Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
  • A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
  • A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
  • A61K8/0208—Tissues; Wipes; Patches
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
  • A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
  • A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
  • A61K9/7084—Transdermal patches having a drug layer or reservoir, and one or more separate drug-free skin-adhesive layers, e.g. between drug reservoir and skin, or surrounding the drug reservoir; Liquid-filled reservoir patches
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
  • A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
  • A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
  • A61K9/7092—Transdermal patches having multiple drug layers or reservoirs, e.g. for obtaining a specific release pattern, or for combining different drugs
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q19/00—Preparations for care of the skin
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B32—LAYERED PRODUCTS
  • B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
  • B32B7/00—Layered products characterised by the relation between layers; Layered products characterised by the relative orientation of features between layers, or by the relative values of a measurable parameter between layers, i.e. products comprising layers having different physical, chemical or physicochemical properties; Layered products characterised by the interconnection of layers
  • B32B7/04—Interconnection of layers
  • B32B7/06—Interconnection of layers permitting easy separation

Definitions

• the invention relates to a laminate for application to an acceptor, comprising:
• the invention further relates to a method for its production and its use.
• the suitability of laminates for application to an acceptor, for example on the skin is essentially determined by the quality of a laminate contact surface.
• the type and quality of the skin contact area also determine the amount of active ingredient perfusing through the skin per unit of time.
• various types of laminates to be applied to the skin - wound plasters, bandages, "tapes", TTS etc. - are subject to repeated mechanical loads, depending on the application site, by stretching, compressing, kinking, which can lead to partial detachment, fraying Edges or blistering.
• systems intended for therapeutic applications must have a number of other characteristics, such as, for example, support or protective functions or compatibility with wound fluid or skin moisture. Therefore, in the case of laminates to be applied to the skin, a wide variability of use is required from case to case, which results from the different application locations on the body.
• a laminate in the case of a rheumatoid plaster applied to smooth skin areas with underlying smooth muscles, a laminate must meet significantly lower requirements with regard to its durability under the action of bending and stretching forces than a laminate that applies to skin areas with underlying striated muscles, for example arm muscles. or thigh muscles, or also in the area of a joint, for example on the knee.
• a laminate should not only have a supporting or protective function, as is the case with knee protection bandages or tapes to protect the fingers, for example in sports climbers, but should also serve to apply a wide range of different active ingredients, one is in this regard high variability desired, for example with regard to the time course of an emerging active ingredient release rate per unit time. It should also be possible to have different effects in a laminate. Incorporate substances and thereby adjust their release by means of control layers in such a way that a delayed delivery to and / or through the skin is achieved. It should also be possible to incorporate a reservoir for the active ingredient which is used up in the course of the application.
• More specific requirements for active substance-containing plasters relate, for example, to good adhesion to a substrate, low water permeability and / or absorption of active substance, good light protection and / or thermal insulation.
• the use of an occlusive effect for example increasing the water content in the skin layers under a plaster, is another essential feature of a series of TTS, which can be achieved as a backing layer by the targeted use of water vapor barrier films.
• TTS water vapor barrier films
• the films or layer materials available often have only a few of the desired properties. In the therapeutic field, for example, this can result in corresponding systems being either elastic, but permeable to water vapor, or impermeable, but largely inelastic.
• the degree of freedom with regard to one is also from case to case Selection of different active ingredients restricted or not available at all.
• DE 36 34 016 C2 describes a sheet-like therapeutic system for the administration of active ingredients to the skin, with active ingredient reservoirs, with active ingredient delivery surfaces and with the skin adhesion surface arranged on the same level on the skin side, with the characteristic that either the skin adhesion surface in an uninterrupted manner over the entire skin contact surface is distributed and the interruptions are formed by active substance delivery surface sections, or the active substance delivery surface is distributed in an interrupted manner over the entire skin contact surface and the interruptions are formed by skin adhesion surface sections, and that the size of the active substance delivery surface sections is essentially independent of the contact pressure acting on the therapeutic system .
