Pentagonal self-adhesive layer structure

Abstract

The present invention relates to a self-adhesive layer structure for use in a medical patch having a pentagonal shape including at least one pentagon, a medical patch and a medical patch sheet including such a self-adhesive layer structure(s), a medical patch used in a treatment method, and a process for manufacturing such a medical patch.

Description

[Technical Field]

[0001] The present invention relates to a self-adhesive layer structure for use in a medical patch having a pentagonal shape including at least one pentagon. Furthermore, the present invention relates to a medical patch including a self-adhesive layer structure, and a medical patch sheet including two or more of these self-adhesive layer structures. [Background technology]

[0002] A medical patch is an adhesive patch that is placed on a patient's skin to deliver a specific amount of medication through the skin.

[0003] For thousands of years, drugs have been applied topically to the skin to treat local symptoms. More recently, transdermal delivery technologies have been developed to treat a variety of symptoms beyond the site of topical application. While topical delivery of compounds and / or drugs involves only minimal penetration into the skin layers, thus avoiding systemic effects, transdermal drugs refer to pharmaceutical compounds that are applied to the skin but are intended to penetrate the outermost layer of the skin (skin barrier) into the bloodstream and / or exert their effects on more distant tissues or organs.

[0004] Therefore, the body part to which a medical patch is applied may vary depending on the therapeutic classification of the drug it contains. Systemic transdermal medical patches are typically applied to broad, flat surfaces such as the patient's upper arm, chest, or back. In contrast, topical medical patches must be applied to the area of ​​the symptom to be treated, for example, the patient's hand or foot. Such application sites are particularly challenging due to their uneven surface and complexity, and the shape and size of the medical patch must be carefully considered.

[0005] However, medical patches, especially topical medical patches, are generally only available as large patches that need to be cut based on the application site and / or are almost impossible to apply seamlessly and completely without wrinkles. This requires considerable time and the application skills of the person applying the patch. Wrinkles are undesirable because they not only affect the feel and appearance of the patch at the application site, but also reduce the utilization rate of the active ingredient due to the reduced contact area and can reduce the adhesion of the patch. Furthermore, trimming or cutting the patch carries the risk of contamination because the active ingredient-containing adhesive layer may come into contact with the cutting tool and / or the hands of the person handling the patch.

[0006] For example, the 8% capsaicin patch skin delivery system, managed under the brand name QUTENZA® (Gruenenthal), is recommended to be cut to fit the size and shape of the treatment site. Originally, QUTENZA® covers a rectangular area of ​​14cm x 20cm. This topical system is indicated for the treatment of neuropathic pain associated with postherpetic neuralgia (PHN) in adults, and neuropathic pain associated with diabetic peripheral neuropathy (DPN) of the foot, and has recently been approved for use in adults for the treatment of postoperative neuropathic pain (PSNP). Therefore, it is often used for application to the hands and fingers or the lower legs and feet, and thus needs to be cut to fit small, non-flat application surfaces.

[0007] Therefore, it is desirable to provide a self-adhesive layer structure for medical patches that provides easy coverage of skin areas to be treated, particularly uneven surfaces that are difficult to adhere to. [Overview of the Initiative]

[0008] The object of the present invention is to provide a self-adhesive layer structure for medical patches that is improved compared to patches described in the prior art.

[0009] A further object of the present invention is to provide a self-adhesive layer structure for medical patches that offers easy and time-efficient handling.

[0010] A further object of the present invention is to provide a self-adhesive layer structure for medical patches that enables easy coverage of application sites. In particular, the object is to provide a self-adhesive layer structure for medical patches that enables easy coverage of uneven application sites without the need to cut the medical patch before application. In particular, the object is to provide an improved self-adhesive layer structure for medical patches that facilitates seamless and complete coverage of application sites.

[0011] A further object of the present invention is to provide a self-adhesive layer structure for medical patches that reduces wrinkles during application. In particular, the object is to provide a self-adhesive layer structure for medical patches that provides complete adhesion even in complex skin areas.

[0012] A further object of the present invention is to provide a self-adhesive layer structure for a medical patch that facilitates wrapping around fingers or toes.

[0013] Another objective of the present invention is to provide a self-adhesive layer structure for medical patches that allows for the coverage of a wider area of ​​skin without leaving gaps.

[0014] These and other objectives are achieved by the present invention, which, according to one aspect, relates to a self-adhesive layer structure for use in a medical patch, wherein the self-adhesive layer structure has a pentagonal shape, A) Backing layer, B) An active layer containing polymer I and an active agent, Includes, The backing layer and the active layer have the same extent, providing a pentagonal shape for the self-adhesive layer structure. A pentagon shape includes at least one pentagon, The sides of the pentagon range in length from 0.2 cm to 12.5 cm.

[0015] Surprisingly, the self-adhesive layer structure according to the present invention, having a pentagonal shape including at least one pentagon with a length of 0.2 to 12.5 cm, was found to have advantageous properties in that it improves the coverage of small and / or uneven application sites on the human body. In particular, the pentagonal shape was found to simplify application and reduce wrinkles, without the need to cut the medical patch before application. Therefore, the medical patch is suitable for problematic application sites such as hands or feet.

[0016] According to a particular embodiment of the present invention, the present invention relates to a medical patch, and the medical patch is The self-adhesive layer structure described herein, Release liner and Includes, The release liner has the same extent as the self-adhesive layer structure, or extends in all directions beyond the boundary of the self-adhesive layer structure.

[0017] According to a particular embodiment of the present invention, the present invention relates to a medical patch sheet, and the medical patch sheet is Two or more self-adhesive layer structures as described herein, Release liner and Includes, The release liner has the same extent as the self-adhesive layer structure, or extends in all directions beyond the boundary formed by the self-adhesive layer structure.

[0018] definition Within the scope of the present invention, the term “medical patch” refers to a transdermal delivery system in which an active agent is administered to a patient, and contains an effective amount of the active agent in a self-adhesive layer structure located on a removable protective layer (peel-off liner). In this context, the term “medical patch” is understood to mean an adhesive patch that may be a topical medical patch or a transdermal treatment system (TTS). Even if topical medical patches and TTSs are applied topically in the sense that they are attached to the patient’s skin, the terms “topical” or “topical administration” refer to the administration of an active agent that relies on passive diffusion into the skin itself, thereby producing a local effect at the site of action. In contrast, the term “TTS” refers to a system in which an active agent is administered into the systemic circulation via transdermal delivery.

[0019] Within the scope of the present invention, the term “self-adhesive layer structure” refers to an active agent-containing structure that provides a release surface for the active agent during administration. Because it is “self-adhesive,” it provides adhesion to the skin, typically without requiring further assistance for fixation to the skin. The self-adhesive layer structure, as described herein, optionally includes a skin contact layer in addition to a backing layer and an active layer. Thus, the self-adhesive layer structure contains an effective amount of the active agent.

[0020] As used herein, the term “active agent” refers to a substance intended to be delivered by a self-adhesive layer structure to provide a beneficial or desirable effect on a subject's physical symptoms, systemically or locally, at the site of delivery. Active agents, in particular, include biologically or pharmacologically active compounds, which may also be referred to as active ingredients, active pharmaceutical ingredients, drugs, active components, or active pharmaceutical ingredients (APIs). In this context, the terms “effective dose” or “therapeutably effective dose” refer to the amount of active agent in the self-adhesive layer structure sufficient to provide the desired (therapeutic) effect, such as pain relief / reduction, when administered to a patient via a medical patch. TTSs typically contain more active agent in the system than is actually delivered to the skin or systemic circulation, which is usually necessary to provide sufficient driving force for delivery from the TTS to the systemic circulation.

[0021] Within the scope of the present invention, terms such as "active" and "active agent" refer to active agents in pharmaceutically acceptable chemical and morphological forms and physical states. These forms include, but are not limited to, free base / free acid forms, protonated or partially protonated forms, deprotonated or partially deprotonated forms, active agents in the form of salts, cocrystals, acid / base addition salts formed by the addition of inorganic or organic acids / bases such as hydrochlorides or tartrates, solvates, hydrates, clathrates, complexes, etc. Also included are active agents in the form of particles that may be pulverized, crystalline and / or amorphous, and any mixture of the aforementioned forms.

[0022] The active agent contained in a medium such as a solvent may be dissolved or dispersed, or may be partially dissolved and partially dispersed.

[0023] Where it is stated that an active agent is used in a specific form in the manufacture of a medical patch, this does not preclude interactions between this form of the active agent and other components of the self-adhesive layer structure in the final medical patch, such as salt formation or complex formation. This means that even if the active agent is included in the form of a free base / acid, it may exist in the final medical patch in a 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, a portion of it may exist as a free base in the final medical patch. Unless otherwise indicated, the amount of active agent in the self-adhesive layer structure refers to the amount of active agent included in the medical patch during its manufacture and is calculated based on the active agent itself, without considering other forms. The active agent starting material included in the medical patch during its manufacture may be in the form of particles. The active agent may, for example, be present in the self-adhesive layer structure in the form of particles and / or dissolved.

[0024] In this context, the term “particles” refers to particulate materials in a solid that contain individual particles, the size of which is negligible compared to the material. In particular, particles are solids including plastics / deformable solids, including amorphous and crystalline materials. The term “dispersion” refers to a step or combination of steps in which the starting material (e.g., active agent) is not completely dissolved. Dispersion in the sense of the present invention involves the dissolution of a portion of the starting material (e.g., active agent particles) depending on the solubility of the starting material (e.g., the solubility of the active agent in the coating composition).

[0025] There are two main types of medical patches that use (passive) delivery of active drugs: matrix-type medical patches and reservoir-type medical patches. In matrix-type medical patches, the release of the active drug is mainly controlled by the matrix containing the active drug itself. In contrast, reservoir-type medical patches usually require a rate-limiting membrane to control the release of the active drug. In principle, matrix-type medical patches can also contain a rate-limiting membrane. However, matrix-type medical patches have the advantage of usually not requiring a rate-determining membrane compared to reservoir-type medical patches, and therefore dose dumping due to membrane rupture cannot occur. In summary, matrix-type medical patches are simple to manufacture and easy and convenient to use.

[0026] In this context, “matrix-type medical patch” is understood to mean a system or structure in which the active agent is uniformly dissolved and / or dispersed within a polymer carrier, i.e., a matrix, and together with the active agent and optionally any residual components, forms a matrix layer. In such a system, the matrix layer controls the release of the active agent from the medical patch. Preferably, the matrix layer has sufficient cohesiveness to be self-supporting so that sealing between other layers is not required. Thus, the active layer may be an active matrix layer, in which the active agent is uniformly distributed within the polymer matrix. The active matrix layer may contain two active agent-containing matrix layers, which may be laminated together. A matrix-type medical patch may also take the form of an “adhesive-in-drug” type medical patch, in particular, referring to a system in which the active agent is uniformly dissolved and / or dispersed within a pressure-sensitive adhesive matrix. In this regard, the active matrix layer may be an active pressure-sensitive adhesive layer or an active pressure-sensitive adhesive matrix layer. A medical patch in which the active agent is dissolved and / or dispersed within a polymer gel, such as a hydrogel, is also considered matrix-type according to the present invention.

[0027] Medical patches having a liquid active agent reservoir are referred to as “reservoir-type medical patches.” In such systems, the release of the active agent is preferably controlled by a rate-limiting membrane. In particular, the reservoir is sealed between the backing layer and the rate-limiting membrane. Thus, the active layer may preferably be an active reservoir layer containing a liquid reservoir with the active agent, and the active reservoir layer and the skin contact layer may be separated by a rate-limiting membrane. In the active reservoir layer, the active agent is preferably dissolved in a solvent such as ethanol or water, or in a silicone oil.

[0028] Reservoir-type medical patches are not understood to be matrix-type within the scope of the present invention. However, microreservoir-type medical patches (two-phase systems having deposits (e.g., spheres, droplets) of an inner active drug-containing phase dispersed in an outer polymer phase) are considered to be matrix-type within the scope of the present invention, as they are considered in the art to be a mixed form of matrix-type and reservoir-type medical patches, distinct from homogeneous single-phase matrix-type and reservoir-type medical patches in the concept of drug transport and drug delivery.

[0029] Therefore, a microreservoir type medical patch refers to a microreservoir system in which a liquid active drug preparation is dispersed in an adhesive matrix in the form of small droplets ("microreservoirs"). The size of the resulting droplets depends on the stirring conditions and the shear force applied during stirring. Its size can be determined by optical microscopy (e.g., measurement with a Leica MZ16, including a camera such as the Leica DSC320) by taking photographs of the microreservoirs at different positions at magnifications between 10x and 400x, depending on the required detection limit. The size of the microreservoirs can be determined by using image analysis software. Microreservoir systems are disclosed in U.S. Patents 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 include a polysiloxane as a base polymer and an amphiphilic solvent for microreservoir droplets.

[0030] The self-adhesive layer structure may also be a pressure-sensitive adhesive layer structure.

[0031] Within the scope of the present invention, the term “pressure-sensitive adhesive” (also abbreviated as “PSA”) refers to a material that adheres particularly by finger pressure, is permanently tacky, exhibits strong holding power, and is removable from smooth surfaces without leaving any residue. It can be obtained from a solvent-containing adhesive coating composition, which is applied to a film and after evaporation of a solvent (e.g., n-heptane or ethyl acetate). In this context, the term “solvent” is understood to mean any liquid substance that is preferably a volatile organic liquid such as methanol, ethanol, isopropanol, acetone, ethyl acetate, methylene chloride, hexane, n-heptane, toluene, and mixtures thereof. The pressure-sensitive adhesive layer has self-adhesive properties when in contact with skin. According to certain embodiments, the self-adhesive layer structure according to the present 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 skin contact layer. Adhesive overlays may still be employed to improve adhesion.

[0032] Within the scope of the present invention, the term “active layer” refers to a layer containing an active agent (active agent-containing layer) and providing a release area. This term encompasses active agent-containing reservoir layers (active reservoir layers) and active agent-containing matrix layers (active matrix layers), and in particular active agent-containing microreservoir layers (active microreservoir layers). When the active layer is an active matrix layer, such a layer is present in a matrix-type medical patch. As used herein, the active layer is preferably an active matrix layer and refers to the final solidified layer obtained after coating and drying a solvent-containing coating composition, for example, as described herein. Alternatively, the active matrix layer is obtained after melt coating and cooling. The active matrix layer may also be manufactured by laminating two or more such solidified layers (e.g., a dry layer or a cooled layer) of the same composition to provide a desired area weight. According to certain embodiments, the matrix layer is a pressure-sensitive adhesive matrix layer.

[0033] Within the scope of the present invention, the term “skin contact layer” refers to a layer that may be included in a self-adhesive layer structure that comes into direct contact with the patient’s skin during administration. In this case, other layers of the self-adhesive layer structure do not come into contact with the skin and do not necessarily have self-adhesive properties. The skin contact layer may adhere directly to the active layer, or a membrane may be placed between the active layer and the skin contact layer. In this context, the term “membrane” is understood to mean a layer provided between the active layer and the skin contact layer that is at least semipermeable to the active drug. The membrane may be a microporous membrane or a non-porous partition membrane. Preferred membranes can be selected from the group consisting of polyethylene membranes, polyurethane-coated polyethylene terephthalate / polyethylene membranes, polyurethane membranes, and ethylene vinyl acetate membranes. Additional skin contact layers are preferably present as adhesive layers.

[0034] Within the scope of the present invention, the term "backing layer" refers to a layer supporting the active layer. At least one backing layer in the self-adhesive layer structure of a medical patch, and typically the backing layer of the active layer, is substantially impermeable to the active agent contained in the layer, as well as any additives, during the period of storage and administration, and therefore prevents loss of activity or cross-contamination in accordance with regulatory requirements. According to certain embodiments, the backing layer is also occluding, meaning it is substantially impermeable to water and water vapor. Suitable materials for the backing layer include polyethylene terephthalate (PET), polyethylene (PE), ethylene vinyl acetate copolymer (EVA), polyester, polyurethane, and mixtures thereof. A suitable backing layer may be siliconeized to improve adhesion between the active layer and the backing layer.

[0035] Furthermore, an adhesive overlay may be present. In this context, the term “adhesive overlay” is understood to mean an adhesive layer structure that does not contain an active agent, has a larger area than the self-adhesive layer structure, provides an additional area for adhesion to the skin, but does not provide an area for the release of an active agent. This improves the overall adhesion of the self-adhesive layer structure of the medical patch. The area of ​​the adhesive overlay is added to the overall size of the medical patch, but not to the release area. The adhesive overlay may include a self-adhesive polymer or a mixture of self-adhesive polymers selected from the group consisting of acrylic polymers, polyisobutylene, styrene-isoprene-styrene copolymers, polysiloxanes, and mixtures thereof, which may be identical or different from any polymer or polymer mixture included in the self-adhesive layer structure. The adhesive overlay includes an adhesive layer and a backing layer which may provide occlusive or non-occlusive properties. According to certain embodiments, the backing layer of the adhesive overlay provides non-occlusive properties.

[0036] Within the scope of this invention, the term "area weight" means g / m² 2 This refers to the dry weight of a specific layer, such as the active layer, provided in units. Area weight values ​​have tolerances of ±10%, ±7.5%, or ±5% due to manufacturing variations.

[0037] Unless otherwise specified, "%" means weight percentage.

[0038] Within the scope of the present invention, the term "polymer" (e.g., polymer I or II) refers to any substance consisting of so-called repeating units obtained by polymerizing one or more monomers, and includes homopolymers consisting of one monomer and copolymers consisting of two or more monomers. Polymers can be linear polymers, star polymers, comb polymers, brush polymers, or any monomer arrangement in the case of copolymers, such as alternating, statistical, 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 can have molecular weights of, for example, more than 2,000 daltons, more than 5,000 daltons, or more than 10,000 daltons. Correspondingly, compounds with molecular weights of less than 2,000 daltons, less than 5,000 daltons, or less than 10,000 daltons are usually called oligomers.

[0039] Within the scope of the present invention, the term "silicone polymer" refers to a non-hybrid polymer (i.e., a polymer that does not contain hybrid species) containing polysiloxanes. Polysiloxanes can be prepared from a solvent-free two-component system or from a solution in an organic solvent. There are two fundamentally different types of polysiloxanes: polysiloxanes having free silanol groups and amine-resistant polysiloxanes, which are distinguished in that the free silanol groups are derivatized with trimethylsilyl groups. The methyl groups can be completely or partially substituted with other alkyl radicals or phenyl radicals. The polysiloxanes used herein are synthesized from linear bifunctional oligomers and branched polyfunctional oligomers, the ratio of which determines the physical properties. A higher proportion of polyfunctional oligomers results in a higher degree of crosslinking, higher cohesiveness, and lower tackiness, while a lower proportion of polyfunctional oligomers results in higher tackiness and lower cohesiveness. The silicone polymer is preferably a mixture of high-viscosity and medium-viscosity, or high-viscosity and low-viscosity polysiloxanes. According to a particular embodiment, at least one silicone-based polymer is a silicone-based pressure-sensitive adhesive.

[0040] Within the scope of the present invention, the term "acrylic polymer" refers to an acrylate-based non-hybrid polymer. 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-octylacrylamide, and vinyl acetate.

