EP1441775A1 - Timbre adhesif a matrice contenant des substances actives, a base de gels de polyurethanne - Google Patents

Timbre adhesif a matrice contenant des substances actives, a base de gels de polyurethanne

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Publication number
EP1441775A1
EP1441775A1 EP02754658A EP02754658A EP1441775A1 EP 1441775 A1 EP1441775 A1 EP 1441775A1 EP 02754658 A EP02754658 A EP 02754658A EP 02754658 A EP02754658 A EP 02754658A EP 1441775 A1 EP1441775 A1 EP 1441775A1
Authority
EP
European Patent Office
Prior art keywords
matrix
adhesive
self
active ingredient
polyurethane
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP02754658A
Other languages
German (de)
English (en)
Inventor
Holger Kartheus
Michael Schink
Jürgen-Christian Quandt
Peter Philipp
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Beiersdorf AG
Original Assignee
Beiersdorf AG
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Beiersdorf AG filed Critical Beiersdorf AG
Publication of EP1441775A1 publication Critical patent/EP1441775A1/fr
Withdrawn legal-status Critical Current

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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
    • A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
    • A61K9/7046—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds
    • A61K9/7069—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained otherwise than by reactions only involving carbon to carbon unsaturated bonds, e.g. polysiloxane, polyesters, polyurethane, polyethylene oxide
    • 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
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
    • A61L15/26—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/42—Use of materials characterised by their function or physical properties
    • A61L15/425—Porous materials, e.g. foams or sponges
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/42—Use of materials characterised by their function or physical properties
    • A61L15/58—Adhesives

Definitions

  • the invention relates to self-adhesive, active substance-containing matrix plasters based on polyurethane gels, in particular with active substances which promote blood circulation.
  • the transdermal patch systems can be differentiated according to their structure, for example.
  • an inherent drug reservoir is built up by a homogeneous distribution of the drug in a polymer matrix or a gel matrix.
  • the polymer or gel matrix has self-adhesive properties, so that the matrix does not have to be fixed on the skin by additionally applying an adhesive layer.
  • the active substance-containing matrix is located between a cover layer firmly anchored with it and a removable separating layer.
  • the active ingredient is usually homogeneously mixed into the polymer or gel matrix by dissolving, dispersing, suspending, extruding, kneading, mixing or similar processes, in some cases at elevated temperature.
  • the use of polyurethanes for the controlled release of active substance has only been described in a few cases (Lamba, Woodhouse, Cooper, "Polyurethanes in Biomedical Applications", CRC Press, 1998, p. 240).
  • EP 0 057 839 A1 describes polyurethane gels into which various active substances can also be incorporated and their use as active substance carriers with a depot effect.
  • hydrophilic, self-adhesive polyurethane gel compositions described in WO 97/43328 A1 are preferably used as active substance-free wound dressings for the treatment of chronic wounds. They are characterized, for example, by good skin friendliness, good adhesion, also over a long period of use and painless removability after use.
  • EP 0 016 652 A1 describes an active substance-containing composition which is produced by reacting a polyethylene oxide with polyfunctional isocyanates and which is a crystalline hydrogel in the dry form.
  • a composition with controlled release is obtained by swelling a polymeric carrier produced in this way in a solution of an active substance and subsequent drying.
  • WO 96/31551 A1 is concerned with polyurethane microgels which contain active substances, for example proteins, swell in water and can thereby release the active ingredient.
  • WO 91/02763 A1 and WO 94/22934 A1 also deal with compositions for the controlled release of active substances from hydrogels based on polyurethane-ureas.
  • the known active ingredient-containing polyurethanes are also products that have no self-adhesive properties.
  • Circulation-enhancing active substance plasters are used to treat rheumatic complaints, muscle tension and pain in the area of the musculoskeletal system.
  • Known heat-effective plaster systems contain an adhesive based Rubber, hydrocolloid or hydrogel, in which one or more active ingredients with blood circulation-promoting properties, such as benzyl nicotinate, capsaicin and nonivamide, are incorporated.
  • active substance-containing patch systems also have certain requirements for the adhesive matrix, such as, for example, skin friendliness, good adhesion over a long period of use and painless removability.
  • Self-adhesive, hydrophilic polyurethane gels which are used in the field of chronic wound healing, meet the latter requirements particularly well.
  • active ingredient carriers they only release the active ingredient to a small extent, for example, when active ingredients that promote circulation such as nonivamide, benzyl nicotinate and capsaicin are used.
  • active ingredients that promote circulation such as nonivamide, benzyl nicotinate and capsaicin are used.