• DE 38 09 978 C2 describes a reservoir with a delivery surface for the controlled delivery of active ingredients to solid, liquid or gaseous acceptors, which decreases over time from their use, with the characteristic that at least at one point of the reservoir there is a parallel to the delivery surface "The cross-sectional area of the reservoir is smaller than the dispensing area.
• EP 0 288 734 B1 describes an active substance-containing patch for the controlled administration of active substances to the skin, with an active substance reservoir which is divided essentially perpendicular to the skin contact surface of the patch and has one or more active substances, one Pressure-sensitive adhesive device on the skin side and, if appropriate, a cover layer which can be removed before application of the plaster, the active substance delivery area of the plaster being able to be reduced by a predetermined area by removing part of the active substance reservoir, with the characteristic that at least one active substance reservoir part remains with one or more active substance reservoir parts is removable from the skin, the part of the active substance reservoir remaining on the skin having better adhesion to the skin than to the back.
• the invention is based on the object of providing a laminate of the type mentioned at the outset for application to an acceptor which, for example, When sticking to the skin of a living organism, even with high mechanical stresses, for example due to stretching, compressing, kinking, no detachment, frayed edges or blistering and thus avoiding a resulting reduction in its contact area, and which furthermore allows a wide variability of the possible uses regarding different quality requirements, such as Incorporation of different active substances, time course of an intended active substance release rate, low water permeability, suitability for different active substances etc., enables.
• a peelable protective layer with the invention in that it consists of m Layers, as well as in places made up of n layers, that m and n are integers and that m ⁇ n.
• deterioration of a layer or “damaged” layer is understood to mean cutting through the layer in question, the layer not necessarily having multiple parts, as is the case, for example, when cutting or cutting a sheet.
• the deterioration in the sense of the invention has a minimum extension of 1 mm.
• the laminate can also have at least one further layer, which is also damaged. Further refinements provide that at least one further layer and at least one film form sections lying congruently one above the other.
• the elastic layer can be a film.
• the stretchability of this layer is characterized by an increase in length in the direction of stretch from 0.5% to 95%. A length increase of 5 to 20% can be particularly advantageous here. Further possibilities for an embodiment of the subject of the application result from the fact that sections of a one-piece layer consist of non-stretchable film or of inert film or of a film with water-blocking properties.
• Another embodiment of the laminate provides that at least one of the layers is in one piece and at least one other of these layers is in several parts and consists of adjacent sections.
• the damage to a layer can consist of a number of parallel cuts which alternately coexist in their longitudinal extent or are arranged offset.
• use can also be made of the measure that the stretchability of a layer or the film forming it is achieved either by its elastic property or by compensatory folds between individual sections. At least two layers can then form congruently superimposed sections.
• the stretching of the overall system results in a displacement of the sections against one another or a change in their mutual spacing, which increases comfort significantly because the affected skin area can and does not give in to mechanical loads as usual is prevented by the pavement.
• the individual sections lie close to the skin with optimal contact even with longer application, which means that the entire skin contact area is kept constant over an extended period of time.
• the use of a film that fixes the individual segments guarantees residue-free removal when removing the patch from the skin.
• this film can be selected, for example, from a film quality that is impermeable to water because no elasticity requirements are imposed on its material itself.
• the use of such a laminate structure enables a technically simple combination of otherwise largely exclusive backing layer requirements.
• the thickness of a layer between two film layers, one of the two film layers or both film layers damaged or in one piece or more. can be divided, is in the range between 1 ⁇ m and 500 ⁇ m, preferably between 5 ⁇ m and 150 ⁇ m, particularly preferably between 10 ⁇ m and 30 ⁇ m.
• the laminate in particular for therapeutic applications, comprises at least one base layer, at least as a further layer an active substance-containing layer and, if necessary, a further, for example release control layer and / or a pressure-sensitive adhesive layer and / or a removable protective layer, and that at least one of these Layers is multi-part, that is, it has several areas of different structure in the laminate.
• the one-piece layer can be a stretchable or elastic film
• a further embodiment provides that the laminate has a number of sections, each of which is an independent microsystem of identical structure and is fixed with a highly elastic film as a base layer to form an overall system. With this structure, the laminate can have a different number of layers and locally different active substances or active substance concentrations or active substance combinations or control means for different active substance delivery rates etc. in the individual layers.
