Medical plaster comprising skin irritant active agent.

Abstract

The present invention relates to a medical patch for the administration of an active agent comprising an active agent-containing layer structure, said active agent-containing layer structure comprising a backing layer, an active agent-containing layer and a skin contact layer, wherein the skin contact layer is an adhesive layer which is directly attached to the active agent-containing layer, and wherein the saturation concentration of the active agent in the skin contact layer is less than 0.1 % by weight, as well as to such a medical patch for use in a method of treatment and to a process of manufacture of such a medical patch.

Description

"MEDICAL PLASTER COMPRISING AN ACTIVE SKIN IRRITANT AGENT" Technical Field of the Invention

[001] The present invention relates to a medical patch for the administration of an active agent, wherein the medical patch comprises a layer containing the active agent and a skin contact layer, and wherein the saturation concentration of the active agent in the skin contact layer is less than 0.1% by weight. Furthermore, the present invention relates to manufacturing processes, as well as methods of treatment and uses of the medical patch. BACKGROUND of the invention

[002] The most common routes of drug delivery are oral and parenteral, with most small molecule drugs conventionally administered orally. The oral route has the advantage of pre-determined doses, portability, and the possibility of self-administration by the patient, but is frequently associated with adverse gastrointestinal effects. Parenteral administration, such as intravenous or subcutaneous administration, is not without limitations, such as the invasive nature of injections which cause pain and lower patient acceptance / adherence, in addition to the requirement for administration by a trained administrator.

[003] On the other hand, the skin offers an accessible and convenient location for non-invasive drug administration, for example, using medical patches placed on a patient's skin to administer a specific dose of medication through the skin.

[004] Medications have long been applied topically to the skin to treat local conditions, although more recently, transdermal delivery technology has been developed to treat a range of conditions beyond the application site. While topical delivery of a compound and / or drug is limited to treating conditions Petition 870250073524, dated 08 / 20 / 2025, p. 7 / 155 2 / 129 local actions and avoid systemic effects, transdermal medications refer to pharmaceutical compounds that are applied to the skin and cross not only the stratum corneum, but also the epidermis to reach the bloodstream and / or reach more distant tissues or organs.

[005] Drug delivery through the skin has many advantages over other conventional medication routes. First, the skin, being the largest and most easily accessible organ in the body, allows for many placement options for medical patches. Drug delivery through the skin can thus provide a non-invasive alternative to parenteral routes, avoiding problems such as needle phobia. Furthermore, it can improve patient adherence due to reduced dosing frequencies and is also suitable for patients who are unconscious or vomiting, or those who rely on self-administration. Second, drug delivery through the skin avoids pre-systemic metabolism, thus improving bioavailability. In addition, the pharmacokinetic profiles of drugs are generally more uniform, with fewer peaks, thus minimizing the risk of side effects due to peak concentrations.

[006] On the other hand, the drug, adhesive, or other excipients contained in the medical patch may be an irritant that causes reactions at the application site, including skin irritation such as irritant contact dermatitis (ICD) or allergic contact dermatitis (ACD). ACD is a type IV cell-mediated hypersensitivity reaction that usually presents with lesions that can range from erythema and papules to vesicles and blisters. ICD develops when the drug, adhesive, or excipient damages the skin surface faster than the skin can repair, presenting with skin lesions similar to those of ACD. Common signs and symptoms at the application site include localized redness (erythema) or itching, at. Petition 870250073524, dated 08 / 20 / 2025, p. 8 / 155 3 / 129 times accompanied by swelling (edema). Generally, the severity is mild to moderate and the nature is transient. Most are localized to the application area and disappear spontaneously within a few days after removal of the adhesive. However, some medical patches may even cause systemic reactions and / or pain, depending on the irritant substance they contain.

[007] In fact, the occurrence of these (cutaneous) reactions is not limited to the application site, as contamination with the irritant substance can occur during the application of the medical patch. In particular, the irritant substance can come into contact with the fingers or other parts of the hands of the person applying the medical patch, with the risk of subsequently being transferred to other particularly sensitive areas of the body, such as the eyes. Due to this risk associated with skin-irritating medical patches and, in particular, with the skin-irritating active agents contained in medical patches, their application requires adequate precautions and is often limited to medical professionals only, depriving the medical patch of the advantage of (otherwise possible) self-administration by the patient.

[008] Therefore, it is desirable to provide a medical patch for the administration of an active (irritant) agent, which allows for safe and uncomplicated handling. In particular, there is a need for a medical patch, preventing contamination with the active agent contained therein, even in case of ignorance, negligence, carelessness, inattention and / or lack of skill on the part of the person applying the medical patch. Objects and Summary of the Invention

[009] One objective of the present invention is to provide a medical plaster that overcomes the disadvantages of the current administration of irritating active agents. Petition 870250073524, dated 08 / 20 / 2025, page 9 / 155 4 / 129

[0010] Another objective of the present invention is to provide a medical patch for the administration of an active agent, which can be applied / removed safely and easily. In particular, the objective is to provide a medical patch for the administration of an active agent, which can be safely applied / removed by a patient or another person who is not a medical professional.

[0011] Another objective of the present invention is to provide a medical patch for the administration of an active agent, which avoids substantial contamination with the active agent. In particular, the objective is to provide a medical patch for the administration of an irritating active agent, requiring only few or no precautions during the application / removal of the medical patch.

[0012] Another objective of the present invention is to provide a medical patch for the administration of an active agent, which reduces the problem of unwanted skin reactions.

[0013] It is also an object of the present invention to provide a medical patch for the administration of an active agent, providing a permeation rate that is sufficient to achieve a therapeutically effective dose and having improved adhesive properties.

[0014] Another objective of the present invention is to provide a medical patch for the administration of an active agent, which can be used in a treatment method.

[0015] These and other objectives are achieved by the present invention, which in one aspect relates to a medical patch for the administration of an active agent comprising an active agent-containing layer structure, said active agent-containing layer structure comprising: A) a support layer; B) a layer containing an active agent comprising (i) an active agent, and Petition 870250073524, dated 08 / 20 / 2025, page 10 / 155 5 / 129 (ii) a polymer I; and C) a skin contact layer comprising a polymer II; wherein the skin contact layer is an adhesive layer that is directly attached to the layer containing the active agent, and wherein the saturation concentration of the active agent in the skin contact layer is less than 0.1% by weight.

[0016] It has been surprisingly discovered that a medical patch according to the present invention, comprising a skin contact layer in which the active agent is sparingly soluble, is still capable of providing sufficient drug distribution. Because the active agent is sparingly soluble, for example, having a saturation concentration of less than 0.1% in the skin contact layer, only a negligible amount of active agent is present on the surface of the skin contact layer, so that the medical patch has advantageous properties with respect to undesirable skin reactions and thus allows safe application and / or removal.Thus, an inventive medical patch with a skin contact layer in which the saturation concentration of the active agent is negligible, with a separate layer containing the active agent (which is not in skin contact), prevents the active agent from being released before and / or after the medical patch is applied and maintained on the patient's skin. In particular, the inventive medical patch with a skin contact layer comprising a polymer II in which the saturation concentration of the active agent is negligible, and a separate layer containing the active agent comprising a polymer I in which the saturation concentration of the active agent is also negligible, practically excludes contamination with the agent. Petition 870250073524, dated 08 / 20 / 2025, page 11 / 155 6 / 129 active ingredient. Thus, the invention allows medical plasters, even those containing irritating active agents, to be touched without special precautions, even by non-medical professionals, preferably by the patient themselves.

[0017] In a particular aspect, the present invention relates to a medical patch for administering an active agent comprising a self-adhesive layer structure containing the active agent, said self-adhesive layer structure containing the active agent comprising: A) a support layer; B) a matrix layer containing an active agent comprising (i) an active agent in an amount of at least 0.5% by weight, based on the total weight of the matrix layer containing the active agent; (ii) a polymer I selected from the group consisting of silicone-based polymers and natural or synthetic rubber-based polymers; and (iii) a solubilizer; and C) a skin contact layer comprising a polymer II; wherein the skin contact layer is an adhesive layer that is directly attached to the layer containing the active agent, and wherein the saturation concentration of the active agent in the skin contact layer is less than 0.1% by weight.

[0018] According to certain embodiments of the invention, the medical plaster according to the invention is for use in a treatment method, in particular for use in a treatment method of Petition 870250073524, dated 08 / 20 / 2025, page 12 / 155 7 / 129 pain, or for use in a method of treating neuropathic pain, or nociceptive pain, or for use in a method of treating joint pain, or cancer pain, or for use in a method of treating pain associated with a joint condition, such as arthritis.

[0019] According to certain embodiments of the invention, the present invention relates to the use of a medical plaster according to the invention for the manufacture of a medicament, in particular for the manufacture of a medicament to treat pain, or for the manufacture of a medicament to treat neuropathic pain, or nociceptive pain, or for the manufacture of a medicament to treat joint pain, or cancer pain, or for the manufacture of a medicament to treat pain associated with a joint condition, such as arthritis.

[0020] According to certain embodiments of the invention, the invention relates to a method of treatment, in particular a method of treatment of pain, or a method of treatment of neuropathic pain, or nociceptive pain, or a method of treatment of joint pain, or cancer pain, or a method of treatment of pain associated with a joint condition, such as arthritis, including the application of a medical plaster according to the invention to the skin of a patient.

[0021] In addition, the invention relates to a method of manufacturing a layer structure containing the active agent of a medical plaster according to the invention. Definitions

[0022] In the context of this invention, the term “medical patch” refers to a dermal delivery system by which the active agent is administered to a patient, and which comprises an effective amount of the active agent in a structure containing the active agent (self-adhesive) located in a peelable protective layer (release coating). In this context, the term “medical patch” is understood to mean an adhesive that may be a topical medical patch or a Petition 870250073524, dated 08 / 20 / 2025, page 13 / 155 8 / 129 Transdermal Therapeutic System (TTS). Even though topical medical patches, as well as TTS, are applied topically in the sense that they are fixed to the patient's skin, the term "topical" or "topical administration" refers to the administration of the active agent based on passive diffusion within the skin itself, which creates a local effect at a point of action. In contrast, the term "TTS" refers to a system by which the active agent is administered into the systemic circulation via transdermal distribution.

[0023] In the context of this invention, the term “active agent-containing layer structure” refers to the active agent-containing structure that provides the delivery area for the active agent during administration. The active agent-containing layer structure comprises at least one support layer, an active agent-containing layer comprising the active agent, and a skin contact layer, as described herein. The active agent-containing layer structure therefore comprises a therapeutically effective amount of the active agent. In certain embodiments, the active agent-containing layer structure is a self-adhesive active agent-containing layer structure, thus providing adhesion to the skin, so that normally no additional aid is required for fixation to the skin.

[0024] As used herein, the term “active agent” refers to any substance of interest to be administered by the layer structure containing the active agent to provide a beneficial or desirable effect on the subject’s body condition, either systemically or locally at the distribution site. An active agent in particular includes biologically or pharmacologically active compounds, which may also be called an active, drug substance, drug, active ingredient, active pharmaceutical ingredient (API), or the like. In this context, an “irritant active agent” is understood to mean, and in particular, Petition 870250073524, dated 08 / 20 / 2025, page 14 / 155 9 / 129 “skin irritant active agent” means an active agent that causes (reversible) inflammation or irritation on a body surface, including the eyes, respiratory tract, skin, or mucous membranes, upon contact. The degree of irritation may depend on the concentration, duration of contact, and personal factors (health status, sensitization). Considering OECD guideline TG 404, the potential skin irritation of medical patches can be determined, for example, by subjective in vivo observations followed by quantification to obtain a scoring index, such as the Primary Irritation Index (PII).For quantification, the following skin irritation scoring system can be used: Erythema and eschar formation - 0 (no erythema), 1 (very mild erythema (almost imperceptible)), 2 (well-defined erythema), 3 (moderate to severe erythema), 4 (severe erythema (from beetroot-red to crimson-red) to mild eschar formation (deep lesions)); Edema formation - 0 (no edema), 1 (very mild edema (almost imperceptible)), 2 (mild edema (area edges well-defined by defined elevation)), 3 (moderate edema (elevated ~ 1 mm)), 4 (severe edema (elevated more than 1 mm and extending beyond the exposure area)). Skin irritation is generally presumed with a PII > 0.5.

[0025] As used herein, the term “effective amount” or “therapeutically effective amount” refers to an amount of active agent in the structure of the layer containing the active agent that is sufficient to provide, if administered by the medical patch to a patient, the desired (therapeutic) effect, such as pain relief. A TTS generally contains more active agent in the system than is actually delivered to the skin and systemic circulation, which is usually necessary to provide sufficient driving force for the delivery of the TTS to the systemic circulation.

[0026] In the context of this invention, the terms “active”, “active agent” and the like refer to the respective active agent in any Petition 870250073524, dated 08 / 20 / 2025, page 15 / 155 10 / 129 chemical and morphological form and pharmaceutically acceptable physical state. These forms include, without limitation, the active agent in its free base / free acid form, protonated or partially protonated form, deprotonated or partially deprotonated form, salts, cocrystals and, in particular, acid / base addition salts formed by the addition of an inorganic or organic acid / base, such as hydrochloride or tartrate salts, solvates, hydrates, clathrates, complexes and so forth, as well as the active agent in the form of particles, which may be micronized, crystalline and / or amorphous, and any mixtures of the forms mentioned above.

[0027] The active agent, when contained in a medium, such as a solvent, can be dissolved or dispersed or partly dissolved and partly dispersed.

[0028] When the active agent is mentioned as being used in a specific form in the manufacture of the medical plaster, this does not exclude interactions between that form of the active agent and other ingredients of the layer structure containing the active agent, for example, salt formation or complexation, in the final medical plaster. This means that even if the active agent is included in its free base / acid form, it may be present in the final medical plaster in protonated or partially protonated / or deprotonated or partially deprotonated form or in the form of an acid addition salt, or, if included in the form of a salt, parts of it may be present as free base in the final medical plaster.Unless otherwise indicated, in particular, the quantity of the active agent in the structure of the layer containing the active agent refers to the quantity of the active agent included in the medical plaster during the manufacture of the medical plaster and is calculated based on the active agent itself, but not on other forms thereof. The starting material of the active agent included in the medical plaster during the manufacture of the medical plaster may be... Petition 870250073524, dated 08 / 20 / 2025, page 16 / 155 11 / 129 tar in particulate form. The active agent may, for example, be present in the structure of the layer containing the active agent in particulate form and / or dissolved.

[0029] In this context, the term “particles” refers to a solid, particulate material comprising individual particles whose dimensions are negligible compared to the material. In particular, the particles are solid, including plastic / deformable solids, including amorphous and crystalline materials. The term “dispersion” refers to a step or a combination of steps in which a starting material (e.g., the active agent) is not fully dissolved. Dispersion within the meaning of the invention comprises the dissolution of a portion of the starting material (e.g., particles of the active agent), depending on the solubility of the starting material (e.g., the solubility of the active agent in the coating composition).

[0030] There are two main types of medical patches that use active (passive) agent delivery: matrix-type medical patches and reservoir-type medical patches. The release of the active agent in a matrix-type medical patch is primarily controlled by the matrix, which includes the active agent itself. In contrast, a reservoir-type medical patch typically requires a rate-control membrane to control the release of the active agent. In principle, a matrix-type medical patch can also contain a rate-control membrane. However, matrix-type medical patches are advantageous because, compared to reservoir-type medical patches, rate-control membranes are generally not required, and dose spillage due to membrane rupture cannot occur. In short, matrix-type medical patches are less complex to manufacture and easier and more convenient to use. Petition 870250073524, dated 08 / 20 / 2025, p. 17 / 155 12 / 129

[0031] In this context, a “matrix-type medical patch” is understood to be a system or structure in which the active agent is dissolved and / or homogeneously dispersed within a polymeric support, i.e., the matrix, which forms a matrix layer with the active agent and, optionally, the remaining ingredients. In this system, the matrix layer controls the release of the active agent from the medical patch. Preferably, the matrix layer has sufficient cohesion to be self-supporting, so that no sealing between other layers is necessary. Consequently, the layer containing the active agent may be a matrix layer containing the active agent, in which the active agent is homogeneously distributed within a polymeric matrix. The matrix layer containing the active agent may comprise two matrix layers containing the active agent, which may be laminated together.Medical matrix patches may, in particular, be in the form of a "drug-in-patch" type medical patch, referring to a system in which the active agent is dissolved and / or homogeneously dispersed within a pressure-sensitive adhesive matrix. In this context, the matrix layer containing the active agent may also be a pressure-sensitive adhesive layer containing the active agent or a pressure-sensitive adhesive matrix layer containing the active agent. A medical patch comprising the active agent dissolved and / or dispersed within a polymeric gel, for example, a hydrogel, is also considered to be of the matrix type according to the present invention.

[0032] Medical patches with a reservoir containing a liquid active agent are called “reservoir-type medical patches”. In such a system, the release of the active agent is preferentially controlled by a rate-control membrane. In particular, the reservoir is sealed between the backing layer and the rate-control membrane. Consequently, the layer containing the Petition 870250073524, dated 08 / 20 / 2025, page 18 / 155 13 / 129 The active agent may be an active reservoir layer, preferably comprising a liquid reservoir containing the active agent, wherein the active reservoir layer and the skin contact layer may be separated by a rate control membrane. In the active reservoir layer, the active agent is preferably dissolved in a solvent, such as ethanol or water, or in silicone oil.

[0033] Medical patches of the reservoir type should not be understood as being of the matrix type, within the meaning of the invention. However, micro-reservoir type medical patches (biphasic systems with deposits (e.g., spheres, droplets) of an internal phase containing active agent dispersed in an external polymer phase), considered in the art as a mixed form of a matrix type medical patch and a reservoir type medical patch that differ from a homogeneous monophasic matrix type medical patch and a reservoir type medical patch in the concept of drug transport and drug distribution, are considered to be of the matrix type within the meaning of the present invention.

[0034] Thus, a microreservoir-type medical patch refers to a microreservoir system in which a liquid active agent preparation is dispersed in an adhesive matrix in the form of small droplets (microreservoirs). The size of the resulting droplets depends on the agitation conditions and the shear forces applied during agitation. It can be determined by an optical microscopic measurement (e.g., by Leica MZ16 including a camera, e.g., Leica DSC320) taking pictures of the microreservoir layer at different positions at a magnification factor between 10 and 400 times, depending on the required detection limit. Using image analysis software, the sizes of the microreservoirs can be determined. The systems Petition 870250073524, dated 08 / 20 / 2025, page 19 / 155 Microreservoir systems are disclosed in U.S. Patents Nos. 3,946,106, 4,053,580, 4,814,184, and 5,145,682, each of which is incorporated herein by reference. Specific microreservoir systems are described in International Patent Publication WO0101967, the disclosure of which is incorporated herein by reference. These microreservoir systems contain polysiloxanes as the base polymer and amphiphilic solvents for the microreservoir droplets.

[0035] The structure of the layer containing the active agent may be a pressure-sensitive adhesive layer structure.

[0036] Within the meaning of this invention, the term pressure-sensitive adhesive (also abbreviated as PSA) refers to a material that, in particular, adheres to finger pressure, is permanently adhesive, exerts a strong holding force, and must be removable from smooth surfaces without leaving residue. It can be obtained from an adhesive coating composition containing solvent after coating a film and evaporating the solvents (e.g., n-heptane or ethyl acetate). In this context, the term solvent means any liquid substance, preferably a volatile organic liquid, such as methanol, ethanol, isopropanol, acetone, ethyl acetate, methylene chloride, hexane, n-heptane, toluene, and mixtures thereof. A pressure-sensitive adhesive layer, in contact with the skin, is self-adhesive.In certain embodiments, the structure of the layer containing the active agent according to the invention includes a pressure-sensitive adhesive layer for skin contact, which may be provided in the form of a pressure-sensitive adhesive matrix or in the form of an additional layer, i.e., a pressure-sensitive adhesive layer for skin contact. An adhesive overlayer may also be employed to enhance adhesion.

[0037] Within the meaning of this invention, the term active agent-containing layer refers to a layer containing the agent Petition 870250073524, dated 08 / 20 / 2025, page 20 / 155 15 / 129 active ingredient that provides the release area. The term encompasses reservoir layers containing the active agent and matrix layers containing the active agent, and in particular, microreservoir layers containing the active agent. If the layer containing the active agent is a matrix layer containing the active agent, this layer will be present in a matrix-type medical plaster. As used herein, the layer containing the active agent is preferably a matrix layer containing the active agent, and refers to the final solidified layer, for example, obtained after coating and drying of a solvent-containing coating composition, as described herein. Alternatively, a matrix layer containing the active agent is obtained after melt-and-cool coating.The matrix layer containing the active agent can also be manufactured by laminating two or more solidified layers (e.g., dry or chilled layers) of the same composition to provide the desired area weight. In certain embodiments, the matrix layer is a pressure-sensitive adhesive matrix layer.

[0038] Within the meaning of this invention, the term skin contact layer refers to the layer included in the structure of the layer containing the active agent that is in direct contact with the patient's skin during administration. The other layers of the structure of the layer containing the active agent do not come into contact with the skin and do not necessarily have self-adhesive properties. The skin contact layer is either directly attached to the layer containing the active agent, or a membrane is located between the layer containing the active agent and the skin contact layer. In this context, the term "membrane" is understood to mean a layer that is provided between the layer containing the active agent and the skin contact layer and is at least semi-permeable to the active agent. The membrane may be a microporous film or a non-porous partition membrane. Petition 870250073524, dated 08 / 20 / 2025, page 21 / 155 16 / 129 sa. Preferred membranes may be selected from the group consisting of polyethylene membranes, polyethylene terephthalate / polyethylene membranes coated with polyurethane, polyurethane membranes and ethylene vinyl acetate membranes. The additional skin contact layer is present as an adhesive layer.

[0039] The sizes of an additional skin contact layer and the layer containing the active agent are generally coextensive and correspond to the delivery area. However, the area of ​​the additional skin contact layer may also be larger than the area of ​​the layer containing the active agent. In this case, the delivery area still refers to the area of ​​the layer containing the active agent.

[0040] Within the meaning of the invention, the term “support layer” refers to a layer that supports the layer containing the active agent. At least one support layer in the structure of the layer containing the active agent of the medical patch, and generally the support layer of the layer containing the active agent, is substantially impermeable to the active agent, as well as optionally to any additive contained in the layer during the storage and administration period, thus preventing loss of active ingredient or cross-contamination, in accordance with regulatory requirements. In certain embodiments, the support layer is also occlusive, i.e., substantially impermeable to water and water vapor. Suitable materials for a support layer include polyethylene terephthalate (PET), polyethylene (PE), ethylene vinyl acetate copolymer (EVA), polyesters, polyurethanes, and mixtures thereof.Suitable support layers can be siliconized to improve adhesion of the active agent-containing layer to the support layer. Alternatively, suitable support layers can be left unsiliconized to improve adhesion of the active agent-containing layer to the support layer.

[0041] In addition, an adhesive layer may be present. Petition 870250073524, dated 08 / 20 / 2025, page 22 / 155 17 / 129 In this context, the term "adhesive overlay" is understood as a layer free of the active agent and larger in area than the structure of the self-adhesive layer containing the active agent, providing additional adhesion area to the skin but no area for release of the active agent. This improves the overall adhesive properties of the medical plaster. The area of ​​said adhesive overlay increases the overall size of the medical plaster but does not increase the release area. The adhesive overlay may comprise a self-adhesive polymer or a mixture of self-adhesive polymers selected from the group of acrylic polymers, polyisobutylenes, styrene-isoprene-styrene copolymers, polysiloxanes and mixtures thereof, which may be identical to or different from any polymer or mixture of polymers included in the structure of the self-adhesive layer containing the active agent. The adhesive overlay comprises a backing layer that may provide occlusive or non-occlusive properties and an adhesive layer.In certain applications, the backing layer of the adhesive overlay provides non-occlusive properties.

[0042] In the context of this invention, the term “area weight” refers to the dry weight of a specific layer, for example, the matrix layer containing the active agent, given in g / m2. Area weight values ​​are subject to a tolerance of ± 10% or ± 7.5%, due to manufacturing variability.

[0043] Unless otherwise indicated, “%” refers to % by weight (% by weight).

