structures have a hexagonal shape selected from a total of two or three different shapes.

[0535] 58. The medical patch sheet according to item 47, wherein

[0536] The self-adhesive layer structures have a hexagonal shape comprising a convex hexagon and a double hexagon formed from two identical convex hexagons sharing two adjacent vertices and a common edge.

[0537] 59. The medical patch sheet according to any one of items 44 to 56, wherein

[0538] The self-adhesive layer structures all have the same hexagonal shape.

[0539] 60. The medical patch sheet according to item 59, wherein

[0540] The self-adhesive layer structures are double hexagons formed from two identical convex hexagons sharing two adjacent vertices and a common edge.

[0541] 61. A method for manufacturing a medical patch according to item 43 or a medical patch sheet according to any one of items 44 to 60, the method comprising the steps of:

[0542] A. 1.1) coating an active agent-containing coating composition comprising

[0543] (i) a polymer I, and

[0544] (ii) an active agent, on a release liner;

[0545] 1.2) drying the coated coating composition to provide an active agent-containing self-adhesive layer structure;

[0546] 1.3) laminating the active agent-containing self-adhesive layer structure with a backing layer; and

[0547] B. singulating at least one hexagonal shape from the active agent-containing self-adhesive layer structure to obtain the medical patch or the medical patch sheet.

Claims

1. A self-adhesive layer structure for a medical patch, the self-adhesive layer structure having a hexagonal shape and comprising: A) backing layer; as well as B) an active layer comprising polymer I and an active agent; in The backing layer and the active layer are coextensive and provide the hexagonal shape of the self-adhesive layer structure, The hexagonal shape comprises at least one hexagon, wherein Each pair of opposite sides of the hexagon is parallel, and The sides of the hexagon have a length of 0.2 to 10 cm.

2. The self-adhesive layer structure according to claim 1, wherein The self-adhesive layer structure is a pressure-sensitive adhesive layer structure.

3. The self-adhesive layer structure according to claim 1 or 2, wherein The at least one hexagon is at least one convex hexagon.

4. The self-adhesive layer structure according to claim 3, wherein The hexagonal shape includes one or two convex hexagons.

5. The self-adhesive layer structure according to any one of claims 1 to 4, wherein The hexagonal shape is a convex hexagon.

6. The self-adhesive layer structure according to any one of claims 1 to 4, wherein The hexagonal shape is a double hexagon formed by two identical convex hexagons that share two adjacent vertices and their common sides.

7. The self-adhesive layer structure according to any one of claims 3 to 6, wherein The hexagon is equilateral, or The hexagon is non-equilateral and has three sides of equal length and three other sides of equal length, or Four sides of equal length and two other sides of equal length.

8. The self-adhesive layer structure according to any one of claims 1 to 7, wherein The sides of the hexagon have a length of 0.3 to 8 cm, 0.5 to 4 cm, 0.8 to 3.5 cm, or 0.9 to 2 cm.

9. The self-adhesive layer structure according to any one of claims 1 to 8, wherein The hexagon is a regular hexagon.

10. The self-adhesive layer structure according to any one of claims 1 to 9, wherein The active agent is capsaicin, and wherein The active layer preferably comprises the capsaicinoid in a concentration of 1 wt-% to 15 wt-%, 2 wt-% to 12 wt-%, 4 wt-% to 10 wt-%, or about 8 wt-%.

11. A medical patch comprising The self-adhesive layer structure according to any one of claims 1 to 10 and Release liner, The release liner is coextensive with the self-adhesive layer structure or extends beyond the boundaries of the self-adhesive layer structure in all directions.

12. A medical patch comprising Two or more self-adhesive layer structures according to any one of claims 1 to 10 and Release liner, The release liner is coextensive with the self-adhesive layer structure or extends in all directions beyond the boundaries formed by all the self-adhesive layer structures.

13. The medical patch sheet according to claim 12, comprising 2 to 400, 4 to 300, 6 to 120 or 8 to 30 self-adhesive layer structures, wherein preferably the self-adhesive layer structures are closely laid on a flat surface.

14. The medical patch according to claim 12 or 13, wherein The self-adhesive layer structures are adjacent to each other by sharing two adjacent vertices and their common edges and separated from each other by the common edge, which is cut so as to be independently peeled from the release liner, or By being connected to each other by the common edges, the common edges are weakened to facilitate tearing.

15. The medical patch sheet according to any one of claims 12 to 14, wherein The self-adhesive layer structures are connected to each other by at least one and preferably two or more common bonding bridges for joint peeling from the release liner, and wherein The common connecting bridge preferably provides at a vertex and connecting at least two and preferably three self-adhesive layer structures, or At one edge, two self-adhesive layer structures are connected.

16. The medical patch sheet according to any one of claims 12 to 15, wherein The self-adhesive layer structures have a hexagonal shape selected from a total of two or three different shapes, or wherein the self-adhesive layer structures all have the same hexagonal shape.

17. A method for producing the medical patch according to claim 11 or the medical patch sheet according to any one of claims 12 to 16, comprising the following steps: A.1.1) coating the release liner with an active agent-containing coating composition, the active agent-containing coating composition comprising (i) polymer I, and (ii) active agent; 1.2) drying the applied coating composition to provide a self-adhesive layer structure containing an active agent; 1.3) laminating the active agent-containing self-adhesive layer structure with a backing layer; as well as B. Slicing at least one hexagonal shape from the active agent-containing self-adhesive layer structure to obtain the medical patch or the medical patch sheet.

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