  • One reason for this is that the property profile of known, in particular hydrophilic, polyurethane gel products is tailored for moist wound healing, for example the ability to absorb liquid from the wound and not to release active substances into the intact skin.
  • the object of the invention is to provide an active substance-containing matrix plaster for the controlled delivery of active substances to the skin and / or in the wound, which is self-adhesive and which can be produced economically.
  • the present invention relates to self-adhesive, active substance-containing matrix plasters for the controlled delivery of active substances to the skin or into the wound with an absorbent, self-adhesive matrix based on polyurethane gels, the active substance being present in the matrix and penetration enhancers being added to the matrix.
  • the penetration enhancers include, for example, lipophilic solubilizers / enhancers lipophilic solubilizers / enhancers such as oleic acid decyl ester, isopropyl myristate and palmitate (IPM and IPP), 2-octyldodecanol and / or other fatty acid esters.
  • lipophilic solubilizers / enhancers lipophilic solubilizers / enhancers such as oleic acid decyl ester, isopropyl myristate and palmitate (IPM and IPP), 2-octyldodecanol and / or other fatty acid esters.
  • Fatty acid esters C 8 -C 18 with short-chain alcohols or fatty alcohols are more preferably used as enhancers.
  • Fatty alcohols are a collective name for the linear, saturated or unsaturated primary alcohols (1-alkanols) with 6 to 22 carbon atoms that can be obtained by reducing the triglycerides, fatty acids or fatty acid methyl esters.
  • Fatty alcohols are neutral, colorless, high-boiling, oily liquids or soft, colorless masses that are sparingly to insoluble in water, but easily soluble in alcohol and ether.
  • the following table shows physicochemical data of the fatty alcohols.
  • Further preferred penetration enhancers are diesters and diethers of polyethylene glycol 6 to 12 with C 8 -C 18 fatty alcohols or C 8 -C 18 fatty acids.
  • Polyethylene glycols of the general formula belong to the class of polyethers under polyethylene glycols:
  • Polyethylene glycols are produced industrially by a basic, catalyzed polyaddition of ethylene oxide (oxirane) in mostly small water-containing systems with ethylene glycol as the starting molecule. They have molar masses in the range from approx. 200 to 5,000,000 g / mol, corresponding to degrees of polymerization n of approx. 5 to> 100,000.
  • Propylene glycol di-esters with C 8 -C 18 fatty alcohols are more preferably used as enhancers.
  • Gylcerin di- and triesters with C 8 -C 8 fatty alcohols are further preferably used as enhancers.
  • Suitable as a matrix are absorbent, self-adhesive polyurethanes, in foamed or non-foamed form, which can additionally contain fillers or auxiliaries, such as absorbent materials.
  • Suitable polyurethanes are the subject of DE 196 18 825 A1, in which hydrophilic, self-adhesive polyurethane gels are disclosed, which consist of a) 2 to 6 hydroxyl group-containing polyether polyols with OH numbers from 20 to 112 and an ethylene oxide (EO) content of > 10% by weight, b) antioxidants, c) bismuth (III) carboxylates based on carboxylic acids with 2 to 18 C atoms as catalysts and d) hexamethylene diisocyanate, soluble in the polyols, with a product of the functionalities of the polyurethane-forming components a) and d) of at least 5.2, the amount of catalyst c) being 0.005 to 0.25% by weight, based on the polyol a), the amount of antioxidants b) is in the range from 0.1 to 1.0% by weight, based on polyol a) and a ratio of free NCO groups of component d) to the free OH
  • 3 to 4 very particularly preferably 4-hydroxyl group-containing polyether polyols having an OH number in the range from 20 to 112, preferably 30 to 56.
  • the ethylene oxide content in the polyether polyols used according to the invention is preferably> 20% by weight.
  • the polyether polyols are known per se and are obtained, for example, by polymerizing epoxides, such as ethylene oxide, propylene oxide, butylene oxide or tetrahydrofuran, by themselves or by addition of these epoxides, preferably ethylene oxide and propylene oxide - optionally in a mixture with one another or separately in succession
  • epoxides such as ethylene oxide, propylene oxide, butylene oxide or tetrahydrofuran
  • starter components with at least two reactive hydrogen atoms such as water, ethylene glycol, propylene glycol, diethylene glycol, dipropylene glycol, glycerin, trimethylolpropane, pentaerythritol, sorbitol or succrose.