[0044] In the context of this invention, the term “polymer (I or II)” refers to any substance consisting of so-called repeating units obtained by the polymerization of one or more monomers, and includes homopolymers consisting of one type of monomer and copolymers consisting of two or more types of monomers. Polymers can be of any architecture, such as linear polymers, Petition 870250073524, dated 08 / 20 / 2025, page 23 / 155 18 / 129 Star polymers, comb polymers, brush polymers, of any arrangement of monomers in the case of copolymers, for example, alternating, block copolymers or graft polymers. The minimum molecular weight varies depending on the type of polymer and is known to those skilled in the art. Polymers may have, for example, a molecular weight above 2000, above 5000 or even above 10,000 Daltons. Correspondingly, compounds with a molecular weight below 2000, below 5000 or below 10,000 Daltons are generally called oligomers.

[0045] In the sense of the invention, the term “acrylic polymer” refers to a non-hybrid polymer based on acrylates. It may be a polymer obtained 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-octylacrylate and vinyl acetate.

[0046] In the sense of the invention, the term “silicone-acrylic hybrid polymers” refers to a hybrid polymer based on silicones and acrylates in the form of a pressure-sensitive adhesive. Acrylic-silicone 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 acrylic-silicone hybrid PSA is supplied, the arrangement of the silicone phase and the acrylic phase provides a continuous acrylic or silicone outer phase and a corresponding discontinuous inner phase that is different. If the acrylic-silicone hybrid PSA is supplied in n-heptane, the composition will contain a continuous silicone outer phase and a discontinuous acrylic inner phase. If the acrylic-silicone hybrid PSA composition is supplied in ethyl acetate, the composition will contain a continuous acrylic outer phase and a discontinuous silicone inner phase.

[0047] In the context of the invention, the term “silico-based polymer” Petition 870250073524, dated 08 / 20 / 2025, p. 24 / 155 19 / 129 ne” refers to a non-hybrid polymer (i.e., a polymer that does not include a hybrid species) comprising polysiloxanes. Polysiloxanes can be made from two-component solvent-free systems or from a solution in organic solvents. They exist in two fundamentally different variants: polysiloxanes that have free silanol groups and amine-resistant polysiloxanes that are distinguished because the free silanol groups are derivatized by trimethylsilyl groups. The methyl groups can be wholly or partially replaced by other alkyl radicals or, alternatively, by phenyl radicals. Polysiloxanes, as used herein, are synthesized from linear bifunctional and branched polyfunctional oligomers, the ratio of which determines their physical properties.More polyfunctional oligomers result in a more cross-linked adhesive with greater cohesion and less adhesion; less polyfunctional oligomers result in greater adhesion and less cohesion. It is preferable that the silicone-based polymer be a mixture of high- and medium-adhesion, or high- and low-adhesion, polysiloxanes. In certain embodiments, at least one silicone-based polymer is a silicone-based pressure-sensitive adhesive.

[0048] In the context of this invention, the term “silicone gel adhesive” refers to an elastic, gelatinous material formed from lightly cross-linked silicone polymers. It can be prepared from a gel-forming composition, as described further below, after curing. In particular, the silicone gel adhesive is formed during the curing of polysiloxanes comprising reactive groups, such as Si-H reactive groups and aliphatic unsaturated groups, which react with each other in the presence of a hydrosilylation catalyst. In certain embodiments, the silicone gel adhesive is based on a polydimethylsiloxane network, which can be formed in an addition reaction (hydrosilylation) between polydimethylsiloxane groups with a vinyl function. Petition 870250073524, dated 08 / 20 / 2025, page 25 / 155 20 / 129 (polymer) and siloxanes with a hydrogen function (crosslinking agent). Consequently, silicone gel adhesive is typically applied using a curable gel-forming composition (of 2 components), which solidifies after curing.

[0049] In the sense of the invention, the term “natural or synthetic rubbers” refers to an elastomer that can be obtained by the polymerization of an unsaturated hydrocarbon, such as isoprene (2-methyl-1,3-butadiene), or by the copolymerization of such hydrocarbons with styrene, butadiene or the like. It includes natural and synthetic polyisoprene, polybutylene and polyisobutylene, styrene / butadiene polymers, styrene-isoprene-styrene block copolymers, hydrocarbon polymers such as butyl rubber, halogen-containing polymers such as polyacrylic nitrile, polytetrafluoroethylene, polyvinyl chloride, polyvinylidene chloride and polychlorodiene, as well as other copolymers thereof. In certain embodiments, natural or synthetic rubbers may be styrenic triblock copolymers or polyisobutylenes.

[0050] In the meaning of this invention, the term “saturation concentration” refers to the concentration of the active agent corresponding to the equilibrium state in which the solvent (i.e., polymer I of the active agent-containing layer or polymer II of the skin contact layer) can no longer dissolve solute (i.e., the active agent) and, as a result, the solid solute is present in equilibrium with the solid solution at a defined temperature (ambient temperature – unmodified temperature found in enclosed environments in the laboratory where the experiments are conducted and generally between 15 and 35 °C, or about 18 to 25 °C). The saturation concentration of the active agent can be indicated in % by weight, based on the total weight of the active agent layer or the skin contact layer, respectively. The saturation concentration can be determined, for example, using a method described by Liu, P., Gargiulo, Petition 870250073524, dated 08 / 20 / 2025, page 26 / 155 21 / 129 P., Wong, J. and Novartis. Pharm. Research. Vol. 14, p. 317 (1997), herein referred to as the “sandwich method,” in which a multilayer laminate is prepared comprising an upper and lower protective layer intercalated with a donor layer and an acceptor layer separated by a partition membrane that is permeable to the active agent. Since the donor layer contains an excess of the active agent and the acceptor layer is substantially free of the active agent, the active agent diffuses from the donor layer through the partition membrane to the acceptor layer until saturation concentration is reached. The donor layer and the acceptor layer are fabricated from the respective polymer II of the skin contact layer (or from the respective polymer I of the layer containing the active agent). 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 systems are stored for a certain time, for example, 7 days, at room temperature, to allow the active agent to diffuse from the donor layer to the acceptor layer. Then, the remaining concentration of the active agent in the donor layer is determined by HPLC (high-performance liquid chromatography) to finally obtain the saturation concentration of the active agent in the respective polymer II of the skin contact layer (or in the respective polymer I of the layer containing the active agent).

[0051] As used herein, solubility parameters (SPs) are defined as the sum of all intermolecular attractive forces, which, as a numerical estimate, are empirically related to the extent of mutual solubility of chemical species. The most convenient method for determining solubility parameters is the Hildebrand method, which calculates the solubility parameter from molecular weight, boiling point, and density data. Petition 870250073524, dated 08 / 20 / 2025, page 27 / 155 22 / 129 commonly available for many materials: SP = (ΔEv / ν)1 / 2, where V = molecular weight / density and ΔEv = vaporization energy. For materials, such as high molecular weight polymers, which have vapor pressures too low to be detected, several methods have been developed using the sum of atomic and group contributions to vaporization. Such a method of calculating the solubility parameter of a material was described, for example, by Small, J. Applied Chem. Vol. 3, p. 71 (1953). Some solubility parameters (calculated by Small's method) of exemplary polymers useful in the practice of the invention are as follows: Polydimethylsiloxane 14.9 MPa1 / 2, polyisobutylene 15.7 MPa1 / 2, polyethylene / butylene 16.2 MPa1 / 2, polyisoprene 16.6 MPa1 / 2, polyethylene 16.6 MPa1 / 2, polybutadiene 16.6 MPa1 / 2, polybutadiene-co-styrene (75 / 25 to 72 / 28) 17.4 MPa1 / 2, polystyrene 18.6 MPa1 / 2, polymethyl methacrylate 19.0 MPa1 / 2, polymethylacrylate 19.8 MPa1 / 2.

[0052] In the context of this invention, the term "solubilizer" refers to an agent that increases the solubility of the active agent in the matrix layer containing the active agent.

[0053] It should be noted that in pharmaceutical formulations, the components of the formulation are categorized according to their physicochemical and physiological properties and according to their function. This means, in particular, that a substance or compound that falls into one category is not excluded from falling into another category of formulation component. A person skilled in the art is able to determine based on their general knowledge to which category or categories of formulation components a given substance or compound belongs. For example, the solubilizer as defined above may also act as, for example, a permeation enhancer. On the other hand, a permeation enhancer, as used in the meaning of this invention, does not increase the necessary... Petition 870250073524, dated 08 / 20 / 2025, page 28 / 155 23 / 129 specifically the solubility of the active agent in the layer containing the active agent.

[0054] Within the meaning of the invention, the term soluble polyvinylpyrrolidone refers to polyvinylpyrrolidone, also known as povidone, which is soluble with more than 10% in at least ethanol, preferably also in water, diethylene glycol, methanol, n-propanol, 2-propanol, n-butanol, chloroform, methylene chloride, 2-pyrrolidone, macrogol 400, 1,2-propylene glycol, 1,4-butanediol, glycerol, triethanolamine, propionic acid and acetic acid. Examples of commercially available polyvinylpyrrolidones include Kollidon® 12 PF, Kollidon® 17 PF, Kollidon® 25, Kollidon® 30 and Kollidon® 90 F supplied by BASF or povidone K90F. The different grades of Kollidon® are defined in terms of the K value, reflecting the average molecular weight of the polyvinylpyrrolidone grades. 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. 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. The preferred grades of Kollidon® are Kollidon® 12 PF, Kollidon® 30, and Kollidon® 90 F. In this context, the term "K-value" refers to a value calculated from the relative viscosity of polyvinylpyrrolidone in water according to the European Pharmacopoeia (Ph.Eur.) and USP monographs for "Povidone".For all grades and types of polyvinylpyrrolidone, it is preferable that the amount of peroxides be within certain limits, in particular, the amount of peroxide be equal to or less than 500 ppm, equal to or less than 150 ppm, or equal to or less than 150 ppm. Petition 870250073524, dated 08 / 20 / 2025, p. 29 / 155 24 / 129 less than 100 ppm.

[0055] In the sense of the invention, the term “hexagonal shape” refers to the two-dimensional shape of the structure of the layer containing the active agent that is provided by the support layer and the layer containing the active agent, or by the support layer, the layer containing the active agent and the skin contact layer, respectively, and which can be seen when observing the structure of the layer containing the active agent from above towards the support layer. By hexagonal shape, in the sense of the present invention, is meant any shape that can be formed by a hexagon or by an aggregation of two or more hexagons. This means that the hexagonal shape according to the invention as a whole need not be in the shape of a hexagon, but must be constituted by at least one hexagon. The vertices of the hexagonal shape may be acute or rounded.If two or more hexagons constitute the hexagonal shape, they may be integrally connected to each other, i.e., only separable, for example, by cutting the structure of the layer containing the active agent, or they may be detachable from each other using, for example, a perforated line. The support layer and the layer containing the active agent, or the support layer, the layer containing the active agent, and the skin contact layer, respectively, as well as optionally the membrane, are coextensive, i.e., they have the same planar extent and / or share the same boundary. In other words, the support layer and the layer containing the active agent, or the support layer, the layer containing the active agent, and the skin contact layer, respectively, as well as optionally the membrane, each provides a shape in the form of at least one congruent hexagon.

[0056] In the sense of the invention, the term “hexagon” refers to a polygon with six sides. In a “convex hexagon”, each of the six Petition 870250073524, dated 08 / 20 / 2025, p. 30 / 155 25 / 129 points where two sides of the hexagon meet in pairs (vertices) point outwards. Two adjacent vertices are connected respectively by one of the six sides (common side). Non-adjacent vertices can be connected by one of the nine diagonals located within the closed hexagonal chain (boundary) of the convex hexagon. A convex hexagon requires the shortest total boundary length compared to other polygons with the same area.

[0057] A convex hexagon can also be described as a six-sided polygon with interior angles (vertex angles) each less than 180°. The total of the interior angles of any simple (non-self-intersecting) hexagon is 720°. Thus, a (convex) hexagon whose vertex angles are each equal to 120° is also called equiangular. A (convex) hexagon with all sides of equal length is also called equilateral. If a (convex) hexagon is both equilateral and equiangular, it is also called regular.

[0058] The (convex) hexagon can be symmetrical, in particular mirror symmetrical or rotationally symmetrical. In this context, mirror symmetry, also known as reflection symmetry, is understood as symmetry with respect to a reflection. This symmetrical function of a two-dimensional shape is that if the shape were folded in half about the mirror axis, the two halves would be identical: the two halves would be mirror images of each other. Therefore, a regular hexagon has six axes of symmetry, because there are six different ways to fold it and make all sides coincide. Rotational symmetry of order n, also called n-times rotational symmetry, of a two-dimensional shape with respect to a specific point is understood as that rotation by an angle of 360° / n (180°, 120°, 90°, 72°, 60°, etc.) does not alter the shape. Thus, a regular hexagon has rotational symmetry of order 6, because it looks the same after rotation. Petition 870250073524, dated 08 / 20 / 2025, page 31 / 155 26 / 129 each partial turn around an angle of 60°.

[0059] In the sense of the invention, the term “parallelogon” refers to a (convex) hexagon in which all pairs of opposite sides (two sides separated from each other by the same number of sides in both contour directions, i.e., by two sides in a hexagon) are parallel and the two sides of each pair of parallel opposite sides are equal in length. This includes a parallelogon that has a total of three different side lengths or that has a total of only two different side lengths, as well as a parallelogon that has all sides of equal length. The term “parallelogon” includes, for example, a shape obtained by stretching a parallelogram or a shape obtained by stretching a rhombus and, in particular, by separating a parallelogram or rhombus, respectively, at two of its non-adjacent vertices and by introducing a pair of parallel opposite sides of equal length.In this context, the term "parallelogram" refers to a simple four-sided polygon with two pairs of parallel sides. If all four sides are the same length, the parallelogram is also called a "rhombus".

[0060] In the sense of the invention, the term “aspect ratio” refers to the relationship between height and width, wherein the width and length are distances between two points on the boundary of the (convex) hexagon, and the greater of the two distances is considered the width. In this context, the width of the (convex) hexagon is understood to be the length of the greatest distance between any two points on the boundary, which is generally the length of the longest diagonal of the (convex) hexagon between two diametrically opposite vertices. The height of the (convex) hexagon is understood to be the greatest available distance 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 Petition 870250073524, dated 08 / 20 / 2025, p. 32 / 155 27 / 129 line formed by connecting the two points that define the width (see above). The height / width ratio corresponds to the ratio between inradius (radius of the inscribed circle) and circumradius (radius of the circumscribed circle), if available. The height-to-width ratio of a regular hexagon is 3:2.

[0061] Regular hexagons fit together to tile the plane, forming a honeycomb pattern. The honeycomb pattern is composed of regular hexagons arranged side by side, which tile the plane, that is, they completely fill the entire surface they cover, so that there are no gaps between them. This occurs because the 120° angle is the angle at which the sides meet at the vertices when the hexagons are aligned side by side, so that exactly three hexagons meet at each vertex. The honeycomb pattern appears not only in honeycombs, but also in many other places in nature, such as in organic compounds (benzyl rings, proteins).

[0062] The hexagonal mosaic, also called hexagonal tessellation, is a regular mosaic of the Euclidean plane, in which exactly three hexagons meet at each vertex. In addition to using regular hexagons (Fig. 1a), the hexagonal mosaic can also be made with, for example, other (hexagonal) parallelogons, in particular with a parallelogon obtained by stretching a rhombus (Fig. 1b) or obtained by stretching a parallelogram (Fig. 1c). These hexagonal shapes can tile the Euclidean plane by translation. Other hexagonal shapes can cover the plane with different orientations. In this context, the term "tiling the plane" is understood as covering a given plane (flat surface or curved surface) without leaving empty spaces. The plane covering can be carried out with or without overlapping adjacent layer structures containing the active agent, according to the present invention. Preferably, avoid overlapping as much as possible. Petition 870250073524, dated 08 / 20 / 2025, p. 33 / 155 28 / 129

[0063] Within the meaning of the invention, the term “pentagonal shape” refers to the two-dimensional shape of the structure of the layer containing the active agent that is provided by the support layer and the layer containing the active agent, or by the support layer, the layer containing the active agent and the skin contact layer, respectively, and which can be seen when observing the structure of the layer containing the active agent from above towards the support layer. A pentagonal shape within the meaning of the present invention is understood to be any shape that can be formed by a pentagon or by an aggregation of two or more pentagons. This means that the pentagonal shape according to the invention as a whole need not have to be in the shape of a pentagon, but must be constituted by at least one pentagon. The vertices of the pentagonal shape may be acute or rounded.If two or more pentagons constitute the pentagonal shape, they may be integrally connected to each other, i.e., separable only by, for example, cutting the structure of the layer containing the active agent, or they may be detachably connected to each other using, for example, a perforated line. The support layer and the layer containing the active agent, or the support layer, the layer containing the active agent, and the skin contact layer, respectively, as well as optionally the membrane, are coextensive, i.e., they have the same planar extent and / or share the same boundary. In other words, the support layer and the layer containing the active agent, or the support layer, the layer containing the active agent, and the skin contact layer, respectively, as well as optionally the membrane, each provides a shape in the form of at least one congruent pentagon.

[0064] In the sense of the invention, the term “pentagon” refers to a five-sided polygon. In a “convex pentagon”, each of the five points where two sides of the pentagon meet in pa Petition 870250073524, dated 08 / 20 / 2025, p. 34 / 155 29 / 129 vertices point outwards. A vertex is formed by two of the five sides (adjacent sides). Two adjacent vertices are connected by one of the five sides (common side). Non-adjacent vertices can be connected by one of the five diagonals located within the closed pentagonal chain (boundary) of the convex pentagon.

[0065] A convex pentagon can also be described as a five-sided polygon with interior angles (vertex angles) each less than 180°. The total of the interior angles of any simple pentagon (that does not self-intersect) is 540°. Thus, a (convex) pentagon whose vertex angles are each equal to 108° is also called equiangular. A (convex) pentagon with all sides of equal length is also called equilateral. If a (convex) pentagon is both equilateral and equiangular, it is also called regular. If a (convex) pentagon has at least one of the five vertex angles of a different size and / or at least one of the five sides of a different length, it is here referred to as irregular.

[0066] The (convex) pentagon can be symmetrical, in particular mirror symmetrical. In this context, mirror symmetry, also known as reflection symmetry, is understood as symmetry with respect to a reflection. This symmetrical function of a two-dimensional shape is that if the shape were folded in half about the mirror axis, the two halves would be identical: the two halves would be mirror images of each other. Preferred (convex) pentagons according to the present invention have at least one, in particular exactly one, axis of symmetry.

[0067] In the sense of the invention, the term “type I pentagon” as well as “type II pentagon” refers to a mirror-image symmetrical convex pentagon with exactly one axis of symmetry, having two Petition 870250073524, dated 08 / 20 / 2025, page 35 / 155 30 / 129 internal angles of 90° and three internal angles of 120°, one of which is bisected by the axis of symmetry. Furthermore, the “type I pentagon” and the “type II pentagon” both have one pair of sides of equal length and another pair of sides of equal length (which may have the same or different lengths), as well as a remaining side that is bisected by the axis of symmetry (the remaining side having the same or different length as one pair of sides of equal length and / or the other pair of sides of equal length). Finally, the “type I pentagon” differs from the “type II pentagon” because the two 90° internal angles are adjacent, therefore one pair of sides of equal length is parallel (the sides are parallel to each other and also to the axis of symmetry).

[0068] Irregular pentagons with two interior angles adding up to 180° fit together to tile the plane. There are 15 known convex monohedral pentagonal tilings, the most recent of which was discovered in 2015 (Fig. 1; columns 1, 2 and 3, from top to bottom): - Type 1: B + C = 180°, A + D + E =360° - Type 2: B + D = 180°, c = e - Type 3: A = C = D = 120°, a = b, d = c+ e - Type 4: B = D = 90°, b = c, d = e - Type 5: A = 60°, D = 120°, a = b, d = e - Type 6: B + D = 180°, 2B = E, a = d = e, b = c - Type 7: B + 2E = 2C + D = 360°, b = c = d =e - Type 8: 2B + C = D + 2E = 360°, b = c = d =e - Type 9: 2A + C = D + 2E = 360°, b = c = d =e - Type 10: A = 90°, B + E = 180°, B + 2C = 360°, a = b = c + e - Type 11: A = 90°, C + E = 180°, 2B + C = 360°, 2a + c = d = e Petition 870250073524, dated 08 / 20 / 2025, p. 36 / 155 31 / 129 - Type 12: A = 90°, C + E = 180°, 2B + C = 360°, 2a = d = c + e - Type 13: B = E = 90°, 2A + D = 360°, d = 2a = 2e - Type 14: A = 90°, B "145.34°, C" 69.32°, D "124.66°, E" 110.68°, 2a = 2c = d = e - Type 15: A = 150°, B = 60°, C = 135°, D = 105°, E = 90°, a = c = e, b = 2a

[0069] This list was demonstrated to be complete by Rao in 2017 (Rao, Michael: “Exhaustive search for convex pentagons that brick the plane.”).

[0070] The pentagonal tiling, also called pentagonal mosaic, is a tiling of the plane in which each individual piece has the shape of a pentagon. Regular pentagons do not tile the Euclidean plane; however, they can tile a sphere with three pentagons and the hyperbolic plane with four or more pentagons around each vertex. The above types of pentagons that can monohedrally tile the Euclidean plane (i.e., with one type of tiling) generally have no symmetry, although some have special cases with mirror symmetry. For example, the Type I pentagon of the present invention is a mirror-symmetric case of Type 1, and the Type II pentagon is a mirror-symmetric case of Type 3 or Type 4.A pentagon of type I, in which the sides of the pair of parallel sides of equal length, as well as the remaining side, have a length that is ^3 times the length of the sides of the other pair of sides of equal length, can tile the Euclidean plane in prismatic pentagonal tiling (Fig. 2a). A pentagon of type II, in which the remaining side has a length that is ^3-1 times the length of the sides of one pair of sides of equal length and the other pair of sides of equal length, can tile the Euclidean plane in Cairo pentagonal tiling (Fig. 2b). Petition 870250073524, dated 08 / 20 / 2025, page 37 / 155 32 / 129

[0071] Furthermore, pentagons have a peculiar relationship with hexagons, as some types of hexagons can be subdivided into pentagons. For example, a convex hexagon can be subdivided into two Type 1 pentagons, three or nine Type 3 pentagons, or four Type 4 pentagons. Thus, a Type I pentagon, in which the sides of the pair of parallel sides of equal length have a length that is half the length of the sides of the other pair of sides of equal length, and the remaining side has a length that is 1 / 3 times the length of the sides of the other pair of sides of equal length, can provide a monohedral pentagonal covering with overlaps of regular hexagons, each comprising two pentagons.Furthermore, a type II pentagon, in which the sides of one pair of equal-length sides have a length that is half the length of the remaining side, and the sides of the other pair of equal-length sides have a length that is 2 / ^3 times the length of the remaining side, can provide a monohedral pentagonal covering with overlaps of regular hexagons, each comprising three pentagons.

[0072] In the sense of the invention, the term “medical patch sheet” refers to a series of medical patches that share a common release coating. Each of the medical patches represents an individual dosage unit that can be applied to the patient's skin after being removed from the protective coating. The amount of active agent contained in the medical patch refers to the amount of active agent contained in the active agent-containing layer structure of the medical patch. The amount of active agent contained in the medical patch sheet refers to the total amount of active agent contained in all the active agent-containing layer structures of the medical patches that constitute the medical patch sheet. Consequently, the release area of ​​the patch Petition 870250073524, dated 08 / 20 / 2025, page 38 / 155 33 / 129 medical patch refers to the area provided by the structure of the layer containing the active agent of the medical patch, and the release area of ​​the medical patch sheet refers to the area provided by all the structures of the layer containing the active agent of the medical patches that constitute the medical patch sheet.

[0073] In the sense of the invention, the term “release coating” refers to a detachable protective layer, attached to the layer containing the active agent or to the skin contact layer of the structure(s) of the layer containing the active agent. The release coating may have any suitable two-dimensional geometric shape and preferably has a polygonal shape, in particular a rectangular or square shape. Preferably, the area of ​​the release coating covers the total area of ​​all the active agent-containing layer structures of the medical patches that constitute the medical patch sheet.The release coating can be coextensive with the structures of the layer containing the active agent or extend beyond the boundary formed by all the structures of the layer containing the active agent in all directions; that is, the polygonal chain formed by the outer sides of the hexagons and / or pentagons of the structures of the layer containing the active agent lies completely within or over the polygonal chain formed by the sides of the release coating. Suitable release coatings can be polyethylene terephthalate (PET) or polypropylene (PP) films, optionally provided with a silicone or fluoropolymer coating. This included, for example, commercially available release coatings such as the Scotchpak® 9741 / 9742 / 9744 release coatings from 3M.