[0041] Within the scope of the present invention, the term “silicone-acrylic hybrid polymer” refers to a silicone and acrylate-based hybrid polymer in the form of a pressure-sensitive adhesive. Silicone-acrylic hybrid pressure-sensitive adhesives are described, for example, in EP2599847 and WO2016 / 130408. It has been found that the arrangement of the silicone and acrylic phases, providing a continuous silicone or acrylic outer phase and a corresponding discontinuous internal phase, differs depending on the solvent in which the silicone-acrylic hybrid PSA is supplied. When the silicone-acrylic hybrid PSA is supplied in n-heptane, the composition comprises a continuous silicone outer phase and a discontinuous acrylic internal phase. When the silicone-acrylic hybrid PSA composition is supplied in ethyl acetate, the composition comprises a continuous acrylic outer phase and a discontinuous silicone internal phase.

[0042] Within the scope of the present invention, the term "natural or synthetic rubber" refers to elastomers obtained by polymerizing unsaturated hydrocarbons such as isoprene (2-methyl-1,3-butadiene) or by copolymerizing such hydrocarbons with styrene, butadiene, etc. This includes hydrocarbon polymers such as natural and synthetic polyisoprene, polybutylene, polyisobutylene, styrene / butadiene polymers, styrene-isoprene-styrene block copolymers, and butyl rubber; halogen-containing polymers such as polyacrylonitrile, polytetrafluoroethylene, polyvinyl chloride, polyvinylidene chloride, and polychlorodiene; and other copolymers thereof. In certain embodiments, the natural or synthetic rubber may be styrene triblock copolymer or polyisobutylene.

[0043] Within the scope of the present invention, the term "polyisobutylene" refers to a polymer obtained by polymerization of isobutene.

[0044] Within the scope of the present invention, the term "styrene-isoprene-styrene block copolymer" refers to a polymer obtained by living ion copolymerization by sequentially introducing styrene, 2-methyl-1,3-butadiene (isoprene), and styrene into a reactor. The styrene content typically varies between 15 and 40%.

[0045] Within the scope of the present invention, the term "silicone gel adhesive" refers to an elastic, gel-like material formed by lightly crosslinking a silicone polymer. This can be prepared from gel-forming compositions, as further described below, upon curing. In particular, silicone gel adhesives are formed upon curing of polysiloxanes containing reactive groups such as Si-H reactive groups and aliphatic unsaturated groups that react with each other in the presence of a hydrosilylation catalyst. According to certain embodiments, silicone gel adhesives are based on a polydimethylsiloxane network that can be formed by an addition reaction (hydrosilylation) between vinyl-functionalized polydimethylsiloxane groups (polymer) and a hydrogen-functionalized siloxane (crosslinking agent). Therefore, silicone gel adhesives are typically applied using a curable gel-forming (two-component) composition that solidifies upon curing.

[0046] Within the scope of the present invention, the term “saturated concentration” refers to the concentration of the active agent corresponding to an equilibrium state in which the solvent (i.e., polymer II of the skin contact layer) cannot dissolve any further solute (i.e., the active agent). As a result, the solid solute exists in equilibrium with the solid solution at a defined temperature (room temperature – the unmodified temperature determined in the laboratory where the experiment is conducted, typically within the range of 15–35°C, or approximately 18–25°C). The saturated concentration of the active agent can be expressed in weight percent based on the total weight of the active agent layer or the skin contact layer. The saturated concentration can be measured using, for example, the method described in Liu, P., Gargiulo, P., Wong, J., and Novartis. Pharm. Research. Vol. 14, p. 317 (1997) (referred to herein as the “sandwich method”). In this method, a multilayer laminate is prepared, comprising an upper protective layer and a lower protective layer sandwiching a donor layer and an acceptor layer separated by a partition membrane permeable to the active agent. The donor layer contains an excess of the active agent, while the acceptor layer contains substantially no active agent; therefore, the active agent diffuses from the donor layer through the partition membrane to the acceptor layer until it reaches a saturation concentration. The donor and acceptor layers are prepared from polymer II of the respective skin contact layer (or polymer I of the respective active agent-containing layer). The donor layer is supersaturated with the active agent, and the acceptor layer is prepared similarly to the donor layer but without the active agent. The prepared sandwich system is stored at room temperature for a period of time, e.g., 7 days, to allow the active agent to diffuse from the donor layer to the acceptor layer. Subsequently, the residual active agent concentration in the donor layer is measured by HPLC (high-performance liquid chromatography) to finally obtain the saturation concentration of the active agent in polymer II of the respective skin contact layer (or polymer I of the respective active agent-containing layer).

[0047] As used herein, the solubility parameter (SP) is defined as the sum of all intermolecular attractions that are empirically related to the degree of mutual solubility of chemical species as a numerical estimate. The most convenient way to determine the solubility parameter is the method of Hildebrand, which calculates the solubility parameter from data on molecular weight, boiling point, and density that are generally available for many substances. The formula is SP = (ΔE v / V) 1 / 2 where V = molecular weight / density and ΔE v = vaporization energy. For substances with too low vapor pressure to be detected, such as high molecular weight polymers, several methods have been developed that use the sum of the contributions of atoms and groups to vaporization. Such methods for calculating the solubility parameter of a material are described, for example, in Small, J. Applied Chem. Vol. 3, p. 71 (1953). The solubility parameters (calculated by the method of Small) of exemplary polymers useful in the implementation of the present invention are shown below: polydimethylsiloxane 14.9 MPa 1 / 2 , polyisobutylene 15.7 MPa 1 / 2 , polyethylene / butylene 16.2 MPa 1 / 2 , polyisoprene 16.6 MPa 1 / 2 , polyethylene 16.6 MPa 1 / 2 , polybutadiene 16.6 MPa 1 / 2 , polybutadiene-co-styrene (75 / 25 to 72 / 28) 17.4 MPa 1 / 2 , polystyrene 18.6 MPa 1 / 2 , polymethyl methacrylate 19.0 MPa 1 / 2 , polymethyl acrylate 19.8 MPa 1 / 2 .

[0048] Within the scope of the present invention, the term “soluble polyvinylpyrrolidone” refers to polyvinylpyrrolidone, also known as povidone, that is more than 10% soluble in at least ethanol, preferably water, polyvinylpyrrolidone, 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® 12PF, Kollidon® 17PF, Kollidon® 25, Kollidon® 30, and Kollidon® 90F, or povidone K90F, supplied by BASF. Different grades of Kollidon® are defined with respect to the K value, which reflects the average molecular weight of the polyvinylpyrrolidone grade. Kollidon® 12 PF features a K-value range of 10.2 to 13.8, corresponding to a nominal K-value of 12. Kollidon® 17 PF features a K-value range of 15.3 to 18.4, corresponding to a nominal K-value of 17. Kollidon® 25 features a K-value range of 22.5 to 27.0, corresponding to a nominal K-value of 25, and Kollidon® 30 features a K-value range of 27.0 to 32.4, corresponding to a nominal K-value of 30. Kollidon® 90F features a K-value range of 81.0 to 97.2, corresponding to a nominal K-value of 90. Preferred Kollidon® grades are Kollidon® 12 PF, Kollidon® 30, and Kollidon® 90F. 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 the USP monograph for "Povidone". For all grades and types of polyvinylpyrrolidone, the amount of peroxide is preferably within a certain limiting range, in particular, the amount of peroxide is 500 ppm or less, more preferably 150 ppm or less, and most preferably 100 ppm or less.

[0049] Within the scope of the present invention, the term "pentagonal shape" refers to the two-dimensional shape of the self-adhesive layer structure comprising the backing layer and the active layer, or the backing layer, the active layer, and the skin contact layer, as seen when the self-adhesive layer structure is viewed from above on the backing layer. In the sense of the present invention, a pentagonal shape is understood as any shape that can be formed by one pentagon or a collection of two or more pentagons. This means that a pentagonal shape according to the present invention does not have to have a pentagonal shape as a whole, but is composed of at least one pentagon. The vertices of the pentagon may be pointed or rounded. If two or more pentagons constitute a pentagonal shape, they may be integrally connected to each other, i.e., they may be separable only by cutting the self-adhesive layer structure, for example, or they may be separably connected to each other using perforations, for example. The backing layer and the active layer, or the backing layer, the active layer, and the skin contact layer, and optionally the films, are symmetry, i.e., they have the same planar extent and / or share the same boundary. In other words, the backing layer and the active layer, or the backing layer, the active layer and the skin contact layer, and optionally the film, each provide at least one congruent pentagonal shape.

[0050] Within the scope of the present invention, the term "pentagon" refers to a polygon with five sides. In a "convex pentagon," each of the five points (vertices) where two sides of the pentagon meet in pairs faces outward. Each 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 are connected by one of the five diagonals that lie inside the closed chain (boundary) of the convex pentagon.

[0051] A convex pentagon can also be described as a polygon with five sides, each having an interior angle (vertex angle) less than 180°. The sum of the interior angles of a simple (non-self-intersecting) pentagon is 540°. Therefore, a (convex) pentagon with each vertex angle equal to 108° is also called an equiangular pentagon. A (convex) pentagon with all sides of equal length is also called an equilateral pentagon. If a (convex) pentagon is both an equilateral and equiangular pentagon, it is also called a regular pentagon. If a (convex) pentagon has at least one of its five vertex angles of a different size and / or at least one of its five sides of a different length, it is referred to as a non-regular pentagon in this specification.

[0052] The (convex) pentagon may be symmetric, and in particular, mirror symmetry. In this context, mirror symmetry is also called reflective symmetry and is understood to mean symmetry with respect to reflection. The symmetric feature of such a two-dimensional shape is that when the shape is folded in half along the mirror axis, the two halves are identical, that is, the two halves are mirror images of each other. The preferred (convex) pentagon according to the present invention has at least one, in particular exactly one, axis of symmetry.

[0053] In the sense of the present invention, the terms “Type I pentagon” and “Type II pentagon” refer to a mirror-symmetric convex pentagon having exactly one axis of symmetry, two interior angles of 90°, and three interior angles of 120°, one of which is divided in the middle by the axis of symmetry. Furthermore, both “Type I pentagons” and “Type II pentagons” have a pair of sides of equal length, another pair of sides of equal length (which may be the same length or different lengths), and a remaining side divided by the central axis of symmetry (the remaining side may be the same length as or different from the pair of sides of equal length and / or the other pair of sides of equal length). Finally, unlike “Type II pentagons,” the pair of sides of equal length are parallel in “Type I pentagons” because the two 90° interior angles are adjacent (the sides are parallel to each other, as are the axis of symmetry).

[0054] Non-regular pentagons whose two interior angles sum to 180° can be combined to form tiles on a plane. Fifteen types of unihedral convex pentagon tilings are known, the most recent of which was discovered in 2015 (Figure 1; from top to bottom: columns 1, 2, and 3): -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 -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

[0055] This list was shown to be complete by Rao in 2017 (Rao, Michael: "Exhaustive search of convex pentagons which tile the plane.").

[0056] Pentagonal tiling, also known as pentagonal tessellation, is a tiling of a plane in which each piece is shaped like a pentagon. Regular pentagons do not tile the Euclidean plane, but three pentagons can tile a sphere, and four or more pentagons can tile a hyperboloid. The above types of pentagons that can tile the Euclidean plane with a single tile (i.e., with one type of tile) are generally symmetrical, but there are special cases that have mirror symmetry. For example, the Type I pentagon of the present invention is a mirror-symmetric case of Type I, and the Type II pentagon is a mirror-symmetric case of Type III or Type IV. A Type I pentagon in which the lengths of the sides of one pair of equal-length parallel sides and the remaining side are √3 times the lengths of the other pair of equal-length parallel sides can tile the Euclidean plane with prism pentagonal tiling (Figure 2a). A type II pentagon in which the length of the remaining side is √3-1 times the length of the side of one pair of equal sides, and √3-1 times the length of the side of another pair of equal sides, can tile the Euclidean plane with Cairo pentagon tiling (Figure 2b).

[0057] Furthermore, pentagons have a special relationship with hexagons because some 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, where the length of one pair of equal parallel sides is half the length of the other pair of equal sides, and the length of the remaining side is √3 times the length of the other pair of equal sides, can provide a monohedral pentagonal tiling by overlapping regular hexagons, each containing two pentagons. Similarly, a type II pentagon, where the length of one pair of equal sides is half the length of the remaining side, and the length of the other pair of equal sides is 2 / √3 times the length of the remaining side, can provide a monohedral pentagonal tiling by overlapping regular hexagons, each containing three pentagons.

[0058] In this context, the term "hexagon" refers to a polygon with six sides. In a "regular hexagon," all sides are of equal length, and the angles at all vertices are equal to 120°. A regular hexagon is mirror symmetry with six axes of symmetry, and furthermore, it is rotationally symmetry of degree 6, as it looks the same when partially rotated by an angle of 60°.

[0059] Within the scope of the present invention, the term "tiling a plane" is understood to mean covering a specific plane (flat or curved surface) without gaps. Tiling a plane can be carried out whether or not the adjacent self-adhesive layer structures according to the present invention overlap. Preferably, overlaps should be avoided as much as possible.

[0060] Within the scope of the present invention, the term “sheet of medical patches” refers to a number of medical patches sharing a common release liner. Each medical patch represents an individual dose unit that can be applied to a patient’s skin after being removed from the release liner. The amount of active agent in a medical patch refers to the amount of active agent contained in the self-adhesive layer structure of the medical patch. The amount of active agent in a sheet of medical patches refers to the total amount of active agent contained in all the self-adhesive layer structures of the medical patches constituting the sheet of medical patches. Therefore, the release area of ​​a medical patch refers to the area provided by the self-adhesive layer structure of the medical patch, and the release area of ​​a sheet of medical patches refers to the area provided by all the self-adhesive layer structures of the medical patches constituting the sheet of medical patches.

[0061] Within the scope of the present invention, the term “release liner” refers to a removable protective layer attached to the active layer or skin contact layer of a self-adhesive layer structure. The release liner may have any suitable two-dimensional geometric shape, preferably polygonal, particularly rectangular or square. According to certain embodiments, the area of ​​the release liner encompasses the total area of ​​all self-adhesive layer structures of the medical patch constituting the sheet of medical patches. According to the present invention, the release liner has the same extent as the self-adhesive layer structures or extends beyond the boundaries formed by all self-adhesive layer structures in all directions; that is, the polygonal chain formed by the outer edges of the pentagons of the self-adhesive layer structures is entirely located within or on the polygonal chain formed by the edges of the release liner. Suitable release liners may be polyethylene terephthalate (PET) or polypropylene (PP) films, optionally coated with silicone or fluoropolymer. This includes commercially available release liners such as 3M's Scotchpak® release liners 9741 / 9742 / 9744.

[0062] Within the scope of the present invention, the term “weakened” refers to the result of any action (weakening) that allows for easier separation of two sections of a self-adhesive layer structure or two different self-adhesive layer structures, even though the two sections / self-adhesive layer structures remain connected to each other. Such weakening may include, but is not limited to, folding, scratching, perforating, piercing, puncturing, punching, or cutting. According to certain embodiments, weakening is carried out by perforation. In this context, the term “perforated” is understood to mean having a small hole. Perforation may be achieved, for example, by needling or laser cutting.

[0063] Within the scope of the present invention, the term “fastening bridge” refers to a single point between two, three, or four self-adhesive layer structures, particularly between two, three, or four pentagonal shapes, such as two, three, or four convex pentagons, where the main portion of the common edge is cut or weakened, but the layer structures remain connected. This is preferably achieved by leaving a connection during a separation process, which may be carried out, for example, by punching or cutting. The fastening bridge(s) allow for the jointed peeling of the self-adhesive layer structures from the release liner. In addition, the fastening bridge(s) are preferably very thin so that they can be easily cut, for example, by pulling on a portion of the self-adhesive layer structure to separate it from the others.

[0064] Within the scope of the present invention, the term “patient” refers to a person who exhibits specific symptoms or clinical signs of symptoms that suggest the need for treatment, a person who is receiving preventive or prophylactic treatment for a condition, or a person who has been diagnosed with a condition that requires treatment. Preferably, the patient suffers from neuropathic pain, or mixed pain of neuropathic pain and / or nociceptive pain, such as arthralgia or cancer pain.

[0065] The term "neuropathic pain" refers to pain caused by lesions or diseases of the somatosensory nervous system. In this context, the term "chronic neuropathic pain" is understood to mean neuropathic pain that lasts for at least three months. When suffering from neuropathic pain, most patients complain of continuous or intermittent spontaneous pain, such as burning, stabbing, or pressure, which may be triggered particularly by light touch or cold. Ectopic activity in nerve endings, compressed nerves or nerve roots, dorsal root ganglia, and the thalamus can cause spontaneous pain in a variety of situations. Neuropathic pain includes peripheral neuropathic pain, which particularly affects peripheral nerves, i.e., nerves outside the brain and spinal cord. In particular, neuropathic pain in the sense of this invention relates to postoperative neuropathic pain, postherpetic neuralgia, and neuropathic pain associated with diabetic peripheral neuropathy of the hands and feet.

[0066] In this context, the term “postoperative neuropathic pain” is understood to mean chronic pain that develops after a surgical procedure and persists beyond the healing process, i.e., for at least three months after surgery. The pain may be localized to the surgical or injured site, radiate to the area innervated by the nerves located at that site, or radiate to dermatomes (after surgery or injury to deep somatic or visceral tissues). Chronic postoperative pain is a result of nerve damage and may be due to the surgery itself or other causes of pain, including infection or malignancy.

[0067] In this context, the term “postherpetic neuralgia” is also understood as postherpetic neuralgia and refers to pain that occurs when nerves are damaged by a past infection with herpes zoster, commonly known as shingles. The symptoms of postherpetic neuralgia are limited to or localized to the skin area where shingles developed, particularly the band-like area of ​​the trunk, and usually appear on one side of the body. Less common symptoms of postherpetic neuralgia include itching, numbness, or a “prickly sensation.”

[0068] In this context, the term "diabetic peripheral neuropathy," also known as "diabetic neuropathy," is understood to mean pain that occurs when nerves are damaged as a result of diabetes. Diabetic neuropathy can affect any nerve, but it is most commonly felt in the extremities, such as the hands and feet.

[0069] Within the scope of the present invention, the term “arthralgia” refers to joint symptoms such as discomfort, pain, or distress in any of the joints of a patient’s body, including the joints of the spine, shoulders, hips, elbows, and knees. This includes, in particular, arthralgia caused by arthritis, such as osteoarthritis. In this context, the term “osteoarthritis” is understood to mean a degenerative disease characterized by cartilage erosion, bone hypertrophy, subchondral sclerosis, and changes in the synovial membrane and joint capsule. Clinically, it is characterized by joint pain, stiffness, and functional limitations. While pain in osteoarthritis has traditionally been considered nociceptive, some patients also suffer from neuropathic pain. Specifically, arthralgia may be knee pain, elbow pain, hip pain, shoulder pain, hand or foot pain, or back (hip) pain.

[0070] In the context of this invention, the term "cancer pain" refers to nerve damage caused by cancer itself, and / or neuropathic cancer pain caused by treatments such as chemotherapy, radiation therapy, and surgery. Cancer pain caused by the tumor itself usually includes both nociceptive and neuropathic components, and mixed pain is more common than neuropathic cancer pain caused by cancer treatment. Most cancer pain caused by chemotherapy is purely neuropathic. Neuropathic cancer pain is nerve-related (typically neuronal) pain characterized as burning or electrical sensations, but may also manifest as decreased sensation or actual muscle weakness.

[0071] Within the scope of the present invention, the term "coating composition" refers to a composition comprising all components of the active layer or the skin contact layer, which may be coated onto a backing layer or release liner to form the active layer and the skin contact layer upon drying.