  • the isocyanate component is monomeric or trimerized hexamethylene diisocyanate or by biuret, uretdione, allophanate groups or by prepolymerization with polyether polyols or mixtures of polyether polyols based on the known starter components with 2 or> 2 reactive H atoms and epoxides such as ethylene oxide or propylene oxide with an OH number from ⁇ 850, preferably 100 to 600, modified hexamethylene diisocyanate.
  • the use of modified hexamethylene diisocyanate is preferred, in particular by means of prepolymers with polyether diols with an OH number of 200 to 600 modified hexamethylene diisocyanate.
  • hexamethylene diisocyanate with polyether diols with an OH number of 200-600, the residual content of monomeric hexamethylene diisocyanate below 0.5% by weight, are very particularly preferred.
  • Possible catalysts for the polyurethane gels according to the invention in the anhydrous polyether polyols a) are bismuth (III) carboxylates based on linear, branched, saturated or unsaturated carboxylic acids having 2 to 18, preferably 6 to 18, carbon atoms.
  • the catalysts are preferably used in amounts of 0.03 to 0.1% by weight, based on the polyol a).
  • antioxidants used for the polyurethane gels according to the invention are, in particular, sterically hindered phenolic stabilizers, such as BHT (2,6-di-tert-butyl-4-methylphenol), Vulkanox BKF (2.2 min -methylene-bis- (6-tert.
  • Irganox 1010 penentaerythrityl tetrakis [3- (3,5-ditert.-butyl-4-hydroxyphenyl) propionate]
  • Irganox 1076 octadecyl-3- ( 3,5-ditert.-butyl-4-hydroxyphenyl) propionate)
  • Ciba-Geigy or tocopherol (vitamin E), preferably those of the ⁇ -tocopherol type.
  • the antioxidants are preferably used in amounts of 0.15 to 0.5% by weight, based on the polyol a).
  • the isocyanate index (ratio of the free NCO groups used in the reaction to the free OH groups) of the polyurethane gel compositions according to the invention is in the range from 0.30 to 0.70, preferably in the range, depending on the functionality of the isocyanate and polyol components used from 0.45 to 0.60.
  • the isocyanate index required for gel formation can be easily estimated using the following formula:
  • the polyurethane gel compositions according to the invention are produced by customary processes, as described, for example, in Becker / Braun, Kunststoff-Handbuch, Vol. 7, Polyurethane, p. 121 ff, Carl-Hauser, 1983.
  • Polyurethanes such as those disclosed in EP 0 665 856 B1 are more preferably used.
  • hydrophilic polyurethane gel foams are therefore available from
  • (A) 25-62% by weight, preferably 30-60% by weight, particularly preferably 40-57% by weight, based on the sum of (A) and (B), of a covalently cross-linked polyurethane as a high-molecular matrix and
  • (C) 0 to 100% by weight, based on the sum of (A) and (B), of fillers and / or additives,
  • the polyurethane gels can be prepared from the starting compounds known per se from polyurethane chemistry by processes known per se, as are described, for example, in DE 31 03 499 A1, DE 31 03 500 A1 and EP 0 147 588 A1. It is essential, however, that the conditions defined above are observed when selecting the gel-forming components, since otherwise tack-free, elastic gels are obtained instead of self-adhesive gels.
  • Preferred polyhydroxyl compounds are polyether polyols, as are mentioned in detail in the above-mentioned laid-open publications. Both (cyclo) aliphatic and aromatic isocyanates are suitable as polyisocyanate components. Preferred (cyclo) aliphatic polyisocyanates are 1,6-hexamethylene diisocyanate and its biurets and trimehsates or hydrogenated diphenylmethane diisocyanate ("MDI”) types.
  • Preferred aromatic polyisocyanates are those obtained by distillation, such as MDI mixtures of 4,4'- and 2,4'-isomers or 4,4'-MDI, and tolylene diisocyanate (“TDI”) types.
  • the diisocyanates can in particular be selected, for example, from the group of unmodified aromatic or aliphatic diisocyanates or from modified products formed by prepolymerization with amines, polyols or polyether polyols.
  • the polyurethane composition can be used without foaming, foaming, unfilling or with additional fillers such as superabsorbents, titanium dioxide, zinc oxide, plasticizers, dyes, etc. Hydrogels in semi-solid to solid form with active components for the central zone can also be used.
  • the polyurethane gels can optionally contain additives known per se from polyurethane chemistry, such as, for example, fillers and short fibers on an inorganic or organic basis, metal pigments, surface-active substances or liquid extenders such as substances with a boiling point above 150 ° C.