[0074] In the sense of the invention, the term “weakened” refers to the result of any action (weakening) that allows for easier separation of two sections of a layered structure. Petition 870250073524, dated 08 / 20 / 2025, page 39 / 155 34 / 129 having an active agent or two different active agent-containing layer structures, although the two active agent-containing layer sections / structures are still connected to each other. This weakening may include, but is not limited to, bending, scratching, puncturing, drilling, punching, or cutting. In certain embodiments, the weakening is achieved by perforation. In this context, the term “perforated” is understood as having small holes made in it. Perforation can be achieved, for example, by needling or laser cutting.

[0075] In the sense of the invention, the term “fixing bridge” refers to a single point between two or three active agent-containing layer structures, in particular between two or three hexagonal and / or pentagonal shapes, where they are still connected, while the main part of the common sides is cut or weakened. It is preferably obtained by leaving the connection during the separation process, which can be carried out by, for example, punching or cutting. The fixing bridge(s) allow(s) the joint removal of active agent-containing layer structures connected in this way from the release coating. Furthermore, the fixing bridge(s) is / are preferably so thin that it / they can be easily undone, for example, by pulling a part of the active agent-containing layer structures in order to separate some of the active agent-containing layer structures from others.

[0076] Within the meaning of the present invention, the term patient refers to an individual who has presented a clinical manifestation of a specific symptom or symptoms, suggesting the need for treatment, who receives preventive or prophylactic treatment against a condition, or who has been diagnosed with a condition to be treated. Preferably, the patient suffers from neuropathic pain, or nociceptive pain, or mixed neuropathic and nociceptive pain, such as joint pain or cancer pain. Petition 870250073524, dated 08 / 20 / 2025, p. 40 / 155 35 / 129

[0077] In the context of this invention, the term “neuropathic pain” refers to pain caused by an injury or disease of the somatosensory nervous system. In this context, the term “chronic neuropathic pain” is understood as neuropathic pain lasting for at least three months. When suffering from neuropathic pain, most patients complain of continuous or intermittent spontaneous pain, for example, burning, stinging, and squeezing, which may be accompanied by evoked pain, particularly upon light touch and cold. Ectopic activity in, for example, nerve ending neuroma, compressed nerves or nerve roots, dorsal root ganglia, and thalamus may, under different conditions, underlie spontaneous pain. Neuropathic pain includes peripheral neuropathic pain that particularly affects peripheral nerves, i.e., nerves located outside the brain and spinal cord.In particular, neuropathic pain, within the meaning of this invention, refers to post-surgical neuropathic pain, as well as neuropathic pain associated with post-herpetic neuralgia or diabetic peripheral neuropathy of the hands or feet.

[0078] In this context, the term “post-surgical neuropathic pain” is understood as chronic pain that develops after a surgical procedure and persists beyond the healing process, i.e., at least three months after surgery. The pain is located in the surgical field or in the area of ​​the lesion, projected to the innervation territory of a nerve located in that area or referred to a dermatome (after surgery / injury in deep somatic or visceral tissues). Chronic post-surgical pain results from nerve damage and can be caused by the surgery itself or by other causes of pain, including infection, malignancy, etc.

[0079] In this context, the term “postherpetic neuralgia”, also known as post-herpetic nerve pain, is understood as pain that occurs if the nerves are damaged due to an infection. Petition 870250073524, dated 08 / 20 / 2025, page 41 / 155 36 / 129 anterior due to herpes zoster, commonly called shingles. Symptoms of post-herpes zoster nerve pain are usually limited or localized to the area of ​​skin where the shingles outbreak first occurred, in the band around the trunk, usually on one side of the body. Less common symptoms of post-herpes zoster nerve pain include itching, numbness, or tingling sensation.

[0080] In this context, the term “diabetic peripheral neuropathy,” also known as diabetic nerve pain, is understood as the pain that occurs when nerves are damaged as a result of diabetes. Although diabetic nerve pain can affect any nerve, it is most often felt in the extremities, such as the hands or feet.

[0081] In the sense of the invention, the term “nociceptive pain” refers to pain caused by structural dysfunctions, such as damage to body tissue. It is the normal response to noxious (intense) stimulation, predictably initiated by the activation of nociceptors, i.e., primary afferent neurons with a high activation threshold that detect signals of damaged tissue or threat of damage. Nociceptive pain can range from sharp, stabbing, or shock-like to dull, aching, or burning, depending on the responsible stimulus, and continues only as long as the noxious stimulus is maintained. That said, sustained or recurrent noxious stimulation can occur in certain disease states, such as osteoarthritis, where changes in the joint may allow normal weight-bearing to produce sufficient forces to activate nociceptors. Nociceptive pain can be subdivided into somatic pain and visceral pain.

[0082] In this context, the term “somatic pain” is understood as nociceptive pain originating from nociceptors in the skin, bones, connective tissue, muscles, or joints. Somatic pain is characterized as localized, intermittent, or constant and described as aching. Petition 870250073524, dated 08 / 20 / 2025, page 42 / 155 37 / 129 sharp, throbbing, or colicky pain. Over time, it can evolve into a dull ache, especially deep somatic pain in the muscles and bones.

[0083] In this context, the term “visceral pain” is understood as nociceptive pain originating from nociceptors within or near internal organs. In particular, visceral pain is mediated by discrete nociceptors in the cardiovascular, respiratory, gastrointestinal, and genitourinary systems and is generally described as deep, oppressive, or colicky, commonly referred to cutaneous sites, which may be tender.

[0084] In the meaning of this invention, the term “joint pain,” also known as arthralgia, refers to a joint condition, such as discomfort, pain, or tenderness in any of the joints of a patient’s body, including the spine, shoulders, hips, elbows, knees, feet, and finger joints. In this context, joints are understood as central structures of the articular system that can be considered as discontinuities in the skeleton that allow controlled mobility, and may present different structures depending on their functional needs. Joint pain can be constant or come and go. It can be the result of disease or injury, but it can also be due to other conditions or factors. In particular, joint pain tends to affect people with arthritis or other long-term (chronic) medical conditions.

[0085] In the context of this invention, the term "joint condition" refers to any disease, disorder, or discomfort affecting or involving one or more joints. The joint condition may be inflammatory, i.e., involving inflammation of the bones or related tissues. It may include angiogenesis, i.e., the growth of new capillary blood vessels from pre-existing vasculature, and / or arthropathy, i.e., a specific abnormal condition that negatively affects the Petition 870250073524, dated 08 / 20 / 2025, p. 43 / 155 38 / 129 structure or function of all or part of the joint(s), in particular arthritis.

[0086] In this context, the term “arthritis” is understood as a form of arthropathy that involves inflammation of one or more joints. Arthritis can be infectious, that is, caused by a bacterial, viral or fungal infection that spreads from another part of the body, or non-infectious, that is, caused by other factors.It may include rheumatoid arthritis, that is, a long-term autoimmune disease that mainly affects the joints; juvenile arthritis, that is, a non-infectious, inflammatory autoimmune joint disease that arises before the age of 16; psoriatic arthritis, a long-term inflammatory arthritis caused by psoriasis; gouty arthritis or pseudogout, that is, a form of inflammatory arthritis caused by needle-shaped uric acid crystals, known as monosodium urate crystals, or caused by dehydrated calcium pyrophosphate crystals, respectively; or osteoarthritis, that is, a degenerative disease characterized by cartilage erosion, bone hypertrophy, subchondral sclerosis, and synovial and capsular changes.The joint condition can result, in particular, in knee pain, elbow pain, hip pain, shoulder pain, hand or foot pain, or back pain (lower back), which are primarily nociceptive at the beginning, but may also include neuropathic elements.

[0087] In the context of this invention, the term “cancer pain” refers to neuropathic cancer pain caused by nerve damage attributable to the cancer itself and / or treatments including chemotherapy, radiation therapy, and surgery. Cancer pain caused by the tumor itself generally involves nociceptive and neuropathic components, and mixed pain is more common than neuropathic cancer pain caused by cancer treatments. Most cancer pain caused by chemotherapy is purely neuropathic in nature. Neuropathic pain from Petition 870250073524, dated 08 / 20 / 2025, p. 44 / 155 39 / 129 Cancer is a pain related to the nerves (usually neurons), characterized as a burning or electric sensation; however, sometimes it manifests as decreased sensitivity or actual muscle weakness.

[0088] According to the invention, the medical patch as described herein is suitable for use in a treatment method, preferably in which the medical patch is applied for a short period of time (application time) but provides the desired pain relief effect for a long period of time (effect time). Within the application time, it is preferable that the medical patch releases almost the entire amount of the active agent contained in the active agent layer of the medical patch. In certain embodiments, the active agent is able to desensitize and defunctionalize a corresponding pain receptor within the application time, so that it can provide sustained pain relief that lasts for the duration of the effect time.

[0089] In the context of this invention, the term “short period of time”, that is, the application time, refers to a period of less than or about 240 minutes, less than or about 180 minutes, less than or about 120 minutes, less than or about 90 minutes, less than or about 60 minutes, less than or about 45 minutes, less than or about 30 minutes, less than or about 15 minutes, or 30 to 90 minutes.

[0090] In the context of this invention, the term “extended period of time”, that is, the time of effect, refers to a period of at least or about 1 week, at least or about 2 weeks, at least or about 1 month, at least or about 1.5 months, at least or about 2 months, at least or about 3 months or 1 to 3 months.

[0091] The interval between two administrations of pharmaceutical forms, also called the dosage interval, needs to be adapted Petition 870250073524, dated 08 / 20 / 2025, p. 45 / 155 40 / 129 of the appropriate method. Within the meaning of the present invention, the term dosing interval refers to the period of time between two consecutive administrations of a medical patch, that is, the interval between two consecutive points in time when a medical patch is applied to the patient's skin. Once applied, the medical patch is kept on the patient's skin only for the duration of the application time and is subsequently removed. However, the interval between doses lasts until a new medical patch is applied to the skin.

[0092] As used herein, the term “medical professional” is understood to mean a provider of health care and advice based on formal training and experience. This refers, in particular, to a person trained in the application and removal of medical plasters (which contain irritating active agents).

[0093] In the context of this invention, the term “coating composition” refers to a composition comprising all the components of the active agent-containing layer or the skin contact layer, respectively, which may be coated onto an intermediate coating, the carrier layer or the release coating to form the active agent-containing layer and the skin contact layer after drying (or curing).

[0094] Within the meaning of this invention, the term “dissolve” refers to the process of obtaining a solution that is clear and contains no particles visible to the naked eye.

[0095] In the context of this invention, the term "crosslinking" refers to the process of crosslinking functional groups that may be contained in the active-free coating composition.

[0096] Within the meaning of this invention, and unless otherwise specified, the expression "approximately" refers to an amount that is ± 10% of the disclosed quantity. In some embodiments, the expression "approximately" refers to an amount that is ± Petition 870250073524, dated 08 / 20 / 2025, p. 46 / 155 41 / 129 5% of the disclosed quantity. In some cases, the expression "approximately" refers to a quantity that is ± 2% of the disclosed quantity. Brief Description of the Drawings

[0097] Fig. 1a represents the cumulative permeated amount of medical plasters prepared according to Example 1.

[0098] Fig. 1b represents the skin permeation rate of medical plasters prepared according to Example 1. Detailed Description MEDICAL PLASTER STRUCTURE

[0099] The present invention relates to a medical patch for administering an active agent. The medical patch may be a topical medical patch or a transdermal therapeutic system. In certain embodiments, the patch is a topical medical patch, in particular for the topical administration of the active agent.

[00100] The medical plaster according to the present invention comprises a layer structure containing an active agent, wherein said layer structure containing the active agent comprises: A) a support layer; B) a layer containing an active agent comprising (i) an active agent, and (ii) a polymer I; and C) a skin contact layer comprising a polymer II; wherein the skin contact layer is an adhesive layer that is directly attached to the layer containing the active agent.

[00101] Preferably, the aforementioned layers of the medical plaster according to the invention are directly attached Petition 870250073524, dated 08 / 20 / 2025, page 47 / 155 42 / 129 to each other, that is, the support layer is directly attached to the layer containing the active agent, which, in turn, is directly attached to the skin contact layer. In other words, the medical plaster according to the present invention comprises its layers in the following order: (1) support layer, (2) layer containing active agent and (3) skin contact layer.

[00102] The support layer, the layer containing the active agent, and the skin contact layer can be coextensive, meaning they have the same planar extent (size). Alternatively, it may be preferable for the support layer and / or the skin contact layer to have a larger area than the layer containing the active agent. With an active agent-containing layer structure constructed in this way, the active agent contained within the active agent-containing layer is even more securely enclosed within it.

[00103] The additional skin contact layer preferably provides adhesion between the active agent-containing layer structure and the patient's skin during administration. In some embodiments, the active agent-containing layer structure is a self-adhesive layer structure. The active agent-containing layer structure, according to the present invention, which comprises an additional skin contact layer, when applied to the patient's skin, provides improved wear properties as well as clean and painless removal. If necessary, for example, in case of repositioning, the medical patch can be removed and reapplied without loss of adhesiveness.Furthermore, the structure of the layer containing the active agent, sandwiched between the skin contact layer (in which the active agent is preferably substantially insoluble) and the support layer (which is preferably substantially impermeable to the active agent), protects the active agent from the patient's skin. Petition 870250073524, dated 08 / 20 / 2025, page 48 / 155 43 / 129 of another person who applies / removes the adhesive before and / or after the application of the medical plaster.

[00104] The medical plaster according to the present invention can be a matrix-type medical plaster or a reservoir-type medical plaster and, preferably, is a matrix-type medical plaster. In certain embodiments, the medical plaster according to the present invention is a matrix-type medical plaster, wherein the active agent is homogeneously dissolved and / or dispersed within a polymeric carrier, i.e., the matrix, which forms, together with the active agent and, optionally, other additives, a matrix layer. In certain embodiments, the matrix layer containing the active agent may comprise at least the active agent and a solubilizer dissolved and / or dispersed within the matrix (i.e., polymer I). Thus, the medical plaster according to the invention can be a micro-reservoir-type medical plaster.

[00105] The structure of the layer containing the active agent according to the invention is normally located in a detachable protective layer (release coating) which is removed immediately before application to the patient's skin surface. Thus, according to certain embodiments, the medicament may further comprise a removable coating. A medical patch protected in this manner is generally stored in a sealed pouch. The packaging may be child-resistant and / or suitable for the elderly. LAYER CONTAINING ACTIVE AGENT

[00106] As described in more detail above, the medical plaster according to the present invention comprises an active agent-containing layer structure comprising inter alia an active agent-containing layer, comprising (i) an active agent, and (ii) a polymer I. Petition 870250073524, dated 08 / 20 / 2025, page 49 / 155 44 / 129

[00107] According to the invention, the layer containing the active agent is placed between the skin contact layer and the support layer, thus preventing it from coming into contact with the patient's skin (or that of another person applying / removing the product). Consequently, the layers of the active agent-containing layer structure are selected so that the active agent-containing layer is the only layer that allows the active agent to concentrate in more than 0.1% by weight (i.e., neither the skin contact layer nor the support layer should be able to carry the active agent in an amount greater than 0.1% by weight).

[00108] Thus, in certain embodiments, the saturation concentration of the active agent in the layer containing the active agent is greater than 1% by weight, greater than 5% by weight, greater than 10% by weight, or greater than 20% by weight. In particular, the saturation concentration of the active agent in polymer I of the layer containing the active agent may be greater than 1% by weight, greater than 5% by weight, greater than 10% by weight, or greater than 20% by weight. Alternatively, the saturation concentration of the active agent in polymer I of the layer containing the active agent may be (effectively) less than 1% by weight, or less than 0.1% by weight, and may be increased locally only by the addition of one or more solubilizers.

[00109] Thus, in specific embodiments, the layer containing the active agent may further comprise a solubilizer, in particular in an amount of 1 to 40% by weight, based on the total weight of the layer containing the active agent. Consequently, the layer containing the active agent may comprise (i) an active agent, (ii) a polymer I, and (iii) a solubilizer. Petition 870250073524, dated 08 / 20 / 2025, page 50 / 155 45 / 129

[00110] Without intending to be limited by theory, it is believed that the safe and uncomplicated handling of the medical patch according to the present invention, relying on the skin contact layer providing a saturation concentration of the active agent of less than 0.1% by weight, can be further improved by selecting polymer I of the layer containing the active agent so as to provide a saturation concentration of the active agent of less than 1% by weight, or less than 0.1% by weight, and adding a solubilizer that forms deposits, for example, droplets with the active agent in a microreservoir system. By increasing the concentration of the active agent only locally in the layer containing the active agent, the active agent can be kept within the layer containing the active agent, provided that the structure of the layer containing the active agent is not in contact with the patient's skin. In this way, it is possible to avoid unwanted skin reactions caused by the active agent.

[00111] In certain embodiments, it is preferable that the layer containing the active agent be a matrix layer containing the active agent, preferably comprising (i) an active agent, in particular in an amount of at least 0.5% by weight, based on the total amount of the layer containing the active agent, (ii) a polymer I, in particular in an amount of 20 to 99% by weight, or 60 to 99% by weight, based on the total amount of the layer containing the active agent, and optionally (iii) a solubilizer, in particular in an amount of 1 to 40% by weight, based on the total weight of the layer containing the active agent.

[00112] The active agent (and optionally the solubilizer) is preferably distributed homogeneously within the layer of Petition 870250073524, dated 08 / 20 / 2025, page 51 / 155 46 / 129 triz containing the active agent. As used herein, an active agent-containing matrix layer is a layer containing the active agent dissolved or dispersed in polymer I, or containing the active agent dissolved in the solubilizer to form an active agent-solubilizer mixture that is dispersed in the form of deposits (in particular droplets) in polymer I. Thus, the active agent-containing matrix layer may comprise the active agent dissolved in the solubilizer as microreservoir droplets distributed within the active agent-containing matrix layer. The proportion of microreservoir droplets in the active agent-containing matrix layer is generally less than about 40% by weight, or less than about 35% by weight, or between about 20% and about 30% by weight.

[00113] In certain embodiments, the layer containing the active agent may comprise the active agent in an amount of at least 0.5% by weight, at least 1% by weight, at least 2% by weight, or at least 5% by weight, based on the total weight of the layer containing the active agent. In these or other embodiments, the layer containing the active agent may comprise the active agent in an amount not exceeding 30% by weight, not exceeding 20% ​​by weight, not exceeding 15% by weight, or not exceeding 10% by weight, based on the total weight of the layer containing the active agent. In particular, the layer containing the active agent may comprise the active agent in an amount of 0.5 to 30% by weight, 1 to 20% by weight, 2 to 15% by weight, or 5 to 10% by weight.

[00114] In certain embodiments, the layer containing the active agent may comprise polymer I in an amount of 20 to 99% by weight, or 60 to 90% by weight, based on the total weight of the layer containing the active agent. It should be understood that the aforementioned percentage amounts by weight refer to the total amount of polymer I. For example, if polymer I is a mixture of polymers Petition 870250073524, dated 08 / 20 / 2025, page 52 / 155 47 / 129 ros, the total amount in the layer containing the active agent is 20 to 99% by weight, based on the total weight of the layer containing the active agent. ACTIVE AGENT

[00115] According to the invention, the layer containing the active agent comprises an active agent.

[00116] The active agent may be any compound responsible for the therapeutic effect(s) of the medical patch comprising the active agent-containing layer structure comprising the active agent-containing layer. In particular, the active agent may be a topically active agent or a systemically active agent. In certain embodiments, the active agent may be at least one irritant active agent, in particular an irritant to the skin.

[00117] For example, the active agent may be an analgesic, such as a TRPV1 agonist.

[00118] According to particular embodiments, the active agent may be a capsaicin analogue. As used herein, the term “capsaicin analogue” refers to a chemical compound that provides a pharmacological effect similar to that of capsaicin, particularly with regard to the TRPV1 receptor. Capsaicin ((6E)-N-[(4-hydroxy-3-methoxyphenyl)methyl]-8-methylnon-6-enamide) is an alkaloid found in the Capsicum family and a potent agonist of the transient receptor potential receptor, subfamily V, member 1 (TRPV1) cation channel, more commonly known as the vanilloid receptor. This receptor is a non-selective cation channel that allows transient influx of Ca2+ when activated during the detection and transduction of nociceptive stimuli.Since calcium in the cell is one of the most versatile second messengers in numerous intracellular signaling pathways, and TRPV1 allows cations to pass through the cell membrane and enter the cell when activated, the resulting depolarization of neurons stimulates it to send itself. Petition 870250073524, dated 08 / 20 / 2025, page 53 / 155 48 / 129 more to the brain. A capsaicin analogue is therefore more precisely understood as a natural or synthetic molecule that clearly demonstrates being an agonist of the TRPV1 receptor and / or that preserves all or part of the aromatic catechol ring in its chemical structure.

[00119] In specific embodiments, the active agent is selected from the group consisting of other capsaicinoids found in the Capsicum family, such as dihydrocapsaicin (N-[(4-hydroxy-3-methoxyphenyl)methyl]-8-methylnonanamide), nordihydrocapsaicin (N-[(4-hydroxy-3-methoxyphenyl)methyl]-7-methyloctanamide), homocapsaicin ((6E)-N-(4-hydroxy-3-methoxybenzyl)-8-methyldec-6-enamide), homodihydrocapsaicin (N-[(4-hydroxy-3-methoxyphenyl)methyl]-9-methyldecanamide) or pseudocapsaicin (N[(4-hydroxy-3-methoxyphenyl)methyl]nonanamide, also referred to as nonivamide), natural analogs of capsaicin, such as, for example, capsiate ((E)-4-hydroxy-3-methoxybenzyl 8-methylnon-6-enoate), gingerol ((5S)-5hydroxy-1-(4-hydroxy-3-methoxyphenyl)decan-3-one), piperine ((2E,4E)-5-(2H1,3-benzodioxol-5-yl)-1-(piperidin-1-yl)penta-2,4-dien-1-one), or resiniferatoxin ([(1 R,2R,6R, 10S,11R,13R,15R, 17R)-13-benzyl-6-hydroxy-4,17dimethyl-5-oxo-15-(prop-1-en-2-yl)-12,14,18-trioxapentacycle [11.4.1.01,10.02,6.011,15] octadeca-3,8-dien-8-yl]methyl 2-(4-hydroxy-3-methoxyphenyl)acetate), and synthetic analogs of capsaicin, such as, for example, arvanil ((5Z,8Z,11Z,14Z)-N-[(4-hydroxy-3-methoxyphenyl)methyl]5,8,11,14-eicosatetraenamide), civamide ((N-[(4-hydroxy-3-methoxyphenyl)methyl]-8-methyl-(Z)-6-nonanamide), N-oleyl homovanilamide (N(9Z-octadecenyl)-3-methoxy-4-hydroxyphenylacetamide), olvanil ((Z)-N-[(4-hydroxy-3-methoxyphenyl)methyl]octadec-9-enamide), palvanyl (N-[(4-hydroxy-3-methoxyphenyl)methyl]hexadecanamide) and phenylacetylrinvanyl ([(Z,7R)-18-[(4hydroxy-3-methoxyphenyl)methylamino]-18-oxo-octadec-9-en-7-yl] 2phenylacetate).

[00120] According to specific embodiments, the active agent is resiniferatoxin. Resiniferatoxin (abbreviated as RTX) is an irritant. Petition 870250073524, dated 08 / 20 / 2025, page 54 / 155 49 / 129 is an ultrapotent toxin produced in the latex of the Euphorbia plant species. It has a Scoville heat rating of 16 billion units, making pure resiniferatoxin approximately 500 to 1000 times hotter than pure capsaicin. Therefore, RTX is quite toxic and can cause chemical burns in minute quantities. It causes intense, burning pain in submicrogram amounts (less than 1 / 1,000,000 of a gram) when ingested orally. However, as it is currently the most potent TRPV1 agonist known, showing approximately 500 times greater binding affinity to TRPV1 than capsaicin, RTX can ablate sensory neurons like a “molecular scalpel” to achieve permanent analgesia. The therapeutic window of RTX is wide, allowing for complete desensitization of pain perception and neurogenic inflammation without causing unacceptable side effects.Currently, intra-articular RTX is undergoing clinical trials to treat moderate to severe knee pain in patients with osteoarthritis. Similar targeted approaches may be useful in treating postoperative pain or pain associated with severe burns.

