MXPA00011071A - Laminate for application onto an acceptor - Google Patents

Abstract

The invention relates to a laminate for application onto an acceptor, comprising at least one intact layer, at least one non-intact layer, at least one additional layer and a removable protective layer. The laminate is characterized in that along a cross-sectional edge of any cross section it consists in places of m layers and in places of n layers, m and n are whole numbers and m>n.

Description

LAM I NADO TO APPLY ON AN ACCEPTOR The invention relates to a laminate for application on an acceptor, comprising: at least one intact layer, at least one sheet with flaws, another layer at least, and a removable protective layer. The invention also relates to a process for its manufacture and its use. The suitability of a laminate intended to be applied on an acceptor, for example on the skin, is essentially determined by the quality of a contact surface of the laminate. In the case of a transcutaneous therapeutic system (STT), the type and quality of the contact surface with the skin also determines the amount of active substance that is perfused through the skin in a unit of time. During the time that the skin supports the laminates of the most diverse types that are applied on it patches, bandages, "strips", STT, etc., they experience repeated mechanical loads, depending on the place of application, derived from stresses of elongation, crushing or bending, which can lead to partial detachment, fraying at the edges or the formation of bubbles. This problem, often observed in laminates applied to the skin, in the case of STT, gives rise to even greater disadvantages, because by reducing the contact surface between the STT and the skin, the amount of active substance that is intended to be perfused. In addition, a laminate intended to be applied to the skin loses mechanical stability due to the stretching and bending stresses, which further aggravate the detachment process. These mechanical stresses exert a more persistent effect on the loss of adhesion, the less elastic a patch in its horizontal elongation. The elasticity of these systems is determined by the moduli of elasticity of the different components or individual layers constituting them. In the case of a STT, it usually lies in the carrier or protective sheet that forms the back layer. In addition, the systems provided for therapeutic applications must have a series of additional features, such as support or protection functions, or compatibility with the exudation of the wound or the moisture of the skin. Therefore, in the laminates to be applied on the skin, it is necessary to have a wide variability of its use case by case, derived from the different places of the body where they are applied. For example, a laminate corresponding to a rheumatic patch, which is applied in flat areas of the skin with underlying smooth muscle, undergoes considerably less efforts in relation to its ability to resist the action of bending and lengthening forces, than a laminate that It is applied to areas of the skin with underlying musculature of transverse fibers, such as the arm or thigh, or that located in the area of a joint, such as the knee. Provided that a laminate of this type should not only have the function of support or protection, as is the case with protective bandages of the knees or tapes that protect the fingers, for example of sports climbers, but should also serve for the application of a broad spectrum of different active substances, it is desirable to achieve a great variability in this respect, for example in relation to the temporal evolution of a rate of release of active substance per unit of time. It should also be possible to insert different active substances into a laminate and regulate their release by means of control layers in such a way that a differentiated transfer in time to the skin and / or through it is carried out. It should also be possible to insert a reservoir for the active substance that is consumed during the course of the application. Other provisions have to make it possible, for example, to also insert into the laminate previous phases of active substances thatAs soon as a predicted inert time has elapsed, they are transferred to the skin once they have been converted into an active substance under the action, for example, of the moisture of the skin and / or substances such as enzymes. The most particular requirements of the patches containing active substance relate, for example, to good adhesion to a substrate, poor water permeability and / or acceptance of active substance, good light fastness and / or good thermal insulation The use of an occlusive effect, for example, the elevation of the water content in the skin layers under a patch, is another fundamental characteristic of a series of STT, which is achieved by the convenient use of sheets impervious to water vapor. In view of such a diverse spectrum of requirements that the laminates that apply to different acceptors in the various applications must meet, their usual embodiments usually do not give satisfactory results. Often, the sheets or layers of available materials possess only a few of the desired properties. In the field of treatment, this limitation may lead, for example, to the corresponding systems being elastic, but permeable to water vapor, or impermeable, but not very elastic. Also the degree of freedom in relation to a selection of active substances is limited from one case to another, or even totally non-existent. DE 36 34 016 C2 describes a laminar therapeutic