[0072] Within the scope of the present invention, the term "dissolve" refers to the process of obtaining a transparent solution that is free of any visible particles.

[0073] Within the scope of the present invention, the term "crosslinking" refers to the process of crosslinking functional groups contained in an inactive coating composition.

[0074] Within the scope of the present invention, and unless otherwise specified, the term “about” refers to an amount that is ±10% of the disclosed amount. In some embodiments, the term “about” refers to an amount that is ±5% of the disclosed amount. In some embodiments, the term “about” refers to an amount that is ±2% of the disclosed amount. [Brief explanation of the drawing]

[0075] [Figure 1] This shows 15 known pentagonal tilings that have convex pentagons. [Figure 2a] This shows a prism pentagon tiling with type I pentagons. [Figure 2b] This shows a Cairo pentagon tiling with a Type II pentagon. [Figure 3a] An exemplary pattern of a medical patch sheet according to the present invention is shown, in which the self-adhesive layer structure is a type I pentagon. [Figure 3b] Another exemplary pattern of the medical patch sheet according to the present invention is shown, in which the self-adhesive layer structure is a type I pentagon. [Figure 3c] An exemplary pattern of a medical patch sheet according to the present invention is shown, in which the self-adhesive layer structure is a double pentagon formed from two identical Type I pentagons that share two adjacent vertices and a common edge. [Figure 3d] Another exemplary pattern of the medical patch sheet according to the present invention is shown, in which the self-adhesive layer structure is a double pentagon formed from two identical Type I pentagons that share two adjacent vertices and a common edge. [Figure 3e] An exemplary pattern of a medical patch sheet according to the present invention is shown, in which the self-adhesive layer structure is selected from a type I pentagon and a double pentagon formed from two identical type I pentagons that share two adjacent vertices and a common edge. [Figure 3f]Another exemplary pattern of a medical patch sheet according to the present invention is shown, in which the self-adhesive layer structure is selected from a type I pentagon and a double pentagon formed from two identical type I pentagons that share two adjacent vertices and a common edge. [Figure 4a] An exemplary pattern of a medical patch sheet according to the present invention is shown, where the self-adhesive layer structure is a type I pentagon arranged in a regular hexagonal shape, each containing two self-adhesive layer structures. [Figure 4b] An exemplary pattern of a medical patch sheet according to the present invention is shown, in which the self-adhesive layer structure is a type II pentagon uniformly arranged in the shape of a regular hexagon, each containing three self-adhesive layer structures. [Figure 4c] An exemplary pattern of a medical patch sheet according to the present invention is shown, where the self-adhesive layer structure is a type II pentagon uniformly arranged in the shape of a regular hexagon, each containing three self-adhesive layer structures and / or each containing nine self-adhesive layer structures. [Figure 4d] An exemplary pattern of a medical patch sheet according to the present invention is shown, in which the self-adhesive layer structure is a type II pentagon unevenly arranged in a regular hexagonal shape, each containing three self-adhesive layer structures. [Figure 5a] The image shows a portion of an exemplary pattern of a medical patch sheet according to the present invention, in which the self-adhesive layer structures are Type I pentagons connected to one another by common fastening bridges, and all adjacent self-adhesive layer structures are connected to each other in groups of three by common fastening bridges located at common vertices. [Figure 5b] The image shows a portion of an exemplary pattern of a medical patch sheet according to the present invention, in which the self-adhesive layer structures are Type II pentagons arranged in a regular hexagonal shape and connected to one another by common fastening bridges, and all adjacent self-adhesive layer structures are connected to each other in groups of three by common fastening bridges provided at common vertices or common vertices located on the edges. [Modes for carrying out the invention]

[0076] Self-adhesive layer structure The present invention relates to a self-adhesive layer structure for use in medical patches, particularly for administering active agents contained therein. In some embodiments, the self-adhesive layer structure is a pressure-sensitive adhesive layer structure.

[0077] The self-adhesive layer structure according to the present invention, in particular the pressure-sensitive adhesive layer structure, has a pentagonal shape, A) Backing layer, B) An active layer containing polymer I and an active agent, Includes, The backing layer and the active layer have the same extent, providing a pentagonal shape for the self-adhesive layer structure.

[0078] In certain embodiments, the self-adhesive layer structure is A) Backing layer, B) An active layer containing polymer I and an active agent, C) a skin contact layer; Includes, The backing layer, active layer, and skin contact layer have the same extent, providing a pentagonal shape for the self-adhesive layer structure. In such embodiments, the self-adhesive layer structure may or may not include a membrane located between the active layer and the skin contact layer. The membrane is preferably a rate-limiting membrane.

[0079] In certain embodiments, the aforementioned layers of the self-adhesive layer structure according to the present invention are directly attached to each other, i.e., the backing layer is directly attached to the active layer, and optionally the active layer is directly attached to an additional skin contact layer. Alternatively, the active layer is directly attached to a film, and the film is directly attached to an additional skin contact layer on the opposite side. In other words, the self-adhesive layer structure according to the present invention comprises its layers in the order of (1) backing layer, (2) active layer, and optionally (3) skin contact layer, or (1) backing layer, (2) active layer, optionally (3) film, and optionally (4) skin contact layer.

[0080] An additional skin contact layer is preferably provided to ensure adhesion between the self-adhesive layer structure and the patient's skin during administration. If the self-adhesive layer structure according to the present invention does not include an additional skin contact layer, sufficient adhesion between the self-adhesive layer structure and the patient's skin during administration is provided by other means, such as an active layer and / or adhesive overlay.

[0081] The backing layer is substantially impermeable to active agents in particular. The backing layer is preferably made of a polyester film or an ethylene vinyl acetate copolymer with a thickness of 10 to 20 μm.

[0082] In certain embodiments, the self-adhesive layer structure is for transdermal or topical delivery of the active drug.

[0083] The self-adhesive layer structure according to the present invention can be used in matrix-type medical patches or reservoir-type medical patches, preferably in matrix-type medical patches. In a particular embodiment, the self-adhesive layer structure according to the present invention is used in a matrix-type medical patch, in which the active agent is uniformly dissolved and / or dispersed in a polymer carrier, i.e., the matrix, and together with the active agent and optionally further additives, forms a matrix layer. Therefore, the active layer is preferably an active matrix layer. Therefore, in a particular embodiment of the self-adhesive layer structure according to the present invention, the active layer is (i) Polymer I and (ii) Active agent and, This is an active matrix layer containing [a specific component].

[0084] In certain embodiments, the self-adhesive layer structure according to the present invention is for use in microreservoir type medical patches. Therefore, the active layer is a microreservoir active layer, particularly, (i) an outer phase containing polymer I, (ii) The inner phase containing the active agent, It has, It is preferable that the inner phase is a dry, biphasic layer in which precipitates dispersed within the outer phase are formed.

[0085] The self-adhesive layer structure according to the present invention is typically located on a removable protective layer (release liner), which is removed immediately before application to the patient's skin surface. Therefore, the self-adhesive layer structure or medical patch may further include a release liner. Such a protected self-adhesive layer structure or medical patch is typically housed in a seam-sealed pouch. The packaging may be designed to be safe for children and / or easy to handle for the elderly.

[0086] active layer As outlined in more detail above, the self-adhesive layer structure according to the present invention includes, in particular, an active layer, which is, (i) Polymer I and (ii) Active agent and, Includes.

[0087] The active agent is preferably uniformly dispersed within the active layer. In certain embodiments, the active layer is an active matrix layer, and more particularly, a microreservoir active layer.

[0088] Therefore, in a particular embodiment of the self-adhesive layer structure, the active layer is (i) an outer phase containing polymer I, (ii) The inner phase containing the active agent, It has, The inner phase is a dry, biphasic layer in which precipitates are dispersed within the outer phase. In certain embodiments, the outer phase is hydrophobic and the inner phase is hydrophilic.

[0089] The outer phase of the dried two-phase layer preferably has a composition containing 75% to 100% polymer I. The inner phase preferably has a composition containing an active agent and a hydrophilic agent that forms a solution together with the active agent. The hydrophilic agent may be a hydrophilic polymer or a polymer mixture, and is specifically selected from the group consisting of polyvinylpyrrolidone, vinylcaprolactam, copolymer of vinyl acetate and ethylene glycol, copolymer of vinylpyrrolidone and vinyl acetate, copolymer of ethylene and vinyl acetate, polyethylene glycol, polypropylene glycol, acrylic polymer, and modified cellulose, all having a K value of 10 to 200.

[0090] The dried two-phase layer further contains an interfacial mediator having a kinematic viscosity of 10 cSt to 100,000 cSt, particularly at 25°C. The interfacial mediator can be present in amounts of 0.1% to 3.5% in the dried two-phase layer and is used to reduce the maximum droplet size of dispersed precipitates of the inner phase in the outer phase within the dried two-phase layer. While we do not wish to be bound by any particular theory, this effect is thought to fill voids at the interface between the dispersed inner and outer phases, thereby increasing the compatibility of the two distinct phases and promoting maximum separation / dispersion of the inner phase in the outer phase. Suitable interfacial mediators include, for example, silicone oils.

[0091] Polymer I contained in the active layer provides sufficient cohesive force to the active layer. According to certain embodiments, polymer I can also provide sufficient adhesion of the self-adhesive layer structure to the patient's skin during administration. In those embodiments, polymer I is selected from pressure-sensitive adhesive polymers. Thus, in preferred embodiments of the present invention, polymer I is a pressure-sensitive adhesive polymer.

[0092] Suitable polymers for polymer I according to the present invention may be selected from silicone polymers, acrylic polymers, silicone-acrylic hybrid polymers, and natural or synthetic rubber-based polymers such as polyisobutylene or styrene-isoprene-styrene block copolymers. These will be described in more detail below. In certain embodiments, the polymer is selected from silicone polymers. In certain embodiments, the polymer is a silicone polymer obtained by polycondensation of silanol-termined polydimethylsiloxane and silicate resin.

[0093] Furthermore, in certain embodiments, the area weight of the active layer is 20-400 g / m². 2 30-200g / m 2 , or 50-120 g / m 2 It is within the range.

[0094] Active drug According to the present invention, the self-adhesive layer structure includes an active layer containing an active agent.

[0095] The active agent may be any compound responsible for the therapeutic effect of the medical patch containing a self-adhesive layer structure. In particular, the active agent may be a topical or systemic active agent. In certain embodiments, the active agent is at least one analgesic. Suitable analgesics include, for example, buprenorphine, capsaicin, diclofenac, fentanyl, ibuprofen, or lidocaine.

[0096] According to certain embodiments, the active agent is a TRPV1 agonist such as capsaicin.

[0097] In one embodiment, the active agent is capsaicin. Therefore, the self-adhesive layer structure is A) Backing layer, B) The active layer, (i) Polymer I and (ii) Capsaicin and, An active layer containing, It may include.

[0098] In particular, the self-adhesive layer structure contains a therapeutically effective amount of capsaicin. In certain embodiments, the self-adhesive layer structure contains capsaicin in amounts of 0.5 to 180 mg, 1.2 to 90 mg, or 19 to 45 mg. In some embodiments, the self-adhesive layer structure contains capsaicin in amounts of about 179 mg. In other embodiments, the self-adhesive layer structure contains capsaicin in amounts of about 90 mg, about 60 mg, about 45 mg, about 30 mg, about 20 mg, about 10 mg, or about 1 mg.

[0099] Therefore, the specific active layer according to the present invention is (i) Polymer I and (ii) Capsaicin and, Includes.

[0100] The active layer contains at least 0.30 mg / cm² per release area. 2 at least 0.50 mg / cm³ 2 , or at least 0.60 mg / cm³ 2 Capsaicin, and / or 1.0 mg / cm² per release area. 2 Less than 0.8 mg / cm³ 2 Less than 0.7 mg / cm³ 2 It may contain less than 0.30 mg / cm² of capsaicin per release area. In particular, the active layer may contain 0.30 mg / cm². 2 ~1.0 mg / cm³ 2 , 0.30 mg / cm³ 2 ~8.0 mg / cm², 0.50 mg / cm² 2 ~8.0 mg / cm³ 2 , 0.60 mg / cm³ 2 ~0.8 mg / cm³ 2 , or 0.60 mg / cm³ 2 ~0.7 mg / cm³ 2 It contains capsaicin.

[0101] In certain embodiments, the active layer contains capsaicin in amounts of 2-20% by weight, 5-15% by weight, or 5-10% by weight. In certain embodiments, the active layer contains capsaicin in amounts of about 8% by weight.

[0102] Furthermore, the active layer may contain at least one silicone-based polymer in an amount of 20-90% by weight or 60-90% by weight, based on the total weight of the active layer. It should be understood that the aforementioned weight percentages refer to the total amount of at least one silicone-based polymer. For example, if two types of silicone-based polymers are present, their total amount in the active layer will be 20-90% by weight or 60-90% by weight, based on the total weight of the active layer.

[0103] Therefore, in one embodiment, the self-adhesive layer structure is for transdermal or topical delivery of capsaicin, and in particular for topical delivery of capsaicin.

[0104] Capsaicin ((6E)-N-[(4-hydroxy-3-methoxyphenyl)methyl]-8-methylnona-6-enamide) is the main bioactive component of chili peppers and is an alkaloid found in the Capsicumaceae family. It is a potent agonist of transient receptor potential cation channel subfamily V member 1 (TRPV1), which is well known as a vanilloid receptor. By binding to the TRPV1 receptor, the capsaicin molecule produces a sensation similar to injury caused by excessive heat or abrasion. Capsaicin has a role as a non-narcotic analgesic and is currently used to treat several pain syndromes, such as neuropathic pain. Such pain is thought to arise from sensitization reactions in the peripheral and central nervous systems and can occur as a result of peripheral injury or as a result of systemic diseases, such as HIV, herpes zoster syphilis, autoimmune diseases, and diabetes. Furthermore, capsaicin has been shown to have beneficial effects on pain relief in osteoarthritis due to its high ability to inhibit the release of substance P, a potent neuropeptide pain modulator, from sensory nerves to the central nervous system. In addition, it has been suggested that capsaicin can kill cancer cells by inducing apoptosis.

[0105] The activator, particularly capsaicin, can be present in the active layer in amounts of 1–25% by weight, 2–20% by weight, or 5–10% by weight. skin contact layer

[0106] As outlined in more detail above, the self-adhesive layer structure according to the present invention may further include a skin contact layer. In this case, the backing layer, the active layer, and the skin contact layer have the same extent and provide a pentagonal shape for the self-adhesive layer structure. In certain embodiments, the skin contact layer is an adhesive, particularly a pressure-sensitive adhesive, which provides adhesion between the self-adhesive layer structure and the patient's skin during administration.

[0107] Surprisingly, self-adhesive layer structures, which include a skin contact layer in which the active agent is poorly soluble and preferably directly attached to the active layer, have advantageous properties in terms of reducing skin irritation, while simultaneously improving drug delivery behavior and adhesion. In particular, because the active agent is poorly soluble, for example, with a saturation concentration in the skin contact layer of less than 0.1%, only a very small amount of the active agent is present on the surface of the skin contact layer, and therefore the medical patch has advantageous properties in terms of undesirable skin reactions, thereby enabling safe application and / or removal. Thus, such a self-adhesive layer structure has a skin contact layer in which the saturation concentration of the active agent is negligible, and a separate active layer (not in contact with the skin), thus preventing the release of the active agent before and / or after the self-adhesive layer structure is applied to and maintained on the patient's skin. On the other hand, it has been shown that such a self-adhesive layer structure with a skin contact layer can still provide sufficient drug delivery and enable faster release of activity.

[0108] Therefore, such self-adhesive layer structures including a skin contact layer are characterized in particular by low solubility of the active agent in the skin contact layer, and in certain embodiments, the saturation concentration of capsaicin in the skin contact layer is preferably less than 0.1% by weight, as measured 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 relates to the amount of active agent present in the skin contact layer based on the total weight of the skin contact layer.

[0109] In certain embodiments, the saturation concentration of the active agent in the skin contact layer is less than the concentration of the active agent that would cause unintended adverse effects, such as skin irritation, upon short-term contact. Such concentrations can be empirically determined by in vivo testing by observing whether or not adverse effects, such as any form of skin irritation (redness, erythema, itching, or other skin reactions), occur after applying a model adhesive layer having a defined capsaicin concentration to the skin for a short period, e.g., 5 seconds, 10 seconds, 30 seconds, or 1 minute. In particular, the highest acceptable saturation concentration that does not yet cause unintended adverse effects, such as skin irritation, can be determined by testing different model layers representing a range of active agent concentrations. On the other hand, whether a medical patch having a set of active agent and skin contact layer results in a saturation concentration that does not cause any adverse effects can be simply determined (without using a range of different concentrations) by testing a model adhesive layer saturated with the active agent, or by applying such a medical patch to the skin as outlined above.

[0110] The skin contact layer may protect the active agent contained in the active layer from the skin of the patient or other person applying / removing the patch before and / or after application of the medical patch. Therefore, the skin contact layer must be substantially free of the active agent. This means that the skin contact layer is usually manufactured as a layer that does not contain the active agent. On the other hand, due to the concentration gradient, the active agent may normally migrate from the active layer to the skin contact layer over time until equilibrium is reached. However, this migration is limited by the saturation concentration of the active agent in the skin contact layer. In certain embodiments, the skin contact layer does not allow the active agent to be present at a concentration exceeding 0.1% by weight.

[0111] Therefore, in certain embodiments, the skin contact layer contains less than 0.1% by weight of the active agent based on the total weight of the skin contact layer. In certain embodiments, the skin contact layer contains less than 0.01% by weight of the active agent based on the total weight of the skin contact layer.

[0112] According to certain embodiments, the skin contact layer contains polymer II. Polymer II in the skin contact layer has a decisive effect on adhesion and further reduces skin irritation due to its elasticity. In certain embodiments, the skin contact layer contains polymer II in an amount of at least 95% by weight, at least 99% by weight, or about 100% by weight, based on the total weight of the skin contact layer. In particular, the skin contact layer may consist essentially of polymer II. It should be understood that the aforementioned weight percentage amounts refer to the total amount of polymer II. For example, if polymer II is a mixture of polymers, the total amount in the skin contact layer is 50-100% by weight, based on the total weight of the skin contact layer.

[0113] A suitable polymer for Polymer II according to the present invention is, in particular, a polymer that can concentrate the active agent to 0.1% by weight or less, 0.05% by weight or less, 0.02% by weight or less, or 0.01% by weight or less, i.e., a polymer in which the active agent is substantially insoluble. Therefore, according to certain embodiments, Polymer II may be a polymer or a mixture of polymers in which the active agent is substantially insoluble.

[0114] Therefore, the solubility parameter of polymer II may differ from that of the active agent, and in particular, it may be at least 5.0 MPa lower than that of the active agent. 1 / 2 at least 6.0 MPa 1 / 2 at least 8.0 MPa 1 / 2 , or at least 10.0 MPa 1 / 2 It may be lower than that. In particular, the solubility parameter of polymer II is preferably 18.5 MPa, as calculated by Small's method. 1 / 2 Less than 18.0 MPa 1 / 2 Less than 17.5 MPa 1 / 2 Less than 17.0 MPa 1 / 2 Less than 16.0 MPa 1 / 2 Less than 15.0 MPa 1 / 2 It may be less than.