• the invention can in principle be used with all skin-active pharmaceutical ingredients or auxiliaries.
• Suitable active substances can be found in the active substance groups of parasympatholytics (e.g. scopolamine, atropine, benactyzine), cholinergics (e.g. physostigmine, nicotine), neuroleptics (e.g. chlorpromazine, haloperidol), monoamine oxidase inhibitors (e.g. tranylcypromine, selegiline) , the sympathomimetics (e.g.
• ephedrine D-norpseudoephedrine, salbutamol, fenfluramine
• the sympatholytics and antisym- Pathotonics e.g. propanolol, timolol, bupranolol, clonidine, dihydroergotamine, naphazoline
• anxiolytics e.g. diazepam, triazolam
• local anesthetics e.g. lidocaine
• central analgesics e.g. fentanyl, sufentanilate
• antirheumatic drugs e.g.
• indomethacin, piroxica, lornoxicam the coronary therapeutic agents (e.g. glycerol trinitrate, isosorbide dinitrate, nitroglycerin), the estrogens, gestagens and androgens, the antihistamines (e.g. diphenhydramine, clemastine, terfenadine), the prostaglandin derivatives, the prostaglandin derivatives Cholecalciferol) and the cytostatics.
• the layer properties there are particular advantages when using light-sensitive substances which occur in numerous organochemical groups of active substances, such as, for example, phenothiazines, certain peptides, dihydropyridines (for example nifedipine), opioids and numerous other groups of active substances.
• active substances such as, for example, phenothiazines, certain peptides, dihydropyridines (for example nifedipine), opioids and numerous other groups of active substances.
• other active ingredients are suitable for the purpose according to the invention if they have a daily therapeutic dose of less than 50 mg and are soluble in both water and organic solvents.
• Ethanol, propanediol and other low molecular weight alcohols, menthol, eucalyptol, limonene and many other terpenes, low molecular weight fatty acids such as e.g. Capric acid and dimethyl sulfoxide may be mentioned as examples of typical additives in such preparations, which could migrate out of the preparation through the backing layer to a greater or lesser extent.
• Polymers such as polyisobutylene, esters of polyvinyl alcohol, polyacrylic and polymethacrylic acid esters, natural rubber, styrene, isoprene and styrene-butadiene polymers or silicone polymers, resin components such as saturated and unsaturated hydrocarbon can be used as a constituent in the base material of the active ingredient-containing layers. 10
• Resins derivatives of abietyl alcohol and ⁇ -pinene
• plasticizers such as phthalic acid esters, triglycerides and fatty acids, and a number of other substances known to the person skilled in the art are used.
• a number of materials, in particular those which are acceptable for pharmaceutical products, are in principle suitable for the layers embodied as a film: polyvinyl alcohol, styrene-diene block copolymers, polyurethanes, polyvinyl chloride, polymethacrylates, polyolefins, polyesters, to name just a few examples.
• an adhesive, adhesive additional adhesive layer which can be removed after application and which can be removed after the system has been applied.
• At least one further layer (1) is laminated on, an intermediate cover being removed if necessary,
• Fig.la a laminate in the section of a sectional plane I-I in Fig.lb;
• Fig.lb the laminate according to Fig.la in top view
• FIG. 2a shows a laminate with a different structure in the section of a sectional plane II-II in FIG. 2a;
• Fig.2b the laminate according to Fig.2a in plan view.
• FIG. 3a shows the laminate according to Fig.3a in the section of a sectional plane I-I in Fig.4,
• Fig. The laminate of 3a or 3b in plan view.
• FIG. 5 shows the laminate in accordance with FIG. 12
• FIG. 8b shows a section along the sectional plane I-I of FIG. 9 a laminate with an alternative layer structure according to FIG. 8 with a number of sections
• FIG. 9 the laminate of Fig. 8, Fig. 8a and 8b in plan view.
• the cross section shown in FIG. 1 a of a laminate for application to an acceptor, for example on the skin, has a segmentation according to the invention with the segments or sections 10a, 10b, 10c selected as examples.