system for the ad ministration of active substances to the skin, with reservoirs of active substance, surfaces of release thereof and a surface of adherence to the skin located at the same level than the previous ones, which is characterized: either because the surface adheres to the skin is distributed without interruption over the whole surface of contact with the skin and because it consists of interruptions in sections of the surface that the active substance yields, or because of the cession of active substance in an uninterrupted manner over the entire contact surface with the skin and consisting of interruptions in sections of the surface adherent to the skin; and because the size of the sections on the surface of assignment of active substance essentially independent of the compression exerted on the therapeutic system. DE 38 09 978 C2 describes a reservoir with a surface for the transfer of active substances, controlled and decreasing over the time of application, to solid, liquid or gaseous acceptors, with the characteristic that at least at one point of the reservoir a transverse surface thereof, parallel to the transfer surface, is smaller than the transfer surface. Thus a deposit can be created that allows a defined and controlled transfer of active substances for a desired or necessary time. In EP 0 288 734 B 1 a patch with active substance for the controlled administration of active substances to the skin is described, with a reservoir divided into parts that are essentially perpendicular to the surface in contact with the skin and containing one or several active substances, with a self-adhesive device on the side of the skin as well as with a covering layer which, if necessary, can be peeled off before applying the patch, in which the release surface of the active substance of the patch can be removed in an area determined in advance if a part of the reservoir is removed. The patch is characterized by being able to separate at least a part of the active substance reservoir while one or several parts of the active substance reservoir remain on the skin, and by having the part of the reservoir that remains on the skin a power of adhesion on the skin. This one greater than on the back side. From the state of the art, the invention proposes the task of preparing a laminate of the type mentioned at the beginning, to be applied on an acceptor, which if adheres, for example, to the skin of a living organism, even if it is subjected to at strong mechanical stresses, such as elongation, crushing or bending, it does not produce detachment, fraying at the edges or formation of bubbles and therefore a decrease in its contact surface, and also allows a wide range of employment possibilities in relation to different quality requirements, such as the incorporation of different active substances, the evolution over time of the expected release rate of active substance, low water permeability, suitability for different active substances, etc. The solution of the task is achieved according to the invention with a laminate that is applied on an acceptor comprising: at least one intact layer, at least one sheet with flaws, another layer as a minimum, and a removable protective layer characterized by being formed so that along a cut edge of any cross section it has partly m layers and partly n layers, because m and n are integers and because m < n. In this context, "imperfections" in a layer are defined as incisions in the affected layer, which does not necessarily consist of several parts, such as when, for example, a sheet is cut or trochanged. However, the laminate can also have at least another layer that is also damaged, other variants provide that at least one other layer and at least one sheet form congruent superimposed sections.The elastic layer can be a sheet. This layer is characterized by an increase in length from 0.5% to 95% The most advantageous length increase is from 5 to 20% Other possibilities of execution of the object of the application result from the fact that the sections of a One-piece layer consists of a non-extensible sheet or of an inert sheet or of a sheet with water impermeability properties. Another variant of the laminate provides that at least one of the layers is a piece and at least one of these layers is of several pieces and consists of adjacent sections. In this way, the damage of a layer can consist of a series of parallel cuts that side by side alternate in their longitudinal course or are displaced. By last, the extensibility of a layer or of the sheet that forms it can also be achieved thanks to its elastic properties or by means of compensatory folds between the different sections. In such a case, at least two layers can form congruent overlapping sections. From all this it follows that, in an application of the lamination as a STT on the skin, the lengthening of the system as a whole results in the mutual displacement of the sections or the modification of their respective distances from one another, which increases to a high degree The comfort of using the patch, because the part of the affected skin can respond normally to mechanical stresses without being hindered by the patch. Furthermore, when the application is more prolonged, the individual sections remain pressed against the skin in optimal contact with it, and therefore the entire contact surface with the skin remains constant for a longer time. On the other hand, the use of a sheet that fixes the individual segments guarantees that there are no remains when separating the patch from the skin. The