[00121] Thus, specific layers containing the active agent according to the invention comprise a capsaicin analogue, such as resiniferatoxin. Consequently, in particular embodiments, the medical patch according to the invention is for the administration (topical or transdermal) of a capsaicin analogue, or for the administration (topical or transdermal) of resiniferatoxin.

[00122] In certain embodiments, the medical plaster and, in particular, the layer containing the active agent do not comprise capsaicin.

[00123] The medical patch, and in particular the layer containing the active agent, comprises the active agent in a therapeutically effective amount. In certain embodiments, the layer containing the active agent may contain at least 0.10 mg / cm2, at least 0.20 Petition 870250073524, dated 08 / 20 / 2025, page 55 / 155 50 / 129 mg / cm2, at least 0.50 mg / cm2 or at least 1.0 mg / cm2 of the active agent per release area. In these or other embodiments, the layer containing the active agent may comprise less than 12.0 mg / cm2, less than 10.0 mg / cm2, less than 6.0 mg / cm2 or less than 3.0 mg / cm2 of the active agent per release area. In particular, the layer containing the active agent may comprise from 0.10 to 12.0 mg / cm2, from 0.20 to 10.0 mg / cm2, from 0.50 to 6.0 mg / cm2 or from 1.0 to 3 mg / cm2 of the active agent per release area. POLYMER I

[00124] According to the invention, the layer containing the active agent comprises a polymer I. This polymer can provide sufficient cohesion and / or adhesion of the layer containing the active agent.

[00125] Polymers that are suitable as polymer I according to the invention are polymers that allow the active agent to be concentrated to more than 0.1% by weight, in particular to a therapeutically effective amount, if necessary, by the use of an appropriate solubilizer. Consequently, in some embodiments, the saturation concentration of the active agent in polymer I may be greater than 1% by weight, greater than 5% by weight, greater than 10% by weight, or greater than 20% by weight. In other embodiments, the saturation concentration of the active agent in polymer I may be (effectively) less than 1% by weight, or less than 0.1% by weight, but may be increased to more than 1% by weight, more than 5% by weight, more than 10% by weight, or more than 20% by weight by the addition of one or more solubilizers.

[00126] Polymer I can be selected from pressure-sensitive adhesive polymers. Thus, in certain embodiments, polymer I can be a pressure-sensitive adhesive or a mixture of pressure-sensitive adhesives.

[00127] In certain embodiments, polymer I may be a polymer Petition 870250073524, dated 08 / 20 / 2025, page 56 / 155 51 / 129 or a mixture of polymers selected from the group consisting of acrylic polymers, acrylic-silicone hybrid polymers, silicone-based polymers and natural or synthetic rubber-based polymers. In particular, polymer I may be a polymer or a mixture of polymers selected from the group consisting of silicone-based polymers and natural or synthetic rubber-based polymers.

[00128] In specific embodiments, polymer I may be a polymer or a mixture of polymers selected from silicone-based polymers, in particular from polysiloxane-based polymers. In more specific embodiments, polymer I may be an amine-compatible polysiloxane.

[00129] In specific embodiments, polymer I may be a polymer or a mixture of polymers selected from natural or synthetic rubbers, in particular from styrenic triblock copolymers and polyisobutylenes. Consequently, polymer I may be a styrenic triblock copolymer, such as a SIS block copolymer, or polymer I may be polyisobutylene. Furthermore, the polymer may be a mixture of a styrenic triblock copolymer and polyisobutylene, in particular a mixture of a SIS block copolymer and polyisobutylene.

[00130] Suitable polymers I according to the invention are commercially available, for example, under the brand names BIO-PSA (pressure-sensitive adhesives based on polysiloxanes), JSR-SIS (pressure-sensitive adhesives based on SIS block copolymers) and OppanolTM (polyisobutylenes).

[00131] Additional polymers can also be added, for example, to increase the cohesion of the layer containing the active agent.

[00132] According to some embodiments, polymer I contained in the layer containing the active agent is different from polymer II contained in the skin contact layer. According to other embodiments, Petition 870250073524, dated 08 / 20 / 2025, page 57 / 155 52 / 129 des, polymer I contained in the layer containing the active agent is the same as polymer II contained in the skin contact layer. In such embodiments, as the saturation concentration of the active agent in polymer I is negligible (as in the skin contact layer and therefore in polymer II), the layer containing the active agent further comprises a solubilizer. SOLUBILIZER

[00133] The medical plaster according to the invention, and in particular the layer containing the active agent, may advantageously comprise a solubilizer.

[00134] As described above, a solubilizer is an agent capable of substantially increasing the solubility of the active agent in the layer containing the active agent, for example, by at least 1 percentage point (relative to the amount of active agent in % by weight in the layer containing the active agent) per 10% by weight, per 5% by weight, per 1% by weight or per 0.5% by weight of the solubilizer added to the layer containing the active agent. This can be achieved by a substance or a mixture of substances that have a relatively high solubility for the active agent. Thus, in certain embodiments, the solubilizer may be a substance or a mixture of substances in which capsaicin or a capsaicin analogue has a solubility of at least 30% by weight, at least 40% by weight or at least 45% by weight.

[00135] The solubilizer can also be released along with the active agent to further act as a penetration enhancer. Without wanting to get bogged down in theory, it is believed that a solubilizer may also have a limited or reduced affinity to polymer I contained in the layer containing the active agent and that, in this way, the driving force of the active agent dissolved in the solubilizer out of the adhesive is kept high (but only appears after the application of the medical patch to the Petition 870250073524, dated 08 / 20 / 2025, page 58 / 155 53 / 129 patient's skin).

[00136] In certain embodiments, the solubilizer may be an amphiphilic solvent. Suitable amphiphilic solvents include butanediols, in particular 1,3-butanediol, dipropylene glycol, tetrahydrofurfuryl alcohol, diethylene glycol dimethyl ether, diethylene glycol monoethyl ether (DGME), diethylene glycol monobutyl ether, propylene glycol, tri- and diethylene glycol carboxylic acid esters, 6-18 C atom polyethoxylated fatty alcohols or 2,2-dimethyl-4-hydroxymethyl-1,3-dioxolane, or any mixture of these or mixtures of these solvents.

[00137] In specific embodiments, the solubilizer is dipropylene glycol, diethylene glycol monoethyl ether or dimethyl isosorbide. Diethylene glycol monoethyl ether and dimethyl isosorbide are available, for example, under the trade names Transcutol® and Dottisol®, respectively.

[00138] The solubilizer may also be selected from the group consisting of glycerol, polyglycerol, propylene glycol and polyoxyethylene esters of medium and / or long-chain fatty acids, such as glyceryl monolinoleate, medium-chain glycerides and medium-chain triglycerides, nonionic solubilizers made by the reaction of castor oil with ethylene oxide and any mixtures thereof which may also contain fatty acids or fatty alcohols, cellulose and methylcellulose and their derivatives, such as hydroxypropylcellulose and hypromellose acetate succinate, various cyclodextrins and their derivatives, nonionic triblock copolymers with a central hydrophobic polyoxypropylene chain flanked by two hydrophilic polyoxyethylene chains known as poloxamers, water-soluble derivatives of vitamin E, agglomerated or pharmaceutical-grade spherical isomalt, a graft copolymer based on polyethylene glycol, polyvinyl acetate and polyvinylcaprolactam,also abbreviated as PVAc-PVCap-PEG and known as Soluplus®, purified grades of naturally derived castor oil, Petition 870250073524, dated 08 / 20 / 2025, page 59 / 155 54 / 129 specifically, polyethylene glycol 400, polyoxyethylene sorbitan monooleate (such as polysorbate 80) or glucono-delta-lactone, corn and potato starch, as well as any of the soluble polyvinylpyrrolidones, but also insoluble / crosslinked polyvinylpyrrolidones, such as crospovidones, mentioned herein. In addition, the permeation enhancers and / or crystallization inhibitors mentioned below may also act as solubilizers.

[00139] In particular, suitable solubilizers may include mixtures of propylene glycol monoesters and fatty acid diesters, which are commercially available, for example, under the brand name Capryol™, such as propylene glycol monocaprylate (type II), a mixture of propylene glycol esters of caprylic acid, mainly composed of monoesters and further comprising a small fraction of diesters with a proportion of not less than 90% monoesters and not more than 10% diesters (commercially available as Capryol™ 90 supplied by Gattefossé), and polyethylene glycol ethers, in particular polyethylene glycol fatty alcohol ethers, such as those commercially available as Brij®, for example, polyethylene glycol dodecyl ether with an average molecular weight Mn of about 362 commercially available as Brij® L4.

[00140] A certain minimum amount of solubilizer is advantageous because it will help prevent recrystallization of the active agent in the layer containing the active agent. On the other hand, if the amount of solubilizer is too high, the cohesion of the layer containing the active agent may be impaired, making it necessary to find a balance. Furthermore, regarding the advantageous effect of preventing recrystallization of the active agent, a crystallization inhibitor and a solubilizer can complement each other. Finally, the amount of crystallization inhibitor and / or solubilizer needed for effective prevention of recrystallization of the active agent also depends on the amount of active agent present. Petition 870250073524, dated 08 / 20 / 2025, page 60 / 155 55 / 129 in the layer containing the active agent. SKIN CONTACT LAYER

[00141] As described in more detail above, the medical plaster according to the present invention comprises an active agent-containing layer structure comprising inter alia a skin contact layer, wherein the skin contact layer is an adhesive layer that is directly attached to the active agent-containing layer.

[00142] The medical plaster according to the present invention is characterized, in particular, by the saturation concentration of the active agent in the skin contact layer being less than 0.1% by weight, preferably 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% by weight, less than 0.02% by weight, or less than 0.01% by weight. Preferably, the saturation concentration of the active agent in the skin contact layer is about 0% by weight. The saturation concentration is related to the amount of active agent present in the skin contact layer, based on the total weight of the skin contact layer.

[00143] In certain embodiments, the saturation concentration of the active agent in the skin contact layer is lower than the concentration of the active agent, resulting in any unintended adverse effect, such as skin irritation after contact after a short period of time. Such concentration can be determined empirically by means of in vivo tests, observing whether an adverse effect, such as any form of skin irritation (redness, erythema, itching or other skin reaction), occurs or not after application of model adhesive layers with defined concentrations of active agent to the skin for a short period of time, for example, 5 seconds, 10 seconds, Petition 870250073524, dated 08 / 20 / 2025, page 61 / 155 56 / 129 seconds or 1 minute. In particular, different model layers representing a range of active agent concentrations can be tested to determine the highest acceptable saturation concentration that will still not cause any unintended adverse effects, such as a skin irritation reaction. On the other hand, whether or not a medical patch with a certain set of active agent and skin contact layer results in a saturation concentration that does not result in any adverse effects can be simply determined (without a range of different concentrations) by testing a model adhesive layer that is saturated with the active agent, or said medical patch, i.e., applying it to the skin as described above.

[00144] According to the invention, the skin contact layer protects the active agent contained in the layer containing the active agent from the skin of the patient or other person applying / removing the patch before and / or after application of the medical patch.The skin contact layer must therefore be substantially free of the active agent. This means that the skin contact layer is normally manufactured as an active agent-free layer. However, due to the concentration gradient, the active agent can generally migrate from the layer containing the active agent to the skin contact layer over time, until an equilibrium is reached. This migration is, however, limited by the saturation concentration of the active agent in the skin contact layer. Consequently, the skin contact layer does not allow the active agent to be present at a concentration greater than 0.1% by weight.

[00145] Thus, in certain embodiments, the skin contact layer comprises the active agent in an amount less than 0.1% by weight, based on the total weight of the skin contact layer. In specific embodiments, the skin contact layer with Petition 870250073524, dated 08 / 20 / 2025, page 62 / 155 57 / 129 contains the active agent in an amount less than 0.01% by weight, based on the total weight of the skin contact layer.

[00146] In certain embodiments, the skin contact layer may comprise polymer II in an amount of at least 95% by weight, at least 99% by weight, or in an amount of about 100% by weight, based on the total weight of the skin contact layer. The amount of polymer II in the skin contact layer may vary from 50 to 95% by weight, 60 to 99% by weight, or 75 to 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 aforementioned percentage amounts by weight 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. POLYMER II

[00147] According to the invention, the skin contact layer comprises a polymer II. This polymer can be decisive for the adhesive properties of the skin contact layer and can further reduce skin irritation inter alia due to its resilience.

[00148] Polymers that are suitable as polymer II according to the invention are polymers that allow the active agent to concentrate at 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 can be a polymer or a mixture of polymers in which the active agent is substantially insoluble.

[00149] Consequently, the polymer solubility parameter Petition 870250073524, dated 08 / 20 / 2025, p. 63 / 155 58 / 129 ro II may differ, in particular, it may be less than the solubility parameter of the active agent by at least 5.0 MPa1 / 2, at least 6.0 MPa1 / 2, at least 8.0 MPa1 / 2 or at least 10.0 MPa1 / 2. In particular, the solubility parameter of polymer II may be less than 18.5 MPa1 / 2, less than 18.0 MPa1 / 2, less than 17.5 MPa1 / 2, less than 17.0 MPa1 / 2, less than 16.0 MPa1 / 2 or less than 15.0 MPa1 / 2, preferably as calculated by Small's method.

[00150] Polymer II may be selected from pressure-sensitive adhesive polymers. Thus, in certain embodiments, polymer II may be a pressure-sensitive adhesive or a mixture of pressure-sensitive adhesives.

[00151] In certain embodiments, polymer II may be a polymer or a mixture of polymers selected from the group consisting of acrylic-silicone hybrid polymers, silicone-based polymers, silicone gel adhesives, and natural or synthetic rubber-based polymers. In particular, polymer II may be a polymer or a mixture of polymers selected from the group consisting of silicone-based polymers and silicone gel adhesives.

[00152] In some embodiments, polymer II may be a silicone gel adhesive.

[00153] In other embodiments, polymer II may not be a silicone gel adhesive. Thus, according to such embodiments, the skin contact layer does not comprise silicone gel adhesives.

[00154] In addition, polymer II may be a polymer or a mixture of polymers selected from silicone-based polymers, in particular from polysiloxane-based polymers, such as amine-compatible polysiloxanes, or polymer II may be a polymer or a mixture of polymers selected from natural or synthetic rubbers, in particular from styrene triblock copolymers. Petition 870250073524, dated 08 / 20 / 2025, page 64 / 155 59 / 129 nicos and / or polyisobutylenes, as a SIS and / or polyisobutylene block copolymer.

[00155] Suitable Polymers II according to the invention are commercially available, for example, under the brand names Soft Skin Adhesives (two-part silicone adhesive that cures by mixing the two components). Alternative suitable Polymers II according to the invention are commercially available, for example, under the brand names BIO-PSA (pressure-sensitive adhesives based on polysiloxanes), JSR-SIS (pressure-sensitive adhesives based on SIS block copolymers) and Oppanol™ (polyisobutylenes).

[00156] Additional polymers can also be added, for example, to improve the adhesion of the contact layer to the skin. ACRYLIC POLYMER

[00157] The terms acrylic polymer and acrylate polymer are synonymous with acrylate-based polymers. In certain embodiments, acrylic polymers are acrylate-based pressure-sensitive adhesives. Acrylate-based pressure-sensitive adhesives may also be referred to as acrylate-based pressure-sensitive adhesives or acrylate pressure-sensitive adhesives.

[00158] Acrylate-based pressure-sensitive adhesives may preferably have a solids content between 30% and 60%. These acrylate-based pressure-sensitive adhesives may or may 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 trade name Duro Tak®. These acrylate-based pressure-sensitive adhesives are based on monomers selected from one or more of the following: acrylic acid, 2-ethylhexylacrylate, glycidyl methacrylate, 2-hydroxyethylacrylate, methyl acrylate, methyl methacrylate, butyl acrylate, butyl methacrylate, t-octylacrylamide, and vinyl Petition 870250073524, dated 08 / 20 / 2025, page 65 / 155 60 / 129 acetate, and are supplied as ethyl acetate, heptane, n-heptane, hexane, methanol, ethanol, isopropanol, 2,4-pentanedione, toluene or xylene or mixtures thereof.

[00159] Specific pressure-sensitive adhesives based on acrylate are commercially available as: - Duro-Tak™ 387-2287 or Duro-Tak™ 87-2287 (a copolymer based on vinyl acetate, 2-ethylhexyl acrylate, 2-hydroxyethyl acrylate and glycidyl methacrylate supplied as a solution in ethyl acetate without a crosslinking agent), - Duro-Tak™ 387-2516 or Duro-Tak™ 87-2516 (a copolymer based on vinyl acetate, 2-ethylhexyl acrylate, 2-hydroxyethyl acrylate and glycidyl methacrylate supplied as a solution in ethyl acetate, ethanol, n-heptane and methanol with a titanium crosslinking agent), - Duro-Tak™ 387-2051 or Duro-Tak™ 87-2051 (a copolymer based on acrylic acid, butyracrylate, 2-ethylhexylacrylate and vinyl acetate, supplied as a solution in ethyl acetate and heptane), - Duro-Tak™ 387-2353 or Duro-Tak™ 87-2353 (a copolymer based on acrylic acid, 2-ethylhexylacrylate, glycidyl methacrylate and methyl acrylate, supplied as a solution in ethyl acetate and hexane), - Duro-Tak™ 87-4098 (a copolymer based on 2-ethylhexyl acrylate and vinyl acetate, supplied as a solution in ethyl acetate). - Duro-Tak™ 387-9301 (a copolymer based on methyl acrylate, 2-ethylhexyl acrylate and t-octyl acrylamide, supplied as a solution in ethyl acetate).

[00160] Consequently, the acrylic polymer can be selected from acrylic polymers comprising functional groups, Petition 870250073524, dated 08 / 20 / 2025, page 66 / 155 61 / 129 wherein the functional groups are selected from 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 may not comprise carboxylic acid groups or neutralized carboxylic acid groups or both groups, or may not comprise acid groups, or may not comprise functional groups.

[00161] Depending on the type of commercially available acrylic polymer used and depending on whether a crosslinking agent is added to the coating composition, the polymer in the finished layer containing the active agent or in the skin contact layer is crosslinked (and preferably is crosslinked by an aluminum and / or titanium crosslinking agent) or is not crosslinked by a crosslinking agent. ACRYLIC SILICONE HYBRID POLYMER

[00162] Silicone acrylic hybrid polymers comprise a polymerized hybrid species that includes silicone-based subspecies and acrylate-based subspecies that have been polymerized together. The silicone acrylic hybrid polymer, therefore, comprises a silicone phase and an acrylic phase. In certain embodiments, the silicone acrylic hybrid polymer is a silicone acrylic hybrid pressure-sensitive adhesive.

[00163] Hybrid silicone acrylic pressure-sensitive adhesives are generally supplied and used in solvents such as n-heptane and ethyl acetate. The solids content of pressure-sensitive adhesives is generally between 30% and 80%. The expert is aware that the solids content can be modified by adding an appropriate amount of solvent.

[00164] The weight ratio of silicone to acrylate in pressure-sensitive acrylic silicone hybrid adhesive may be 5:95 to 95:5, or 20:80 to 80:20, or 40:60 to 60:40, or the silicone ratio Petition 870250073524, dated 08 / 20 / 2025, page 67 / 155 62 / 129 for acrylate can be about 50:50.

[00165] Suitable commercially available hybrid silicone and acrylic pressure-sensitive adhesives include the PSA series 7-6100 and 7-6300 manufactured and supplied in n-heptane or ethyl acetate by Dow Corning (7-610X and 7-630X; X=1 based on n-heptane / X=2 based on ethyl acetate). For example, the silicone and acrylic hybrid PSA 7-6102, which has a silicone / acrylate ratio of 50 / 50, is characterized by a solution viscosity at 25 °C and about 50% ethyl acetate solids content of 2,500 cP and a complex viscosity at 0.1 rad / sa 30 °C of 1.0e7 Poise. The PSA hybrid acrylic and silicone 7-6302, which has a silicone / acrylate ratio of 50 / 50, has a solution viscosity at 25°C and approximately 50% ethyl acetate solids content of 1,500 cP and a complex viscosity of 0.1 rad / sa at 30°C of 4.0e6 Poise.

[00166] It has been found that, depending on the solvent in which the acrylic-silicone hybrid PSA is supplied, the arrangement of the silicone phase and the acrylic phase that provides a continuous acrylic or silicone outer phase and a corresponding discontinuous inner phase is different. If the acrylic-silicone hybrid pressure-sensitive adhesive is supplied in n-heptane, the composition will contain a continuous silicone outer phase and a discontinuous acrylic inner phase. If the acrylic-silicone hybrid pressure-sensitive adhesive is supplied 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 acrylic-silicone hybrid pressure-sensitive adhesive is supplied, the resulting pressure-sensitive adhesive layer or film corresponds to the phase arrangement of the solvent-containing adhesive coating composition.For example, in the absence of any substance that could induce a phase reversal in a hybrid acrylic-silicone pressure-sensitive adhesive composition. Petition 870250073524, dated 08 / 20 / 2025, page 68 / 155 63 / 129 cone, a pressure-sensitive adhesive layer prepared from an acrylic-silicone hybrid pressure-sensitive adhesive in n-heptane provides a continuous silicone outer phase and a discontinuous acrylic inner phase; a pressure-sensitive adhesive layer prepared from an acrylic-silicone hybrid pressure-sensitive adhesive in ethyl acetate provides a continuous acrylic outer phase and a discontinuous silicone inner phase. The phase arrangement of the compositions can, for example, be determined in peel strength tests with pressure-sensitive adhesive films or layers prepared from acrylic-silicone hybrid PSA compositions that are bonded to a silicone-coated surface. The pressure-sensitive adhesive film contains a continuous silicone outer phase if it cannot or can hardly be removed from the pressure-sensitive adhesive film (laminated onto a backing film) due to the interlocking of the two silicone surfaces.The blockage results from the adhesion of two silicone layers comprising similar surface energies. The silicone adhesive shows good spreading on the silicone liner and therefore can create good adhesion to the liner. While the silicone liner film can be easily removed, the pressure-sensitive adhesive film contains a continuous outer acrylic phase. The acrylic adhesive does not spread well due to the different surface energies and therefore has low or almost no adhesion to the silicone liner.

[00167] The acrylic-silicone hybrid polymer may be a hybrid acrylic-silicone pressure-sensitive adhesive obtained from a pressure-sensitive adhesive composition containing silicone, comprising acrylate or methacrylate functionality. It will be understood that the pressure-sensitive adhesive composition containing silicone comprising acrylate or methacrylate functionality may include only acrylate functionality, only methacrylate functionality. Petition 870250073524, dated 08 / 20 / 2025, page 69 / 155 64 / 129 to either acrylate or methacrylate functionalities.

[00168] The pressure-sensitive silicone acrylic hybrid adhesive may comprise the reaction product of (a) a pressure-sensitive adhesive composition containing silicone comprising acrylate or methacrylate functionality, (b) an ethylenically unsaturated monomer, and (c) an initiator. That is, the pressure-sensitive silicone acrylic hybrid adhesive is the product of the chemical reaction between these reagents ((a), (b), and (c)). In particular, the pressure-sensitive silicone acrylic hybrid adhesive may include the reaction product of (a) a pressure-sensitive adhesive composition containing silicone comprising acrylate or methacrylate functionality, (b) a (meth)acrylate monomer, and (c) an initiator (i.e., in the presence of the initiator). That is, the pressure-sensitive silicone acrylic hybrid adhesive may include the product of the chemical reaction between these reagents ((a), (b), and (c)).

[00169] The reaction product of (a) a pressure-sensitive adhesive composition containing silicone comprising acrylate or methacrylate functionality, (b) an ethylenically unsaturated monomer and (c) an initiator may contain a continuous external silicone phase and a discontinuous internal acrylic phase or the reaction product of (a), (b) and (c) may contain a continuous external acrylic phase and a discontinuous internal silicone phase.

[00170] The silicone acrylic hybrid polymer may comprise a 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.

[00171] The acrylic silicone hybrid polymer may comprise a reaction product of a silicone polymer, a silicone resin and an acrylic polymer, wherein the silicone resin contains triorganosiloxy R3SiO1 / 2 units where R is an organic group, and uni Petition 870250073524, dated 08 / 20 / 2025, page 70 / 155 65 / 129 tetrafunctional siloxy compounds SiO4 / 2 in a molar ratio of 0.1 to 0.9 R3SiO1 / 2 units for each SiO4 / 2.

