WO2007006529A1 - Systeme therapeutique transdermique presentant une matiere odoriferante - Google Patents
Systeme therapeutique transdermique presentant une matiere odoriferante Download PDFInfo
- Publication number
- WO2007006529A1 WO2007006529A1 PCT/EP2006/006728 EP2006006728W WO2007006529A1 WO 2007006529 A1 WO2007006529 A1 WO 2007006529A1 EP 2006006728 W EP2006006728 W EP 2006006728W WO 2007006529 A1 WO2007006529 A1 WO 2007006529A1
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- WO
- WIPO (PCT)
- Prior art keywords
- transdermal system
- layer
- alkyl
- fragrance
- perfume
- Prior art date
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/485—Morphinan derivatives, e.g. morphine, codeine
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- 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
- A61K9/7053—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
- A61K9/7061—Polyacrylates
Definitions
- a fragrance-containing transdermal therapeutic system A fragrance-containing transdermal therapeutic system
- the present invention is an optionally packaged, transdermal, therapeutic system for administering at least one pharmaceutical active substance comprising a layer sequence
- At least one layer has an optionally releasable by force, encapsulated fragrance and / or the optionally present package includes a fragrance that is released when opened.
- Transdermal therapeutic systems are also used for the administration of pharmaceutical agents. These are capable of continuously delivering an active ingredient through the skin at a certain rate for a fixed period of time to a human or animal organism.
- transdermal therapeutic systems have proven particularly useful for the administration of systemically active pharmaceutical agents, such as analgesics, because they allow painless, convenient, and simple administration of an agent to the patient over an extended period of time. This also improves the willingness to comply with the therapy compared to other dosage forms.
- the object of the present invention was therefore to provide a system for the transdermal administration of pharmaceutical active substances, preferably of opioids, in which the acceptance for use in the patient is markedly improved, since the aforementioned disadvantages of the prior art are eliminated.
- This object according to the invention is achieved by providing a possibly transdermal therapeutic system present in a package for administering at least one pharmaceutical active substance comprising a layer sequence
- a detachable from the adhesive layer protective layer which is characterized in that at least one layer of the system optionally releasable by force, encapsulated fragrance and / or the possibly existing packaging has a fragrance when opening the possibly existing packaging and / or released during application of the system.
- the fragrance is present in such a form that it is released at least partially directly and noticeably, particularly preferably entirely immediately, upon opening the packaging and / or the application.
- Phenyl or naphthyl compounds which may be condensed with 1 or 2 unsaturated or saturated 5- to 7-membered aliphatic rings, wherein the rings are each 1, 2 or 3 heteroatom (s) selected from the group consisting of oxygen, nitrogen and Sulfur ring member (s) may have (s) and with 1, 2, 3, 4 or 5 identical or different substituents selected from the group comprising C- ⁇ - 5 alkyl, -OH and -O-Ci -5- alkyl may be substituted ;
- the system particularly preferably contains as fragrance at least one natural or nature-identical compound selected from the group comprising anethole, benzaldehyde, benzyl acetate, benzyl alcohol, benzyl formate, isoboron acetate, camphene, neral, citronellal, citronellol, citronellyl acetate, para-cymene, decanal, dihydrolinalool, Dihydromyrcenol, dimethylphenylcarbinol, eucalyptol, geraniol, geranylacetate, geranylnitrile, cis-3-hexenylacetate, hydroxycitronellal, limonene, linalool, linalooloxide, linalylacetate, linalylpropionate, methylanthranilate, alpha-methylionone, methylnonylacetaldehyde, methylphenylcarbinylacetate, men
- At least one naturally occurring mixture of fragrances can also be used.
- at least one fragrance mixture is selected from the group comprising rosemary oil, sandalwood oil, violet oil, lemongrass oil, lavender flower oil, eucalyptus oil, peppermint oil, chamomile oil, Clove Leaf Oil, Cinnamon Oil, Thyme Oil, Tea Tree Oil, Cajeput Oil, Niaouli Oil, Manuka Oil, Citrus Oil, Mountain Pine Oil, Jasmine Oil, Geranium Oil, Cumin Oil, Pine Needle Oil, Bergamot Oil, Turpentine Oil, Linalol Oil, Blood Orange Oil, Cypress Oil, Fir Oil, Fennel Oil, Grapefruit Oil, Ginger Oil, Pine Oil, Lavandin Oil, Lemongrass Oil, Lime oil, tangerine oil, lemon balm oil, myrrh oil, patchouli oil, rosewood oil and thuja oil.
- the fragrances are volatile.
- they are further processed according to the invention as oils.
- the perfume is encapsulated, preferably initially encased in microcapsules and / or cyclodextrins.