• the individual sections 10a-c can have different layers to achieve predetermined effects. At least one of these layers 1 and 5 is in one piece and at least one other of these layers 2, 3, 4 is in several parts and these form individual sections 10a, 10b, 10c. 13
• the segments 10a have the different layers 1-5, whereby the layer 1 is in one piece and represents a base layer, to which individual segments are fixed to form an overall system.
• Layer 2 can be, for example, an active substance-containing reservoir layer, while layer 3 is, for example, a release control layer for controlling the release of active substance to the skin, which in turn carries a separate pressure-sensitive adhesive layer 4.
• the one-piece protective layer 5, which is removed in a known manner before the application of the laminate this is hermetically protected between production, transport and application against loss of active ingredient and / or penetration of a foreign substance.
• Section 10b has layers 1, 2, 3 and 5, i.e. there is no separate pressure-sensitive adhesive layer, but the release control layer can be provided with a pressure-sensitive adhesive.
• the segments 10c also have four layers, namely 1, 2, 4 and 5, i.e. they do not have a release control layer 3, but the matrix 2 is coated with a pressure-sensitive adhesive layer 4 and is not provided with a pressure-sensitive adhesive.
• a pressure-sensitive adhesive plaster for example a TTS
• the exemplary configuration of the segments IOa-IOc in FIG .la is only intended to provide illustrative examples of the fact that, due to the segmentation, a previously unattainable variety of design options is given by the individual segments or sections.
• Such a layer structure could, for example, also include 14
• the segmentation also has the further grave advantage that, without prejudice to the elastic modulus of the individual layers, a laminate is realized when using a highly elastic base layer 1, which is able to withstand the highest demands due to repeated mechanical loads.
• a laminate is realized when using a highly elastic base layer 1, which is able to withstand the highest demands due to repeated mechanical loads.
• partial detachment, fraying of the edges or blistering is reliably avoided after application to the skin due to the high flexibility of the entire laminate, even with repeated mechanical stress due to kinking, stretching and compression, and the intended perfusion of the active ingredient through the skin contact surface is thus achieved without problems.
• the use of relatively inelastic layer materials within the individual segments or sections then does not play a disadvantageous role because, in the presence of an elastic base layer 1, the individual sections can easily follow the movements of the skin when stretching or compressing by changing the distance.
• FIG. 2a shows on the cross section of a somewhat differently structured laminate that an elasticity of the base layer 1 can be achieved even with a comparatively stiff starting material of the base film 1 by means of folds 6 between the individual sections 10d and 10e.
• the three segments 10d have a layer structure with the base layer 1 and the layers 15
• the segments or sections 10e each have an active substance reservoir 2 and a water vapor-permeable layer 3 under the base layer 1, which layer is activated by skin moisture and therefore triggers the perfusion of active substance after a delay.
• the course of the folds 6 of the base layer 1 can be seen in the top view of FIG. 2b, from which the high adaptability of the laminate to skin movements can be seen.
• the expansion of the overall system results in a displacement of the segments 10 against one another. This increases the wearing comfort, since the affected area of the skin can give in to the mechanical stresses as usual, without being stressed by the glued-on laminate.
• the individual segments 10 lie close to the skin even with a longer application, as a result of which the entire system / skin / contact area can be kept constant over a comparatively longer period of time.
• the use of a film 1 which fixes the individual segments guarantees that the individual segments 10 are removed without leaving any residue.
• the highest requirements can be achieved with regard to, for example, the desired low water permeability, because the material properties of the backing layer 1 of the base system do not have their own elasticity requirements under- 16
• 3a shows in section a laminate according to the invention with a highly elastic backing layer 1 and below it a film 11 made of non-elastic material, which in turn receives the possibility of transverse expansion according to the double arrow 13 by means of separating cuts 12.
• the reservoir layer 2 which also has separating cuts (12) and is therefore cross-flexible, with a large number of individual sections 10 and 10a.
• the underside is covered with a removable protective film 5 before application.
• the sections 10a appear wider because of the different position of the sectional plane I-I in FIG. 3b.
• FIG. 5 shows a further embodiment of the invention in plan view.
• the damage to at least one layer is carried out in two directions 12a and 12b. This ensures bidirectional expansion of the laminate with the advantages described.