[00172] The acrylic polymer may comprise at least one alkoxysilyl functional monomer, polysiloxane-containing monomer, halosilyl functional monomer, or halosilyl alkoxy functional monomer. In certain embodiments, the acrylic polymer is prepared from alkoxysilyl functional monomers selected from the group consisting of trialkoxysilyl (meth)acrylates, dialkoxyalkylsilyl (meth)acrylates, and mixtures thereof, or comprises end-capped alkoxysilyl functional groups. The alkoxysilyl functional groups may preferably be selected from the group consisting of trimethoxysilyl groups, dimethoxymethylsilyl groups, triethoxysilyl groups, dietoxymethylsilyl groups, and mixtures thereof.

[00173] The acrylic polymer can also be prepared from a mixture comprising polysiloxane-containing monomers, preferably from a mixture comprising polydimethylsiloxane mono(meth)acrylate.

[00174] The acrylic-silicone hybrid polymer can be prepared by a) reacting the silicone polymer with silicone resin to form a resulting product, b) reacting the resulting product from a) with an acrylic polymer containing reactive functionality, wherein the components react in an organic solvent.

[00175] The acrylic silicone hybrid polymer can be prepared by a) reacting a silicone resin with an acrylic polymer containing reactive functionality to form a resulting product, b) reacting the resulting product from a) with silicone polymer, wherein the components react in an organic solvent.

[00176] The acrylic silicone hybrid polymer can be prepared by a) reacting a silicone polymer with an acrylic polymer containing reactive functionality to form a resulting product, b) Petition 870250073524, dated 08 / 20 / 2025, page 71 / 155 66 / 129 reaction of the resulting product from a) with silicone resin, in which the components react in an organic solvent.

[00177] Other suitable acrylic polymers, silicone resins and silicone polymers that can be used to chemically react together a silicone polymer, a silicone resin and an acrylic polymer to provide an acrylic-silicone hybrid polymer in accordance with the preceding paragraphs are detailed in WO 2010 / 124187. SILICONE-BASED POLYMER

[00178] Silicone-based polymer is a non-curable polymer that is typically applied by a hot melt or solvent-based process and preferably does not undergo further curing to solidify.

[00179] Silicone-based polymers are based on polysiloxanes. They can therefore also be referred to as polysiloxane-based polymers. Silicone-based polymers are generally obtained by polycondensation of polydimethylsiloxane blocked at the silanol end with a silicate resin. Amine-compatible silicone-based polymers can be obtained by reacting the silicone-based polymer with trimethylsilyl (e.g., hexamethyldisilazane) to reduce the silanol content of the polymer and thus provide greater stability in the presence of amines. As a result, the residual silanol functionality is at least partially, preferably mostly, or completely covered with trimethylsiloxy groups.

[00180] Thus, in specific embodiments, the silicone-based polymer may be an amine-compatible polysiloxane, obtained by polycondensation of a polydimethylsiloxane blocked at the silanol end with a silicate resin, followed by at least partial trimethylsilylation of the residual silanol functionality.

[00181] In certain embodiments, the silicone-based polymer may Petition 870250073524, dated 08 / 20 / 2025, page 72 / 155 67 / 129 being a pressure-sensitive adhesive based on polysiloxanes or a mixture of pressure-sensitive adhesives based on polysiloxanes.

[00182] These pressure-sensitive adhesives provide adequate grip and rapid adhesion to various skin types, including moist skin, suitable adhesive and cohesive qualities, long-lasting adhesion to the skin, a high degree of flexibility, moisture permeability, and compatibility with many active ingredients and film substrates. These pressure-sensitive adhesives are based on a polymer resin concept, in which, through the condensation reaction of polydimethylsiloxane blocked at the silanol end with a silica resin (also called silicate resin), a polysiloxane-based pressure-sensitive adhesive is prepared. For amine stability, the residual functionality of the silanol is additionally covered with trimethylsiloxy groups. The polydimethylsiloxane content blocked at the silanol end contributes to the viscous component of the viscoelastic behavior and affects the wetting and spreading properties of the adhesive.The resin acts as an adhesive and reinforcing agent and contributes to the elastic component. The correct balance between the polydimethylsiloxane blocked at the silanol end and the resin provides the correct adhesive properties.

[00183] As previously indicated, the adhesion of the silicone-based polymer can be modified by the resin-to-polymer ratio, i.e., the ratio of silanol-blocked polydimethylsiloxane to silicate resin, which is preferably in the range of 50:50 to 70:30, or 55:45 to 65:35. Adhesion will be increased with increasing amounts of polydimethylsiloxane relative to the resin. High-adhesion silicone-based polymers preferably have a resin-to-polymer ratio of 55:45, medium-adhesion silicone-based polymers preferably have a resin-to-polymer ratio of 60:40, and silicone-based polymers of Petition 870250073524, dated 08 / 20 / 2025, page 73 / 155 68 / 129 low adhesion preferably has a resin-to-polymer ratio of 65:35.

[00184] According to certain embodiments, silicone-based polymers can be obtained by polycondensation of a polydimethylsiloxane blocked at the silanol end 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 a specific embodiment, silicone-based polymers can be a mixture of pressure-sensitive adhesives obtained by polycondensation of a polydimethylsiloxane blocked at the silanol end with a silicate resin with a resin-to-polymer ratio of 55:45 or 60:40.

[00185] In addition, according to certain embodiments, polysiloxane-based polymers may be a mixture of pressure-sensitive adhesives with

[00186] a solution viscosity at 25 °C and about 60% solids content in heptane of 450 mPa if / or a complex viscosity of 0.01 rad / s at 30 °C of 1^108 Poise, and

[00187] a solution viscosity at 25 °C and about 60% solids content in heptane of 500 mPa if / or a complex viscosity of 0.01 rad / s at 30 °C of 5x106 Poise.

[00188] Silicone-based polymers are generally supplied and used in solvents such as n-heptane, ethyl acetate, or other volatile silicone fluids. The solids content of polysiloxane-based pressure-sensitive adhesives in solvents is generally between 60 and 85%, between 70 and 80%, or between 60 and 75%. The expert is aware that the solids content can be modified by adding an appropriate amount of solvent.

[00189] High-adhesion silicone-based polymers preferably have a complex viscosity at 0.01 rad / s and 30 °C of approximately Petition 870250073524, dated 08 / 20 / 2025, p. 74 / 155 69 / 129 of 5 x 106 Poise, medium-adhesion silicone-based polymers preferably have a complex viscosity at 0.01 rad / s and 30 °C of about 5 x 107 Poise, and low-adhesion silicone-based polymers preferably have a complex viscosity at 0.01 rad / s and 30 °C of about 5 x 108 Poise. High-adhesion amine-compatible silicone polymers preferably have a complex viscosity at 0.01 rad / s and 30 °C of about 5 x 10⁶ Poise, medium-adhesion amine-compatible silicone polymers preferably have a complex viscosity at 0.01 rad / s and 30 °C of about 5 x 10⁸ Poise, and low-adhesion amine-compatible silicone polymers preferably have a complex viscosity at 0.01 rad / s and 30 °C of about 5 x 10⁹ Poise.The preferred pressure-sensitive adhesives based on polysiloxanes according to the invention are characterized by a solution viscosity at 25 °C and 60% n-heptane solids content of more than about 150 mPa s, or from about 200 mPa s to about 700 mPa s, preferably measured using a Brookfield RVT viscometer equipped with a number 5 spindle at 50 rpm. They can also be characterized by a complex viscosity at 0.01 rad / s and 30 °C of less than about 1 x 10⁹ Poise or from about 1 x 10⁵ to about 9 x 10⁸ Poise.

[00190] Suitable silicone-based polymers are commercially available under the BIO-PSA brand names. 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 Liveo™ BIO-PSA series (7-4100, 7-4200 and 7-4300 series) manufactured and typically supplied in n-heptane or ethyl acetate. For example, BIO-PSA 7-4201 is characterized by a solution viscosity at 25 °C and approximately 60% solids content in heptane of 450 mPa and a complex viscosity of 0.01 rad / s at 30 °C. Petition 870250073524, dated 08 / 20 / 2025, p. 75 / 155 70 / 129 of 1x10⁸ Poise. BIO-PSA 7-4301 has a solution viscosity at 25 °C and approximately 60% solids content in heptane of 500 mPa if a complex viscosity of 0.01 rad / s at 30 °C of 5x10⁶ Poise.

[00191] Pressure-sensitive adhesives based on polysiloxanes can be obtained according to the following diagram: Heat Soluble silicate resin PDMS locked at the end with silanol Polycondensation OH +nh3X Silanol endblocked PDMS f Heat HO o Soluble silicate resin Polycondensation

[00192] These pressure-sensitive adhesives based on polysiloxanes are available under the trade names Liveo™ BIOPSA 7-4401, BIO-PSA-7-4501, or BIO-PSA 7-4601, which are supplied in n-heptane solvent (indicated by code “01”), or under the trade names Liveo™ BIO-PSA 7-4402, BIO-PSA 7-4502, and BIO 74602, which are supplied in ethyl acetate solvent (indicated by code “02”). The typical solids content in the solvent is in the range of 60 to 75%. Code 44 indicates a resin / polymer ratio of 65:35, resulting in weak adhesion; code 45 indicates a resin / polymer ratio of 60:40, resulting in medium adhesion; code 46 indicates a resin / polymer ratio of 55:45, resulting in high adhesion.

[00193] Pressure-sensitive adhesives compatible with polysiloxane-based amines can be obtained according to the following Petition 870250073524, dated 08 / 20 / 2025, page 76 / 155 71 / 129 scheme: Heat Trimethylsilylation Soluble silicate resin Polycondensation PDMS locked at the end with silanol. OH HO' OH OH HO Soluble silicate resin + NH Silanol endblocked PDMS' Heat H?O Polycondensation OH

[00194] These amine-compatible, pressure-sensitive adhesives based on polysiloxanes are available under the trade names Liveo™ BIO-PSA 7-4101, BIO-PSA-7-4201, or BIO-PSA 7 4301, which are supplied in n-heptane solvent (indicated by code “01”), or under the trade names Liveo™ BIO-PSA 7-4102, BIO-PSA 7-4202, and BIO 7-4302, which are supplied in ethyl acetate solvent (indicated by code “02”). The typical solids content in the solvent is in the range of 60 to 75%. Code 41 indicates a resin / polymer ratio of 65:35, resulting in weak adhesion; code 42 indicates a resin / polymer ratio of 60:40, resulting in medium adhesion; code 43 indicates a resin / polymer ratio of 55:45, resulting in high adhesion. SILICONE GEL ADHESIVE

[00195] Silicone gel adhesive is an elastic and gel-like material. Petition 870250073524, dated 08 / 20 / 2025, p. 77 / 155 72 / 129 noso formed by the light cross-linking of silicone polymers. Thus, in contrast to the silicone-based polymers used here, the silicone gel adhesive is based on a curable gel-producing composition. The silicone gel adhesive ensures the adhesion of the medical plaster to the skin, while reducing the problem of skin irritation. In addition, the distribution of the drug by the medical plaster is not negatively affected; surprisingly, the skin permeation behavior is even improved.

[00196] Silicone gel adhesives are also called silicone gels and, for example, are described in WO 2011 / 022199 A2.

[00197] Silicone gel adhesive is generally formed of linear or branched silicones with reactive groups. These reactive groups undergo a crosslinking reaction during curing. Examples of crosslinking reactions include the hydrosilylation reaction in which a silicone with a Si-H reactive group reacts with a silicone with an unsaturated aliphatic reactive group 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 l18 and US 4,991,574, which are incorporated herein by reference. An alternative reaction is condensation curing, in which an alkoxy and / or hydroxy-containing siloxanes are cured with a catalyst, as described in US 4,831,070, which is incorporated herein by reference.

[00198] In certain embodiments, silicone gel adhesives can be obtained by reacting a gel-forming 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 curing can be accelerated by heating to elevated temperatures, e.g. Petition 870250073524, dated 08 / 20 / 2025, page 78 / 155 73 / 129 plo, from 40 to 140 °C, or by applying UV light.

[00199] Suitable alkenyl groups contain from 2 to about 6 carbon atoms and are exemplified by, but not limited to, vinyl, allyl, and hexenyl. The alkenyl groups in this component may be located in terminal, pendant (non-terminal), or both terminal and pendant positions. The remaining silicone-linked organic groups in the alkenyl-substituted polydiorganosiloxane are independently selected from the group consisting of monovalent hydrocarbon groups and monovalent halogenated hydrocarbons free of aliphatic unsaturation. These groups typically contain from 1 carbon to about 20 carbon atoms, alternatively from 1 carbon to 8 carbon atoms, and are exemplified by, but not limited to, alkyl, such as methyl, ethyl, propyl, and butyl; aryl, such as phenyl; and halogenated alkyl, such as 3,3,3-trifluoropropyl. Typically, at least 50% of the organic groups in alkenyl-substituted polydiorganosiloxane are methyl groups.The structure of alkenyl-substituted polydiorganosiloxane is typically linear; however, it may contain some branching due to the presence of trifunctional siloxane units. The viscosity of alkenyl-substituted polydiorganosiloxane can be any desired value. For example, it can be >0 mm² / s to 100,000 mm² / s, alternatively 50 mm² / s to 80,000 mm² / s, or alternatively 300 mm² / s to 3,000 mm² / s.

[00200] Methods for preparing the alkenyl (i) substituted polydiorganosiloxanes of the present invention, such as condensation of the corresponding halosilanes or equilibration of cyclic polydiorganosiloxanes, are well known in the art.

[00201] Alkenyl-substituted polydiorganosiloxanes can be used in the gel-producing composition in an amount of 10 to 90% by weight, based on the weight of the composition, alternatively 40 to 90% by weight, alternatively 50 to 80% by weight. The amount Petition 870250073524, dated 08 / 20 / 2025, p. 79 / 155 74 / 129 of alkenyl groups present in alkenyl-substituted polydiorganosiloxane is typically in the range of 0.05 to 1% by weight, alternatively 0.05 to 1% by weight, based on the weight of the alkenyl-substituted polydiorganosiloxane.

[00202] Hydrogen atoms bonded to organosiloxane-containing silicone (ii) are also known in the art, as described, for example, in US Patent 3,983,298. The hydrogen atoms in this component may be located in terminal, pendant (non-terminal) positions or in both terminal and pendant positions. The remaining silicone-bonded organic groups in this component are independently selected from the group consisting of monovalent hydrocarbons and monovalent halogenated hydrocarbon groups free of aliphatic unsaturation. These groups typically contain from 1 carbon to about 20 carbon atoms, alternatively from 1 carbon to 8 carbon atoms, and are exemplified by, but not limited to, alkyl, such as methyl, ethyl, propyl and butyl; aryl, such as phenyl; and halogenated alkyl, such as 3,3,3-trifluoropropyl.In one embodiment of the invention, at least 50 percent of the organic groups on the hydrogen atoms bonded to the organosiloxane-containing silicone are methyl. The structure of the organosiloxane-containing silicone-bonded hydrogen atoms is typically linear, but may contain some branching due to the presence of trifunctional siloxane units. The viscosity of the organosiloxane-containing silicone-bonded hydrogen atoms can be any desired value. For example, it can be >0 mm² / s to 100,000 mm² / s, or alternatively, 5 mm² / s to 500 mm² / s.

[00203] Methods for preparing the organosiloxane containing silicon-bonded hydrogen atoms of the present invention by cohydrolysis of suitable chlorosilanes are known in the art; US Patent No. 2,877,255 to Clark; Japanese Patent Application Publi Petition 870250073524, dated 08 / 20 / 2025, page 80 / 155 75 / 129 cado (KOKAI) SHO 62(1987)-39660 to Mogi et al.; and US Patents No. 5,446,185 and No. 5,493,040 to Cobb et al., which are all incorporated herein by reference.

[00204] Organosiloxanes containing silicon-bonded hydrogen atoms can be used in the gel-producing composition in an amount of 1 to 30% by weight, based on the weight of the composition, alternatively 5 to 20% by weight, and alternatively 5 to 15% by weight. In one embodiment, the amount of hydrogen group present in the organosiloxane containing silicon-bonded hydrogen atoms is between 0.05 and 1.44% by weight, based on the weight of the organosiloxane containing silicon-bonded hydrogen atoms.

[00205] In gel-forming compositions, (i) and (ii) are preferably present such that the ratio of (H as SiH):(Alkenyl as Si-Alkenyl) is generally in the range of 0.1:1 to 10:1.

[00206] The hydrosilylation catalyst (iii) promotes the addition reaction of alkenyl-substituted polydiorganosiloxane with silicon-linked hydrogen-containing organosiloxane. 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 preferred catalysts due to their high level of activity in hydrosilylation reactions. One class of platinum catalysts are the chloroplatinic acid complexes with certain vinyl-containing organosiloxane compounds disclosed by Willig in US Pat No. 3,419,593, which is incorporated herein by reference.A specific catalyst of this type is the product of the reaction of chloroplatinic acid and 1,3-diethenyl-1,1,3,3. Petition 870250073524, dated 08 / 20 / 2025, p. 81 / 155 76 / 129 tetramethyldisiloxane.

[00207] The hydrosilylation catalyst is present in a sufficient amount to cure the composition of the present invention. Typically, the catalyst concentration is sufficient to provide from 0.1 ppm to 500 ppm (parts per million), alternatively from 1 ppm to 100 ppm, alternatively from 1 ppm to 50 ppm of a platinum group metal, based on the weight of (i) and (ii).

[00208] In view of the foregoing, in a particular embodiment, silicone gel adhesives can be obtained by reacting a gel-producing composition comprising (i) a vinylmethylsiloxane and dimethylsiloxane copolymer with (ii) methylhydrogen polysiloxane with trimethylsilyl terminal groups in the presence of (iii) a platinum catalyst, wherein (i) and (ii) are preferably present such that the ratio of (H as SiH):(Alkenyl as Si-Alkenyl) is generally in the range of 0.1:1 to 10:1.

[00209] An optional ingredient is a hydroxyl-substituted silicone resin, as described in U.S. Patent Application No. 20070202245, which is incorporated herein by reference. The resin is typically composed of groups with the formula R33SiO1 / 2 (“M” groups) and groups with the formula SiO4 / 2 (“Q” groups) where R3 is an alkyl group with 1 to 6 carbon atoms or an alkylene group with 1 to 6 carbon atoms, typically methyl or vinyl. If an alkenyl group is present in the resin, typically the mol% of R groups present as alkenyl groups is < 10 mol%, alternatively 5%. The numerical ratio of M groups to Q groups is typically in the range of 0.6:1 to 4:1, or alternatively 0.6:1 to 1.0:1. Silicone resin typically contains 0.1 to 5% by weight, or alternatively 1.0 to 5% by weight, of hydroxyl groups bonded to the silicone.

[00210] The resin can be used in the gel-producing composition in an amount of 2 to 45% by weight, based on the weight of the composition. Petition 870250073524, dated 08 / 20 / 2025, page 82 / 155 77 / 129 gel and resin producing position; alternatively, 5 to 40% by weight, alternatively, 10 to 35% by weight.

[00211] Thus, in particular embodiments, silicone gel adhesives may be a silicone gel adhesive reinforced with silicate resin containing from about 2 to about 45% by weight of at least a hydroxyl-substituted silicate resin.

[00212] In specific embodiments, silicone gel adhesive is a 2-component silicone adhesive system that cures upon mixing the two components. An example of a commercially available two-component silicone adhesive includes Liveo™ Soft Skin Adhesives (e.g., MG 7-9700, MG 7-9800, MG 7-9850, and MG 79900), supplied in a kit that includes components A and B. It is a soft, filler-free, platinum-catalyzed elastomeric silicone adhesive for bonding medical devices to the skin with medium adhesion strength and gentle removal. The two components A and B are preferably mixed in a 1:1 ratio.

[00213] The silicone gel adhesive layer can be produced by processes known in the art. For example, the gel can be preformed (e.g., as a sheet) by molding, calendering, extrusion, spraying, brushing, hand application, casting, or coating onto a substrate, such as a coating. Or the silicone gel layer can be made by applying the gel-producing composition to a substrate by spraying, coating, stick coating, etc. Once applied to the substrate, the gel-producing composition is cured to produce the silicone gel adhesive on the substrate. Polymer based on natural or synthetic rubbers.

[00214] Polymers based on natural or synthetic rubbers include hydrocarbon polymers such as polyisoprene (natural and synthetic), polybutylene and polyisobutylene, styrene polymers Petition 870250073524, dated 08 / 20 / 2025, page 83 / 155 78 / 129 no / butadiene, styrene-isoprene-styrene block copolymers, butyl rubber, halogen-containing polymers such as polyacrylic nitrile, polytetrafluoroethylene, polyvinyl chloride, polyvinylidene chloride and polychlorodiene, and other copolymers thereof. The polymers may, in particular, be used in combination with an adhesion agent as defined below.

[00215] According to certain embodiments, the polymer may be a styrenic triblock copolymer selected from the group consisting of styrene-ethylene-styrene (SES) block copolymers, styrene-butadiene-styrene (SBS) block copolymers, styrene-isoprene-styrene (SIS) block copolymers, styrene-ethylene / butylene-styrene (S-EB-S) block copolymers, styrene-ethylene / butylene / propylene-styrene (s-EBS-S) block copolymers, styrene-isoprene / butadiene-styrene (S-IB-S) block copolymers and mixtures thereof.

[00216] In certain embodiments, the polymer may be at least one SIS block copolymer. The at least one SIS block copolymer may consist of three blocks of polystyrene, polyisoprene, and polystyrene and, in particular, has a molecular weight of about 100,000 to 200,000. In specific embodiments, the SIS block copolymer may comprise polystyrene and polyisoprene blocks in a ratio of about 10:90 (%) to about 30:70 (%), or in a ratio of about 15:85 (%) or about 22:78 (%).

[00217] In other embodiments, the polymer is at least one polyisobutylene and may be a combination of two different types of polyisobutylenes, in particular a combination of low molecular weight polyisobutylene and high molecular weight polyisobutylene. In specific embodiments, the ratio of low molecular weight polyisobutylene to high molecular weight polyisobutylene is in the range of 75:25 to 90:10. Petition 870250073524, dated 08 / 20 / 2025, page 84 / 155 79 / 129

[00218] Suitable SIS block copolymers according to the invention are commercially available, for example, under the brand names JSR-SIS. Specific SIS block copolymer-based pressure-sensitive adhesives are available under the trade names JSR-SIS5229 and JSR-SIS5002.

[00219] Suitable polyisobutylenes, according to the invention, are commercially available, for example, under the trade name Oppanol®. Combinations 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 polyisobutylene to high molecular weight polyisobutylene are in the range of 100:1 to 1:100, 95:5 to 40:60 or 90:10 to 75:25. A specific example of a polyisobutylene combination is 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 a weight-average molecular weight distribution Mw / Mn of 2.9. Oppanol® B10 has a viscosity average molecular weight Mv of 40,000, and a weight-average molecular weight Mw of 53,000 and a weight-average molecular weight distribution Mw / Mn of 3.2.Oppanol® B12 has a viscosity average molecular weight Mv of 55,000, a weight-average molecular weight Mw of 70,000, and a molecular weight average Mw / Mn distribution of 3.2. A suitable polyisobutylene adhesive is also commercially available, for example, under the brand name Duro-Tak™ 87-6908. ADDITIONAL ADDITIVES

[00220] The medical plaster according to the invention, and in particular the layer containing the active agent and / or the skin contact layer, may further comprise at least one additive or excipient. Said additives or excipients are preferably... Petition 870250073524, dated 08 / 20 / 2025, p. 85 / 155 80 / 129 taught from the group consisting of crystallization inhibitors, fillers, skin care substances, pH regulators, preservatives, tackifying agents, softeners, stabilizers and permeation enhancers, in particular among crystallization inhibitors, tackifying agents, softeners, stabilizers and permeation enhancers. Such additives may be present in the layer containing the active agent or in the skin contact layer in an amount of 0.001 to 80% by weight, for example, 1 to 20% by weight or 0.01 to 10% by weight, based on the total weight of the layer containing the active agent.