  • additives known per se from polyurethane chemistry such as, for example, fillers and short fibers on an inorganic or organic basis, metal pigments, surface-active substances or liquid extenders such as substances with a boiling point above 150 ° C.
  • organic fillers are heavy spar, chalk, gypsum, kieserite, soda, titanium dioxide, cerium oxide, quartz sand, kaolin, carbon black and hollow microspheres.
  • organic fillers for example, powders based on polystyrene, polyvinyl chloride, urea formaldehyde and polyhydrazodicarbonamide can be used.
  • the short fibers are, for example, glass fibers of 0.1 to 1 mm in length or fibers of organic origin, such as polyester or polyamide fibers.
  • Metal powders such as iron or copper powder, can also be used in the gel formation.
  • the dyes or colored pigments known per se in the coloring of polyurethanes on an organic or inorganic basis such as, for example, iron oxide or chromium oxide pigments, pigments based on phthalocyanine or monoazo, can be used.
  • Surface-active substances may be mentioned, for example, cellulose powder, activated carbon and silica preparations.
  • polymeric vinyl compounds, polyacrylates and other copolymers or adhesives based on natural materials up to a content of 10% by weight, based on the weight of the gel mass, which are customary in adhesive technology, can optionally be added.
  • Preferred water-absorbent materials are water-absorbent salts of polyacrylates and their copolymers known as superabsorbers, in particular the sodium or potassium salts. They can be uncrosslinked or networked and are also available as commercial products. Products such as those disclosed in DE 37 13 601 A1 are particularly suitable, and also superabsorbents of the new generation with only small proportions of dry water and high swelling capacity under pressure. Preferred products are weakly crosslinked polymers based on acrylic acid / sodium acrylate. Such sodium polyacrylates are available as Favor T (Chemische Fabrik Stockhausen GmbH, Germany).
  • absorbers for example carboxymethyl cellulose and karaya, are also suitable.
  • the degree of foaming can be varied within wide limits by the amounts of foaming agent incorporated.
  • the matrix has a thickness of 10 to 1000 ⁇ m, very particularly 30 to 300 ⁇ m.
  • a large number of substance groups which are free from hydroxyl, carboxyl or amine functionalities which are reactive toward the polyurethane crosslinking reaction are used as active substances, for example essential oils, skin-care cosmetic additives, pharmaceutically active substances or antiseptics.
  • Transdermal therapeutic systems which are doped with essential oils and their components (e.g. eucalyptus oil, peppermint oil, camphor, menthol) have a long-term therapeutic effect for colds,
  • Hydroxyl functionality in the menthol does not affect the polyurethane crosslinking reaction, which can be explained by the lower reactivity of the secondary OH group in the menthol molecule.
  • Essential oils are concentrates obtained from plants, which are used as natural raw materials mainly in the perfume and food industry and which consist more or less of volatile compounds, such as real essential oils, citrus oils, absolute, resinoids.
  • essential oils are mixtures of volatile components that are produced from vegetable raw materials by steam distillation.
  • Real essential oils consist exclusively of volatile components, the boiling point of which is predominantly between 150 and 300 ° C. Unlike, for example, fatty oils, they do not leave a permanent, transparent grease stain when dabbed on filter paper.
  • Essential oils mainly contain hydrocarbons or monofunctional compounds such as aldehydes, esters, ethers and ketones.
  • Parent compounds are mono- and sesquiterpenes, phenylpropane derivatives and longer-chain aliphatic compounds.
  • Some essential oils are dominated by one ingredient (e.g. eugenol in clove oil with more than 85%), others are extremely complex.
  • the organoleptic properties are often shaped not by the main components, but by minor or trace components, such as the 1,3,5-undecatrienes and pyrazines in Galbanum oil.
  • Many of the commercially important essential oils have hundreds of identified components.
  • a large number of ingredients are chiral, with an enantiomer predominating or being present very often, such as (-) - menthol in peppermint oil or (-) - linalyl acetate in lavender oil.
  • the matrix contains 0.1 to 20% by weight, in particular 1 to 10% by weight, of essential oils, in particular from the group consisting of eucalyptus oil, peppermint oil, chamomile oil, camphor, menthol, citrus oil, cinnamon oil, thyme oil, Lavender oil, clove oil, tea tree oil, cajeput oil, niaouli oil, kanuka oil, manuka oil, mountain pine oil are selected.
  • Citrus oils are essential oils that come from the peels of citrus fruits (bergamot,
  • Citrus oils largely consist of monoterpene hydrocarbons, mainly limonene (exception: bergamot oil, which only contains approx. 40%).