use of a sheet artificially converted into elastic by means of compensatory folds between the different segments allows it to be chosen, for example, with the quality of being impermeable to water, since its material does not have to meet any elasticity requirement. The use of a laminate structure such as this allows the simple technical unification of conditions of the back layer that would otherwise be mutually exclusive. To achieve the invention, it can be advantageous if the thickness of a layer between two laminar layers, where one or both of the laminar layers can be damaged or have one or more pieces, is in the range between 1 μm and 500 μm. μm, preferably between 5 μm and 1 50 μm, and particularly preferably between 1 μm and 30 μm. A variant of the invention provides that the laminate intended especially for therapeutic applications has at least one support layer, at least one other layer containing the active substance and, if necessary, one more layer, for example to control the release of the active substance. and / or a self-adhesive layer and / or a removable protective layer, and that at least one of said layers is of several pieces, that is, that there are several zones of different structures in the laminate. The one-piece layer may be an extensible or elastic sheet. Another variant provides that the laminate has a series of sections that represent independent microsystems of identical structure and that are fixed with a sheet of high elasticity that makes the support layer with which they form a complete system. In this variant, the laminate may have a different series of layers and carry in the individual layers locally different active substances, or various concentrations or combinations of active substances, or control means for different rates of release of active substance, etc. For therapeutic applications in particular, the invention is usable in principle with all active substances or auxiliary agents for the skin. Suitable active substances are found in the groups of parasympatholytics (eg scopolamine, atropine, benacticin), of the colmergics (for example, physostigmine, nicotine), neuroleptics (eg, chloropromazine, halopepdol), monoamine oxidase inhibitors (eg, tranylcypromine, selegiline), sympathomimetics (eg, ephedrine, D-norpseudoephedrine, salbutamol, fenfluramine), sympatholytics and of the antisimpatotomcos (for example, propanolol, timolol, bupranolol, clonidine, dihydroergota mine, nafazohna), of the anxiolytics (for example, diazepam, tpazolam), of local anesthetics (for example, lidocaine), of central analgesics (for example, fentanyl, sufentanil), of antirheumatics (for example, , indomethacin, piroxicam, lornoxicam), of coronary therapeutics (for example, glyceroltpnitrate, isosorburodinitrate, nitroglycerin), estrogens, progestagens and androgens, antihistamines (eg diphenhydramma, clemastine, terfenadmin), prostaglandin derivatives, vitamins (eg, vitamin E, cholecalciferol) and of the cytostatics According to the structuring of the properties of the layers, special advantages are also obtained with the use of light-sensitive substances, present in organic chemical products, such as for example phenothiazines, certain peptides, dihydropipdines (for example, nifedipine), opioids and other numerous groups of active substances. There are also other substances suitable for the purposes of the invention if the therapeutic target dose is less than 50 mg and if they are soluble in water and in organic solvents. Mention ethanol, propanediol and other low molecular weight alcohols. , menthol, eucalyptol, limonene and many other terpenes, low molecular weight fatty acids com or for example, caprinic acid, dimethyl sulfoxide, as typical examples of additional substances in these preparations, which could migrate from the preparation with more or less intensity through the posterior layer. They can be used as base material of the layers containing substance activates certain polymers such as polnsobutylene, esters of polyvinyl alcohol, esters of polyacrylic and polymethacrylic acid, natural rubber, styrene, isoprene and styrene-butadiene polymers or silicone polymers, resinous components such as saturated and unsaturated hydrocarbon resins, alcohol derivatives abietinic and ß-pinene, plasticizers such as the esters of phthalic acid, tpglicépdos and fatty acids, as well as a sene of other substances known to specialists To form the layers executed in the form of a sheet are ideal in principle vain materials, acceptable especially for pharmaceutical products polyvinyl alcohol, polymers and n block of styrene dichloride, polyurethane, polyvinyl chloride, polymetaccharides, polyolefins and polyesters, to mention just a few examples The inclusion of an additional protective layer with adhesive, detachable after application and facilitating the application of The skin of the transcutaneous therapeutic system, which can be removed after placing the system. A method of manufacturing a laminate of the type of the invention is characterized by: Applying sections on a one-piece layer or sheet Punching the layer to a removable protective sheet, Bonding another layer or sheet, Remove the protective sheet. Another method of manufacturing a laminate according to the invention is characterized by: Preparation of a laminate comprising at least one sheet (2, 5), Stamping of the layers (11) to at least one layer (5), Bonding at least one other layer (1), in which if necessary an intermediate coating is removed, Where appropriate, removal of a stabilizing layer from the bonded layers.