[00221] It should be noted that in pharmaceutical formulations, the components of the formulation are categorized according to their physicochemical and physiological properties and according to their function. This means, in particular, that a substance or compound that falls into one category is not excluded from falling into another category of formulation component. For example, a certain polymer may be a crystallization inhibitor but also a tackifying agent. Some substances may, for example, be a typical softener but at the same time act as a permeation enhancer. A person skilled in the art is able to determine based on their general knowledge to which category or categories of formulation components a given substance or compound belongs. Details are provided below regarding excipients and additives which, however, should not be understood as being exclusive.Other substances not explicitly listed in this description may also be used according to the present invention, and the substances and / or compounds explicitly listed for a formulation component category are not excluded from being used as another formulation component within the meaning of the present invention. Petition 870250073524, dated 08 / 20 / 2025, page 86 / 155 81 / 129

[00222] In certain embodiments, the medical patch, in particular the layer containing the active agent, may further comprise a crystallization inhibitor. Suitable examples of crystallization inhibitors include polyvinylpyrrolidone, vinyl acetate / vinylpyrrolidone copolymer, and cellulose derivatives. The crystallization inhibitor is preferably polyvinylpyrrolidone, more preferably soluble polyvinylpyrrolidone. The crystallization inhibitor may increase the solubility of the active agent or inhibit the crystallization of the active agent.

[00223] In certain embodiments, the medical plaster, in particular the layer containing the active agent, may further comprise a viscosity-increasing agent. The addition of such agents allows the active agent to be dispersed more easily, in particular in a suitable solubilizer. The viscosity-increasing agent may be selected from the group consisting of cellulose derivatives and high molecular weight polyacrylic acids, and any mixture thereof, in particular ethylcellulose.

[00224] In certain embodiments, the medical plaster, in particular the layer containing the active agent, may further comprise a stabilizer, wherein the stabilizer is preferably selected from tocopherol and its ester derivatives and ascorbic acid and its ester derivatives. Preferred stabilizers include sodium metabisulfite, ascorbyl esters of fatty acids such as ascorbyl palmitate, ascorbic acid, butylated hydroxytoluene, tocopherol, tocopheryl acetate and tocopheryl linoleate.

[00225] In certain embodiments, the medical plaster, in particular the layer containing the active agent and / or the skin contact layer, may further comprise a softener / plasticizer. Exemplary softeners / plasticizers include linear or branched alcohols, saturated or unsaturated with 6 to 20 carbon atoms, triglycerides and polyethylene glycols. Petition 870250073524, dated 08 / 20 / 2025, page 87 / 155 82 / 129

[00226] In certain embodiments, the medical patch, in particular the layer containing the active agent and / or the skin contact layer, may also comprise a pH regulator. Suitable pH regulators include mild acids and bases, including amine derivatives, inorganic alkaline derivatives and polymers with basic or acidic functionality.

[00227] In certain embodiments, the medical patch, in particular the layer containing the active agent and / or the skin contact layer, may also 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.

[00228] In certain embodiments, the medical plaster, in particular the skin contact layer, may further comprise a skin care substance. These substances may be used to prevent or reduce skin irritation, as detectable by the dermal response score. Suitable skin care substances include sterol compounds such as cholesterol, dexpanthenol, alpha-bisabolol, and antihistamines.

[00229] Fillers such as silica gels, titanium dioxide and zinc oxide can be used in conjunction with the medical plaster, in particular the layer containing the active agent, to influence certain physical parameters, such as cohesion and bond strength, in the desired manner.

[00230] If the structure of the layer containing the active agent, and in particular the skin contact layer, needs to have self-adhesive properties, and one or more polymers are selected that do not provide sufficient self-adhesive properties, an adhesion agent is added. The tackifying agent may be an alicyclic saturated hydrocarbon resin, a glycerol ester of rosin. Petition 870250073524, dated 08 / 20 / 2025, page 88 / 155 83 / 129 hydrogenated, liquid paraffin or a mixture thereof, in particular a mixture comprising a saturated alicyclic hydrocarbon resin and liquid paraffin, or a mixture comprising a hydrogenated rosin glycerol ester and liquid paraffin. Furthermore, the tackifying agent may be selected from polyvinylpyrrolidone (which, due to its ability to absorb water, is able to maintain the adhesive properties of the matrix layer and therefore can be considered a tackifying agent in a broad sense), triglycerides, polyethylene glycols, dipropylene glycol, resins, resin esters, terpenes and their derivatives, ethylene vinyl acetate adhesives, dimethylpolysiloxanes and polybutenes, preferably polyvinylpyrrolidone and more preferably soluble polyvinylpyrrolidone.

[00231] In certain embodiments, the medical plaster, in particular the layer containing the active agent, may also comprise a permeation enhancer. Permeability enhancers are substances that influence the barrier properties of the stratum corneum in order to increase the permeability of the active agent.Some examples of permeation enhancers are polyhydric 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 dimethyldecylphosphoxide, methylcetylsulfoxide, dimethylaurylamine, dodecylpyrrolidone, isosorbide, dimethylacetonide, dimethylsulfoxide, decylmethylsulfoxide, and dimethylformamide, salicylic acid, amino acids, benzyl nicotinate, and higher molecular weight aliphatic surfactants such as lauryl sulfate salts. Other agents include oleic and linoleic acids, ascorbic acid, panthenol, butylated hydroxytoluene, tocopherol, tocopheryl acetate, tocopheryl linoleate, propyl oleate, and isopropyl palmitate. If the layer containing the active agent... Petition 870250073524, dated 08 / 20 / 2025, page 89 / 155 84 / 129 further comprise a permeation enhancer, the permeation enhancer shall preferably be selected from among diethylene glycol monoethyl ether (Transcutol®), diisopropyl adipate, isopropyl myristate, isopropyl palmitate, lauryl lactate and dimethylpropylene urea. MEDICAL PLASTER FORMAT

[00232] In some embodiments, the structure of the layer containing the active agent has a hexagonal or pentagonal shape which is provided by the support layer, the layer containing the active agent and the additional skin contact layer, respectively. The hexagonal shape comprises at least one hexagon, in particular all pairs of opposite sides of the hexagon are parallel and the sides of the hexagon have a length of 0.2 to 10 cm.

[00233] The pentagonal shape comprises at least one pentagon, in particular the sides of the pentagon have a length of 0.2 to 12.5 cm.

[00234] The hexagonal shape can comprise from one to ten, such as one, two, three, four, or five hexagons, preferably with the hexagons being adjacent and / or not overlapping. The pentagonal shape can comprise from one to ten, such as one, two, three, four, six, or nine pentagons, preferably with the pentagons being adjacent and / or not overlapping. The two or more hexagons or pentagons are preferably fully connected to each other. Hexagonal or pentagonal shapes may, but do not have to, include perforations.

[00235] In certain embodiments, at least one hexagon is at least one convex hexagon, and the hexagonal form comprises Petition 870250073524, dated 08 / 20 / 2025, page 90 / 155 85 / 129 minus a convex hexagon, in which all pairs of opposite sides of the convex hexagon are parallel, and the sides of the convex hexagon have a length of 0.2 to 10 cm. The hexagonal form may comprise one or two convex hexagons, in particular integrally connected to each other. In certain embodiments, at least one pentagon is at least a convex pentagon, and the pentagonal form comprises at least one convex pentagon, in which the sides of the convex pentagon have a length of 0.2 to 12.5 cm. The pentagonal form may comprise from one to three convex pentagons, in particular integrally connected to each other. In particular embodiments, the hexagonal form is a convex hexagon, or the pentagonal form is a convex pentagon. In some embodiments, the convex pentagon may be irregular. In other forms, the convex pentagon can be regular.

[00236] The hexagonal or pentagonal shape of the active agent-containing layer structure is advantageous in terms of easy and less time-consuming handling of a medical plaster containing the active agent-containing layer structure. It allows for simplified coverage of skin areas without the need for cutting before application, thus reducing the risk of contamination of the cutting tool or fingers with the active ingredient, and also the risk of contamination of the adhesive at the cut site. Furthermore, irregular or rounded skin surfaces can be covered without wrinkling, thus providing complete adhesion, and even complicated areas, such as fingers or toes, can be easily surrounded using the active agent-containing layer structure.In particular, when the hexagonal or pentagonal shape comprises at least one convex hexagon or pentagon, the hexagonal or pentagonal shape requires only a short side length relative to the area provided, thus reducing the risk of the edges of the medical plaster detaching. Petition 870250073524, dated 08 / 20 / 2025, page 91 / 155 86 / 129

[00237] In one embodiment, the hexagonal or pentagonal form is a double hexagon or double pentagon formed from two identical convex hexagons or pentagons, respectively, sharing two adjacent vertices on their common side. The double hexagon or double pentagon can be obtained by mirroring a convex hexagon or pentagon on one of its sides (mirror axis), wherein the mirror axis then includes the common side. The double hexagon or double pentagon can be divisible by the common side to obtain two equal convex hexagons or pentagons, which can be applied together or separately. Thus, in another embodiment, the hexagonal or pentagonal form is a double hexagon or double pentagon formed from two identical convex hexagons or pentagons sharing two adjacent vertices on their common side, wherein said common side is perforated for easy removal.In another embodiment, the pentagonal form is a triple pentagon formed by three identical convex pentagons sharing two adjacent vertices and their common side in pairs. The triple pentagon can be obtained by mirroring the first convex pentagon along one of its sides (mirror axis 1), wherein mirror axis 1 includes the common side shared by the first and second convex pentagons, and mirroring the second convex pentagon along one of its other four sides (mirror axis 2), wherein mirror axis 2 includes the common side shared by the second and third convex pentagons. The triple pentagon can be divided along its common sides to obtain three equal convex pentagons, which can be applied together or separately.Thus, in a particularly preferred embodiment, the pentagonal shape is a triple pentagon formed by three identical convex pentagons sharing two adjacent vertices and their common side in pairs, where said common side is perforated for easy removal. The double or triple pentagon, as described... Petition 870250073524, dated 08 / 20 / 2025, p. 92 / 155 87 / 129 described above, may be present, for example, in the form of a hexagon, in particular in the form of a regular hexagon.

[00238] Hexagonal shapes, in particular convex hexagons or double hexagons, can have mirror symmetry and / or rotational symmetry. Hexagonal shapes can be mirror symmetrical with at least one axis of symmetry, such as two, three, or four axes of symmetry, in particular six axes of symmetry. Alternatively or additionally, hexagonal shapes can be rotationally symmetrical having an order of at least 2, such as 3 or 4, in particular having 6 times rotational symmetry. Thus, in certain embodiments, hexagonal shapes are mirror symmetrical with at least four axes of symmetry and / or have at least 4 times rotational symmetry, in particular they are mirror symmetrical with six axes of symmetry and additionally have 6 times rotational symmetry. Pentagonal shapes, such as that of a regular hexagon, can have mirror symmetry and / or rotational symmetry.Preferred pentagonal shapes are mirror-symmetric with 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 pentagonal shapes are rotationally symmetric having an order of at least 2, such as 3 or 4, in particular having 6 times rotational symmetry. Thus, particularly preferred pentagonal shapes are mirror-symmetric with at least four axes of symmetry and / or have at least quadruple rotational symmetry, in particular are mirror-symmetric with six axes of symmetry and additionally have 6 times greater rotational symmetry.

[00239] When the structure of the layer containing the active agent has a hexagonal shape, the hexagon, in particular the convex hexagon, has three pairs of parallel opposite sites, which may have different or equal lengths. The two sides of each pair of sides Petition 870250073524, dated 08 / 20 / 2025, page 93 / 155 88 / 129 opposite parallels can have the same length, that is, the hexagon can be a parallelogram. The parallelogonal can be obtained by elongating a parallelogram, which has double rotational symmetry, or by elongating a rhombus, which has double rotational symmetry and is additionally mirror-symmetric with two axes of symmetry.

[00240] In certain forms, the six sides of the hexagon, in particular the convex hexagon, or the five sides of the pentagon, in particular the convex pentagon, are equal in length, that is, the hexagon or pentagon is equilateral.

[00241] Alternatively, the hexagon is not equilateral and has three sides of equal length and three other sides of equal length. The three sides of equal length and the other three sides of equal length should preferably be alternated. Such hexagons are preferably mirror-symmetric, with three axes of symmetry. In another alternative, the hexagon is not equilateral and has four sides of equal length and two other sides of equal length. This includes, in particular, a hexagon obtained by stretching a rhombus.

[00242] In certain forms, the hexagon is not equilateral and the ratio between the shorter side and the longer side is 1:4 or less, 1:3 or less, 1:2 or less, 1:1.5 or less, or is approximately 1:1.

[00243] The sides of the hexagon according to the invention have a length of 0.2 to 10 cm. The sides of the hexagon may also 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 particular, two, three, four or six sides of the hexagon may 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, Two sides of the hexagon can have a length of approximately 0.5 cm, approximately 0.9 cm, or approximately 1.5 cm, and four sides... Petition 870250073524, dated 08 / 20 / 2025, p. 94 / 155 89 / 129 of the hexagon can have a length of about 1.8 cm, about 2.8 cm, or about 3.2 cm, or Three sides of the hexagon can have a length of approximately 0.5 cm, approximately 0.9 cm, or approximately 1.5 cm, and three sides of the hexagon can have a length of approximately 1.8 cm, approximately 2.8 cm, or approximately 3.2 cm, or - Four sides of the hexagon can have a length of about 0.5 cm, about 0.9 cm, or about 1.5 cm, and two sides of the hexagon can have a length of about 1.8 cm, about 2.8 cm, or about 3.2 cm.

[00244] 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.

[00245] 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. The aspect ratio of the hexagon can also be 3:2 or less.

[00246] Alternatively, the pentagon is not equilateral and has four sides of equal length, or the pentagon is not equilateral and has two sides of equal length and two other sides of equal length. Such pentagons are preferably mirror-symmetrical with an axis of symmetry, wherein the remaining side is bisected by the axis of symmetry. The pentagon, in particular the convex pentagon, according to the invention may have - five sides of equal length, - five sides of different lengths, - two sides of equal length and three sides of different lengths, - three sides of equal length and two sides of length Petition 870250073524, dated 08 / 20 / 2025, page 95 / 155 90 / 129 different ment, - three sides of equal length and two sides of a different length, - four sides of equal length and one side of a different length, or - one pair of sides of equal length and another pair of sides of equal length (the remaining side having a different length from the pair of sides of equal length and the other pair of sides of equal length).

[00247] In certain embodiments, the pentagon is not equilateral and the ratio of one side (any side) to another side (any other side) is about 1:1, or about 1:2 / ^3, or about 1:¾ or about 1:2, or about 1:2¾. In some embodiments, the pentagon is not equilateral and the ratio between the shorter side and the longer side is 1:2. In other embodiments, the pentagon is not equilateral and the ratio between the shorter side and the longer side is 1:2^3.

[00248] The sides of the pentagon according to the invention have a length of 0.2 to 12.5 cm. The sides of the pentagon can have a length of 0.3 to 10 cm, 0.6 to 5 cm, 0.7 to 4.5 cm, or 0.9 to 2.4 cm. In particular, one, two, three, four, or five sides of the pentagon have a length of about 0.5 cm, about 1 cm, about 1.3 cm, about 1.7 cm, about 2 cm, about 2.5 cm, about 3.1 cm, or about 4.5 cm. For example, Two sides of the pentagon have a length of approximately 0.5 cm, approximately 1 cm, or approximately 1.3 cm; two sides of the pentagon have a length of approximately 1.3 cm, approximately 1.7 cm, approximately 2 cm, or approximately 2.5 cm; and the remaining side has a length of approximately 2.5 cm, approximately 3.1 cm, or approximately 4.5 cm. Two sides of the pentagon have a length of approximately 1 cm or approximately 1.3 cm. Petition 870250073524, dated 08 / 20 / 2025, p. 96 / 155 91 / 129 to approximately 1.3 cm, approximately 1.7 cm, or approximately 2 cm, and the remaining side has a length of approximately 1.7 cm, approximately 2 cm, or approximately 2.4 cm.

[00249] The height of the pentagon can be in the range of 0.4 to 16.5 cm, 0.9 to 8.5 cm, 1.4 to 7.5 cm, or 1.6 to 4.5 cm. The width of the pentagon can be in the range of 0.4 to 15.5 cm, 0.9 to 8 cm, 1.3 to 7 cm, or 1.5 to 4 cm.

[00250] The (convex) pentagon according to the invention may belong to Type 1-15, as described above. In particular, the (convex) pentagon may be a Type 1 pentagon, or a Type 3 pentagon, or a Type 4 pentagon.

[00251] In certain embodiments, two sides of the pentagon are parallel. In particular, the pentagon has two parallel sides of equal length and two other sides of the same length or of equal length. Alternatively, none of the sides of the pentagon are parallel.

[00252] In certain embodiments, the pentagon is mirror-symmetric with at least one axis of symmetry. In specific embodiments, the pentagon is mirror-symmetric with at least one axis of symmetry and has two (parallel) sides of equal length, as well as two other sides of equal or different length, wherein the remaining sides are bisected by the axis of symmetry, and / or has two interior angles of 90°, as well as three interior angles of 120°, wherein one of the latter is bisected by the axis of symmetry. The pentagon can be a type I pentagon or a type II pentagon.

[00253] In certain forms, the hexagon, particularly the convex hexagon, is equiangular. These convex hexagons each have one interior angle equal to 120°. Alternatively, the hexagon is not equiangular, and the smallest angle is 60° or greater, 80° or greater, 90° or greater, or 110° or greater. In particular, the smallest angle is 60° or greater. Petition 870250073524, dated 08 / 20 / 2025, p. 97 / 155 92 / 129 80° or greater, 90° or greater, or 110° or greater, and less than 120°. Furthermore, a hexagon can have two interior angles of equal size (minor angles) and four other interior angles of equal size (major angles), where the minor angles are approximately 90°.

[00254] In another embodiment, the hexagon, in particular the convex hexagon, is regular. Such regular hexagons are preferably mirror symmetrical with six axes of symmetry and, additionally, have a rotational symmetry of 6 times. In a certain embodiment, the hexagonal form is a double hexagon formed by two identical convex hexagons sharing two adjacent vertices on their common side, where the two identical convex hexagons are regular.

[00255] In certain embodiments, the pentagon, in particular the convex pentagon, is not equiangular, wherein preferably one interior angle and another interior angle sum to 180°. The interior angle and the other interior angle summing to 180° may be adjacent or non-adjacent. In some embodiments, one interior angle is 60° and another interior angle is 120°. Alternatively, one interior angle and another interior angle are 90° each. Preferred (convex) pentagons according to the invention have two interior angles of 90° and at least one interior angle of 120°. Particularly preferred (convex) pentagons according to the invention have two interior angles of 90° and three interior angles of 120°.

[00256] In some very particular forms, the pentagon is a special type I pentagon with the following properties: The pentagon is mirror-symmetrical, having exactly one axis of symmetry. The pentagon has two adjacent interior angles of 90° and three adjacent interior angles of 120°. The pentagon has two parallel sides of equal length. Petition 870250073524, dated 08 / 20 / 2025, p. 98 / 155 93 / 129 ment and two other sides of equal length, as well as one remaining side, where The ratio of the two parallel sides of equal length to the other two sides of equal length is approximately 1:2, and / or - the ratio of the two parallel sides of equal length to the remaining side is approximately 1:2¾ and / or The ratio between the other two sides of equal length and the remaining side is approximately 1:30.

[00257] In other very particular forms, the pentagon is a special type II pentagon with the following properties: The pentagon is mirror-symmetrical, having exactly one axis of symmetry. The pentagon has two adjacent interior angles of 120° and two non-adjacent interior angles of 90° separated by another interior angle of 120°. The pentagon has two sides of equal length and two other sides of equal length, as well as one remaining side, where - the ratio of the two sides of equal length to the other two sides of equal length is approximately 1:¾ and / or - the ratio of the two sides of equal length to the remaining side is approximately 1:2, and / or The ratio of the other two sides of equal length to the remaining side is approximately 1:2 / 3. MEDICAL PLASTER SHEET

[00258] In certain embodiments of the present invention, and in particular when the structure of the layer containing the active agent has a hexagonal or pentagonal shape, the structure of the layer containing the active agent can also be used in a sheet of medical plasters, comprising a series of layered structures. Petition 870250073524, dated 08 / 20 / 2025, page 99 / 155 94 / 129 having the active agent disposed in a removable coating.

[00259] This medical plaster sheet comprises two or more layered structures containing active agents, as described above, and a release coating, wherein the release coating is coextensive with the active agent-containing layer structures or extends beyond the boundary of the active agent-containing layer structure in all directions.

[00260] By using a series of layered structures containing active agents, the surface of the skin area to be treated can be covered by interlacing the layered structures containing active agents side by side, without wrinkling. When doing so, if the layer structure containing the active agent has a hexagonal or pentagonal shape, this shape helps avoid gaps and / or overlaps.

[00261] The number of active agent-containing layer structures provided in a medical patch sheet to be removed from the release coating depends on the size(s) of the active agent-containing layer structures. Suitable medical patch sheets may comprise, for example, 2 to 400, 3 to 300 or 4 to 300, 4 to 120 or 6 to 120, or 6 to 30 or 8 to 30 active agent-containing layer structures. In certain embodiments, the medical patch sheet comprises 2 to 15 or 150 to 300 active agent-containing layer structures. In other embodiments, the medical patch sheet comprises 2, 3, 4, 5, 6, 7 or 8 active agent-containing layer structures. Alternatively, the medical plaster sheet may comprise 150, 180, 200, 240, or 300 layered structures containing the active agent. The layer structures containing the active agent may be identical or different.

[00262] The structures of the layer containing the active agent can Petition 870250073524, dated 08 / 20 / 2025, pp. 100 / 155 95 / 129 can be arranged in the release coating in any pattern, adjacent to each other (grouping the plane) or leaving small spaces to facilitate the capture of layer structures containing the individual active agent. In some embodiments, the layer structures containing the active agent are arranged in the release coating in a space-saving manner. In particular, the layer structures containing the active agent are arranged side-by-side in the release coating. Thus, the layer structures containing the active agent can be arranged in two or more parallel rows relative to the longitudinal axis of the release coating, wherein each row can comprise 2 to 20, 3 to 12, or 4 to 8 layer structures containing the active agent.For example, the layer structures containing the active agent can be arranged in 20 rows, where each row comprises 15 layer structures containing the active agent, in particular 15 identical layer structures containing the active agent. According to another example, the layer structures containing the active agent can be arranged in 4 rows, where each row comprises 3 to 6 layer structures containing the active agent, in particular 3 to 6 identical layer structures containing the active agent. In other embodiments, the layer structures containing the active agent are arranged in one or more types of recurring geometric patterns, where preferably each geometric pattern comprises 2 to 15, 3 to 12, or 4 to 9 layer structures containing the active agent. These types of geometric patterns may include polygons, such as hexagons.Thus, the layer structures containing the active agent can be arranged in the form of one or more hexagons, in particular regular hexagons, where preferably each of the (regular) hexagons comprises 2, 3, 4 or 9, in particular 2 or 3 layer structures containing the active agent. In specific embodiments, the structures of... Petition 870250073524, dated 08 / 20 / 2025, pp. 101 / 155 96 / 129 layers containing the active agent may be arranged in the form of one or more regular hexagons, wherein each of the regular hexagons comprises two special pentagons of type I, as described above, or each of the regular hexagons comprises three special pentagons of type II, as described above.

[00263] In a specific embodiment, the layer structures containing the active agent tile the plane, in particular they tile the plane in a monohedral fashion, as in a prismatic pentagonal tile or a Cairo pentagonal tile. Layer structures containing active agents that tile the plane may be parallelogons, in particular regular hexagons. The layer structures containing the active agent may also have hexagonal shapes selected from regular hexagons and / or double hexagons formed by two identical regular hexagons sharing two adjacent vertices and their common side. Furthermore, the layer structures containing the active agent that tile the plane are pentagons of Type 1-15, in particular Type 1 pentagons, or Type 3 pentagons, or Type 4 pentagons, such as the (special) Type I or Type II pentagons, as described above.The layer structures containing the active agent can also have pentagonal shapes selected from double pentagons formed by two identical convex pentagons sharing two adjacent vertices and their common side, and / or triple pentagons formed by three identical convex pentagons sharing two adjacent vertices and their common side in pairs, which may be present in the form of a (regular) hexagon. The layer structures containing the active agent can be separate from each other or connected to each other. They can join by sharing a common vertex in pairs and / or in groups of three and / or four. If the common vertex is shared only in pairs, this shared vertex can be on one side, particularly centrally. Petition 870250073524, dated 08 / 20 / 2025, pp. 102 / 155 97 / 129 on one side, of a third pentagon.