  • Camphor is understood to mean 2-bornanon, 1,7,7-trimethylbicyclo [2.2.1] heptan-2-one, see figure below.
  • Peppermint oils are essential oils obtained by steam distillation from leaves and inflorescences of various types of peppermint, occasionally also those from Mentha arvensis.
  • Menthol has three asymmetric carbon atoms and therefore occurs in four diastereomeric pairs of enantiomers (see the formula images, the other four enantiomers are the corresponding mirror images).
  • the diastereomers that can be separated by distillation are called neoisomenthol, isomenthol, neonnenthol [(+) - form: component of Japanese peppermint oil] and menthol.
  • the most important isomer is (-) - menthol (levomenthol), shiny, strongly peppermint-smelling prisms.
  • menthol When rubbed on the skin (especially on the forehead and temples), menthol creates a pleasant feeling of cold due to surface anesthesia and irritation of the cold-sensitive nerves during migraines and the like; in fact, the areas in question show normal or elevated temperature.
  • the other isomers of menthol do not have these effects.
  • cosmetic additives that care for the skin can advantageously be added to the matrix, in particular from 0.2 to 10% by weight, very particularly from 0.5 to 5% by weight.
  • the skin care cosmetic additives can be selected very advantageously from the group of lipophilic additives, in particular from the following group:
  • additives from the group of refatting substances, for example Purcellin oil, Eucerit® and Neocerit.
  • the additives or additives are also particularly advantageously selected from the group of NO synthase inhibitors, in particular if the preparations according to the invention are used for treatment and prophylaxis of the symptoms of intrinsic and / or extrinsic skin aging and for the treatment and prophylaxis of the harmful effects of ultraviolet radiation on the skin.
  • the preferred NO synthase inhibitor is nitroarginine.
  • ubiquinones are classified as Q-1, Q-2, Q-3 etc. or according to the number of C atoms as U-5, U-10 U-15 and so on. They preferably occur with certain chain lengths, for example in some microorganisms and the like.
  • Yeast with n 6. Q10 predominates in most mammals, including humans.
  • Coenzyme Q10 which is characterized by the following structural formula, is particularly advantageous:
  • Creatine and / or creatine derivatives are also preferred additives for the purposes of the present invention. Creatine is characterized by the following structure:
  • Preferred derivatives are creatine phosphate and creatine sulfate, creatine acetate, creatine ascorbate and the derivatives esterified on the carboxyl group with mono- or polyfunctional alcohols.
  • additives or combinations of additives mentioned which can be used in the preparations according to the invention is of course not intended to be limiting, apart from the criterion of the hydroxyl or carboxyl group reactive towards isocyanate.
  • the additives can be used individually or in any combination with one another.
  • pharmaceutically active substances can be added to the matrix of the active substance-containing matrix patch, preferably up to 40% by weight, particularly 0.01 to 25% by weight, very particularly 0.1 to 10% by weight.
  • Typical active ingredients are - without claiming to be complete in the context of the present invention:
  • Antifungals naftifine (E) -N-cinnamyl-N-methyl-l-naphthalene methanamine)
  • Clotrimazole (1 - [(2-chlorophenyl) diphenylmethyl] -1 H-imidazole)
  • Nonsteroidal anti-inflammatory drugs methyl salicylate etofenamate
  • Keratolytics urea Other active ingredients that are beneficial for wound healing, such as silver sulfadiazine, can also be used.
  • Hyperaemic active ingredients such as natural active ingredients of cayenne pepper or synthetic active ingredients such as nonivamide, nicotinic acid derivatives, preferably bencyl nicotinate or propyl nicotinate, or anti-inflammatory drugs and / or analgesics can also be mentioned particularly advantageously and within the meaning of the invention.
  • Capsaicin is an example
  • Disinfectants are substances that are used for disinfection, i.e. h., are suitable for combating pathogenic microorganisms (e.g. bacteria, viruses, spores, small and mold fungi), generally by applying them to the surface of skin, clothing, equipment, rooms, but also drinking water, food, seeds ( Pickling) and as a floor disinfectant.
  • pathogenic microorganisms e.g. bacteria, viruses, spores, small and mold fungi
  • Disinfectants to be used particularly locally, for example for wound disinfection, are also referred to as antiseptics.
  • the lactic acid derivatives such as esters and oligo- and polylactic acid, are to be used as antiseptics.
  • Lactic acid esters include the esters of the general formula which are often referred to as lactates of the respective alcohol component
  • Lactic acid isopropyl ester (isopropyl lactate), C6H12O3, M R 132.15, D. 0.9980, boiling point 167 ° C
  • Polylactic acid is a polyester based on lactic acid, from whose lactide it can be produced by ring-opening polymerization.