[0115] Polymer II can be selected from pressure-sensitive adhesive polymers. Therefore, in certain embodiments, Polymer II may be a pressure-sensitive adhesive or a mixture of pressure-sensitive adhesives.

[0116] In certain embodiments, Polymer II may be a polymer or mixture of polymers selected from the group consisting of silicone-acrylic hybrid polymers, silicone-based polymers, silicone gel adhesives, and natural rubber or synthetic rubber-based polymers. These will be described in more detail below. In particular, Polymer II may be a polymer or mixture of polymers selected from the group consisting of silicone-based polymers and silicone gel adhesives. In some embodiments, Polymer II may be a silicone gel adhesive. Such a self-adhesive layer structure includes an additional skin-contact layer containing the silicone gel adhesive, which improves adhesion when applied to the patient's skin and can be removed cleanly and painlessly. If necessary, for example, when moving to another location, the self-adhesive layer structure can be peeled off and reapplied without losing its adhesiveness.

[0117] Furthermore, Polymer II may be a polymer or mixture of polymers selected from silicone polymers, particularly polysiloxane-based polymers such as amine-compatible polysiloxanes, or Polymer II may be a polymer or mixture of polymers selected from natural rubber or synthetic rubber, particularly styrene triblock copolymers and / or polyisobutylene such as SIS block copolymers and / or polyisobutylene.

[0118] A preferred polymer II according to the present invention is commercially available under the trade name Soft skin adhesives (a two-component silicone adhesive that hardens when two components are mixed). Alternatively, a preferred polymer II according to the present invention is commercially available under the trade names BIO-PSA (a pressure-sensitive adhesive based on polysiloxane), JSR-SIS (a pressure-sensitive adhesive based on SIS block copolymer), and Oppanol™ (polyisobutylene).

[0119] Additionally, for example, additional polymers may be added to enhance the adhesion of the skin contact layer.

[0120] According to some embodiments, polymer II contained in the skin contact layer is different from polymer I contained in the active layer. According to other embodiments, polymer II contained in the skin contact layer is the same as polymer I contained in the active layer.

[0121] According to a particular embodiment, the area weight of the skin contact layer is 80-500 g / m². 2 This is possible. In certain embodiments, the skin contact layer may be 100-350 g / m². 2 , 150~320g / m 2 , or 180-280g / m 2 It may have an area weight.

[0122] Silicone polymers Suitable silicone polymers are non-curing polymers, typically applied by hot-melt or solvent-based processes, and preferably do not undergo further curing to solidify.

[0123] Silicone polymers are based on polysiloxanes; therefore, they are also called polysiloxane-based polymers. Silicone polymers are generally obtained by polycondensation of silanol-termined polydimethylsiloxane with silicate resins. Amine-compatible silicone polymers can be obtained by reacting the silicone polymer with trimethylsilyl (e.g., hexamethyldisilazane) to reduce the silanol content of the polymer, thereby improving its stability in the presence of amines. As a result, the residual silanol functionality is capped at least partially, preferably mostly or completely, with trimethylsiloxy groups.

[0124] Therefore, in certain embodiments, the silicone polymer is an amine-compatible polysiloxane, preferably obtained by polycondensing a silanol-termined polydimethylsiloxane with a silicate resin, and then at least partially trimethylsilylation of the remaining silanol functionality.

[0125] In certain embodiments, the silicone polymer is a pressure-sensitive adhesive or a mixture of pressure-sensitive adhesives, i.e., a polysiloxane-based pressure-sensitive adhesive or a mixture of polysiloxane-based pressure-sensitive adhesives.

[0126] Polysiloxane-based pressure-sensitive adhesives offer appropriate viscosity, rapid adhesion to various skin types including moist skin, suitable adhesive and cohesive properties, long-term adhesion to skin, high flexibility, moisture permeability, and compatibility with many active agents and film-substrates. Such pressure-sensitive adhesives are based on the resin-in-polymer concept, where the polysiloxane-based pressure-sensitive adhesive is prepared by the condensation reaction of silanol-termined polydimethylsiloxane with a silica resin (also called a silicate resin). For amine stability, residual silanol functionalities are additionally capped with trimethylsiloxy groups. The content of silanol-termined polydimethylsiloxane contributes to the viscous element of the viscoelastic behavior and affects the wetting and diffusion properties of the adhesive. The resin acts as a tackifier and reinforcing agent, participating in the elastic element. A proper balance between silanol-termined polydimethylsiloxane and the resin provides appropriate adhesive properties.

[0127] As previously shown, the tackiness of silicone polymers can be altered by the resin-to-polymer ratio, i.e., the ratio of silanol-termined polydimethylsiloxane to silicate resin, preferably in the range of 50:50 to 70:30 or 55:45 to 65:35. Tackiness increases as the amount of polydimethylsiloxane relative to the resin increases. High-viscosity silicone polymers preferably have a resin-to-polymer ratio of 55:45, medium-viscosity silicone polymers preferably have a resin-to-polymer ratio of 60:40, and low-viscosity silicone polymers preferably have a resin-to-polymer ratio of 65:35.

[0128] According to certain embodiments, the pressure-sensitive adhesive may be obtained by polycondensation of silanol-terminated polydimethylsiloxane and silicate resin, preferably with a resin-to-polymer ratio of 50:50 to 70:30, or 55:45, 60:40, or 65:35. Thus, in one embodiment, the silicone polymer is a mixture of pressure-sensitive adhesives obtained by polycondensation of silanol-terminated polydimethylsiloxane and silicate resin, with a resin-to-polymer ratio of 55:45 or 60:40.

[0129] Furthermore, according to certain embodiments, the silicone polymer is The solution viscosity at 25°C and with a solid content of approximately 60% in heptane is 450 mPa·s and / or 0.01 rad / s, and the complex viscosity at 30°C is 1 × 10⁻⁶ 8 Poise, The solution viscosity at 25°C and with a solid content of approximately 60% in heptane is 500 mPa·s and / or 0.01 rad / s, and the complex viscosity at 30°C is 5 × 10⁻⁶. 6 It is a mixture of pressure-sensitive adhesives, known as poise.

[0130] Polysiloxane-based pressure-sensitive adhesives are supplied and used in a solvent such as n-heptane, ethyl acetate, or other volatile silicone fluids. The solids content of the polysiloxane-based pressure-sensitive adhesive in the solvent is typically 60–85%, preferably 70–80% or 60–75%. Those skilled in the art recognize that the solids content can be altered by adding an appropriate amount of solvent.

[0131] The high-viscosity silicone polymer preferably has a complex viscosity of about 5 × 10 at 0.01 rad / s and 30°C. 6 The poise, medium viscosity silicone polymer preferably has a complex viscosity of about 5 × 10 at 30°C and a viscosity of 0.01 rad / s. 7 The poise, low-viscosity silicone polymer preferably has a complex viscosity of about 5 × 10 at 30°C and a viscosity of 0.01 rad / s. 8It is a poise polymer. The high viscosity amine-compatible silicone polymer preferably has a complex viscosity of about 5 × 10 at 30°C and a viscosity of 0.01 rad / s. 6 A poise, medium viscosity amine-compatible silicone polymer is preferably 0.01 rad / s and has a complex viscosity of about 5 × 10 at 30°C. 8 The poise, low-viscosity amine-compatible silicone polymer preferably has a complex viscosity of about 5 × 10 at 30°C and a viscosity of 0.01 rad / s. 9 It is poise. The preferred polysiloxane-based pressure-sensitive adhesive according to the present invention is characterized by a solution viscosity at 25°C and with a solids content of 60% in n-heptane, which is preferably greater than about 150 mPa·s, or between about 200 mPa·s and about 700 mPa·s, measured using a Brookfield RVT viscometer with spindle #5 at 50 RPM. These also have a viscosity of about 1 x 10 at 0.01 rad / s at 30°C. 9 Less than poise, or about 1 x 10⁻¹⁰ 5 ~approximately 9x10 8 The complex viscosity of Poise may also be a characteristic feature.

[0132] Suitable silicone polymers are commercially available under the trade name BIO-PSA. Examples of commercially available silicone PSA compositions include the standard Liveo® BIO-PSA series (7-4400, 7-4500, and 7-4600 series) and the amine-compatible (end-capped) Liveo® BIO-PSA series (7-4100, 7-4200, and 7-4300 series), which are manufactured in n-heptane or ethyl acetate and are typically supplied. For example, BIO-PSA 7-4201 has a solution viscosity of 450 mPa·s at 25°C and in heptane with a solid content of approximately 60%, and a viscosity of 1 × 10⁻¹⁶ at 0.01 rad / s at 30°C. 8 It is characterized by the complex viscosity of Poise. BIO-PSA7-4301 has a solution viscosity of 500 mPas at 25°C and with a solid content of approximately 60% in heptane, and a viscosity of 5 × 10⁻⁶ at 0.01 rad / s at 30°C. 6 It has a complex viscosity in Poise.

[0133] A polysiloxane-based pressure-sensitive adhesive is obtained according to the following scheme. [ka] Such polysiloxane-based pressure-sensitive adhesives are available under the trade names Liveo® BIO-PSA7-4401, BIO-PSA7-4501, or BIO-PSA7-4601, supplied in the solvent n-heptane (indicated by code "01"), or under the trade names Liveo® BIO-PSA7-4402, BIO-PSA7-4502, and BIO7-4602, supplied in the solvent ethyl acetate (indicated by code "02"). Typical solids content in the solvent ranges from 60 to 75%. Code "44" indicates low viscosity with a resin-to-polymer ratio of 65:35, code "45" indicates medium viscosity with a resin-to-polymer ratio of 60:40, and code "46" indicates high viscosity with a resin-to-polymer ratio of 55:45.

[0134] A polysiloxane-based amine-compatible pressure-sensitive adhesive is obtained according to the following scheme. [ka] Such polysiloxane-based amine-compatible pressure-sensitive adhesives are available under the trade names Liveo® BIO-PSA7-4101, BIO-PSA-7-4201, or BIO-PSA7-4301, supplied in the solvent n-heptane (indicated by code "01"), or under the trade names Liveo® BIO-PSA7-4102, BIO-PSA7-4202, and BIO7-4302, supplied in the solvent ethyl acetate (indicated by code "02"). Typical solids content in the solvent ranges from 60 to 75%. Code "41" indicates low viscosity with a resin-to-polymer ratio of 65:35, code "42" indicates medium viscosity with a resin-to-polymer ratio of 60:40, and code "43" indicates high viscosity with a resin-to-polymer ratio of 55:45.

[0135] Acrylic polymer As used herein, the terms acrylic polymer and acrylate polymer are synonymous with acrylate-based polymers. According to certain embodiments, the acrylic polymer is an acrylate-based pressure-sensitive adhesive. Acrylate-based pressure-sensitive adhesives may also be called acrylate-based pressure-sensitive adhesives or acrylate pressure-sensitive adhesives. Acrylate-based pressure-sensitive adhesives may preferably be provided in the form of a solution having a solids content of 30% to 60%. Acrylate-based pressure-sensitive adhesives may or may not contain 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®. Such acrylate-based pressure-sensitive adhesives are based on monomers selected from one or more of acrylic acid, 2-ethylhexyl acrylate, glycidyl methacrylate, 2-hydroxyethyl acrylate, methyl acrylate, methyl methacrylate, butyl acrylate, butyl methacrylate, t-octylacrylamide, and vinyl acetate, and are provided in ethyl acetate, heptane, n-heptane, hexane, methanol, ethanol, isopropanol, 2,4-pentanedione, toluene, or xylene or mixtures thereof. The following specific acrylate-based pressure-sensitive adhesives are available. -Duro-Tak(trademark) 387-2287 or Duro-Tak(trademark) 87-2287 (a copolymer based on vinyl acetate, 2-ethylhexyl acrylate, 2-hydroxyethyl acrylate, and glycidyl methacrylate, provided as a solution in ethyl acetate without a crosslinking agent), -Duro-Tak(trademark) 387-2516 or Duro-Tak(trademark) 87-2516 (a copolymer based on vinyl acetate, 2-ethylhexyl acrylate, 2-hydroxyethyl acrylate, and glycidyl methyl acrylate, provided as a solution in ethyl acetate, ethanol, n-heptane, and methanol containing a titanium crosslinking agent), -Duro-Tak(trademark) 387-2051 or Duro-Tak(trademark) 87-2051 (a copolymer based on acrylic acid, butyl acrylate, 2-ethylhexyl acrylate, and vinyl acetate, provided as a solution in ethyl acetate and heptane), -Duro-Tak® 387-2353 or Duro-Tak® 87-2353 (a copolymer based on acrylic acid, 2-ethylhexyl acrylate, glycidyl methacrylate, and methyl acrylate, provided as a solution in ethyl acetate and hexane), -Duro-Tak(trademark) 87-4098 (a copolymer based on 2-ethylhexyl acrylate and vinyl acetate, provided as a solution in ethyl acetate), -Duro-Tak(trademark) 387-9301 (a copolymer based on methyl acrylate, 2-ethylhexyl acrylate, and t-octylacrylamide, provided as a solution in ethyl acetate).

[0136] Therefore, the acrylic polymer can be selected from acrylic polymers containing functional groups selected from hydroxyl groups, carboxylic acid groups, neutralized carboxylic acid groups, and mixtures thereof. In certain embodiments, the functional group is limited to hydroxyl groups. The acrylic polymer may not contain carboxylic acid groups or neutralized carboxylic acid groups or both, may not contain acidic groups, or may not contain any functional groups at all.

[0137] Depending on the type of commercially available acrylic polymer used and whether or not a crosslinking agent is added to the coating composition, the polymer in the final active layer or skin contact layer may be crosslinked (and preferably crosslinked with an aluminum crosslinking agent and / or a titanium crosslinking agent), or not crosslinked with a crosslinking agent.

[0138] Silicone acrylic hybrid polymer As used herein, silicone-acrylic hybrid polymers include polymerized hybrid species comprising a silicone-based subspecies and an acrylate-based subspecies polymerized together. Therefore, silicone-acrylic hybrid polymers comprise a silicone phase and an acrylic phase. According to certain embodiments, silicone-acrylic hybrid polymers are silicone-acrylic hybrid pressure-sensitive adhesives. Silicone-acrylic hybrid pressure-sensitive adhesives are typically supplied and used in a solvent such as n-heptane or ethyl acetate. The solids content of pressure-sensitive adhesives is typically 30% to 80%. Those skilled in the art will recognize that the solids content can be altered by adding an appropriate amount of solvent.

[0139] According to certain embodiments, the weight ratio of silicone to acrylate in the silicone-acrylic hybrid pressure-sensitive adhesive is 5:95 to 95:5, or 20:80 to 80:20, or 40:60 to 60:40, or the silicone-to-acrylate ratio is approximately 50:50. Suitable commercially available silicone-acrylic hybrid pressure-sensitive adhesives include the PSA series 7-6100 and 7-6300 (7-610X and 7-630X; X=1 n-heptane-based / X=2 ethyl acetate-based) manufactured and supplied by Dupont® in n-heptane or ethyl acetate. For example, the 7-6102 silicone-acrylic hybrid PSA having a 50 / 50 silicone / acrylate ratio is characterized by a solution viscosity of 2,500 cP with a solids content of approximately 50% in ethyl acetate at 25°C and a complex viscosity of 1.0e7 poise at 0.1 rad / s at 30°C. 7-6302 silicone-acrylic hybrid PSA, having a 50 / 50 silicone / acrylate ratio, has a solution viscosity of 1,500 cP at 25°C with approximately 50% solids content in ethyl acetate, and a complex viscosity of 4.0e6 poise at 30°C at 0.1 rad / s.

[0140] Depending on the solvent in which the silicone-acrylic hybrid pressure-sensitive adhesive is supplied, the arrangement of the silicone and acrylic phases differs, providing a continuous silicone or acrylic outer phase and a corresponding discontinuous internal phase. When the silicone-acrylic hybrid pressure-sensitive adhesive is supplied in n-heptane, the composition includes a continuous silicone outer phase and a discontinuous acrylic internal phase. When the silicone-acrylic hybrid pressure-sensitive adhesive is supplied in ethyl acetate, the composition includes a continuous acrylic outer phase and a discontinuous silicone internal phase. After the solvent in which the silicone-acrylic hybrid pressure-sensitive adhesive is supplied is evaporated, the phase arrangement of the resulting pressure-sensitive adhesive film or layer corresponds to the phase arrangement of the solvent-containing adhesive coating composition. For example, if there is no substance that can induce a reversal of the phase arrangement of the silicone-acrylic hybrid pressure-sensitive adhesive composition, a pressure-sensitive adhesive layer prepared from a silicone-acrylic hybrid pressure-sensitive adhesive in n-heptane will provide a continuous silicone outer phase and a discontinuous acrylic internal phase, while a pressure-sensitive adhesive layer prepared from a silicone-acrylic hybrid pressure-sensitive adhesive in ethyl acetate will provide a continuous acrylic outer phase and a discontinuous silicone internal phase. The phase configuration of the composition can be determined, for example, by a peel force test using a pressure-sensitive adhesive film or a layer prepared from a silicone-acrylic hybrid PSA composition bonded to a silicone-coated release liner. If the silicone-coated release liner cannot be peeled from the pressure-sensitive adhesive film (laminated to the backing film) or can barely be peeled due to blocking of the two silicone surfaces, the pressure-sensitive adhesive film contains a continuous silicone outer phase. The blocking occurs due to the adhesion of two silicone layers having similar surface energies. The silicone adhesive spreads well on the silicone-coated liner and can therefore form good adhesion to the liner. If the silicone-coated release liner peels off easily, the pressure-sensitive adhesive film contains a continuous acrylic outer phase. The acrylic adhesive spreads poorly due to its different surface energy and has low or almost no adhesion to the silicone-coated liner.

[0141] The silicone-acrylic hybrid polymer may be a silicone-acrylic hybrid pressure-sensitive adhesive obtained from a silicone-containing pressure-sensitive adhesive composition containing acrylate or methacrylate functional groups. It should be understood that the silicone-containing pressure-sensitive adhesive composition containing acrylate or methacrylate functionality may contain acrylate functionality only, methacrylate functionality only, or both acrylate and methacrylate functionality.

[0142] A silicone-acrylic hybrid pressure-sensitive adhesive may comprise (a) a silicone-containing pressure-sensitive adhesive composition containing an acrylate or methacrylate functional group, (b) an ethylenically unsaturated monomer, and (c) a reaction product with an initiator. That is, a silicone-acrylic hybrid pressure-sensitive adhesive is the product of a chemical reaction between these reactants ((a), (b), and (c)). In particular, a silicone-acrylic hybrid pressure-sensitive adhesive may comprise (a) a silicone-containing pressure-sensitive adhesive composition containing an acrylate or methacrylate functional group, (b) a (meth)acrylate monomer, and (c) a reaction product with an initiator (i.e., in the presence of an initiator). That is, a silicone-acrylic hybrid pressure-sensitive adhesive may comprise the product of a chemical reaction between these reactants ((a), (b), and (c)).

[0143] The reaction product of (a) a silicone-containing pressure-sensitive adhesive composition containing an acrylate or methacrylate functional group, (b) an ethylenically unsaturated monomer, and (c) an initiator may include a continuous silicone outer phase and a discontinuous acrylic inner phase, or the reaction products of (a), (b), and (c) may include a continuous acrylic outer phase and a discontinuous silicone inner phase.

[0144] The silicone-acrylic hybrid polymer may contain a reaction product of a silicone polymer, a silicone resin, and an acrylic polymer, where the acrylic polymer is covalently self-crosslinked and covalently bonded to the silicone polymer and / or silicone resin.