[00264] In certain embodiments, the structures of the layer containing the active agent are joined by sharing two adjacent vertices and their common side and are separated from each other by the common side being cut for independent removal of the release coating. Alternatively, the structures of the layer containing the active agent may be adjacent, sharing two adjacent vertices and their common side, and are connected to each other by the common side, which is weakened to facilitate detachment. In particular, the common side may be perforated to facilitate tearing. The medical plaster sheet may also comprise adjacent layers containing the active agent, sharing two adjacent vertices and their common sides, some of which are separated from each other by the common side which is cut for independent removal of the release coating, and some of which are connected to each other by the common side which is weakened for easy removal.For example, the structures of the layer containing the active agent may be arranged in two or more parallel rows relative to the longitudinal axis of the release coating, wherein each row comprises 2 to 20 structures of the layer containing the active agent that are joined together by sharing two adjacent vertices and their common side, wherein the rows are separated from each other for independent removal and the structures of the layer containing the active agent within a row are connected to each other by the common side, which is perforated for easy removal. In certain embodiments, all the structures of the layer containing the active agent are separated from each other by the common side being cut for independent removal of the release coating.

[00265] In certain modes, the structures of the layer containing the active agent are joined together by sharing at least one vertex. Petition 870250073524, dated 08 / 20 / 2025, pp. 103 / 155 98 / 129 and at least a portion of an adjacent side and are separated from each other by the adjacent side being cut for independent removal of the release coating. Alternatively, the structures of the layer containing the active agent join each other by sharing at least one vertex and at least a portion of an adjacent side and are connected to each other by the adjacent side, which is weakened for easy removal. In particular, the adjacent side is perforated to facilitate tearing. In some embodiments, the structures of the layer containing the active agent join by sharing two adjacent vertices and their common side and are separated from each other by the common side being cut for independent removal of the release coating. Alternatively, the structures of the layer containing the active agent join by sharing two adjacent vertices and their common side and are connected to each other by the common side, which is weakened to facilitate detachment.In particular, the common side is perforated to facilitate tearing. The medical plaster sheet may also comprise layered structures containing the active agent adjacent to each other, sharing at least one vertex and at least a portion of an adjacent side, or two adjacent vertices and their common sides, wherein some of which are separated from each other by the adjacent side or by the common side being cut for independent removal of the release coating, and some of which are connected to each other by the adjacent side or by the common side which is weakened for easy removal. In certain embodiments, all layered structures containing the active agent are separated from each other by the adjacent side or by the common side being cut for independent removal of the release coating.For example, the structures of the layer containing the active agent can be arranged in two or more parallel rows with respect to the longitudinal axis of the release coating, wherein each row comprises from 2 to 20. Petition 870250073524, dated 08 / 20 / 2025, pp. 104 / 155 99 / 129 structures of the layer containing the active agent that join together by sharing at least one vertex and at least part of an adjacent side and / or two adjacent vertices and their common side, wherein the rows are separated from each other for independent removal and the structures of the layer containing the active agent within a row are connected to each other by the common side, which is perforated for easy removal.In another example, the layer structures containing the active agent can be arranged in the form of two or more regular hexagons, wherein each hexagon comprises 2, 3, or 9 layer structures containing the active agent that are joined together by sharing at least one vertex and at least part of an adjacent side and / or two adjacent vertices and their common side, wherein the hexagons are separated from each other for independent removal and the layer structures containing the active agent within a hexagon are connected to each other by the common side, which is perforated for easy removal.

[00266] In certain embodiments, the structures of the active agent-containing layer are connected to each other by at least one, and preferably two or more, common fixation bridges for joint removal of the release coating. The fixation bridge(s) may provide a single point(s) at which the structures of the active agent-containing layer are connected to each other, even if they are separated from each other by the adjacent side or by the common side being cut at least in part. This allows for the joint removal of the thus connected active agent-containing layer structures from the release coating to be applied to the patient's skin, which is particularly advantageous in the case of a large number and / or small area of ​​active agent-containing layer structures. Alternatively, some fixation bridges may be undone, for example, torn off, for joint removal of a number Petition 870250073524, dated 08 / 20 / 2025, pages 105 / 155 100 / 129 smaller of layer structures containing the active agent connected.

[00267] In other embodiments, the common fastening bridge is provided at a vertex and connects at least two or at least three layer structures containing the active agent. Alternatively, the common fastening bridge may be provided on one side and connect two layer structures containing the active agent. In a given sheet of medical plasters, the neighboring layer structures containing the active agent are all connected to each other in pairs by at least two common fastening bridges provided at two adjacent vertices or on their common side, such as at the two adjacent vertices. In particular, the neighboring layer structures containing the active agent are all connected to each other in groups of three by a common fastening bridge provided at the common vertex. This refers, in particular, to layer structures containing active agents that tile the plane.Thus, in one embodiment, the structures of the layer containing the active agent are regular hexagons and are connected to each other by at least one fastening bridge for removing the release coating joint, wherein the neighboring structures of the layer containing the active agent are all connected to each other in threes by a common fastening bridge provided at the common vertex.

[00268] In other embodiments, the common attachment bride is provided at a vertex and / or a side and connects at least two, and preferably three or four active agent-containing layer structures, such as - two layered structures containing active agent connected by two common fastening bridges provided at two adjacent vertices, or - three layered structures containing active agent connected by a common fastening bridge provided at a vertex with Petition 870250073524, dated 08 / 20 / 2025, pp. 106 / 155 101 / 129 shared by two layer structures containing active agent located on one side of the third layer structure containing active agent, or at the common vertex, or - four self-adhesive layered structures connected by a common fastening bridging provided at the common vertex.

[00269] In a specific sheet of medical plasters, the adjacent layered structures containing the active agent are all connected to each other in pairs by at least two common fastening bridges provided at two adjacent vertices or on their common side and / or provided at one vertex and one adjacent side, preferably at the two adjacent vertices. In particular, the adjacent layered structures containing the active agent are all connected to each other in groups of three or four by a common fastening bridge provided at one vertex and / or one side, in particular at the common vertex. This refers, in particular, to layered structures containing active agents that tile the plane.Thus, in a preferred embodiment of the medical plaster sheet according to the invention, the structures of the layer containing the active agent are (special) pentagons of type I or type II, as described above, and are connected to each other by at least one fastening bridge for removing the release coating joint, wherein the neighboring structures of the layer containing the active agent are all connected to each other in groups of three or four by a common fastening bridge provided at a shared vertex situated on one side or at the common vertex.

[00270] In certain embodiments, the layer structures containing the active agent have hexagonal and / or pentagonal shapes selected from two or three different shapes in total. In other embodiments, the layer structures containing the active agent have hexagonal shapes comprising convex hexagons and double hexagons formed by two identical convex hexagons sharing two Petition 870250073524, dated 08 / 20 / 2025, pp. 107 / 155 102 / 129 adjacent vertices and their common side, in particular regular hexagons and double hexagons formed by two identical regular hexagons, or the layer structures containing the active agent have pentagonal shapes comprising convex pentagons and double pentagons formed by two identical convex pentagons sharing two adjacent vertices and their common side, in particular (special) type I pentagons, as described above, and double pentagons formed by two identical (special) type I pentagons, as described above. Alternatively, all structures in the layer containing the active agent have the same hexagonal or pentagonal shape. In specific embodiments, the layer structures containing the active agent are double hexagons formed by two identical convex hexagons sharing two adjacent vertices and their common side, in particular double hexagons formed by two identical regular hexagons.In this context, convex (regular) hexagons or double hexagons formed by two identical convex (regular) hexagons, respectively, are congruent. In specific embodiments, the layer structures containing the active agent are non-equilateral convex pentagons with two 90° interior angles and three 120° interior angles, and two parallel sides of equal length and two other sides of equal length, wherein the ratio of the shorter side to the longer side is approximately 1:2^3. Alternatively, the layer structures containing the active agent are non-equilateral convex pentagons with two 90° interior angles and three 120° interior angles, and two sides of equal length and two other sides of equal length, wherein the ratio of the shorter side to the longer side is approximately 1:2.In particular, the structures of the layer containing the active agent are (special) pentagons of type I or type II, as described above, which can be arranged in the form of regular hexagons. Petition 870250073524, dated 08 / 20 / 2025, pp. 108 / 155 103 / 129

[00271] In certain embodiments, the sheet of medical plasters (all medical plasters made of the sheet as a whole) has a release area of ​​1 cm2 to 300 cm2. TREATMENT METHOD / MEDICAL USE

[00272] The medical plaster according to the present invention is suitable for use in a treatment method and, in particular, in a treatment method for a human patient.

[00273] In certain embodiments, the medical plaster according to the invention is for use in a treatment method wherein the medical plaster is preferably applied to the patient's skin for less than 90 minutes, less than 60 minutes, or less than 30 minutes. In certain embodiments, the medical plaster according to the invention is for use in a treatment method with a dosing interval of at least or about 1.5 months, at least or about 2 months, or at least or about 3 months. Therefore, it is preferable that a medical plaster be applied only after an interval of at least 90 days following the removal of a previous medical plaster.

[00274] In certain embodiments, the medical plaster according to the invention is for use in a method of treating pain. In particular, the medical plaster according to the invention is for use in a method of treating neuropathic pain, such as chronic neuropathic pain, preferably including post-herpetic neuralgia, post-surgical neuralgia, such as, for example, post-herniotomy pain, post-thoracotomy pain or post-mastectomy pain, post-traumatic neuropathy, polyneuropathy such as, for example, painful diabetic neuropathy, chemotherapy-induced neuropathy, neuropathy caused by tumors, HIV-associated neuropathy, alcohol-related neuropathy, small fiber neuropathy or complex regional pain syndrome, radiculopathy or compression syndromes such as carpal tunnel syndrome, or in a method of treating peripheral neuropathic pain. Petition 870250073524, dated 08 / 20 / 2025, pp. 109 / 155 104 / 129 neuropathic pain associated with postherpetic neuralgia or diabetic peripheral neuropathy (DPN) of the hands and feet, or postsurgical neuropathic pain, and / or the medical patch according to the invention is for use in a method of treating nociceptive pain, such as acute nociceptive pain, preferably including somatic pain or visceral pain.

[00275] In specific embodiments, the medical plaster according to the invention is for use in a method of treating joint pain or cancer pain. In particular, the medical plaster according to the invention is for use in a method of treating pain associated with a joint condition, in particular associated with arthritis, such as, for example, infectious or non-infectious arthritis, preferably in a method of treating pain associated with rheumatoid arthritis, juvenile arthritis, psoriatic arthritis or osteoarthritis, such as, for example, hip arthritis, knee arthritis, foot arthritis or finger joint arthritis.

[00276] In connection with the foregoing, the medical plaster according to the invention is preferably applied to at least one surface of the patient's body, in particular selected from the back, buttocks, hips, legs, knees, feet or hands. The preferred application time of a medical plaster according to the invention is less than or about 60 minutes on the back, buttocks, hips or legs, and less than or about 30 minutes on the knees, feet or hands.

[00277] In specific embodiments, the medical plaster according to the invention is not applied / removed by medical professionals, in particular, the medical plaster according to the invention is applied / removed by the patient himself.

[00278] In one particular aspect, the present invention also relates to the use of the medical plaster as described herein for the manufacture of a medicament, in particular for the Petition 870250073524, dated 08 / 20 / 2025, pp. 110 / 155 105 / 129 manufacture of a medicament to treat pain, such as for the manufacture of a medicament to treat neuropathic pain or nociceptive pain, or for the manufacture of a medicament to treat joint pain or cancer pain. According to a more specific aspect, the present invention also relates to the use of the medical plaster as described herein for the manufacture of a medicament to treat pain associated with a joint condition, such as arthritis.

[00279] According to a specific aspect, the present invention also relates to a method of treatment, in particular a method of treatment of pain, such as a method of treatment of neuropathic pain, or nociceptive pain, or a method of treatment of joint pain, or cancer pain, including the application of a medical plaster, as described herein, to the skin of a patient. According to a more specific aspect, the present invention also relates to a method of treatment of pain associated with a joint condition, such as arthritis, including the application of a medical plaster, as described herein, to the skin of a patient. MANUFACTURING PROCESS

[00280] The medical plaster according to the present invention can be manufactured using a process comprising the steps of i. prepare the layer containing the active agent; ii. prepare the skin contact layer; and iii. laminate the skin contact layer onto the layer containing the active agent to obtain the structure of the layer containing the active agent.

[00281] The preparation of the layer containing the active agent can be carried out before or after the preparation of the skin contact layer, or the preparation of both layers can be carried out in parallel before lamination. Alternatively, the layer containing the active agent is prepared first and the skin contact layer is prepared Petition 870250073524, dated 08 / 20 / 2025, page 111 / 155 106 / 129 either the layer containing the active agent is applied directly to the skin contact layer, or the skin contact layer is prepared first and the layer containing the active agent is applied directly to the skin contact layer.

[00282] In some embodiments, the invention relates to a method of manufacturing an active agent-containing layer structure of a medical plaster as described herein, comprising the steps of: 1) combine at least the components 1. active agent, and 2. Polymer I, to obtain a coating composition containing an active agent; 2.1) Coating the coating composition containing the active agent in a first intermediate coating; and 2.2) Dry the coating composition containing the active agent to form the active agent-containing layer. 2.3) Laminate the layer containing the active agent obtained by drying the coating composition containing the active agent coated in the first intermediate coating with the support layer.

[00283] The method may also include the following steps: 3.1) coating an active agent-free coating composition comprising at least polymer II onto a second intermediate coating; and 3.2) dry or cure the active agent-free coating composition to form the skin contact layer; and optionally 3.3) Laminate the skin contact layer obtained by drying or curing the active agent-free coating composition. Petition 870250073524, dated 08 / 20 / 2025, page 112 / 155 107 / 129 coated in the second intermediate coating with a release coating.

[00284] The method may also include the following steps: 4.1) remove the first and second intermediate coatings from the layer containing the active agent and from the skin contact layer; and 4.2) Laminate the open side of the skin contact layer onto the open side of the layer containing the active agent to obtain the structure of the layer containing the active agent.

[00285] In other embodiments, the invention relates to a method of manufacturing an active agent-containing layer structure of a medical plaster as described herein, comprising the steps of: 1) combine at least the components 1. active agent, and 2. Polymer I, to obtain a coating composition containing an active agent; 2.1) Coat the coating composition containing the active agent onto a support layer; and 2.2) Dry the coating composition containing the active agent to form the active agent-containing layer. 3.1) Coating an active agent-free coating composition comprising at least polymer II in a release coating; and 3.2) dry or cure the active agent-free coating composition to form the skin contact layer; and optionally 4) Laminate the open side of the skin contact layer onto the open side of the layer containing the active agent to obtain the Petition 870250073524, dated 08 / 20 / 2025, pp. 113 / 155 108 / 129 structure of the layer containing the active agent.

[00286] The active agent-containing layer and the skin contact layer are preferably prepared separately, as indicated above, and then laminated together by removing the intermediate coatings (if any) and laminating the open sides of the two layers together to provide an active agent-containing layer structure. Alternatively, the active agent-free coating composition is coated and dried or cured directly onto the active agent-containing layer, or the active agent-containing coating composition is coated and dried directly onto the skin contact layer before application of a release coating or support layer, respectively.

[00287] In this manufacturing process, in step 1) the components are preferably combined in a solvent to obtain the coating composition. The solvent can be selected from alcoholic solvents, in particular methanol, ethanol, isopropanol and mixtures thereof, and from non-alcoholic solvents, in particular ethyl acetate, n-propyl acetate, hexane, n-heptane, petroleum ether, toluene and mixtures thereof, preferably from non-alcoholic solvents such as ethyl acetate or n-heptane.

[00288] The active agent may be dissolved or homogeneously dispersed in the coating composition containing the active agent. It may be supplied in an amphiphilic solvent, which must not mix or may mix only to a small extent with the solvent of the coating composition containing the active agent.

[00289] Polymer I and / or Polymer II may not be curable and therefore normally applied by a solvent-based process. Consequently, Polymer I and / or Polymer II may be supplied in a solvent, wherein the solids content in the solvent is preferably 40 to 75% by weight. The solvent may be selected from Petition 870250073524, dated 08 / 20 / 2025, pp. 114 / 155 109 / 129 between alcoholic solvents and non-alcoholic solvents, as described above.

[00290] The coating composition containing the active agent and / or the coating composition without the active agent can be solidified by drying 2.2) or 3.2) to form the layer containing the active agent or the skin contact layer, respectively. Drying is preferably carried out at a temperature of 20 to 90 °C. Alternatively, the skin contact layer can be formed after curing, i.e., crosslinking, which is preferably carried out at a temperature of 40 °C to 140 °C. Examples

[00291] The present invention will now be more fully described with reference to the accompanying examples. It should be understood, however, that the following description is merely illustrative and should in no way be taken as a limitation of the invention. The numerical values ​​given in the examples regarding the quantity of ingredients in the composition or the weight of the area may vary slightly due to manufacturing variability. EXAMPLE 1

[00292] The skin permeation rate and utilization of capsaicin for two medical patches containing capsaicin were determined by in vitro experiments.

[00293] The two patches differ from each other only by the presence or absence of an additional skin contact layer. They were prepared identically, except that the preparation and coating steps of an active-free coating composition and lamination of the resulting active-free layer with the previously prepared capsaicin-containing layer were performed only for one of the two patches, but not for the other. Coating composition containing capsaicin Petition 870250073524, dated 08 / 20 / 2025, pp. 115 / 155 110 / 129

[00294] For both adhesives, the formulation of the coating composition containing capsaicin is summarized in Table 1.1 below. The % solids values ​​refer to amounts (Amt) in % by weight. Table 1.1 Ingredient (Trade Name) Solids [%] Capsaicin 8 Polysiloxane in n-heptane Solids content 70% by weight (Liveo™ BIO-PSA 7-4301 and BIO-PSA 7-4201) 70 Transcutol (diethylene glycol monoethyl ether) 19.2 Ethyl cellulose 0.8 Silicone oil 360MED Fluid 12,500 cSt. 2 Total 100 Area weight [g / m2] 80 Capsaicin content [pg / cm2] 640 Preparation of a coating composition containing capsaicin.

[00295] Transcutol was initially thickened with ethyl cellulose under agitation (100-300 rpm).

[00296] A container was loaded with the polysiloxane and silicone oil mixture and stirred (100-300 rpm) for at least 5 minutes before the ethylcellulose / Transcutol solution was added. After a further 10 minutes of stirring (100-300 rpm), capsaicin was added. The mixture was then stirred at approximately 250-300 rpm until a homogeneous mixture was obtained (at least 60 min). Coating composition containing capsaicin

[00297] The resulting capsaicin-containing coating composition was applied to a fluoropolymer-coated polyester film (Scotchpak™ 1022). The solvent was removed at room temperature for approximately 20 to 30 minutes. Petition 870250073524, dated 08 / 20 / 2025, pp. 116 / 155 111 / 129

[00298] The coating thickness was chosen so that solvent removal would result in a capsaicin-containing layer area weight of approximately 80.0 g / m2.

[00299] The resulting capsaicin-containing microreservoir layer was then laminated with a support layer (polyester film, 19 µm). Coating composition without active ingredients

[00300] For the medical plaster comprising a skin contact layer, the active-free coating composition formulation is summarized in Table 1.2 below. % solids values ​​refer to amounts (Amt) in % by weight. Table 1.2 Ingredient (Trade Name) Quantity [g] Solids [%] Component A of the Soft Skin Adhesive Kit (Liveo™ MG 7-9900 (A)) 25 50 Component B of the Soft Skin Adhesive Kit (Liveo™ MG 7-9900 (B)) 25 50 Total 50 100 Area weight [g / m2] 230 Preparation of the active ingredient-free coating composition

[00301] Both components were weighed separately, and then component A was added to the mixing container, followed by component B. The mixture was then mixed at approximately 100 rpm for approximately 10 minutes until a homogeneous mixture of Component A and Component B was obtained. Coating composition free of active ingredients

[00302] Over a period of approximately 30 minutes, the resulting active-free coating composition was coated onto an adhesive-equipped sheet. The coating temperature was set to 120 °C. The resulting active-free layer was heated to es Petition 870250073524, dated 08 / 20 / 2025, pp. 117 / 155 112 / 129 at temperature for approximately 40 min.

[00303] The coating thickness was chosen so that solvent removal would result in an active ingredient-free layer thickness (skin contact) of approximately 230 g / m2.

[00304] The resulting active ingredient-free layer (skin contact) was laminated with a release coating (FEP, fluorinated ethylene propylene, 125 pm). Lamination of the capsaicin-containing layer and the active ingredient-free layer (skin contact)

[00305] The active ingredient-free layer (skin contact) was then laminated with the capsaicin-containing layer. For this purpose, the adhesive sheets used for coating and drying the layers were removed and the resulting open sides of the active ingredient-containing layer and the active ingredient-free layer (skin contact) were laminated together, resulting in a self-adhesive capsaicin-containing layer structure comprising the backing layer, the capsaicin-containing layer and the active ingredient-free layer (skin contact), wherein the capsaicin-containing layer is attached to the backing layer, and the active ingredient-free layer (skin contact) is attached to the capsaicin-containing layer, and wherein the structure is closed by a release liner, which is attached to the active ingredient-free layer (skin contact). Preparation of medical plaster

[00306] Individual medical patches were perforated from the self-adhesive capsaicin-containing layer structure obtained as described above. The medical patches were then sealed in pouches of primary packaging material. Measuring skin permeation

[00307] The permeate quantity of the two medical plasters prepared as described above was determined by in vitro experiments. Petition 870250073524, dated 08 / 20 / 2025, pp. 118 / 155 113 / 129 according to the OECD Guideline (adopted on April 13, 2004), performed with a 10.0 ml Franz diffusion cell. Split-thickness human skin from cosmetic surgery (female abdomen, date of birth 1981) was used. A heat-separated epidermis was used in all medical patches. Cuts with a release area of ​​1.171 cm2 were perforated from the medical patch. The amount of capsaicin permeated into the Franz cell receptor medium (0.9% sodium chloride solution with 0.1% saline azide as an antibacterial agent) at a temperature of 32 ± 1°C was measured and the corresponding skin permeation rate was calculated.

[00308] The results are shown in Table 1.3 and Figure 1A. Table 1.3 Cumulative amount permeated with SS* [pg / cm2] Elapsed time [min] Plaster with skin contact layer (n = 6) Plaster without skin contact layer (n = 6) SD Rate SD Rate 30 0.07 0.11 0.07 0.11 60 0.31 0.23 0.32 0.27 90 0.72 0.30 0.68 0.38 120 1.20 0.38 1.09 0.49 180 2.31 0.56 2.05 0.64 240 3.49 0.68 3.15 0.73 *: The standard deviation was calculated based on method n.

[00309] The corresponding skin permeation rates (Δ flow rate) were calculated based on the respective permeated quantity.

[00310] The results are shown in Table 1.4 and Figure 1B. Table 1.4 Skin permeation rate (Δ flow rate) with SD* [pg / cm2 min] Elapsed time [min] Plaster with skin contact layer (n = 6) Plaster without skin contact layer (n = 6) SD Rate SD Rate 15 0.0023 0.0035 0.0024 0.0038 45 0.0081 0.0047 0.0082 0.0056 Petition 870250073524, dated 08 / 20 / 2025, pp. 119 / 155 114 / 129 Skin permeation rate (Δ flow rate) with SD* [pg / cm2 min] Elapsed time [min] Plaster with skin contact layer (n = 6) Plaster without skin contact layer (n = 6) SD Rate SD Rate 75 0.0135 0.0026 0.0121 0.0039 105 0.0161 0.0028 0.0135 0.0039 150 0.0186 0.0034 0.0160 0.0029 210 0.0195 0.0024 0.0184 0.0042 *: The standard deviation was calculated based on method n. Exemplary plasters 2a to 2D, 3a to 3D, 4a to 4D AND 5A to 5D

[00311] Based on the results obtained in Example 1, as described above, the concept of other patches considered particularly suitable and their possible tests will be described below. Coating composition containing active agent

[00312] The formulation of possible coating compositions containing active agents 2, 3, 4 and 5 is summarized in Table 2.1 below. The % solids values ​​refer to quantities (Amt) in % by weight. Table 2.1 Ingredient (Trade Name) Coating composition containing active agent 2 3 4 5 Solids [%] Solids [%] Solids [%] Solids [%] Resiniferatoxin 5 - 10 5 - 10 5 - 10 5 - 10 Acrylic polymer (e.g., acrylic adhesive in ethyl acetate and n-hexane. Solids content of 40.5% by weight. Duro-Tak™ 87-2510) 90 - 95 - - - Petition 870250073524, dated 08 / 20 / 2025, pages 120 / 155 115 / 129 Ingredient (Trade Name) Coating composition containing active agent 2 3 4 5 Solids [%] Solids [%] Solids [%] Solids [%] Silicone-based polymer (e.g., n-heptane silicone adhesive. 70% solids content by weight. Liveo™ BIO-PSA 7-4301) - 90 - 95 75 - 90 - Polyisobutylene (e.g., n-heptane isobutylene adhesive, 40% solids content by weight. Oppanol® B12 / N100, 80:20) - - - 90-95 Solubilizer (e.g., Diethylene glycol monoethyl ether. Transcutol®) - - 5 - 15 - Total 100 100 100 100 Preparation and coating of the coating composition containing the active agent.