  • the matrix contains, in particular, a hydrophilic filler based on cellulose and its derivatives, the average grain size of which is in the range from 20 to 60 ⁇ m, because it was surprisingly found in the selection of the fillers that fillers in particular were found on the Based on silicon dioxide or cellulose, the latter having an isotropic shape and do not tend to swell when in contact with water. Fillers with a particle size of less than or equal to 100 ⁇ m are particularly suitable.
  • hydrophilic fillers in a non-polar matrix is known in the literature. They are described explicitly for use in transdermal therapeutic systems in EP 0 186 019 A1. Here, however, only up to a concentration of 3 to 30% by weight, without mentioning details of these fillers. Experience shows that systems with a filler content of more than 30% by weight clearly lose stickiness and become hard and brittle. As a result, they lose the basic requirement of a transdermal therapeutic system. Fillers based on microcrystalline or amorphous cellulose are preferably used in substantially higher concentrations without adversely affecting the adhesive properties, in particular if they have an isotropic shape with a particle size of no greater than 100 ⁇ m. Higher levels of fillers are desirable in order to improve the wearing properties, particularly after long and repeated use.
  • the matrix on the side facing away from the skin or the wound can be covered with a carrier material, for example consisting of foils (for example made of PUR, polyester, PE or PP), nonwovens, fabrics, foams, metallized foils, composites, cotton etc.
  • a carrier material for example consisting of foils (for example made of PUR, polyester, PE or PP), nonwovens, fabrics, foams, metallized foils, composites, cotton etc.
  • the occlusive foils are preferred from the group of suitable carrier materials.
  • a metallocene polyethylene nonwoven is also suitable.
  • the metallocene polyethylene nonwoven preferably has the following properties:
  • nonwovens which are mechanically consolidated, can be used as carrier materials, namely by sewing over with separate threads or by
  • Nonwoven which can be cross-paneled, for example, and is sewn on using separate threads in fringed or tricot layers.
  • This nonwoven knitted fabric is known under the name “Malivlies”, also from the Malimo company.
  • carrier materials that can be used in such a way that they fulfill the properties of a functional dressing are preferred.
  • Textiles such as woven fabrics, knitted fabrics, scrims, nonwovens, laminates, nets, foils, foams and papers are listed as examples. These materials can also be pretreated or post-treated. Common pretreatments are corona and hydrophobizing; Common post-treatments are calendering, tempering, laminating, punching and mounting.
  • the matrix is applied to a carrier material, preferably in such a way that the periphery of the carrier material is at least partially not covered by the matrix.
  • an adhesive can be coated between the matrix and the carrier material, specifically based on PUR, acrylates or rubber.
  • the matrix and / or the carrier material coated with the adhesive can be covered with the customary release paper.
  • the matrix plaster according to the invention can have any shape, a regular shape such as rectangular, square, circular or oval being preferred. Preferred embodiments of the subject matter of the invention and several figures are described below by way of example without wishing to restrict the invention unnecessarily.
  • NVA nonivamide
  • IPP isopropyl palmitate
  • the Levagel (polyether polyol from Bayer, Leverkusen) and Desmodur (polyisocyanate based on hexamethylene diisocyanate from Bayer, Leverkusen) are weighed into a vessel and homogeneously mixed with the nonivamide / isopropyl palmitate mixture for a few minutes with stirring ,
  • samples are prepared on pig skin and the release is determined quantitatively after 24 hours.
  • FIG. 1 illustrates a preferred geometric shape of the matrix plaster.
  • the plaster has a circular shape (diameter 100 mm) and consists of a polyurethane matrix 2 that is chamfered towards the edge.
  • the polyurethane matrix 2 is initially beveled evenly and ends in a 20 mm wide ring, in which the thickness is kept constant.
  • the polyurethane matrix 2 is essentially semi-convex in the middle and is accordingly comparable to a semi-convex lens.
  • the thickness of the polyurethane matrix 2 is 2.3 mm in the middle and 0.7 mm at the edge.
  • the polyurethane matrix 2 is covered with a siliconized paper 1 in order to avoid contamination or contamination of the matrix 2.
  • FIG. 2 illustrates another preferred geometric shape of the matrix patch.
  • the plaster has an ellipsoidal shape (length of the axes 42 mm or 68 mm) and consists of a polyurethane matrix 2 which is beveled towards the edge.