[0145] The silicone-acrylic hybrid polymer may include a reaction product of a silicone polymer, a silicone resin, and an acrylic polymer, where the silicone resin is a triorganosiloxy unit R3SiO where R is an organic group. 1 / 2 , and tetrafunctional siloxy units SiO 4 / 2 Each SiO 4 / 2 For comparison, 0.1~0.9R3SiO 1 / 2 Contains in molar ratios per unit.

[0146] The acrylic polymer may contain at least an alkoxysilyl functional monomer, a polysiloxane-containing monomer, a halosilyl functional monomer, or an alkoxyhalosilyl functional monomer. In certain embodiments, the acrylic polymer is prepared from an alkoxysilyl functional monomer selected from the group consisting of trialkoxysilyl (meth)acrylate, dialkoxyalkylsilyl (meth)acrylate, and mixtures thereof, or contains a terminally capped alkoxysilyl functional group. The alkoxysilyl functional group may preferably be selected from the group consisting of trimethoxysilyl, dimethoxymethylsilyl, triethoxysilyl, diethoxymethylsilyl, and mixtures thereof.

[0147] Acrylic polymers can be prepared from a mixture containing polysiloxane-containing monomers, preferably a mixture containing polydimethylsiloxane mono(meth)acrylate.

[0148] A silicone-acrylic hybrid polymer can be prepared by a) reacting a silicone polymer with a silicone resin to form a resulting product, and b) reacting the resulting product from a) with an acrylic polymer containing a reactive functional group, wherein the components are reacted in an organic solvent.

[0149] A silicone-acrylic hybrid polymer can be prepared by a) reacting a silicone resin with an acrylic polymer containing reactive functional groups to form a resulting product, and b) reacting the resulting product from a) with a silicone polymer, wherein the components are reacted in an organic solvent.

[0150] A silicone-acrylic hybrid polymer can be prepared by a) reacting a silicone polymer with an acrylic polymer containing reactive functional groups to form a resulting product, and b) reacting the resulting product from a) with a silicone resin, wherein the components are reacted in an organic solvent.

[0151] More suitable acrylic polymers, silicone resins, and silicone polymers that can be used to provide silicone-acrylic hybrid polymers according to the preceding paragraph by chemically reacting silicone polymers, silicone resins, and acrylic polymers are described in detail in WO2010 / 124187.

[0152] Polymers based on natural or synthetic rubber Examples of polymers based on natural or synthetic rubber include hydrocarbon polymers such as (natural and synthetic) polyisoprene, polybutylene, and polyisobutylene, styrene / butadiene polymers, styrene-isoprene-styrene block copolymers, butyl rubber, polyacrylonitrile, polytetrafluoroethylene, polyvinyl chloride, polyvinylidene chloride, polychlorodiene, and other halogen-containing polymers, as well as other copolymers thereof. These polymers may be used in combination with tackifiers, particularly as defined below.

[0153] According to certain embodiments, the polymer may be a styrene-based triblock copolymer selected from the group consisting of styrene-ethylene-styrene (SES) block copolymer, styrene-butadiene-styrene (SBS) block copolymer, styrene-isoprene-styrene (SIS) block copolymer, styrene-ethylene / butylene-styrene (S-EB-S) block copolymer, styrene-ethylene / butylene / propylene-styrene (s-EBS-S) block copolymer, styrene-isoprene / butadiene-styrene (S-IB-S) block copolymer, and mixtures thereof.

[0154] 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 have a molecular weight of about 100,000 to 200,000. In certain embodiments, the SIS block copolymer may contain polystyrene and polyisoprene blocks in a ratio of about 10:90% to about 30:70%, or about 15:85%, or about 22:78%.

[0155] In other embodiments, the polymer is at least one type of polyisobutylene, and may be a combination of two different types of polyisobutylene, particularly a combination of low molecular weight polyisobutylene and high molecular weight polyisobutylene. In certain embodiments, the ratio of low molecular weight polyisobutylene to high molecular weight polyisobutylene is in the range of 75:25 to 90:10.

[0156] A suitable styrene-isoprene-styrene (SIS) block copolymer according to the present invention is commercially available, for example, under the brand name JSR-SIS. Specific SIS block copolymer-based pressure-sensitive adhesives are available under the trade names JSR-SIS5229 and JSR-SIS5002.

[0157] Suitable polyisobutylenes used herein are available under the trade name Oppanol®. Combinations of high molecular weight polyisobutylenes (B100 / B80) and low molecular weight polyisobutylenes (B10, B11, B12, B13) may 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. Specific examples of polyisobutylene combinations are B10 / B100 in a ratio of 85 / 15, or B12 / B100 in a ratio of 80 / 20. Oppanol® B100 has a viscosity-average molecular weight of 1,110,000 M v , and a weight-average molecular weight of 1,550,000 M w, as well as the average molecular weight distribution M of 2.9 w / M n Oppanol® B10 has a viscosity-average molecular weight of 40,000 M v , and weight-average molecular weight M of 53,000 w , as well as the average molecular weight distribution M of 3.2 w / M n Oppanol® B12 has a viscosity-average molecular weight Mv of 55,000, a weight-average molecular weight Mw of 70,000, and an average molecular weight distribution Mw / Mn of 3.2. Suitable polyisobutylene adhesives are also commercially available, for example, under the trade name Duro-Tak® 87-6908.

[0158] Silicone gel adhesive Silicone gel adhesives are elastic, gel-like materials formed from lightly crosslinked silicone polymers. Therefore, in contrast to the silicone polymers used herein, silicone gel adhesives are based on curable gel-forming compositions. When used in skin contact layers, silicone gel adhesives provide adhesion of medical patches to the skin while simultaneously mitigating skin irritation. Furthermore, drug delivery of the medical patch is not adversely affected, and remarkably, skin permeability is improved.

[0159] Silicone gel adhesives, also known as silicone gels, are described, for example, in WO2011 / 022199A2.

[0160] Silicone gel adhesives are generally formed from linear or branched silicones having reactive groups on them. Such reactive groups undergo crosslinking reactions during curing. An example of a crosslinking reaction is hydrosilylation, in which a silicone having Si-H reactive groups reacts with a silicone having aliphatic unsaturated reactive groups in the presence of a hydrosilylation catalyst. These materials are described, for example, in US5,656,279, US5,891,076, EP0322118 and US4,991,574, which are incorporated herein by reference. An alternative reaction is condensation curing, in which an alkoxy and / or hydroxy-containing siloxane is cured with a catalyst, as described in US4,831,070, which is incorporated herein by reference.

[0161] Generally, silicone gel adhesives are obtained by reacting a gel-forming composition comprising (i) at least one alkenyl-substituted polydiorganosiloxane, (ii) at least one organosiloxane containing silicone-bonded hydrogen atoms, and (iii) at least one catalyst for the reaction between SiH groups and Si-alkenyl groups. These compositions cure at normal ambient temperatures, but curing can be accelerated by heating to high temperatures, for example, 40-140°C, or by irradiation with UV light.

[0162] Suitable alkenyl groups include, but are not limited to, vinyl, allyl, and hexenyl groups, which comprise two to about six carbon atoms. The alkenyl groups in this component may be located at terminal, pendant (non-terminal), or both terminal and pendant positions. The remaining silicon-bonded organic groups in the alkenyl-substituted polydiorganosiloxane are independently selected from the group consisting of non-aliphatic unsaturated monovalent hydrocarbon groups and monovalent halogenated hydrocarbon groups. These groups typically comprise one to about 20 carbon atoms, or one to eight carbon atoms, and are not limited to, but are methyl, ethyl, propyl, and butyl alkyl groups; phenyl aryl groups; and 3,3,3-trifluoropropyl alkyl halides. Typically, at least 50% of the organic groups in the alkenyl-substituted polydiorganosiloxane are methyl. The structure of the alkenyl-substituted polydiorganosiloxane is typically linear, but may include some branching due to the presence of trifunctional siloxane units. The viscosity of the alkenyl-substituted polydiorganosiloxane can be any desired value. For example, 0 mm 2 / s super~100,000mm 2 / s, or 50mm 2 / s~80,000mm 2 / s, or 300mm 2 / s~3,000mm 2 It can be set to / s.

[0163] Methods for preparing the alkenyl-substituted polydiorganosiloxane (i) of the present invention, such as condensation of the corresponding halosilane or equilibration of the cyclic polydiorganosiloxane, are well known in the art.

[0164] Alkenyl-substituted polydiorganosiloxanes can be used in gel-forming compositions in amounts of 10% to 90% by weight, 40% to 90% by weight, or 50% to 80% by weight, based on the weight of the composition. The amount of alkenyl groups present in the alkenyl-substituted polydiorganosiloxane is typically in the range of 0.05% to 1% by weight, or 0.05% to 1% by weight, based on the weight of the alkenyl-substituted polydiorganosiloxane.

[0165] Organosiloxanes containing silicon-bonded hydrogen atoms (ii) are also known in the art, for example, as described in U.S. Patent No. 3,983,298. The hydrogen atoms in this component may be located at terminal, pendant (non-terminal), or both terminal and pendant positions. The remaining silicon-bonded organic groups in this component are independently selected from the group consisting of non-aliphatic unsaturated monovalent hydrocarbon groups and monovalent halogenated hydrocarbon groups. These groups typically contain one to about 20 carbon atoms, or one to eight carbon atoms, and include, but are not limited to, alkyl groups such as methyl, ethyl, propyl, and butyl; aryl groups such as phenyl; and alkyl halides such as 3,3,3-trifluoropropyl. In one embodiment of the present invention, at least 50% of the organic groups in the silicon-bonded hydrogen atom-containing organosiloxane are methyl. The structure of the silicon-bonded hydrogen atom-containing organosiloxane is typically linear, but may include some branching due to the presence of trifunctional siloxane units. The viscosity of organosiloxanes containing silicon-bonded hydrogen atoms can be any desired viscosity. For example, 0 mm 2 / s super~100,000mm 2 / s, or 5mm 2 / s~500mm 2 It can be set to / s.

[0166] Methods for preparing the silicon-bonded hydrogen atom-containing organosiloxanes of the present invention by appropriate co-hydrolysis of chlorosilanes are known in the art, and all of the following references are incorporated herein by reference: US Patent No. 2,877,255 to Clark; Japanese Laid Open Patent Application (KOKAI) SHO62 (1987)-39660 to Mogi et al.; and US Patent Nos. 5,446,185 and US No. 5,493,040 to Cobb et al.

[0167] Organosiloxanes containing silicone-bonded hydrogen atoms can be used in gel-forming compositions in amounts of 1% to 30% by weight, 5% to 20% by weight, or 5% to 15% by weight, based on the weight of the composition. In one embodiment, the amount of hydrogen groups present in the organosiloxane containing silicone-bonded hydrogen atoms is 0.05% to 1.44% by weight, based on the weight of the organosiloxane containing silicone-bonded hydrogen atoms.

[0168] In the gel-forming composition, it is preferable that (i) and (ii) exist such that the ratio of (H as SiH):(alkenyl as Si-alkenyl) is generally in the range of 0.1:1 to 10:1.

[0169] Hydrosilylation catalysts (iii) facilitate the addition reaction between alkenyl-substituted polydiorganosiloxanes and organosiloxanes containing silicon-bonded hydrogen. Any known hydrosilylation catalysts can be used, including platinum group metals, compounds containing platinum group metals, or microencapsulated platinum group metals or compounds containing them. These platinum group metals include platinum, rhodium, ruthenium, palladium, osmium, and iridium. Platinum and platinum compounds are preferred catalysts due to their high activity in hydrosilylation reactions. One type of platinum catalyst is a complex of chloroplatinic acid and a specific vinyl-containing organosiloxane compound, disclosed by Willig in U.S. Patent No. 3,419,593 (incorporated herein by reference). A specific catalyst of this type is the reaction product of chloroplatinic acid and 1,3-diethenyl-1,1,3,3-tetramethyldisiloxane.

[0170] The hydrosilylation catalyst is present in an amount sufficient to cure the composition of the present invention. Typically, the catalyst concentration is sufficient to provide platinum group metals in amounts of 0.1 ppm to 500 ppm (parts per million), or 1 ppm to 100 ppm, or 1 ppm to 50 ppm, based on the weights of (i) and (ii).

[0171] From the above viewpoint, in one embodiment of the present invention, the silicone gel adhesive is obtained by reacting (i) a gel-forming composition comprising a copolymer of vinylmethylsiloxane and dimethylsiloxane with (ii) methylhydrogenpolysiloxane having a trimethylsilyl terminal group and (iii) a platinum catalyst. Here, preferably, (i) and (ii) are 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.

[0172] An optional component is a hydroxy-substituted silicone resin described in U.S. Patent Application No. 2007-0202245, which is incorporated herein by reference. This resin is typically of formula R3 3SiO 1 / 2 Groups having the formula "M" group and SiO 4 / 2 It contains a group having ("Q" group), where R 3 The R groups are alkyl groups having 1 to 6 carbon atoms or alkylene groups having 1 to 6 carbon atoms, typically methyl or vinyl. When alkenyl groups are present in the resin, the mol-% of the R groups present as alkenyl groups is typically less than 10 mol-%, or 5 mol-%. The number ratio of M groups to Q groups is typically in the range of 0.6:1 to 4:1, or 0.6:1 to 1.0:1. Silicone resins typically contain 0.1% to 5% by weight, or 1.0% to 5% by weight, of silicone-bonded hydroxyl groups.

[0173] The resin can be used in the gel-forming composition in an amount of 2% to 45% by weight, or 5% to 40% by weight, or 10% to 35% by weight, depending on the weight of the gel-forming composition and the resin.

[0174] Therefore, in one embodiment, the silicone gel adhesive may be a silicate resin-reinforced silicone gel adhesive containing about 2 to about 45% by weight of at least one hydroxyl-substituted silicate resin.

[0175] According to certain embodiments, the silicone gel adhesive is a two-part silicone adhesive system that hardens when two components are mixed. Examples of such commercially available two-part silicone adhesives include Liveo® Soft Skin Adhesives (MG7-9700, MG7-9800, MG7-9850, and MG7-9900, etc.), which are provided as a kit containing components A and B. This is a platinum-catalyzed, soft, filler-free elastomeric silicone adhesive for bonding medical devices to skin with moderate adhesion and mild release. The two components A and B are preferably mixed in a 1:1 ratio.

[0176] A silicone gel adhesive layer can be manufactured by processes known in the art. For example, the gel can be pre-formed (e.g., as a sheet) on a substrate such as a liner by molding, calendering, extrusion, spraying, brushing, hand application, casting, or coating. Alternatively, a silicone gel layer can be manufactured by applying a gel-generating composition to a substrate by spraying, coating, bar coating, etc. The gel-generating composition applied to the substrate is cured, and a silicone gel adhesive is formed on the substrate.

[0177] Further additives The self-adhesive layer structure according to the present invention, particularly the active layer, may further contain at least one additive or excipient. The additive or excipient is preferably selected from the group consisting of additional polymers, crosslinking agents, crystallization inhibitors, solubilizers, fillers, tackifiers, plasticizers, stabilizers, softeners, skincare substances, permeability enhancers, pH adjusters, and preservatives. Such additives may be present in the active layer in an amount of 0.001 to 15% by weight, for example, 1 to 10% by weight, or 0.01 to 5% by weight, based on the total weight of the active layer. In certain embodiments, the total amount of all additives is 0.001% to 25% of the matrix layer composition. Where a range for the amount of a particular additive is provided below, such range refers to the amount per individual additive.

[0178] It should be noted that in pharmaceutical formulations, formulation components are categorized according to their physicochemical and physiological properties and their functions. This means, in particular, that a substance or compound classified in one category may not be classified in another category of formulation components. For example, a particular polymer may be both a crystallization inhibitor and a tackifier. Some substances may, for example, be typical emollients while simultaneously acting as permeability enhancers. Those skilled in the art can, based on general knowledge, determine which category(s) of formulation components a substance or compound belongs to. Details regarding excipients and additives are provided below, but these are not to be understood as being mutually exclusive. Other substances not expressly listed herein may also be used in accordance with the present invention, and substances and / or compounds expressly listed in one category of formulation components are not excluded from use as other formulation components within the scope of the present invention.

[0179] In certain embodiments, the active layer may further contain additional polymers, preferably selected from dimethylpolysiloxane and ethylcellulose. For example, dimethylpolysiloxane such as dimethicone is preferably used to increase the adhesion of the active layer, and ethylcellulose preferably functions as a viscosity increaser. Other polymers of particular interest are those with enhanced water absorption capacity, as increased water and / or moisture absorption helps maintain / improve the adhesion of the self-adhesive layer structure. Thus, the active layer may further contain at least one additional polymer selected from polymers that improve the water and / or moisture absorption of the matrix layer. Such polymers are well known in the art. Of these, polyvinylpyrrolidone, particularly soluble polyvinylpyrrolidone, is particularly suitable and preferred. Other polymers are also suitable as additional polymers, particularly those that reduce low-temperature flow. The polymer matrix may exhibit low-temperature flow because such polymer compositions often exhibit the ability to flow very slowly despite very high viscosity. Therefore, during storage, the matrix may flow to some extent beyond the edges of the backing layer. This is a problem related to storage stability and can be prevented by the addition of certain polymers. For example, basic acrylate polymers (e.g., Eudragit E100, which is a copolymer based on dimethylaminoethyl methacrylate, butyl methacrylate, and methyl methacrylate) can be used to reduce low-temperature flow. Thus, the active layer may also contain additional basic polymers, in particular amine-functionalized acrylates such as Eudragit E100. The additional polymer may be present in an amount of, for example, 0-20% of the active layer, preferably 0.5-5% or 5-15% of the active layer.

[0180] In certain embodiments, the active layer may further contain a crosslinking agent. The crosslinking agent may be selected from the group consisting of aluminum and titanium crosslinking agents such as aluminum acetylacetonate, titanium acetylacetonate, or polybutyl titanate, and is preferably a titanium crosslinking agent. The amount of crosslinking agent may be in the range of 0.005 to 1%, preferably 0.01 to 0.1%, of the active layer. The active layer may also contain a self-crosslinking polymer, i.e., a polymer containing a crosslinking functional group such as a glycidyl group that reacts upon heating. Therefore, the active layer preferably contains the above-mentioned crosslinking agent and self-crosslinking polymer.

[0181] In certain embodiments, the active layer may further contain a crystallization inhibitor. Suitable examples of crystallization inhibitors include polyvinylpyrrolidone, vinyl acetate / vinylpyrrolidone copolymers, and cellulose derivatives. The crystallization inhibitor is preferably polyvinylpyrrolidone, and more preferably soluble polyvinylpyrrolidone. The crystallization inhibitor may increase the solubility of the active agent or inhibit the crystallization of the active agent. The crystallization inhibitor may be present in an amount of 0.5 to 10% by weight based on the total weight of the active layer.