Other features, characteristics and advantages of the invention can be deduced from the following explanations of an exemplary embodiment represented in the schematic drawings. They show the following: Fig.1 a: Section of a laminate according to a secant plane I - I in Fig. 1 B; Fig. 1b: Top view of the laminate according to Fig. 1a; Fig. 2a: Section of a laminate of another structure according to a secant plane II-II in Fig.2b; Fig.2b: Top view of the laminate according to Fig.2a; Fig.3a: Section of a laminate with a series of sections along the secant plane II-II of Fig.4; Fig.3b: Section of the laminate of fig.3a according to the secant plane I-I of Fig.4; Fig.4: Top view of the laminate of Fig.3a or 3b; Fig.5: Top view of the laminate according to Fig.4 with additional damages; Fig. 6: Example of a laminate of several pieces with suitable defects of at least one layer, where the flaws form sections or segments; Fig. 7: Example of a one-piece laminate with suitable defects of at least one layer, where the flaws do not form sections or segments; Fig.8: Section of a laminate with a series of sections along the secant plane I - I of Fig.9; Fig. 8a: Section of a laminate with alternating arrangement of layers according to Fig.8, and with a series of sections along the secant plane I-I of Fig.9; Fig.8b: Section of a laminate with alternating arrangement of layers according to Fig.8 and with a series of sections along the secant plane I-I of Fig.9; Fig 9 Top view of the laminate of Fig 8, Fig 8a or 8b The cross section of Fig. 1 a, corresponding to a laminate for application on an acceptor, for example on the skin, has a segmentation according to the invention, with an example of favorable choice of segments or sections 1 0a, 10b, 1 0c, etc. Thanks to the high variability achieved with this segmentation, the individual sections 10a-c may have different layers for the achievement of the intended effects. At least one of the layers 1 or 5 are in one piece and at least one of these layers 2, 3, 4 is in several pieces, and these form individual sections 10a, 1 0b 1 0c Segments 1 0a have the different layers 1 -5, of which the layer 1 is one piece and represents a support layer to which individual segments are fixed, which together form a complete system. layer 2, for example, can be a reservoir of active substances, while layer 3 is, for example, a ca release control board for regulating the release of active substances to the skin, and which in turn supports a separate self-adhesive layer 4 With the one-piece protective layer 5, which emerges in the known manner before application, is protected tightly laminate between manufacturing, transport and application, against the loss of active substances and / or against the penetration of foreign substances Section 1 0b has layers 1, 2, 3 and 5, that is, it does not have a layer separate adhesive, but the release control layer can be endowed with adhesive properties The segments 10c also have 4 layers, which are 1, 2, 4 and 5 That is, they do not have the release control layer 3, but rather the matrix 2 is covered with a self-adhesive layer and does not have adhesive properties by itself. According to the known formation of a self-adhesive patch, for example of a STT, it could only consist of three layers, which would be a cap to support 1, a deposit with adhesive properties 2 and a removable protective layer 5 With the example of arrangement of the segments 10a-10c of figure 1 a is to illustrate how thanks to the segmentation a large number of possibilities is obtained of execution hitherto unattainable by virtue of the different segments or sections A stratified structure of this kind can be carried out rationally, for example, with a known printing method But the segmentation also has another decisive advantage, and that is, without prejudice to the modulus of elasticity of the different layers, with the use of a very elastic support layer 1 a laminate is obtained that supports the maximum Repeated mechanical stress For this reason, once the laminate is placed on the skin, the high flexibility of the set allows to avoid with complete safety the partial detachment, fraying by the edges or formation of bubbles even if subjected to repeated mechanical bending, elongation and crushing, and therefore the correct perfusion of the active substance through the contact surface is achieved. Then the use of relatively non-elastic layer materials within the different segments or sections does not represent any inconvenience, because with the existence of a Elastic support layer 1, the individual sections can follow without difficulty d the movements of the skin when it is lengthened or compressed by varying its distance With a simple look at the arrangement of the different sections or segments 1 0a-1 0c of Figure 1b, any non-expert can recognize and understand the overall elasticity gain of the laminate of the invention thanks to the segmentation In the cross section of figure 2a a laminate of somewhat different structure is shown, where the elasticity of the support layer 1 can be achieved, even with starting material relatively rigid of the carrier sheet 1, by means of folds 6 between sections 1 0d or 1 0e The three segments 1 0d have a structure layered with the support layer 1 and the layers 2 ', 2", 4', 4", which represent, for