  • the polyurethane matrix 2 is initially beveled evenly and ends in an approximately 11 mm wide ring in which the thickness is kept constant.
  • the polyurethane matrix 2 is essentially semi-convex in the middle and is accordingly comparable to a semi-convex lens.
  • the PU matrix 2 is covered on the side facing away from the skin with a PE film 3.
  • the thickness of the polyurethane matrix 2 including PE film 3 is 1.6 mm in the middle and
  • the polyurethane matrix 2 is covered with a siliconized paper 1 in order to avoid contamination or contamination of the matrix 2.
  • FIG. 3 illustrates a further preferred geometric shape of the matrix patch.
  • the patch has an ellipsoidal shape (length of the axes 110 mm or 65 mm) and consists of a polyurethane matrix 2 that is beveled towards the edge.
  • the polyurethane matrix 2 is essentially semi-convex, and is accordingly comparable to a semi-convex lens with an axis length of 72 mm or 34 mm.
  • the PU matrix 2 is covered on the side facing away from the skin with a PE film 3, which is coated over the entire surface with the adhesive layer 4 based on polyurethane, which contains IPP.
  • the entire periphery of the adhesive layer 4 is not covered with the polyurethane matrix 2. In this way, two concentric zones of chemically different adhesive compositions 2, 4 result, which differ in terms of adhesion, absorption capacity and cushioning properties.
  • the thickness of the polyurethane matrix 2 together with PU film 3 and adhesive layer 4 is 1.3 mm in the middle and 0.15 mm at the edge.
  • the polyurethane matrix 2 is covered with a siliconized paper 1 in order to avoid contamination or contamination of the matrix 2.
  • FIG. 4 illustrates a further preferred geometric shape of the matrix patch.
  • the plaster has a circular shape (diameter 100 mm), consists of a foamed polyurethane matrix 2, which is beveled towards the edge.
  • the polyurethane matrix 2 is essentially semi-convex, and is accordingly comparable to a semi-convex lens with a diameter of 60 mm.
  • the PU matrix 2 is covered on the side facing away from the skin with a PU film 3 which is coated over the entire surface with the adhesive layer 6 based on acrylate. In the embodiment of the plaster shown here, the entire periphery of the adhesive layer 6 is not covered with the polyurethane matrix 2. In this way, two concentric zones of chemically different adhesive compositions 2, 6 result, which differ in terms of adhesion, absorption capacity and cushioning properties.
  • the thickness of the polyurethane matrix 2 together with PU film 3 and adhesive layer 6 is 1.5 mm in the middle and 0.1 mm at the edge.
  • the polyurethane matrix 2 is covered with a siliconized paper 1 in order to avoid contamination or contamination of the matrix 2.
  • FIG. 5 illustrates a further preferred geometric shape of the wound dressing.
  • the plaster has a square shape, the corners of the square are rounded (diameter of the square 50 mm), consists of a water-vapor-permeable foamed polyurethane matrix 2, which is beveled towards the edge.
  • the polyurethane matrix 2 is essentially semi-convex and circular, and is accordingly comparable to a semi-convex lens with a diameter of 33 mm.
  • the PU matrix 2 is covered on the side facing away from the skin with a PU film 3 which is coated over the entire surface with the adhesive layer 6 based on rubber.
  • the entire periphery of the adhesive layer 6 is not covered with the polyurethane matrix 2. In this way, two concentric zones of chemically different adhesive compositions 2, 6 result, which differ in terms of adhesion, absorption capacity and cushioning properties.
  • the thickness of the polyurethane matrix 2 together with PU film 3 and adhesive layer 6 is 1.5 mm in the middle and 0.1 mm at the edge.
  • FIG. 6 shows three further embodiments of a matrix plaster according to the invention, namely in cross section.
  • the matrix patch consists of three individual layers.
  • the doped wound dressing made of polyurethane 2, the matrix 2 is completely covered on the side facing away from the wound or the skin with a carrier material 8.
  • the carrier material 8 is, for example, polymer films, nonwovens, fabrics and their combinations, and films or textile materials made from polymers such as polyethylene, polypropylene and polyurethane or natural fibers.
  • the self-adhesive matrix 2 On the side facing the wound or skin, the self-adhesive matrix 2 is completely covered with a release paper 1.
  • the matrix 2 has a relatively high layer thickness in the center of the plaster, while they are thin in the edge region of the plaster.
  • the matrix 2 between the matrix 2 and the carrier material 8 there is an additional adhesive coating 9 applied over the entire surface of the carrier material 8.
  • the matrix 2 does not extend over the entire surface of the carrier material 8 No matrix 2 is applied in the edge region of the carrier material 8.