[00313] The preparation and coating of the coating composition containing the active agent may be carried out using methods known to the expert, for example, substantially as described in Example 1, optionally using additional solvent during the preparation of the coating composition containing the active agent, which will evaporate upon drying the coated composition. Coating composition without active ingredients

[00314] The formulation of the active ingredient-free coating compositions a through d is summarized in Table 2.2 below. The % solids values ​​refer to amounts (Amt) in % by weight. Table 2.2 Petition 870250073524, dated 08 / 20 / 2025, pp. 121 / 155 116 / 129 Ingredient (Trade Name) active ingredient-free coating compositions abcd Solids [%] Solids [%] Solids [%] Solids [%] Acrylic silicone hybrid polymer (e.g., nHexane acrylic silicone hybrid pressure-sensitive adhesive). Solids content of about 50% by weight. Dow-Corning® 76301) 100 - - - Silicone-based polymer (e.g., heptane silicone adhesive. 70% solids content by weight. Liveo™ BIO-PSA 7-4301) - 100 - - Styrene-isoprene-styrene copolymer (e.g., SIS 5229P) - - 60 - Polyisobutylene (e.g., heptane isobutylene adhesive, 40% solids content by weight. Oppanol® B12 / N100, 80:20) - - - 100 Terpene resin - - 35 - Viscous paraffin - - 5 - Total 100 100 100 100 Preparation and coating of the active ingredient-free coating composition.

[00315] The preparation and coating of the coating composition containing the active agent can be carried out using method Petition 870250073524, dated 08 / 20 / 2025, pp. 122 / 155 117 / 129 of those known to the expert, for example, substantially as described in Example 1, optionally using additional solvent during the preparation of the coating composition containing the active agent, which will evaporate upon drying the coated composition. Lamination of the layer containing the active ingredient and the layer free of the active ingredient (in contact with the skin).

[00316] The active ingredient-free layers (in contact with the skin) can then be laminated with the layers containing the active agent obtained using methods known to the expert, for example, substantially as described in Example 1. The combination of formulations 2 to 5 eaac results in adhesives 2a to 2d, 3a to 3d, 4a to 4d and 5a to 5d. Preparation of medical plaster

[00317] Individual medical patches can then be perforated from the layer structure containing the active agent obtained and sealed in pouches of the primary packaging material, as described above.

[00318] The invention relates in particular to the following additional items: 1. Medical patch for the administration of an active agent, characterized in that it comprises a layer structure containing the active agent, said layer structure containing the active agent comprising: A) a support layer; B) a layer containing an active agent comprising (i) an active agent, and (ii) a polymer I; and C) a skin contact layer comprising a polymer II; Petition 870250073524, dated 08 / 20 / 2025, pp. 123 / 155 118 / 129 wherein the skin contact layer is an adhesive layer that is directly attached to the layer containing the active agent, and wherein the saturation concentration of the active agent in the skin contact layer is less than 0.1% by weight. 2. Medical plaster according to item 1, in which the saturation concentration of the active agent in the skin contact layer is less than 0.05% by weight, less than 0.02% by weight, or less than 0.01% by weight. 3. Medical plaster according to item 1 or 2, wherein polymer II is a polymer or a mixture of polymers in which the active agent is substantially insoluble. 4. Medical plaster according to any one of items 1 to 3, wherein polymer II is a pressure-sensitive adhesive or a mixture of pressure-sensitive adhesives. 5. Medical plaster according to any one of items 1 to 4, wherein polymer II is a polymer or a mixture of polymers selected from the group consisting of acrylic and silicone hybrid polymers, silicone-based polymers, silicone gel adhesives and polymers based on natural or synthetic rubbers. 6. Medical plaster according to any one of items 1 to 5, wherein polymer II is a polymer or a mixture of polymers selected from the group consisting of silicone-based polymers and silicone gel adhesives. 7. Medical plaster according to any of items 1 to 6, wherein polymer II is selected from silicone-based polymers. Petition 870250073524, dated 08 / 20 / 2025, pp. 124 / 155 119 / 129 8. Medical plaster according to item 7, wherein the silicone-based polymers are obtainable by polycondensation of a polydimethylsiloxane blocked at the silanol end 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. 9. Medical plaster according to item 7 or 8, wherein the silicone-based polymers are a mixture of pressure-sensitive adhesives obtained by polycondensation of a polydimethylsiloxane blocked at the silanol end with a silicate resin with a resin to polymer ratio of 55:45 or 60:40. 10. Medical plaster according to any one of items 7 to 9, wherein the silicone-based polymers are a mixture of pressure-sensitive adhesives with a solution viscosity at 25 °C and about 60% heptane solids content of 450 mPa if / or a complex viscosity at 0.01 rad / sa 30 °C of 1x10⁸ Poise, and a solution viscosity at 25 °C and about 60% heptane solids content of 500 mPa if / or a complex viscosity at 0.01 rad / sa 30 °C of 5x10⁶ Poise. 11. Medical plaster according to any one of items 1 to 10, where polymer II is an amine-compatible polysiloxane. 12. Medical plaster according to item 11, wherein the amine-compatible polysiloxane is obtainable by polycondensation of a polydimethylsiloxane blocked at the silanol end with a silicate resin, followed by at least partial trimethylsilylation of the residual silanol functionality. Petition 870250073524, dated 08 / 20 / 2025, pp. 125 / 155 120 / 129 13. Medical plaster according to any of items 1 to 6, wherein polymer II is selected from silicone gel adhesives. 14. Medical plaster according to item 13, wherein silicone gel adhesives are obtainable by reacting a gel-producing composition comprising (i) at least one alkenyl-substituted polydiorganosiloxane, (ii) at least one organosiloxane containing silicon-linked hydrogen atoms, and (iii) at least one catalyst for the reaction of SiH groups with Si-alkenyl groups. 15. Medical plaster according to item 13 or 14, wherein silicone gel adhesives are obtainable by reacting a gel-producing composition comprising (i) a vinylmethylsiloxane and dimethylsiloxane copolymer with (ii) methylhydrogen polysiloxane with trimethylsilyl terminal groups in the presence of (iii) a platinum catalyst. 16. Medical plaster according to any one of items 13 to 15, wherein the silicone gel adhesives are silicone gel adhesives reinforced with silicate resin containing from about 2 to about 45% by weight of at least a hydroxyl-substituted silicate resin. 17. Medical plaster in accordance with any of items 1 to 16, provided that the skin contact layer does not comprise silicone gel adhesives. 18. Medical plaster according to any one of items 1 to 17, wherein the skin contact layer comprises polymer II. Petition 870250073524, dated 08 / 20 / 2025, pages 126 / 155 121 / 129 in an amount of at least 95% by weight, at least 99% by weight, or in an amount of approximately 100% by weight, based on the total weight of the skin contact layer. 19. Medical plaster according to any one of items 1 to 18, wherein the skin contact layer comprises the active agent in an amount less than 0.1% by weight, or less than 0.01% by weight based on the total weight of the skin contact layer. 20. Medical plaster according to any of items 1 to 19, wherein the active agent is an irritant active agent. 21. Medical plaster according to any of items 1 to 20, in which the active agent is an analogue of capsaicin. 22. Medical plaster according to any one of items 1 to 21, wherein the active agent is selected from the group consisting of arvanil, capsiate, civamide, dihydrocapsaicin, homocapsaicin, homodihydrocapsaicin, gingerol, nordihydrocapsaicin, olvanil, palvanil, piperine, phenylacetylrinvanil and resiniferatoxin. 23. Medical plaster according to any of items 1 to 22, in which the active agent is resiniferatoxin. 24. Medical plaster according to any of items 1 to 23, provided that the layer containing the active agent does not comprise capsaicin. 25. Medical plaster according to any of items 1 to 24, wherein the active agent is present in the agent-containing layer. Petition 870250073524, dated 08 / 20 / 2025, pp. 127 / 155 122 / 129 active in an amount of at least 0.10 mg / cm2, at least 0.20 mg / cm2, at least 0.50 mg / cm2 or at least 1.0 mg / cm2. 26. Medical plaster according to any one of items 1 to 25, wherein the active agent is present in the active agent-containing layer in an amount less than 12.0 mg / cm2, less than 10.0 mg / cm2, less than 6.0 mg / cm2 or less than 3.0 mg / cm2. 27. Medical plaster according to any one of items 1 to 26, wherein the layer containing the active agent comprises the active agent in an amount of 0.5 to 30% by weight, 1 to 20% by weight, 2 to 15% by weight or 5 to 10% by weight, based on the total weight of the layer containing the active agent. 28. Medical plaster according to any one of items 1 to 27, wherein the layer containing the active agent comprises polymer I in an amount of 20 to 99% by weight, or 60 to 90% by weight, based on the total weight of the layer containing the active agent. 29. Medical plaster according to any one of items 1 to 28, wherein polymer I is a pressure-sensitive adhesive or a mixture of pressure-sensitive adhesives. 30. Medical plaster according to any one of items 1 to 29, wherein polymer I is a polymer or a mixture of polymers selected from the group consisting of acrylic polymers, acrylic-silicone hybrid polymers, silicone-based polymers and polymers based on natural or synthetic rubbers. 31. Medical plaster according to any of items 1 to 30, where Petition 870250073524, dated 08 / 20 / 2025, pp. 128 / 155 123 / 129 Polymer I is a polymer or a mixture of polymers selected from the group consisting of silicone-based polymers and polymers based on natural or synthetic rubbers. 32. Medical plaster according to any one of items 1 to 31, wherein polymer I is selected from silicone-based polymers. 33. Medical plaster according to item 32, wherein the silicone-based polymers are obtainable by polycondensation of a polydimethylsiloxane blocked at the silanol end 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. 34. Medical plaster according to item 32 or 33, wherein the silicone-based polymers are a mixture of pressure-sensitive adhesives obtained by polycondensation of a polydimethylsiloxane blocked at the silanol end with a silicate resin with a resin to polymer ratio of 55:45 or 60:40. 35. Medical plaster according to any one of items 32 to 34, wherein the silicone-based polymers are a mixture of pressure-sensitive adhesives with a solution viscosity at 25 °C and about 60% heptane solids content of 450 mPa if / or a complex viscosity at 0.01 rad / sa 30 °C of 1χ108 Poise, and a solution viscosity at 25 °C and about 60% heptane solids content of 500 mPa if / or a complex viscosity at 0.01 rad / sa 30 °C of 5^106 Poise. 36. Medical plaster cast according to any of the items Petition 870250073524, dated 08 / 20 / 2025, pp. 129 / 155 124 / 129 to 35, where polymer I is an amine-compatible polysiloxane. 37. Medical plaster according to item 36, wherein the amine-compatible polysiloxane is obtainable by polycondensation of a polydimethylsiloxane blocked at the silanol end with a silicate resin, followed by at least partial trimethylsilylation of the residual silanol functionality. 38. Medical plaster according to any one of items 1 to 37, wherein polymer I is selected from styrenic triblock copolymers and polyisobutylenes. 39. Medical plaster according to item 38, wherein the styrenic triblock copolymer is selected from the group consisting of styrene-ethylene-styrene (SES) block copolymers, styrene-butadiene-styrene (SBS) block copolymers, styrene-isoprene-styrene (SIS) block copolymers, styrene-ethylene / butylene-styrene (S-EB-S) block copolymers, styrene-ethylene / butylene / propylene-styrene (S-EBP-S) block copolymers, styrene-isoprene / butadiene-styrene (S-IB-S) block copolymers and mixtures thereof. 40. Medical plaster according to any one of items 1 to 39, wherein polymer I is a SIS block copolymer or a polyisobutylene, or a mixture thereof. 41. Medical plaster according to item 40, wherein the SIS block copolymer comprises polystyrene and polyisoprene blocks in a ratio of 10:90 (%) to 30:70 (%). 42. Medical plaster according to item 40 or 41, wherein the SIS block copolymer consists of three polyethylene blocks. Petition 870250073524, dated 08 / 20 / 2025, pp. 130 / 155 125 / 129 styrene, polyisoprene and polystyrene. 43. Medical plaster according to any one of items 1 to 42, wherein polymer I is a mixture of low molecular weight polyisobutylene and high molecular weight polyisobutylene. 44. Medical plaster according to any of items 1 to 43, wherein polymer I is different from polymer II. 45. Medical plaster according to any of items 1 to 43, wherein polymer I is the same as polymer II. 46. ​​Medical plaster according to any of items 1 to 45, wherein the layer containing the active agent further comprises a solubilizer. 47. Medical plaster according to item 46, wherein the solubilizer is a substance or a mixture of substances in which the active agent has a saturation concentration of at least 30% by weight. 48. Medical plaster according to item 46 or 47, wherein the solubilizer is an amphiphilic solvent. 49. Medical plaster according to item 46 or 47, wherein the solubilizer is dipropylene glycol, diethylene glycol monoethyl ether or dimethyl isosorbide. 50. Medical plaster according to any one of items 46 to 49, wherein the layer containing the active agent comprises the solubilizer in an amount of 1 to 40% by weight, based on weight. Petition 870250073524, dated 08 / 20 / 2025, pp. 131 / 155 126 / 129 total of the layer containing the active agent. 51. Medical plaster according to any one of items 1 to 50, wherein the layer containing the active agent and / or the skin contact layer further comprises at least one additive or excipient selected from the group consisting of crystallization inhibitors, viscosity-increasing agents, fillers, skin care substances, pH regulators, preservatives, tackifying agents, softeners, stabilizers and permeation enhancers. 52. Medical plaster according to any of items 1 to 51, in which the backing layer is impermeable to the active agent. 53. Medical plaster according to any one of items 1 to 52, wherein the medical plaster further comprises a releasable coating. 54. Medical plaster according to any of items 1 to 53, wherein the medical plaster is a topical medical plaster. 55. Medical plaster according to any of items 1 to 54, wherein the medical plaster is a transdermal therapeutic system. 56. Medical plaster according to any of items 1 to 55, for use in a treatment method, in particular for use in a pain treatment method, or for use in a treatment method for neuropathic pain, or nociceptive pain, or for use in a treatment method for joint pain, or cancer pain, or for use in a treatment method for pain associated with a Petition 870250073524, dated 08 / 20 / 2025, pages 132 / 155 127 / 129 joint condition, such as arthritis. 57. Medical plaster according to any of items 1 to 55, characterized in that it is for the manufacture of a medicament, in particular for the manufacture of a medicament to treat pain, or for the manufacture of a medicament to treat neuropathic pain, or nociceptive pain, or for the manufacture of a medicament to treat joint pain, or cancer pain, or for the manufacture of a medicament to treat pain associated with a joint condition, such as arthritis. 58. A method of treatment, in particular, a method of treating pain, or a method of treating neuropathic pain, or nociceptive pain, or a method of treating joint pain, or cancer pain, or a method of treating pain associated with a joint condition, such as arthritis, including applying a medical plaster in accordance with any of items 1 to 55 to a patient's skin. 59. A method for manufacturing a layered structure containing the active agent of a medical plaster according to any one of items 1 to 55, comprising the steps of: 1) combine at least the components 1. active agent, and 2. Polymer I, to obtain a coating composition containing an active agent; 2.1) Coating the coating composition containing the active agent onto a first intermediate coating, or coating the coating composition containing the active agent onto the support layer; and 2.2) Dry the coating composition containing the agent. Petition 870250073524, dated 08 / 20 / 2025, pages 133 / 155 128 / 129 active ingredient coated to form the layer containing the active agent. 60. The method according to item 59, also including the step of: 2.3) Laminate the layer containing the active agent obtained by drying the coating composition containing the active agent coated in the first intermediate coating with the support layer. 61. The method according to item 59 or 60, also including the step of: 3.1) coating an active agent-free coating composition comprising at least polymer II in a second intermediate coating; or coating an active agent-free coating composition comprising at least polymer II in a release coating; and 3.2) Dry or cure the active agent-free coating composition to form the skin contact layer. 62. The method according to item 61, also including the step of: 3.3) Laminate the skin contact layer obtained by drying or curing the active agent-free coating composition coated in the second intermediate coating with a release coating. 63. The method according to any of items 59 to 62, also including the step of: 4.1) Remove the first and second intermediate coatings from the active agent-containing layer and the skin contact layer. 64. The method according to any of items 59 to 63, also including the step of: Petition 870250073524, dated 08 / 20 / 2025, pp. 134 / 155 129 / 129 4.2) Laminate the open side of the skin contact layer onto the open side of the layer containing the active agent to obtain the structure of the layer containing the active agent. 65. A medical patch for administering an active agent comprising a self-adhesive layer structure containing the active agent, said self-adhesive layer structure containing the active agent comprising: C) a support layer; D) a matrix layer containing an active agent comprising (i) an active agent in an amount of at least 0.5% by weight, based on the total weight of the matrix layer containing the active agent, (ii) a polymer I selected from the group consisting of silicone-based polymers and natural or synthetic rubber-based polymers, and (iii) a solubilizer; and C) a skin contact layer comprising a polymer II; wherein the skin contact layer is an adhesive layer that is directly attached to the layer containing the active agent, and wherein the saturation concentration of the active agent in the skin contact layer is less than 0.1% by weight.

Claims

CLAIMS 1. Medical plaster for the administration of an active agent, characterized in that it comprises a layer structure containing the active agent, said layer structure containing the active agent comprising: (iii) a support layer; (iv) an active agent-containing layer comprising (v) an active agent, and (vi) a polymer I; and (c) a skin contact layer comprising a polymer II; wherein the skin contact layer is an adhesive layer that is directly attached to the active agent-containing layer, and wherein the saturation concentration of the active agent in the skin contact layer is less than 0.1% by weight.

2. Medical plaster, according to claim 1, characterized in that the saturation concentration of the active agent in the skin contact layer is less than 0.05% by weight, less than 0.02% by weight, or less than 0.01% by weight.

3. Medical plaster, according to claim 1 or 2, characterized in that polymer II is a polymer or a mixture of polymers selected from the group consisting of acrylic-silicone hybrid polymers, silicone-based polymers, silicone gel adhesives and natural or synthetic rubber-based polymers, in particular from the group consisting of silicone-based polymers and silicone gel adhesives. Petition 870250073524, dated 20 / 08 / 2025, pp. 136 / 155 2 / 6 4. Medical plaster, according to any one of claims 1 to 3, characterized in that the skin contact layer comprises polymer II in an amount of at least 95% by weight, at least 99% by weight, or in an amount of about 100% by weight, based on the total weight of the skin contact layer.

5. Medical plaster, according to any one of claims 1 to 4, characterized in that the skin contact layer comprises the active agent in an amount of less than 0.1% by weight, or less than 0.01% by weight based on the total weight of the skin contact layer.

6. Medical plaster, according to any one of claims 1 to 5, characterized in that the active agent is an irritant active agent.

7. Medical plaster, according to any one of claims 1 to 6, characterized in that the active agent is an analogue of capsaicin.

8. Medical plaster, according to any one of claims 1 to 7, characterized in that the active agent is selected from the group consisting of arvanil, capsiate, civamide, dihydrocapsaicin, homocapsaicin, homodihydrocapsaicin, gingerol, nordihydrocapsaicin, olvanil, palvanil, piperine, phenylacetylrinvanil and resiniferatoxin, in particular the active agent is resiniferatoxin.

9. Medical plaster, according to any one of claims 1 to 8, characterized in that the active agent is present in the active agent-containing layer in an amount of at least 0.10 mg / cm2, at least 0.20 mg / cm2, at least 0.50 mg / cm2 or at least 1.0 mg / cm2 and / or the active agent is present in the active agent-containing layer in an amount less than 12.0 mg / cm2, less than 10.0 mg / cm2, less than 6.0 mg / cm2 or less than 3.0 mg / cm2.

10. Medical plaster, according to any one of claims 1 to 9, characterized in that the layer containing the active agent comprises the active agent in an amount of 0.5 to 30% by weight, 1 to 20% by weight, 2 to 15% by weight or 5 to 10% by weight, based on the total weight of the layer containing the active agent.

11. Medical plaster, according to any one of claims 1 to 10, characterized in that the layer containing the active agent comprises polymer I in an amount of 20 to 99% by weight, or 60 to 90% by weight, based on the total weight of the layer containing the active agent.

12. Medical plaster, according to any one of claims 1 to 11, characterized in that polymer I is a polymer or a mixture of polymers selected from the group consisting of acrylic polymers, acrylic-silicone hybrid polymers, silicone-based polymers and natural or synthetic rubber-based polymers, in particular from the group consisting of silicone-based polymers and natural or synthetic rubber-based polymers.

13. Medical plaster, according to any one of claims 1 to 12, characterized in that the layer containing the active agent further comprises a solubilizer, in particular in an amount of 1 to 40% by weight, based on the total weight of the layer containing the active agent.

14. Medical plaster, according to any one of claims 1 to 13, characterized in that the solubilizer is a substance or a mixture of substances in which the active agent has a saturation concentration of at least 30% by weight and / or the solubilizer is dipropylene glycol, diethylene glycol monoethyl ether or dimethyl isosorbide.

15. Medical plaster, according to any one of claims 1 to 14, characterized in that the medical plaster is a topical medical plaster or a transdermal therapeutic system.

16. Medical plaster, according to any one of claims 1 to 15, characterized in that it is for use in a method of treatment, in particular for use in a method of treatment of pain, or for use in a method of treatment of neuropathic pain, or nociceptive pain, or for use in a method of treatment of joint pain, or cancer pain, or for use in a method of treatment of pain associated with a joint condition, such as arthritis.

17. Use of a medical plaster as defined in any of claims 1 to 15, characterized in that it is for the manufacture of a medicament, in particular for the manufacture of a medicament to treat pain, or for the manufacture of a medicament to treat neuropathic pain, or nociceptive pain, or for the manufacture of a medicament to treat joint pain, or cancer pain, or for the manufacture of a medicament to treat pain associated with a joint condition, such as arthritis.

18. Treatment method, in particular, a method of treating pain, or a method of treating neuropathic pain, or nociceptive pain, or a method of treating joint pain, or cancer pain, or a method of treating pain associated with a joint condition, such as arthritis, characterized in that it includes applying a medical plaster in accordance with any of items 1 to 15 to a patient's skin.

19. A method for manufacturing an active agent-containing layer structure of a medical plaster of any of items 1 to 15, characterized in that it comprises the steps of: 1) combining at least components 1. active agent, and 2. polymer I, to obtain an active agent-containing coating composition; 2.1) coating the active agent-containing coating composition onto a first intermediate coating, or coating the active agent-containing coating composition onto the support layer; 2.2) drying the coated active agent-containing coating composition to form the active agent-containing layer; and 2.3) optionally laminating the active agent-containing layer obtained by drying the coated active agent-containing coating composition onto the support layer.

20. Method according to claim 19, characterized in that it further comprises the steps of: 3.1) coating an active agent-free coating composition comprising at least polymer II onto a second intermediate coating; or coating an active agent-free coating composition comprising at least polymer II onto a release coating; 3.2) drying or curing the coated active agent-free coating composition to form the skin contact layer; and 3.3) optionally, laminating the skin contact layer obtained by drying or curing the coated active agent-free coating composition onto the second intermediate coating onto a release coating.

21. Method according to claim 19 or 20, characterized in that it further comprises the steps of: 4.1) optionally removing the first and second intermediate coatings from the active agent-containing layer and the skin contact layer; and 4.2) laminating the open side of the skin contact layer onto the open side of the active agent-containing layer to obtain the structure of the active agent-containing layer.

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