example, contents of active substance with different concentrations The segments or sections 1 e have all, under the support layer 1, a reservoir 2 and a water vapor permeable layer 3, which is activated with the moisture of the skin and therefore triggers the perfusion of active substance after a period of time. delay This stratified structure of figure 2 also serves only as an illustrative example of the variability that allows to achieve the invention in relation to the achievement of desired properties and special functions, together with a high overall elasticity of the system In the top view of the figure 2b the path of the folds 6 of the support layer 1 is observed, from which the great capacity of accommodation of the laminate to the movements of the skin is deduced. The elongation of the overall system results in a mutual displacement of the segments 10. This increases the comfort of supporting the patch, since the affected skin parts can follow the mechanical stresses in the usual way without being hindered by the adherent laminate. In addition, the individual segments 10 remain firm on the skin, whereby the entire system / skin / contact surface remains constant for a relatively longer time. The use of a sheet 1 that fixes the different segments also guarantees the detachment without debris of the different segments 1 0. With the use of a layer system the maximum performance can be obtained in relation, for example, with a low permeability to the ag ua, because the back layer 1 of the basic system is not subject to any elasticity requirement in its material properties. The simple technical unification of conditions of the back layer that would otherwise be mutually exclusive is made possible by the segmentation explained in the invention, together with a high variability for the purposes of the invention. These advantages are also observed in Figures 3a, 3b and 4. In Figure 3a a laminate according to the invention is shown in section with a very elastic back layer 1 and below it a sheet 1 1 of inelastic material, which at its Once it has the ability of transversal elongation shown according to the double arrow 13 thanks to incisions 12. Below is the layer 2 that acts as a reservoir, with a plurality of individual sections 1 0 or 1 0a, which also has incisions (1 2 ) and therefore it is flexible in a transversal sense. The lower side is covered with a protective sheet 5, removable before application Sections 1 0a appear wider in relation to figure 3a due to the different position of the secant plane I-I of figure 3b in the top view of Figure 4 shows the arrangement of the flaws 12 Also, these contribute a high degree, when the material of the sheet is inflexible, to the transverse extensibility according to the arrows 1 3 Another arrangement of the invention is observed in the top view of the Figure 5 With the same layer structure of Figure 4, the defect of at least one layer is realized in two directions 12a and 12b. Thus, bidirectional extensibility of the laminate with the described advantages is guaranteed. Furthermore, the invention welcomes the possibility of combining the advantages of cutting several layers Figures 6 and 7 show, in top view, without detriment to the layered structure, different incision possibilities of at least one layer, which can be executed with advantage in response to the question posed The cross section shown in figure 8, of a laminate for application on an acceptor, for example on the skin, has a segmentation of several layers according to the invention , with a selection of segments or sections 1 1 ac that in the example do not overlap in a congruent manner, but are displaced from each other Analogously to the upper layers of the skin, the stratum corneum, which is constituted by vain rows of flattened cells, the layers 1 1 ac, which may be of non-elastic material, possess the freedom of mutual displacement and therefore guarantee the elasticity of the overall system. a deposit layer of active substance and, if necessary, as in Figure 1 or 2, be made up of other sublayers, such as, for example, a release control layer that regulates the transfer of active substance to the skin and / or a self-adhesive layer. This layer 2 can also be damaged or segmented by incisions (12), as shown in Figure 8, which does not rule out the possibility of forming it in one piece (Figure 8). At least one of layers 1 and 5 of the laminate is in one piece. The layer 5 represents a one-piece protective layer that is removed in the known manner prior to the application of the laminate, and the layer 1 functions as a one-piece support layer, to which individual segments are fixed to form an assembly ( Fig. 8, Fig. 8a). In addition, it may be advantageous to renounce layer 1, as shown in Figure 8b. The water vapor impermeability effect, for example, is achieved by the shifted arrangement of the layers of the system, and the elasticity of the material that is not elastic by the possibility of mutual displacement of the segments. In Figure 9 a top view of the laminate of Figure 8 is shown. The layer structure of Figure 8 serves only as an illustrative example of the variability of a laminate that can be achieved with the invention in relation to the achievement of properties and desired special functions, together with a high overall system elasticity.