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  • General Health & Medical Sciences (AREA)
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  • Dermatology (AREA)
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Abstract

L'invention concerne un timbre adhésif à matrice contenant des substances actives, permettant la libération contrôlée de substances actives à travers la peau, ce timbre étant à base de gels de polyuréthanne. La substance active se trouve dans la matrice et des activateurs de pénétration sont ajoutés à ladite matrice.
EP02754658A 2001-06-13 2002-06-12 Timbre adhesif a matrice contenant des substances actives, a base de gels de polyurethanne Withdrawn EP1441775A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE10128685 2001-06-13
DE2001128685 DE10128685A1 (de) 2001-06-13 2001-06-13 Selbstklebendes, wirkstoffhaltiges Matrixpflaster auf Basis von Polyurethangelen
PCT/EP2002/006429 WO2002100450A1 (fr) 2001-06-13 2002-06-12 Timbre adhesif a matrice contenant des substances actives, a base de gels de polyurethanne

Publications (1)

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EP1441775A1 true EP1441775A1 (fr) 2004-08-04

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EP (1) EP1441775A1 (fr)
DE (1) DE10128685A1 (fr)
WO (1) WO2002100450A1 (fr)

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DE10220114A1 (de) * 2002-05-06 2003-11-20 Beiersdorf Ag Ätherische Öle enthaltendes Matrixpflaster auf Polyurethanbasis
EP1635782A1 (fr) 2003-05-24 2006-03-22 JUVENA (International) AG Milieux de culture de tissus utilises comme composants de cosmetiques
DE10330971B4 (de) * 2003-07-08 2007-03-29 Beiersdorf Ag Verfahren zur Herstellung von Haut- oder Wundauflagen mit verkapselten, wundheilungsfördernden und/oder hautpflegenden Substanzen
DE10341933A1 (de) * 2003-09-11 2005-04-14 Lts Lohmann Therapie-Systeme Ag Medizinische Hautpflaster mit einem Gehalt an ätherischen Ölen zur Behandlung von Erkältungskrankheiten, sowie Verfahren für deren Herstellung
DE102004061406A1 (de) * 2004-12-21 2006-07-06 Bayer Innovation Gmbh Infektionsresistente Polyurethanschäume, Verfahren zu ihrer Herstellung und Verwendung in antiseptisch ausgestatteten Wundauflagen
DE102005050431A1 (de) 2005-10-21 2007-04-26 Lts Lohmann Therapie-Systeme Ag Transdermales therapeutisches System zur Verabreicherung lipophiler und/oder wenig hautpermeabler Wirkstoffe
US20090207790A1 (en) * 2005-10-27 2009-08-20 Qualcomm Incorporated Method and apparatus for settingtuneawaystatus in an open state in wireless communication system
BRPI0718388A8 (pt) * 2006-10-17 2018-03-13 Labtec Gesellschaft Fuer Tech Forschung Und Entwicklung Mbh etiqueta adesiva com agente amargante e agentes fluidificantes para secreções naturais das vias aéreas
EP2072063A1 (fr) 2007-12-22 2009-06-24 Bayer Innovation GmbH Mousse de polyuréthane à base de pré-polymère hydrophile cellulaire résistante aux infections, procédé pour sa fabrication et son utilisation dans des pansements antiseptiques
DE102008059054A1 (de) * 2008-11-26 2010-05-27 Otto Bock Pur Life Science Gmbh Polyurethanpflaster für die transdermale Applikation von Wirkstoffen und Verfahren zu dessen Herstellung
JP5715962B2 (ja) 2009-01-30 2015-05-13 バイヤースドルフ・アクチエンゲゼルシヤフトＢｅｉｅｒｓｄｏｒｆ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ コラーゲン、キトサン、グリコシルアミノグリカンおよび細胞増殖促進ペプチドおよび／または細胞複合体よりなる、化粧品または皮膚科学的調製物
DE102011106089A1 (de) 2011-04-28 2012-10-31 Maria Clementine Martin Klosterfrau Vertriebsgesellschaft Mbh Therapiepflaster
EP3585351A4 (fr) * 2017-02-23 2020-12-30 Alira Health Boston LLC Formulations antimicrobiennes écophiles perturbant des biofilms, leur développement et leurs utilisations
CN115054652B (zh) * 2022-06-10 2023-11-28 山东远大康恒生物科技有限公司 一种具有抗汗匀控功能的三伏贴及其制备方法

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DE10128685A1 (de) 2002-12-19

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