• the invention includes the possibility of advantageously combining the provision of several layers.
• 6 and 7 show a top view, regardless of the layer structure, of various options for the damage to at least one layer. Depending on the requirements, these can be carried out advantageously for the given question. 17
• the cross section shown in FIG. 8 of a laminate for application to an acceptor, for example on the skin, has a segmentation according to the invention of several layers with the segments or sections 11a-c selected as examples, these segments not lying congruently one above the other but being arranged offset with respect to one another .
• the stratum corneum which is made up of several layers of individual planar cells
• the layers 11a-c which can consist of non-elastic material, can be displaced relative to one another and thereby ensure the elasticity of the overall system.
• Layer 2 can be an active substance-containing reservoir layer and, if necessary, can be constructed as in FIGS.
• a release control layer for controlling the release of active substance to the skin and / or a pressure-sensitive adhesive layer.
• This layer 2 can also be damaged or segmented by separating cuts (12), as shown in FIG. 8a, which, however, does not preclude that it can be advantageous to design it in one piece (FIG. 8).
• At least one of the layers 1 and 5 of the laminate is in one piece, layer 5 being a one-piece protective layer which is removed in a known manner before the application of the laminate, and layer 1 functions as a one-piece base layer to which individual segments are fixed to form an overall system (Fig.8, Fig.8a).
• layer 1 functions as a one-piece base layer to which individual segments are fixed to form an overall system (Fig.8, Fig.8a).
• the water vapor barrier effect is achieved through the offset layer structure of the system, possibly made of non-elastic material, and the elasticity through the possibility of the segments being displaced relative to one another.
• Figure 9 shows the laminate according to Figure 8 in plan view. 18th
• the layer structure of FIG. 8 merely serves as an illustrative example of the variability of a laminate that can be achieved with the invention with regard to the achievement of desired special properties and functions, which at the same time is achieved with a high overall elasticity of the system.

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• Health & Medical Sciences (AREA)
• Engineering & Computer Science (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Life Sciences & Earth Sciences (AREA)
• Dermatology (AREA)
• Veterinary Medicine (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Animal Behavior & Ethology (AREA)
• Epidemiology (AREA)
• Chemical & Material Sciences (AREA)
• Medicinal Chemistry (AREA)
• Pharmacology & Pharmacy (AREA)
• Biomedical Technology (AREA)
• Birds (AREA)
• Medicinal Preparation (AREA)
• Materials For Medical Uses (AREA)
• Laminated Bodies (AREA)
• Electroplating Methods And Accessories (AREA)

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• 1998
  • 1998-05-11 DE DE19820999A patent/DE19820999A1/de not_active Withdrawn
• 1999
  • 1999-04-29 JP JP2000547941A patent/JP2002514523A/ja active Pending
  • 1999-04-29 WO PCT/EP1999/002897 patent/WO1999058089A1/de not_active Application Discontinuation
  • 1999-04-29 SK SK1695-2000A patent/SK16952000A3/sk unknown
  • 1999-04-29 IL IL13951099A patent/IL139510A0/xx unknown
  • 1999-04-29 KR KR1020007012650A patent/KR20010071242A/ko not_active Application Discontinuation
  • 1999-04-29 AU AU40354/99A patent/AU4035499A/en not_active Abandoned
  • 1999-04-29 CA CA002332012A patent/CA2332012A1/en not_active Abandoned
  • 1999-04-29 HU HU0101825A patent/HUP0101825A2/hu unknown
  • 1999-04-29 ID IDW20002318A patent/ID26661A/id unknown
  • 1999-04-29 EP EP99923493A patent/EP1077663A1/de not_active Withdrawn
  • 1999-04-29 PL PL99344253A patent/PL344253A1/xx not_active Application Discontinuation
  • 1999-04-29 TR TR2000/03320T patent/TR200003320T2/xx unknown
  • 1999-05-05 TW TW088107283A patent/TW431897B/zh active
• 2000
  • 2000-11-09 ZA ZA200006492A patent/ZA200006492B/en unknown
  • 2000-11-13 NO NO20005731A patent/NO20005731L/no not_active Application Discontinuation

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