[0182] In certain embodiments, the active layer may further contain a solubilizer. The solubilizer preferably improves the solubility of the active agent in the active layer. Preferred solubilizers include, for example, glycerol esters, polyglycerol esters, propylene glycol esters, and polyoxyethylene esters of medium-chain and / or long-chain fatty acids, such as glyceryl monolinoleate, medium-chain glycerides and medium-chain triglycerides, nonionic solubilizers produced by reacting castor oil with ethylene oxide, and any mixtures thereof which may further contain fatty acids or fatty alcohols; cellulose and methylcellulose, and their derivatives, such as hydroxypropylcellulose and hypromellose acetate succinate; various cyclodextrins and their derivatives; and nonionic triblocks having a central hydrophobic chain of polyoxypropylene adjacent to two hydrophilic chains of polyoxyethylene known as poloxamers. Copolymers; water-soluble derivatives of vitamin E; pharmaceutical-grade or aggregated spherical isomalt; polyester glycol, polyvinyl acetate, and polyvinyl caprolactam graft copolymers, also abbreviated as PVAc-PVCap-PEG and known as Soluplus®; refined grades of naturally derived castor oil, polyethylene glycol 400, polyoxyethylene sorbitan monooleate (such as polysorbate 80), or propylene glycol; diethylene glycol monoethyl ether; glucono-delta-lactone; corn and potato starch; and any of the soluble polyvinylpyrrolidones listed below, as well as insoluble / crosslinked polyvinylpyrrolidones such as crospovidone. However, permeation enhancers mentioned below can also act as solubilizers. Furthermore, crystallization inhibitors can also act as solubilizers.

[0183] Fillers such as silica gel, titanium dioxide, and zinc oxide may be used in conjunction with the active layer to influence specific physical parameters such as cohesiveness and bonding strength in a desired manner.

[0184] If the active layer needs to be self-adhesive and one or more polymers that do not provide sufficient self-adhesion are selected, a tackifier is added. The tackifier can be selected from polyvinylpyrrolidone (which can maintain the adhesion of the matrix layer due to its water-absorbing ability and can therefore be considered a tackifier in a broad sense), triglycerides, polyethylene glycol, dipropylene glycol, resins, resin esters, terpenes and their derivatives, ethylene vinyl acetate adhesives, dimethylpolysiloxane and polybutene, preferably polyvinylpyrrolidone, more preferably soluble polyvinylpyrrolidone. The tackifier may be present in an amount of 5-15% of the active layer.

[0185] In certain embodiments, the active layer may further contain a blunting agent / plasticizer. Exemplary blunting agents / plasticizers include linear or branched saturated or unsaturated alcohols, triglycerides, and polyethylene glycols having 6 to 20 carbon atoms.

[0186] In certain embodiments, the active layer may further contain a stabilizer, which 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, tocopherol acetate, and tocopherol linoleate. A combination of tocopherol and ascorbyl palmitate is particularly preferred. When the active layer contains a stabilizer, the amount of the stabilizer may be 0.001 to 2% of the active layer.

[0187] In certain embodiments, the active layer may further contain skincare substances. Such substances may be used to avoid or reduce skin irritation detectable by a skin reaction score. Suitable skincare substances include sterol compounds such as cholesterol, deexpanthenol, α-bisabolol, and antihistamines.

[0188] In certain embodiments, the active layer may further contain a permeability enhancer. A permeability enhancer is a substance that affects the barrier properties of the stratum corneum in the sense that it increases the permeability of the active agent. Examples of permeability enhancers include polyhydric alcohols such as dipropylene glycol, propylene glycol, and polyethylene glycol; oils such as olive oil, squalene, and lanolin; aliphatic ethers such as cetyl ether and oleyl ether; fatty acid esters such as isopropyl myrislate; urea and urea derivatives (such as allantoin); polar solvents such as dimethyldecyl phosphooxide, methyl cetyl sulfoxide, dimethylourarylamine, dodecylpyrrolidone, isosorbitol, dimethylacetonide, dimethyl sulfoxide, decylmethyl sulfoxide, and dimethylformamide; and high molecular weight aliphatic surfactants such as salicylic acid, amino acids, benzyl nicotinate, and lauryl sulfate. Other agents include oleic acid, linoleic acid, ascorbic acid, panthenol, butylated hydroxytoluene, tocopherol, tocopherol acetate, tocopherol linoleate, propyl oleate, and isopropyl palmitate. If the active layer further contains a permeation enhancer, the permeation enhancer is preferably selected from diethylene glycol monoethyl ether (Transktol), diisopropyl adipate, isopropyl myristate, isopropyl palmitate, lauryl lactate, and dimethylpropylene urea. Particularly preferably, the active layer contains a permeation enhancer selected from diethylene glycol monoethyl ether.

[0189] In certain embodiments, the active layer may further contain a pH adjusting agent. Suitable pH adjusting agents include mild acids and bases, including amine derivatives, inorganic alkali derivatives, and polymers having basic or acidic functionality.

[0190] In certain embodiments, the active layer may further contain a preservative. Suitable preservatives include parabens, formaldehyde-releasing agents, isothiazolinone, phenoxyethanol, and organic acids such as benzoic acid, sorbic acid, levulinic acid, and anisic acid.

[0191] pentagonal shape According to the present invention, the self-adhesive layer structure has a pentagonal shape provided by a backing layer and an active layer, or a backing layer, an active layer and an additional skin contact layer. The pentagonal shape includes at least one pentagon, the sides of which have a length from 0.2 cm to 12.5 cm.

[0192] The pentagonal shape may include 1 to 10 pentagons, for example, 1, 2, 3, 4, 6, or 9, preferably the pentagons are adjacent to each other and / or do not overlap. Two or more pentagons are preferably integrally connected to each other. The preferred pentagonal shape does not include perforations.

[0193] In certain embodiments, at least one pentagon is at least one convex pentagon, and the pentagonal shape includes at least one convex pentagon, the sides of which have lengths from 0.2 cm to 12.5 cm. In certain embodiments, the pentagonal shape includes 1 to 3 convex pentagons that are integrally connected to one another. In certain embodiments, the pentagonal shape is a convex pentagon.

[0194] In some embodiments, the convex pentagon may be a non-regular pentagon. In other embodiments, the convex pentagon may be a regular pentagon.

[0195] The pentagonal shape of the self-adhesive layer structure plays a crucial role in making the handling of medical patches containing this self-adhesive layer structure easy and time-saving. It allows for easy coverage of skin areas without cutting before application, thus reducing the risk of contaminating cutting tools or fingers with the active agent, as well as the risk of contaminating the patch at the cut site. Furthermore, it can cover uneven or rounded skin surfaces without wrinkling, achieving perfect adhesion, and complex areas such as fingers and toes can be easily covered using the self-adhesive layer structure. In particular, if the pentagonal shape includes at least one convex pentagon, the pentagonal shape requires only the length of the short side relative to the area provided, thus reducing the risk of the edges of the medical patch peeling off.

[0196] In certain embodiments, the pentagonal shape is a double pentagon formed from two identical convex pentagons that share two adjacent vertices and a common edge. The double pentagon is obtained by mirroring one convex pentagon across one of its edges (mirror axis), in which case the mirror axis includes the common edge. In certain embodiments, the double pentagon is separable at the common edge, yielding two identical convex pentagons that can be attached together or separately. Thus, in certain embodiments, the pentagonal shape is a double pentagon formed from two identical convex pentagons that share two adjacent vertices and a common edge, and the common edge is perforated to allow for easy separation.

[0197] In a further embodiment, the pentagonal shape is a triplicate pentagon formed from three identical convex pentagons, sharing two adjacent vertices and their common edges in pairs. This triplicate pentagon is obtained by mirroring the first convex pentagon across one of its edges (mirror axis 1), where mirror axis 1 includes the common edge shared by the first and second convex pentagons, and by mirroring the second convex pentagon across one of its other four edges (mirror axis 2), where mirror axis 2 includes the common edge shared by the second and third convex pentagons. In a particular embodiment, the triplicate pentagon is divisible by the common edge to obtain three equal convex pentagons, which may be applied together or separately. Therefore, in certain embodiments, the pentagonal shape is a triple pentagon formed from three identical convex pentagons, sharing two adjacent vertices and their common edges in pairs, such common edges being perforated so that they can be easily torn apart.

[0198] The double or triple pentagons described above may also exist in the form of a hexagon, particularly a regular hexagon.

[0199] In certain embodiments, the pentagonal shape is a pentagon, a double pentagon, or a triple pentagon, in particular a convex pentagon, or a double pentagon formed from two identical convex pentagons sharing two adjacent vertices and their common edge, or a triple pentagon formed from three identical convex pentagons sharing two adjacent vertices and their common edge in pairs. In particular, in these embodiments, the double pentagon or triple pentagon is hexagonal in shape, such as a regular hexagon.

[0200] The pentagonal shape in the form of a regular hexagon may have mirror symmetry and / or rotational symmetry. A preferred pentagonal shape is mirror symmetry having at least one axis of symmetry, e.g., two, three, or four axes of symmetry, and especially six axes of symmetry. Alternatively or additionally, a preferred pentagonal shape is rotational symmetry having at least two, e.g., three or four degrees, and especially six rotational symmetry. Thus, a particularly preferred pentagonal shape is mirror symmetry having at least four axes of symmetry and / or at least four rotational symmetry, and especially mirror symmetry having six axes of symmetry and further six rotational symmetry.

[0201] In certain embodiments, the pentagon, particularly the convex pentagon, is an unequal-angled shape, preferably with the sum of one interior angle and another interior angle being 180°. The interior angles that sum to 180° may be adjacent or not. Preferably, one interior angle is 60° and the other interior angle is 120°. Alternatively, one interior angle and the other interior angle are each 90°. A preferred (convex) pentagon according to the present invention has two interior angles of 90° and at least one interior angle of 120°. A particularly preferred (convex) pentagon according to the present invention has two interior angles of 90° and three interior angles of 120°.

[0202] The pentagon according to the present invention, particularly the convex pentagon, may have the following characteristics: -Five sides of equal length, - Five sides of different lengths, -Two sides of equal length and three other sides of different lengths, - Three sides of equal length and two other sides of different lengths, - Three sides of equal length and two sides of other lengths, - Four sides of equal length and one side of another length, or - A pair of sides of equal length and another pair of sides of equal length (the remaining sides are of different lengths than the pair of sides of equal length and the other pair of sides of equal length).

[0203] Therefore, in certain embodiments, the pentagon, particularly the convex pentagon, is equilateral. Alternatively, the pentagon is unequal, having four sides of equal length, or it is unequal, having two sides of equal length and two other sides of equal length. Such a pentagon is preferably mirror symmetry with one axis of symmetry, and the remaining sides are divided in the middle by the axis of symmetry.

[0204] In certain embodiments, the pentagon is a polygon with an irregular shape, where the ratio of one side (any side) to another side (any other side) is approximately 1:1, or approximately 1:2 / √3, or approximately 1:√3, or approximately 1:2, or approximately 1:2√3. In some embodiments, the pentagon is a polygon with an irregular shape, where the ratio of the shortest side to the longest side is 1:2. In other embodiments, the pentagon is a polygon with an irregular shape, where the ratio of the shortest side to the longest side is 1:2√3.

[0205] The sides of the pentagon according to the present invention have a length of 0.2 to 12.5 cm. In certain embodiments, the side lengths of the pentagon are 0.3 to 10 cm, 0.6 to 5 cm, 0.7 to 4.5 cm, or 0.9 to 2.4 cm. In certain embodiments, one, two, three, four, or five sides of the pentagon have a length of approximately 0.5 cm, approximately 1 cm, approximately 1.3 cm, approximately 1.7 cm, approximately 2 cm, approximately 2.5 cm, approximately 3.1 cm, or approximately 4.5 cm. For example, - Two sides of the pentagon are approximately 0.5 cm, 1 cm, or 1.3 cm long, two sides are approximately 1.3 cm, 1.7 cm, 2 cm, or 2.5 cm long, and the remaining side is approximately 2.5 cm, 3.1 cm, or 4.5 cm long, or - Two sides of the pentagon are approximately 1 cm or 1.3 cm long, two sides are approximately 1.3 cm, 1.7 cm, or 2 cm long, and the remaining side is approximately 1.7 cm, 2 cm, or 2.4 cm long.

[0206] The height of the pentagon may be in the range of 0.4–16.5 cm, 0.9–8.5 cm, 1.4–7.5 cm, or 1.6–4.5 cm. The width of the pentagon may be in the range of 0.4–15.5 cm, 0.9–8 cm, 1.3–7 cm, or 1.5–4 cm.

[0207] The (convex) pentagon according to the present invention may belong to the above-described types 1 to 15. In particular, the (convex) pentagon may be a type 1 pentagon, a type 3 pentagon, or a type 4 pentagon.

[0208] In certain embodiments, two sides of a pentagon are parallel. In particular, the pentagon has two parallel sides of equal length and two other sides of the same or other equal length. Alternatively, none of the sides of the pentagon are parallel.

[0209] In certain preferred embodiments, the pentagon is mirror symmetric with at least one axis of symmetry. In further embodiments, the pentagon is mirror symmetric with at least one axis of symmetry and has not only two (parallel) sides of equal length, but also two other sides of the same or other equal length, the remaining side being divided by the axis of symmetry in the middle, and / or has not only two 90° interior angles, but also three 120° interior angles, one of the latter being divided by the axis of symmetry in the middle. In certain embodiments, the pentagon is a type I pentagon or a type II pentagon.

[0210] In some very specific embodiments, the pentagon is a special type I pentagon having the following characteristics: - A pentagon is mirror symmetry, having exactly one axis of symmetry. - A pentagon has two adjacent interior angles of 90° and three adjacent interior angles of 120°. - The pentagon has two parallel sides of equal length, two other sides of equal length, and one remaining side, where - the ratio of the two parallel sides of equal length to the two other sides of equal length is about 1:2, and / or - the ratio of the two parallel sides of equal length to the remaining side is about 1:2√3, and / or - the ratio of the two other sides of equal length to the remaining side is about 1:√3.

[0211] In other very special embodiments, the pentagon is a special type II pentagon having the following characteristics. - The pentagon is mirror symmetric with 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, two other sides of equal length, and one remaining side, where - the ratio of the two sides of equal length to the two other sides of equal length is about 1:√3, and / or - the ratio of the two sides of equal length to the remaining side is about 1:2, and / or - the ratio of the two other sides of equal length to the remaining side is about 1:2 / √3.

[0212] Furthermore, according to a specific embodiment, the area of the hexagonal shape is more than 20 cm 2 sup, for example, more than 24 cm 2 sup, more than 30 cm 2 sup, or more than 40 cm 2 sup, preferably less than 150 cm 2 sup, for example, less than 60 cm 2 sup, or less than 35 cm 2 sup.

[0213] Medical patches and medical patch sheets According to the present invention, the above self-adhesive layer structure is used in a medical patch comprising the self-adhesive layer structure disposed on a release liner. The self-adhesive layer structure is also used in a medical patch sheet comprising a plurality of self-adhesive layer structures disposed on a release liner.

[0214] The medical patch(es) can be either a topical medical patch(es) or a transdermal therapeutic system(s). In certain embodiments, the medical patch(es) is(are) a topical medical patch(es) for local administration of capsaicin in particular.

[0215] In one embodiment, the present invention relates to a medical patch, which comprises the self-adhesive layer structure described herein, a release liner, and the release liner has the same extent as the self-adhesive layer structure or extends in all directions beyond the boundaries of the self-adhesive layer structure.

[0216] In another embodiment, the present invention relates to a medical patch sheet, which comprises two or more self-adhesive layer structures described herein, a release liner, and the release liner has the same extent as the self-adhesive layer structure or extends in all directions beyond the boundaries of the self-adhesive layer structure.

[0217] The release liner protects the self-adhesive layer structure(s) and must be removed before application. The self-adhesive layer structure(s) can be easily peeled off the release liner and applied individually or in combination to the patient's skin. In certain embodiments, the release liner in a medical patch sheet is not intended to separate with the self-adhesive layer structure(s) and remains in place after one or more of the self-adhesive layer structure(s) have been peeled off the sheet. This is advantageous because it facilitates peeling the self-adhesive layer structure(s) from the release liner, which expands the area of ​​the layer structure, and eliminates the need to discard the release liner separately for each self-adhesive layer structure. Therefore, in such embodiments, the release liner does not include any means for simultaneously tearing off each part of the release liner.

[0218] If the release liner extends beyond the boundary of the self-adhesive layer structure, the release liner may be covered by a boundary layer structure having the same layer design as the self-adhesive layer structure (i.e., including a backing layer, an active layer containing polymer I and an activator, and optionally a skin contact layer), as well as the same layer thickness and composition, adjacent to the self-adhesive layer structure and having the same extent as the outer boundary of the release liner. Such a medical patch sheet can be easily manufactured by first preparing a sheet of the desired layer structure on which the release liner is laminated, and then dividing the layer structure through the backing layer, active layer, and optionally a skin contact layer (if any) by punching, cutting, or slitting to a controlled depth, thereby preserving at least a portion of the release liner and obtaining a number of self-adhesive layer structures placed on the release liner surrounded by the boundary layer structure.

[0219] By using multiple self-adhesive layer structures, the surface of the skin area to be treated can be spread out without creating wrinkles by arranging the self-adhesive layer structures side by side. In this way, the pentagonal shape (or multiple pentagonal shapes) of the self-adhesive layer structures can avoid gaps and / or overlaps.

[0220] The number of self-adhesive layer structures provided for peeling from the release liner is determined by the size(s) of the self-adhesive layer structures. A suitable sheet of medical patch may contain 2 to 400, 3 to 300, 4 to 120, or 6 to 30 self-adhesive layer structures. In a particular embodiment, a medical patch sheet may contain 2 to 15 or 150 to 300 self-adhesive layer structures. In a particular embodiment, a medical patch sheet may contain 2, 3, 4, 6, or 8 self-adhesive layer structures. Alternatively, a medical patch sheet may contain 150, 180, 200, 240, or 300 self-adhesive layer structures. The self-adhesive layer structures may be equal or different.

[0221] The self-adhesive layer structures can be arranged on the release liner in any pattern, either adjacent to each other (tiling the plane) or with small gaps between them to facilitate the gripping of individual self-adhesive layer structures. In certain embodiments, the self-adhesive layer structures are arranged on the release liner in a space-saving manner. In particular, the self-adhesive layer structures are arranged side by side on the release liner. In some embodiments, the self-adhesive layer structures are arranged in two or more parallel matrices with respect to the longitudinal axis of the release liner, with each matrice preferably containing 2 to 20, 3 to 12, or 4 to 8 self-adhesive layer structures. For example, the self-adhesive layer structures may be arranged in four matrices, with each matrice containing 3 to 6 self-adhesive layer structures, particularly 3 to 6 identical self-adhesive layer structures (Figures 3a to 3f). In other embodiments, the self-adhesive layer structures are arranged in one or more types of repeating geometric patterns, with each geometric pattern preferably containing 2 to 15, 3 to 12, or 4 to 9 self-adhesive layer structures. Such geometric patterns may include polygons such as hexagons. Therefore, the self-adhesive layer structure may be arranged in the form of one or more hexagons, particularly regular hexagons, preferably, each (regular) hexagon containing 2, 3, 4, or 9, particularly 2 or 3, self-adhesive layer structures (Figures 4a-4d). In certain embodiments, the self-adhesive layer structure may be arranged in the form of one or more regular hexagons, each regular hexagon containing two special pentagons of type I described above, or each regular hexagon containing three special pentagons of type II described above.