Claims (1)

1. REIVIN DICATION EN 1 Multilayer laminate containing at least one intact layer and at least one layer with flaws, characterized by a) being the intact or elastic or elastic layer and b) being the sheet or sheets with inextensible and / or inert and and / or have properties of water vapor impermeability 2 Laminate according to claim 1, characterized in that, when it is intended in particular for therapeutic applications, it consists of at least one support layer (1), of at least one other layer (2) that contains the active substance and, if necessary, a further layer, for example a layer (3) which regulates the release of the active substance and / or a self-adhesive layer (4) and / or a removable protective layer (5) , to present damage to at least one of these layers (1 -5) or to consist of several pieces and to have different areas of different structure 3 Laminate according to one of claims 1 or 2, characterized in that the supporting layer consists of e of a piece (1) in an extendable or elastic sheet 4 Laminate according to one of claims 1 to 3, characterized by having a series of sections (10) that represent independent microsystems of identical structure and that are fixed with an elevated sheet elasticity that makes the support layer (1) with which they form a complete system 5 Laminated according to one or more of claims 1 to 4, characterized in that it is at least one intact stretch or elastic layer, where an increase in length of 0, 5 to 95% in the sense of elongation is favorable and an increase in length of 5 to 20% in the direction of elongation is particularly favorable 6 Laminate according to one or more of claims 1 to 5, characterized by being the blade with imperferable damage and / or inert and / or possessing water vapor impermeability properties 7 Laminate according to one or more of claims 1 to 6, characterized by damage to at least one other layer 8 according to one or more of claims 1 to 7, characterized by forming at least one other layer and at least one sheet sections that are superimposed in a congruent manner. Laminated according to one or more of claims 1 to 8, characterized by forming at least another layer and at least one sheet sections that overlap in a non-congruent manner Laminate according to one or more of claims 1 to 9, characterized in that the elastic layer consists of a sheet 1 Laminate according to one or more of claims 1 to 10, characterized in that the segments (10) consist of a layer of several pieces in a non-extensible and / or inert sheet and / or impermeable to water vapor 12 Laminate according to one or more of claims 1 to 11, characterized in that at least one of the layers (1 -5) of one piece and at least one of the layers (1 -5) of several pieces and consisting of adjacent sections (10) 1 3 Laminate according to one or more of claims 1 to 12 , characterized by consisting the failure of a layer (1 1) in a series of incisions, while the layer remains in one piece 14 Laminated according to one or more of claims 1 to 1 3, characterized in that the defect of a layer (1 1) ) in a series of incisions (1 2) distributed or arbitrarily oriented 15 Laminated according to one or more of claims 1 to 14, characterized in that the defect of a layer (1 1) consists of a series of parallel incisions (12) which juxtaposed alternatively coincide in their longitudinal course or are disposed offset between themselves Laminate according to one or more of claims 1 to 15, characterized by achieving the extensibility of a layer (1) or of the sheet that forms it by its elastic properties or by means of compensatory pleats (6) between individual sections (10) 17 Laminate according to one or more of claims 1 to 16, characterized by forming at least two layers (2, 3) each super sections placed (1 0) in a consistent manner 1 8 Laminate according to one or more of claims 1 to 1 7, characterized in that the thickness of a layer comprised between two laminar layers is found, where one of the two laminar layers or both can present flaws or be of one or several pieces, in the range between 1 μm and 500 μm, preferably between 5 μm and 500 μm. μm and 150 μm and most preferably between 10 μm and 30 μm 1 9 Laminate according to one or more of claims 1 to 1 8, characterized by having the flaw of a layer a minimum extension of 1 mm 20 Method of manufacturing a laminate according to the invention, characterized by - the preparation of a laminate comprising at least one sheet (2, 5), - the punching of the layers (11) to at least one layer (5) - the application of at least one other layer (1), from which, if necessary, an intermediate coating is removed, - where appropriate, removal of one stabilizing layer of the applied layers Process for manufacturing a laminate according to the invention, characterized by applying sections (1 0) in a layer or sheet of a piece (11), punching the layer (11) to a removable protective sheet (5), apply another layer or sheet (1), remove the protective sheet (5) 22 Use of the laminate according to the invention for the coating resistant to the detachment of an acceptor of complex surface geometry, which eliminates the use of laminates not extensible or extensible to an insufficient degree