[0222] In one embodiment, the self-adhesive layer structure tiles a plane, particularly a single plane, such as prism pentagon tiling or Cairo pentagon tiling. Preferred self-adhesive layer structures for tiling a plane are pentagons of types 1 to 15, particularly type 1 pentagons, or type 3 pentagons, or type 4 pentagons, such as the type I or type II (special) pentagons described above. The self-adhesive layer structure may also have pentagonal shapes selected from double pentagons formed from two identical convex pentagons sharing two adjacent vertices and their common edge, and / or triple pentagons formed from three identical convex pentagons sharing two adjacent vertices and their common edge in pairs, which may exist in the form of (regular) hexagons. The self-adhesive layer structures may be separate from each other or connected to each other. They may be adjacent to each other by sharing common vertices in pairs and / or three pairs and / or four pairs. If the common vertices are shared only in pairs, these common vertices may be located on the sides of the third pentagon, particularly in the middle of the sides.

[0223] In certain embodiments, self-adhesive layer structures are adjacent to one another by sharing at least one vertex and at least a portion of adjacent edges, and are separated from each other by the adjacent edges being cut to allow for peeling independently from the release liner. Alternatively, self-adhesive layer structures are adjacent to one another by sharing at least one vertex and at least a portion of adjacent edges, and are connected to each other by adjacent edges that are weakened to allow for easy peeling. In particular, the adjacent edges are perforated to allow for easy tearing. In some embodiments, self-adhesive layer structures are adjacent to one another by sharing two adjacent vertices and their common edge, and are separated from each other by the common edge being cut to allow for peeling independently from the release liner. Alternatively, self-adhesive layer structures are adjacent to one another by sharing two adjacent vertices and their common edge, and are connected to each other by a common edge that is weakened to allow for easy peeling. In particular, the common edge is perforated to allow for easy tearing. The medical patch sheet may also include self-adhesive layer structures, such self-adhesive layer structures adjacent to one another by sharing at least one vertex and at least a portion of adjacent edges, or two adjacent vertices and their common edges, some of which are separated from each other by the adjacent or common edges being cut to peel off independently from the release liner, and some of which are connected to each other by adjacent or common edges that are weakened to be easily torn. In certain embodiments, all self-adhesive layer structures are separated from each other by the adjacent or common edges being cut to peel off independently from the release liner.

[0224] For example, the self-adhesive layer structure may be arranged in two or more parallel rows with respect to the longitudinal axis of the release liner, each row containing 2 to 20 self-adhesive layer structures adjacent to one other by sharing at least one vertex and at least a portion of adjacent edges and / or two adjacent vertices and their common edges, the rows are separated from each other for independent release, and the self-adhesive layer structures within the rows are connected to each other by perforated common edges that allow for easy peeling. In another example, the self-adhesive layer structure may be arranged in the form of two or more regular hexagons, each hexagon containing 2, 3, or 9 self-adhesive layer structures adjacent to each other by sharing at least one vertex and at least a portion of adjacent edges and / or two adjacent vertices and their common edges, the hexagons are separated from each other for independent release, and the self-adhesive layer structures within the hexagons are connected to each other by perforated common edges that allow for easy peeling.

[0225] In certain embodiments, the self-adhesive layer structures are connected to one another by at least one, preferably two or more, common fastening bridges for joint peeling from the release liner. The fastening bridges provide one or more points of connection between the self-adhesive layer structures, even if they are separated from each other by at least partially cutting adjacent or common edges. This allows the thus connected self-adhesive layer structures to be peeled jointly from the release liner and applied to the patient's skin, which is particularly advantageous for a large number and / or small area of ​​self-adhesive layer structures. Alternatively, for joint peeling when there are a small number of such connected self-adhesive layer structures, some of the fastening bridges can be cut, for example, torn. In certain embodiments, the common fastening bridges are provided at vertices and / or edges and connect at least two, preferably three or four, self-adhesive layer structures, such as the following: -Two self-adhesive layer structures connected by two common fastening bridges located at two adjacent vertices, or - Three self-adhesive layer structures connected by a common fastening bridge located at the common vertices of two self-adhesive layer structures on the edge of a third self-adhesive layer structure, or at a common vertex. - Four self-adhesive layer structures connected by a single common fastening bridge located at a common vertex.

[0226] In a preferred medical patch sheet, all adjacent self-adhesive layer structures are connected to each other in pairs by at least two common fastening bridges provided at two adjacent vertices or their common edges, and / or at one vertex and an adjacent edge, preferably at two adjacent vertices. In particular, all adjacent self-adhesive layer structures are connected to each other in groups of three or four by common fastening bridges provided at vertices and / or edges, particularly at common vertices. This is particularly relating to self-adhesive layer structures that tile a plane. Thus, in one embodiment of the medical patch sheet according to the present invention, the self-adhesive layer structures are of the above-described Type I or Type II (special) pentagons, connected to each other by at least one fastening bridge for joint peeling from the release liner, and all adjacent self-adhesive layer structures are connected to each other in groups of three or four (as shown in Figures 5a and 5b) by common fastening bridges provided at common vertices located on edges or common vertices.

[0227] In certain embodiments, the self-adhesive layer structure has a pentagonal shape selected from a total of two or three different shapes. In certain embodiments, the self-adhesive layer structure has a pentagonal shape including a convex pentagon and a double pentagon formed from two identical convex pentagons sharing two adjacent vertices and their common sides, in particular a pentagonal shape including the above-described type I (special) pentagon and a double pentagon formed from two identical (special) pentagons of type I described above. Alternatively, all self-adhesive layer structures have the same pentagonal shape. In some embodiments, the self-adhesive layer structure is an irregular convex pentagon having two interior angles of 90° and three interior angles of 120°, with two parallel sides of equal length and two other sides of equal length, and the ratio of the shortest side to the longest side is approximately 1:2√3. Alternatively, the self-adhesive layer structure is an irregular convex pentagon with two interior angles of 90° and three interior angles of 120°, having two sides of equal length and two other sides of equal length, and the ratio of the shortest side to the longest side is approximately 1:2. In certain embodiments, the self-adhesive layer structure is a (special) pentagon of type I or type II described above, and may be arranged in the form of a regular hexagon.

[0228] In further embodiments, the medical patch sheet according to the present invention further includes one or more additional self-adhesive layer structures having a hexagonal shape including one or two hexagons. In particular, the hexagonal shape may include one or two regular hexagons. In certain embodiments, each additional self-adhesive layer structure is a regular hexagon, and preferably, each (existing) self-adhesive layer structure is a regular pentagon. Such a regular pentagon may be surrounded by five regular hexagons to tile the spheres. Thus, a preferred medical patch sheet may include self-adhesive layer structures having a pentagonal shape selected from regular pentagons and regular hexagons, where each regular pentagon shares its side with a regular hexagon.

[0229] The self-adhesive layer structure of the medical patch sheet according to the present invention may contain the same or different active agents (or multiple agents).

[0230] In certain embodiments, a medical patch (a single medical patch) contains capsaicin in an amount of about 179 mg, or alternatively in amounts of about 90 mg, about 60 mg, about 45 mg, about 30 mg, about 20 mg, about 10 mg, or about 1 mg. Similarly, a medical patch sheet (all medical patches of the sheet as a whole) may contain capsaicin in an amount of about 179 mg or less. A preferred medical patch sheet is - two self - adhesive layer structures, each containing capsaicin in an amount of about 90 mg, or - three self - adhesive layer structures, each containing capsaicin in an amount of about 60 mg, or - four self - adhesive layer structures, each containing capsaicin in an amount of about 45 mg, or - six self - adhesive layer structures, each containing capsaicin in an amount of about 30 mg, or - nine self - adhesive layer structures, each containing capsaicin in an amount of about 20 mg. Alternatively, a preferred medical patch sheet contains up to 300 self - adhesive layer structures, each layer containing capsaicin in an amount of about 0.6 mg. Preferably, the self - adhesive layer structures are of type I or type II (special) pentagons as described above, and are connected to each other by a common fastening bridge for joining and peeling from the release liner. All adjacent self - adhesive layer structures are connected to each other in groups of three or four by a common fastening bridge provided at the shared vertex or common vertex of two self - adhesive layer structures on the side of a third self - adhesive layer structure.

[0231] In certain embodiments, a medical patch (a single medical patch) has a release area of 0.1 cm 2 ~280 cm 2 、0.6 cm 2 ~150 cm 2 、or 1.5 cm 2 ~35 cm 2 In certain embodiments, the area of the medical patch is greater than 20 cm 2 、e.g., greater than 24 cm 2 、greater than 30 cm 2 、or greater than 40 cm 2 、and preferably greater than 150 cm 2Less than, for example, 60cm 2 Less than 35cm 2 It is less than 1 cm². In certain embodiments, the release area of ​​a medical patch sheet (all medical patches that make up the entire sheet) is 1 cm². 2 ~300cm 2 That is the case.

[0232] Treatment method / medical use The medical patch or medical patch sheet according to the present invention may be suitable for use in therapeutic methods, particularly in methods of treating human patients. The symptoms and diseases to be treated will vary depending on the active agent contained in the patch.

[0233] When the activator is capsaicin, the medical patch or medical patch sheet according to the present invention is particularly suitable for use in methods of treating neuropathic pain, especially chronic neuropathic pain, which preferably includes postherpetic neuralgia, postoperative neuralgia (e.g., post-inguinal hernia pain, post-thoracotomy pain or post-mastectomy pain), post-traumatic neuropathy, polyneuropathy (e.g., pain associated with diabetic neuropathy), chemotherapy-induced neuropathy, tumor-related neuropathy, HIV-related neuropathy, alcohol-related neuropathy, small-diameter fibrous neuropathy or complex regional pain syndrome, radiculopathy, or compression syndromes such as carpal tunnel syndrome, and more preferably peripheral neuropathic pain, neuropathic pain associated with postherpetic neuralgia of the limbs or diabetic peripheral neuropathy (DPN), postoperative neuropathic pain, arthralgia, or cancer pain.

[0234] In connection with the foregoing, the medical patch or medical patch sheet (or part thereof) according to the present invention is preferably applied to at least one body surface of a patient, particularly a portion selected from the back, buttocks, legs, feet, or hands. The preferred application time for the medical patch or medical patch sheet according to the present invention is less than 60 minutes or about 60 minutes for the back, buttocks, or legs, and less than 30 minutes or about 30 minutes for the feet or hands.

[0235] Manufacturing process The medical patch(s) or medical patch sheet(s) according to the present invention can be manufactured by a conventional manufacturing process such as a solvent casting method, which includes the steps of preparing a coating composition containing all the components of the active layer, and coating and drying the coating composition.

[0236] In certain embodiments, particularly in the case of capsaicin-containing patches, the process for manufacturing a medical patch or medical patch sheet according to the present invention is as follows: A. 1.1) Coating with an active agent-containing coating composition, wherein the composition is (i) Polymer I and (ii) Active agent and, Includes, Coating the composition onto the release liner, coating, 1.2) Dry the coated coating composition to provide an active agent-containing self-adhesive layer structure, 1.3) Laminating an active drug-containing self-adhesive layer structure with a backing layer, This includes the following steps.

[0237] Polymer I is, in particular, preferably non-curable, and therefore usually applied by a solution-based process, at least one silicone-based polymer. Accordingly, at least one silicone-based polymer is preferably supplied in a solvent, the solids content of which is preferably 40-75% by weight. The solvent is preferably selected from alcoholic solvents, particularly methanol, ethanol, isopropanol and mixtures thereof, and non-alcoholic solvents, particularly ethyl acetate, hexane, heptane, petroleum ether, toluene and mixtures thereof, more preferably selected from non-alcoholic solvents, most preferably ethyl acetate or n-heptane.

[0238] The active agent is preferably capsaicin, which is uniformly dissolved or dispersed in the active agent-containing coating composition. In certain embodiments, capsaicin is provided in an amphiphilic solvent such as diethylene glycol monoethyl ether, 1,3-butanediol, dipropylene glycol, or 2,2-dimethyl-4-hydroxymethyl-1,3-dioxolane, and the capsaicin preparation is dispersed in the capsaicin-containing coating composition in the form of droplets (microreservoir system). The amphiphilic solvent should not be mixed with the solvent for the silicone polymer, or may be mixed only slightly.

[0239] The coated active agent-containing coating composition is solidified by drying. Drying is preferably carried out at a temperature of 20-60°C or 30-40°C.

[0240] In the case of patches that include an additional skin contact layer, these are, A. 1.1) Coating with an active agent-containing coating composition, wherein the composition is (i) Polymer I and (ii) Active agent and, Including, Coating the composition onto the first foil, coating, 1.2) Drying the coated coating composition to form a matrix layer, 1.3) Laminating the active layer with the backing layer, 2.1) Coating with an inactive coating composition, wherein the composition is (i) at least one alkenyl-substituted polydiorganosiloxane, (ii) At least one organosiloxane containing a silicone-bonded hydrogen atom, (iii) comprising at least one catalyst for the reaction between a SiH group and a Si-alkenyl group, Coating the composition onto the second foil, coating, 2.2) Crosslinking the inactive coating composition at a temperature of 50°C to 150°C, or irradiating it with ultraviolet light to form a skin contact layer, 2.3) Laminating the skin contact layer with the release liner, It can be manufactured using a process that includes the following steps.

[0241] The inactive coating composition forms a silicone gel adhesive in the skin contact layer during curing, i.e., when the reactive groups of the silicone polymer are crosslinked. Crosslinking is preferably carried out at a temperature of 40 to 140°C.

[0242] The active layer and the skin contact layer are preferably prepared separately as described above, then the foil is removed, and the two layers are then laminated together by laminating the open sides together to obtain a self-adhesive layer structure of a medical patch, or two or more self-adhesive layer structures of a medical patch constituting a medical patch sheet. Therefore, this process further, A. 3.1) Remove the foil from the active layer and the skin contact layer, 3.2) To obtain an active drug-containing self-adhesive layer structure by laminating the open side of the active layer to the open side of the skin contact layer, This may include the following steps. The active layer may be prepared before or after the preparation of the skin contact layer, or the preparation of the two layers may be carried out in parallel.

[0243] Next, it is preferable to divide the activator-containing self-adhesive layer structure into one or more self-adhesive layer structures having a pentagonal shape by, for example, punching out or cutting the backing layer and the active layer, and optionally the skin contact layer, in accordance with the present invention, and preserving the release liner. Therefore, the process for manufacturing a medical patch or medical patch sheet according to the present invention is further, B. Divide the active drug-containing self-adhesive layer structure into at least one pentagonal shape to obtain a medical patch or medical patch sheet. It can include steps.

[0244] In certain embodiments, the splitting is carried out by punching, particularly by punching using a steel rule die. In some embodiments, the punching tool may be discontinuous in order to provide a fastening bridge.

[0245] The present invention also relates to a medical patch or medical patch sheet that can be obtained by the above process. [Examples]

[0246] Next, the present invention will be described more fully with reference to the attached examples. However, it should be understood that the following description is illustrative only and should not be considered as limiting the present invention in any sense. The numerical values ​​provided in the examples regarding the amount or area weight of components in the composition may vary slightly due to manufacturing variations.

[0247] Example 1: Preparation of a capsaicin-containing medical patch sheet The medical patch according to Example 1 may or may not include an additional skin contact layer. Therefore, the steps of preparing and applying the inactive coating composition and laminating the resulting inactive layer with the previously prepared capsaicin-containing layer are optional.

[0248] Capsaicin-containing coating composition The formulations of the capsaicin-containing coating compositions are summarized in Table 1.1 below. The solids content percentage refers to the amount by weight (Amt).

[0249] [Table 1]

[0250] Preparation of a capsaicin-containing coating composition Transcutol was first thickened with ethylcellulose under stirring (100-300 rpm).

[0251] The polysiloxane mixture and silicone oil were placed in a container and stirred for at least 5 minutes (100-300 rpm) before adding the ethylcellulose / Transcutol solution. After stirring for another 10 minutes (100-300 rpm), capsaicin was added. The mixture was then stirred at approximately 250-300 rpm (for at least 60 minutes) until a homogeneous mixture was obtained. Coating of capsaicin-containing coating composition

[0252] The resulting capsaicin-containing coating composition was coated onto a fluoropolymer-coated polyester film (Scotchpak® 1022). The solvent was removed at room temperature over approximately 20-30 minutes.

[0253] The coating thickness is approximately 80 g / m², determined by the area weight of the capsaicin-containing layer after solvent removal. 2 I chose to make it so.

[0254] Next, the resulting capsaicin-containing microreservoir layer was laminated with a backing layer (polyester film, 19 μm).

[0255] Optionally, the adhesive foil used for coating and drying the capsaicin-containing layer is removed to obtain a capsaicin-containing self-adhesive layer structure including a backing layer and a capsaicin-containing layer. Here, the capsaicin-containing layer is attached to the backing layer.

[0256] Deactivating coating composition The formulation of the inactive coating composition for Example 1 is summarized in Table 1.2 below. The solids content % value refers to the amount in weight % (Amt).

[0257] [Table 2]

[0258] Preparation of an inactive coating composition Both components were weighed separately, and component A was added to a mixing container, followed by component B. The mixture was then mixed at approximately 200 rpm for approximately 5 minutes until a homogeneous mixture of component A and component B was obtained.

[0259] Coating of an inactive coating composition Within a time frame of approximately 30 minutes, the obtained inactive coating composition was coated onto an adhesive foil. The coating temperature was set to 120°C. The resulting inactive layer was heated at this temperature for approximately 40 minutes.

[0260] The coating thickness, after solvent removal, is approximately 230 g / m² for the inactive (skin contact) layer. 2 I chose to make it so.

[0261] The resulting inactive (skin-contact) layer was laminated with a release liner (FEP, fluorinated ethylene propylene, 125 μm).

[0262] Layers of capsaicin-containing layer and inactive (skin contact) layer. Next, an inactive (skin-contact) layer was laminated with the capsaicin-containing layer. For this purpose, the adhesive foil used for coating and drying the layers was removed, and the open sides of the resulting active-containing layer and inactive (skin-contact) layer were laminated together, resulting in a capsaicin-containing self-adhesive layer structure comprising a backing layer, a capsaicin-containing layer, and an inactive (skin-contact) layer. Here, the capsaicin-containing layer is bonded to the backing layer, the inactive (skin-contact) layer is bonded to the capsaicin-containing layer, and this structure is closed by a release liner bonded to the inactive (skin-contact) layer.

[0263] Preparation of medical patches and medical patch sheets Each medical patch was punched out from a capsaicin-containing self-adhesive layer structure obtained as described, comprising either a backing layer and a capsaicin-containing layer, or a backing layer, a capsaicin-containing layer, and an inactive (skin contact) layer, without damaging the common release liner.

[0264] Next, the medical patch sheets were sealed in pouches made of primary packaging material.

[0265] Examples 2A to 2L and Reference Examples: Performance evaluation of placebo medical patches and placebo medical patch sheets Different medical patches and medical patch sheets (without active agents) according to the present invention were prepared based on an adhesive layer without active agents (Examples 2A to 2M). Similarly, rectangular medical patches measuring 20 cm x 14 cm were prepared (Reference Example).

[0266] Coating composition The formulations of the coating compositions are summarized in Table 2.1 below. The solids content percentage refers to the amount in weight percentage (Amt).

[0267] [Table 3]

[0268] Preparation of medical patches and medical patch sheets Individual medical patches were punched out from the inactive self-adhesive layer structure obtained as described above, which was placed on a release liner including a backing layer and an inactive layer, without damaging the common release liner. In this way, medical patches and medical patch sheets having the pentagonal shape shown in Table 2.2 were obtained.

[0269] Subsequently, the performance of the medical patches and medical patch sheets was evaluated by applying each medical patch (or sheet) or medical patch sheet to different skin areas, particularly the ankles / toes, and assessing the coverage of the skin area to be treated (+: low coverage ~ +++: good coverage) and the occurrence of wrinkles (*: no / few wrinkles ~ ***: many wrinkles).

[0270] The results are shown in Table 2.2 below.

[0271] [Table 4-1] [Table 4-2] [Table 4-3]

[0272] In general, pentagonal medical patches / patch sheets provided better coverage and fewer wrinkles than rectangular medical patches. Various pentagonal medical patches / patch sheets performed similarly well on substantially flat or cylindrical surfaces such as the back, thighs, lower limbs, or arms.

[0273] On uneven or curved surfaces such as the ankle or toes, single and multiple pentagons of types I and II showed very good coverage with little to no wrinkles. However, the multi-pentagon pattern, consisting of two regular hexagons with side lengths of 2.4 cm or 2.6 cm, was too large to apply to a single toe and needed to be arranged in a different pattern containing four or two pentagons each.

[0274] Smaller pentagons offered better usability compared to larger pentagons. The best usability results were obtained with pentagons containing one or more Type I pentagons with a minimum side length of 0.9 cm or more, or one or more Type II pentagons with a minimum side length of 1.2 cm or more.

[0275] For curved surfaces, gapless coverage can only be achieved by minimizing the overlap of the pentagonal edges.

[0276] The most effective choice of medical patch(s) / medical patch sheet varies depending on the specific skin area to be treated.

[0277] The present invention relates in particular to the following further provisions. 1. A self-adhesive layer structure used in medical patches, having a pentagonal shape, A) Backing layer, B) An active layer containing polymer I and an active agent, Includes, The backing layer and the active layer have the same extent, providing the pentagonal shape of the self-adhesive layer structure. The aforementioned pentagonal shape includes at least one pentagon, The sides of the aforementioned pentagon have lengths ranging from 0.2 cm to 12.5 cm. The self-adhesive layer structure.

[0278] 2. The self-adhesive layer structure according to Clause 1, wherein the self-adhesive layer structure is a pressure-sensitive adhesive layer structure.

[0279] 3. The self-adhesive layer structure according to clause 1 or 2, wherein the at least one pentagon is at least one convex pentagon.

[0280] 4. The self-adhesive layer structure according to Clause 3, wherein the pentagonal shape includes 1 to 3 convex pentagons.

[0281] 5. The self-adhesive layer structure according to any one of the clauses 1 to 4, wherein the pentagonal shape is a convex pentagon.

[0282] 6. The self-adhesive layer structure according to any one of the clauses 1 to 4, wherein the pentagonal shape is a double pentagon formed from two identical convex pentagons that share two adjacent vertices and a common edge.

[0283] 7. The self-adhesive layer structure according to any one of the clauses 1 to 4, wherein the pentagonal shape is a triple pentagon formed from three identical convex pentagons that share two adjacent vertices and their common edges in pairs.

[0284] 8. The self-adhesive layer structure according to Clause 6 or 7, wherein the common edge is perforated to facilitate separation.

[0285] 9. The aforementioned pentagon is an unequal-sided shape. A self-adhesive layer structure as described in any of clauses 1 to 8, wherein the sum of one interior angle and the other interior angle is 180°.

[0286] 10. One interior angle is 60° and the other interior angle is 120°, or The self-adhesive layer structure described in Clause 9, wherein one interior angle and the other interior angle are each 90°.

[0287] 11. The self-adhesive layer structure according to any one of the clauses 1 to 10, wherein the pentagon has two 90° interior angles and preferably three 120° interior angles.

[0288] 12. The pentagon is an equilateral, or The aforementioned pentagon is an irregular shape, Four sides of equal length, or It has two sides of equal length and two other sides of equal length, A self-adhesive layer structure as described in any of clauses 1 to 11.

[0289] 13. The self-adhesive layer structure according to any of the clauses 1 to 12, wherein the pentagon is an unequal side, and the ratio of one side to another is about 1:1, or about 1:2 / √3, or about 1:√3, or about 1:2, or about 1:2√3.

[0290] 14. The self-adhesive layer structure according to any of the clauses 1 to 13, wherein the pentagon is an unequal-sided shape, and the ratio of the shortest side to the longest side is approximately 1:2 or approximately 1:2√3.

[0291] 15. The self-adhesive layer structure according to any of the clauses 1 to 14, wherein the lengths of the sides of the pentagon are 0.3 to 10 cm, 0.6 to 5 cm, 0.7 to 4.5 cm, or 0.9 to 2.4 cm.

[0292] 16. The self-adhesive layer structure according to any of clauses 1 to 15, wherein one, two, three, four, or five sides of the pentagon have lengths of approximately 0.5 cm, approximately 1 cm, approximately 1.3 cm, approximately 1.7 cm, approximately 2 cm, approximately 2.5 cm, approximately 3.1 cm, or approximately 4.5 cm.

[0293] 17. The self-adhesive layer structure according to any of the clauses 1 to 16, wherein two sides of the pentagon are parallel.

[0294] 18. The self-adhesive layer structure according to any one of the clauses 1 to 17, wherein the pentagon is mirror symmetry having at least one axis of symmetry.

[0295] 19. The self-adhesive layer structure according to any one of the clauses 1 to 18, wherein the active agent is at least one analgesic.

[0296] 20. The self-adhesive layer structure according to Clause 19, wherein the active agent is selected from the group consisting of buprenorphine, capsaicin, diclofenac, fentanyl, ibuprofen, and lidocaine.

[0297] 21. The self-adhesive layer structure according to clause 19 or 20, wherein the active agent is capsaicin.

[0298] 22. The self-adhesive layer structure according to Clause 21, wherein the active layer contains the capsaicin at a concentration of 2-20% by weight, 5-15% by weight, 5-10% by weight, or about 8% by weight.

[0299] 23. The self-adhesive layer structure according to clause 21 or 22, wherein the self-adhesive layer structure comprises capsaicin in an amount of 0.5 to 180 mg, 1.2 to 90 mg, or 19 to 45 mg.

[0300] 24. The self-adhesive layer structure according to any one of the clauses 21 to 23, wherein the self-adhesive layer structure contains capsaicin in an amount of about 179 mg, about 90 mg, about 60 mg, about 45 mg, about 30 mg, about 20 mg, about 10 mg, or about 1 mg.

[0301] 25. A self-adhesive layer structure according to any one of clauses 1 to 24 for transdermal or topical delivery of the active agent.

[0302] 26. The self-adhesive layer structure according to any one of the clauses 1 to 25, wherein the polymer I is a pressure-sensitive adhesive polymer.

[0303] 27. The self-adhesive layer structure according to any one of the clauses 1 to 26, wherein the polymer I is selected from silicone polymers, acrylic polymers, silicone-acrylic hybrid polymers, and polymers based on natural rubber or synthetic rubber.

[0304] 28. The self-adhesive layer structure according to any one of the clauses 1 to 27, wherein the polymer I is a silicone-based polymer obtained by polycondensation of silanol-termined polydimethylsiloxane and silicate resin.

[0305] 29.A) The backing layer and, B) The active layer and, C) a skin contact layer; Includes, The self-adhesive layer structure according to any one of the clauses 1 to 28, wherein the backing layer, the active layer, and the skin contact layer have the same extent and provide the pentagonal shape of the self-adhesive layer structure.

[0306] 30. The self-adhesive layer structure according to Clause 29, wherein the skin contact layer is an adhesive, preferably a pressure-sensitive adhesive.

[0307] 31. The skin contact layer comprises polymer II, the self-adhesive layer structure according to clause 29 or 30.

[0308] 32. The self-adhesive layer structure according to Clause 31, wherein the polymer II is a polymer or a mixture of polymers in which the active agent is substantially insoluble.

[0309] 33. The self-adhesive layer structure according to clause 31 or 32, wherein the polymer II is a pressure-sensitive adhesive or a mixture of pressure-sensitive adhesives.

[0310] 34. The self-adhesive layer structure according to any one of the clauses 31 to 33, wherein the polymer II is a polymer or mixture of polymers selected from the group consisting of silicone acrylic hybrid polymers, silicone polymers, silicone gel adhesives, and polymers based on natural rubber or synthetic rubber.

[0311] 35. The self-adhesive layer structure according to any one of the clauses 31 to 34, wherein the polymer II is a polymer or mixture of polymers selected from the group consisting of silicone polymers and silicone gel adhesives.

[0312] 36. The self-adhesive layer structure according to any one of the clauses 31 to 35, wherein the polymer II is a silicone gel adhesive.

[0313] 37. The skin contact layer comprises a self-adhesive layer structure according to clause 29 or 30, comprising a silicone gel adhesive.

[0314] 38. The self-adhesive layer structure according to Clause 36 or 37, wherein the silicone gel adhesive is obtained by reacting a gel-forming composition comprising (i) at least one alkenyl-substituted polydiorganosiloxane, (ii) at least one organosiloxane containing a silicone-bonded hydrogen atom, and (iii) at least one catalyst for the reaction between the SiH group and the Si-alkenyl group.

[0315] 39. The silicone gel adhesive is a self-adhesive layer structure according to any one of the clauses 36 to 38, obtained by reacting (i) a gel-forming composition comprising a copolymer of vinylmethylsiloxane and dimethylsiloxane, (ii) a methylhydrogenpolysiloxane having a trimethylsilyl terminal group, and (iii) a platinum catalyst in the presence of a platinum catalyst.

[0316] 40. The self-adhesive layer structure according to any one of the clauses 36 to 39, wherein the silicone gel adhesive is a silicate resin-reinforced silicone gel adhesive containing about 2 to about 45% by weight or about 20 to about 30% by weight of at least one hydroxyl-substituted silicate resin.

[0317] 41. The self-adhesive layer structure according to any one of the clauses 1 to 40, wherein the saturation concentration of the active agent in the skin contact layer is less than 0.1% by weight, less than 0.05% by weight, less than 0.02% by weight, or less than 0.01% by weight.

[0318] 42. The self-adhesive layer structure according to any one of the clauses 1 to 41, wherein the active layer comprises further excipients or additives selected from the group consisting of additional polymers, crosslinking agents, crystallization inhibitors, solubilizers, fillers, tackifiers, plasticizers, stabilizers, softeners, skincare substances, permeability enhancers, pH adjusters, and preservatives.

[0319] 43. The self-adhesive layer structure according to Clause 42, wherein the active layer comprises an additional polymer selected from dimethylpolysiloxane and ethylcellulose.

[0320] 44. The self-adhesive layer structure according to clause 42 or 43, wherein the active layer comprises a permeation enhancer selected from diethylene glycol monoethyl ether.

[0321] 45. It is a medical patch, A self-adhesive layer structure as described in any of clauses 1 to 44, Release liner and Includes, The medical patch wherein the release liner has the same extent as the self-adhesive layer structure, or extends in any direction beyond the boundary of the self-adhesive layer structure.

[0322] 46. ​​Medical patch sheet, Two or more self-adhesive layer structures as described in any of clauses 1 to 44, Release liner and Includes, The medical patch sheet wherein the release liner has the same extent as the self-adhesive layer structure, or extends in all directions beyond the boundary formed by the self-adhesive layer structure.

[0323] 47. A medical patch sheet as described in Clause 46, comprising 2-400, 3-300, 4-120, or 6-30 self-adhesive layer structures.

[0324] 48.2 A medical patch sheet as described in Clause 47, comprising 15 or 150-300 self-adhesive layer structures.

[0325] A medical patch sheet according to Clause 47 or 48, comprising 49.2, 3, 4, 6, or 9 self-adhesive layer structures.

[0326] 50. The self-adhesive layer structure is arranged in two or more parallel rows with respect to the longitudinal axis of the release liner, Each row preferably comprises 2 to 20, 3 to 12, or 4 to 8 self-adhesive layer structures, as described in any of the medical patch sheets of clauses 46 to 49.

[0327] 51. The self-adhesive layer structure is arranged in one or more repeating geometric patterns, Each geometric pattern preferably comprises 2 to 15, 3 to 12, or 4 to 9 self-adhesive layer structures, as described in any of clauses 46 to 49 of the medical patch sheet.

[0328] 52. The self-adhesive layer structure is arranged in the form of one or more hexagons, Each hexagon preferably comprises two or three self-adhesive layer structures, according to any of the medical patch sheets in any of the clauses 46 to 51.

[0329] 53. The hexagon is a regular hexagon, as described in Article 52 of the medical patch sheet.

[0330] 54. The self-adhesive layer structure is a medical patch sheet according to any one of the clauses 46 to 53, which tiles a flat surface.

[0331] 55. The self-adhesive layer structures are adjacent to each other by sharing at least one vertex and at least a portion of an adjacent edge. The adjacent edges are cut so that they can be peeled off independently from the release liner, thus separating them from each other, or A medical patch sheet according to any of the clauses 46 to 54, connected to one another by the adjacent edges that have been weakened to facilitate separation.

[0332] 56. The self-adhesive layer structures are adjacent to each other by sharing two adjacent vertices and their common edges. The common edges are cut so that they can be peeled off independently from the release liner, thus separating them from each other, or A medical patch sheet according to any of the clauses 46 to 55, connected to one another by the aforementioned common edges that have been weakened to facilitate separation.

[0333] 57. A medical patch sheet according to Clause 55 or 56, wherein all self-adhesive layer structures are separated from each other by cutting the adjacent or common edges so that they can be peeled off independently from the release liner.

[0334] 58. The medical patch sheet according to Clause 57, wherein the adjacent or common edges are perforated to facilitate separation.

[0335] 59. The medical patch sheet according to any one of the clauses 46 to 54, wherein the self-adhesive layer structure is connected to one another by at least one, preferably two or more common fastening bridges for joint peeling from the release liner.

[0336] 60. The medical patch sheet according to Clause 59, wherein the common fastening bridge is provided at the vertices or edges and connects at least two, preferably three or four, self-adhesive layer structures.

[0337] 61. The medical patch sheet according to Clause 59 or 60, wherein all adjacent self-adhesive layer structures are paired and connected to one another by at least two common fastening bridges provided at two adjacent vertices and / or one vertex and adjacent edges.

[0338] 62. The medical patch sheet according to Clauses 59-61, wherein all adjacent self-adhesive layer structures are connected to each other in groups of three or four by common fastening bridges provided at the vertices and / or edges.

[0339] 63. The medical patch sheet according to any of the clauses 46 to 62, wherein the self-adhesive layer structure has a pentagonal shape selected from a total of two or three different shapes.

[0340] 64. The medical patch sheet according to Clause 63, wherein the self-adhesive layer structure has a pentagonal shape including a convex pentagon and a double pentagon formed from two identical convex pentagons sharing two adjacent vertices and their common edge.

[0341] 65. A medical patch sheet according to any of the clauses 46 to 62, wherein all of the self-adhesive layer structures have the same pentagonal shape.

[0342] 66. The self-adhesive layer structure is Two interior angles of 90° and three interior angles of 120°, It is an unequal-sided convex pentagon having two sides of equal length and two other sides of equal length. The ratio of the shortest side to the longest side is approximately 1:2, or approximately 1:2√3, for the medical patch sheet as described in Clause 65.

[0343] 67. The medical patch sheet according to Clause 66, wherein the two sides of the pentagon are parallel.

[0344] 68. A medical patch sheet according to any of the clauses 65 to 67, further comprising one or more additional self-adhesive layer structures having a hexagonal shape including one or two hexagons.

[0345] 69. A process for manufacturing a medical patch as described in Clause 38, or a medical patch sheet as described in any of Clauses 46 to 68, A. 1.1) Coating with an active agent-containing coating composition, wherein the composition is (i) Polymer I and (ii) Active agent and, The composition includes coating the release liner with the said composition, and the coating process 1.2) The coated coating composition is dried to provide an active agent-containing self-adhesive layer structure, 1.3) Laminating the self-adhesive layer structure containing the active agent with the backing layer, B. Dividing the active agent-containing self-adhesive layer structure into at least one pentagonal shape to obtain the medical patch or the medical patch sheet, The process, including the step of:

Claims

1. A self-adhesive layer structure used in medical patches, having a pentagonal shape, A) Backing layer, B) An active layer containing polymer I and an active agent, Includes, The backing layer and the active layer have the same extent, providing the pentagonal shape of the self-adhesive layer structure. The aforementioned pentagonal shape includes at least one pentagon, The sides of the aforementioned pentagon have lengths ranging from 0.2 cm to 12.5 cm. The self-adhesive layer structure.

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

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

4. The self-adhesive layer structure according to claim 3, wherein the pentagonal shape includes one to three convex pentagons.

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

6. The aforementioned pentagon is an unequal-sided polygon, The sum of one interior angle and the other interior angle is 180°. Preferably, the pentagon has two 90° interior angles and at least one, preferably three, 120° interior angles, the self-adhesive layer structure according to any one of claims 1 to 5.

7. The aforementioned pentagon is an equilateral triangle, or The aforementioned pentagon is an irregular shape, Four sides of equal length, or It has two sides of equal length and two other sides of equal length, Preferably, the ratio of the shortest side to the longest side is about 1:2 or about 1:2√3, the self-adhesive layer structure according to any one of claims 1 to 6.

8. The self-adhesive layer structure according to any one of claims 1 to 7, wherein the length of the side of the pentagon is 0.3 to 10 cm, 0.6 to 5 cm, 0.7 to 4.5 cm, or 0.9 to 2.4 cm.

9. The self-adhesive layer structure according to any one of claims 1 to 8, wherein two sides of the pentagon are parallel.

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

11. It is a medical patch, A self-adhesive layer structure according to any one of claims 1 to 10, Release liner and Includes, The medical patch wherein the release liner has the same extent as the self-adhesive layer structure, or extends in any direction beyond the boundary of the self-adhesive layer structure.

12. It is a medical patch sheet, A self-adhesive layer structure comprising two or more self-adhesive layers according to any one of claims 1 to 10, Release liner and Includes, The medical patch sheet wherein the release liner has the same extent as the self-adhesive layer structure, or extends in all directions beyond the boundary formed by the self-adhesive layer structure.

13. The self-adhesive layer structure is arranged in the shape of one or more hexagons, Each hexagon preferably includes two or three self-adhesive layer structures. Preferably, the hexagon is a regular hexagon, as described in claim 12.

14. The self-adhesive layer structures are adjacent to each other by sharing at least one vertex and at least a portion of an adjacent edge, The adjacent edges are cut so that they can be peeled off independently from the release liner, thus separating them from each other, or A medical patch sheet according to claim 12 or 13, connected to one another by the adjacent edges that have been weakened to facilitate separation.

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

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

17. All of the aforementioned self-adhesive layer structures have the same pentagonal shape. Two interior angles of 90° and three interior angles of 120°, It is an unequal-sided convex pentagon having two sides of equal length and two other sides of equal length. The ratio of the shortest side to the longest side is approximately 1:2, or approximately 1:2√3. Preferably, the two sides of the pentagon are parallel, as described in claim 16.

18. A process for manufacturing a medical patch according to claim 11, or a medical patch sheet according to any one of claims 12 to 17, A. 1.1) Coating with an active agent-containing coating composition, the composition (i) Polymer I and (ii) Active agent and, The composition includes coating the release liner with the said composition, and the coating process 1.2) The coated coating composition is dried to provide an active agent-containing self-adhesive layer structure, 1.3) Laminating the active agent-containing self-adhesive layer structure with the backing layer, B. Dividing the active agent-containing self-adhesive layer structure into at least one pentagonal shape to obtain the medical patch or the medical patch sheet, The process, including the step of:

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