- these microcapsules or cyclodextrins when opening the package and / or by the force when applying and wearing the transdermal therapeutic system to the skin, preferably already by the slight contact pressure of the patient and / or mechanical action perfume directly in the application of the transdermal therapeutic Systems and continuously while wearing free.
- the microcapsules used may have a diameter of 1 to 1000 microns, preferably from about 1 to 500 microns.
- a diameter of 1 to 10 microns in the layer structure of the transdermal system microcapsules with a diameter of 1 to 10 microns, in the cover layer or on the packaging material or in the packaging separated from the transdermal system microcapsules up to 1000 microns, preferably up to 500 microns, more preferably up to 100 microns, be used.
- microcapsules containing the fragrances are known to the person skilled in the art and can be carried out by spray-drying technology (compare CA Finck et al., Microen capsulation in "Ullmann's Encyclopedia of Industrial Chemistry", Wiley-VCH 2002), coacervation technique or coextrusion Capsules containing the fragrance as the content (liquid or solid) are formed in the dripping process, and hydrocolloids such as alginates, gelatin agar-agar, gum-aralicum, latex, polymethacrylates, polyethersulfones, waxes are suitable as shell materials.
- microcapsules whose walls consist of a wafer-thin nanofilm of polyurethane.
- the fragrance and the water-insoluble polymethane component, the isocyanate component mixed, the mixture is dispersed in an emulsifier solution into very fine droplets of microcapsule size with stirring and by addition of an aqueous solution of the second polymethane, the polyamine, carried out the encapsulation.
- the two PU components react in an interfacial polymerization on the surface of the microdroplets to form a solid nanofilm of polyurethane, inside which the fragrance rests.
- Cyclodextrins (CD) that may be used include all known cyclodextrins. Cyclodextrins according to the present invention are understood to mean all cyclodextrins from six to nine glucose units, preferably alpha-, beta- and gamma-cyclodextrins, their derivatives and mixtures thereof, which can form complexes for the inclusion of a perfume. Preference is given to methyl-beta-cyclodextrin, hydroxyethyl-beta-cyclodextrin and / or hydroxypropyl-beta-cyclodextrin.
- the perfume trapped in microcapsules or cyclodextrins which is releasable upon opening of the package and / or by application of force during application of the transdermal system, may be located at different locations in the transdermal system.
- the enclosed fragrance between the adhesive layer c) and the removable protective layer d), preferably on the removable protective layer d), the fragrance being released by the handling at the latest when the protective layer is detached. This is true even if the fragrance is associated with the topcoat, which is also exposed to a force effect during handling to apply the system.
- the adhesive layer the active substance-containing layer and / or an active substance-containing reservoir, if this is present in the transdermal system according to the invention.
- the entrapped perfume is present in or at least one of the layers of the transdermal system Layers connected, preferably on the cover layer, the removable protective layer and / or an optionally present, detachable application aid.
- the packaging may already be equipped with at least one perfume component, preferably a gaseous and / or slightly volatile perfume component, so that the fragrance component is quenched in the atmosphere within the package.
- the packaging in the interior preferably on the inner wall with entrapped perfume, preferably be equipped with encapsulated in microcapsules and / or cyclodextrins fragrances and / or an at least partial perfume layer in the handling of the package, especially when opening and removing the Transdermal system according to the invention then release the perfume at the latest.
- the packaging may also be equipped with at least one chamber and / or be equipped with a separate bag, optionally from fragrance-permeable material, in which the preferably encapsulated fragrance is located.
- This chamber or this bag can with the (remaining) packaging, such. B. on sealed seams, be connected, that at the same time the chamber or the fragrance bag is opened when you open the package. This can be achieved by simultaneously sealing the package and sealing the perfume bag or sealing the perfume chamber. If the package in the sealed seam area is cut open to open the packaging and to remove the transdermal system, at the same time the Perfume chamber or the fragrance bag open, allowing the perfume can flow out. It is also possible to attach perfume-containing microcapsules to the inner wall of the packaging in the marked opening region of the packaging, which can also be opened by slicing the packaging and thus release the fragrance.
- any kind of pharmaceutical agents or pharmaceutical compositions may be used in various physical states, such as molecularly distributed, as crystals or in the form of clusters.
- the pharmaceutical agent may also be encapsulated in liposomes.
- microcapsules The preparation of microcapsules is, as stated above, known in the art.
- Suitable pharmaceutically active compounds are those compounds selected from the group comprising narcotics and analgesics such as benzocaine, lidocaine, prilocaine, non-steroidal anti-inflammatory drugs or antiinflammatory compounds such as indomethacin, diclofenac, sedatives such as sodium pentabarbiturate, phenobarbiturate, secobarbiturate sodium, codeine, carbromat , Psychopharmaca, such as 3- (2-aminopropyl) indole acetate and 3- (2-aminobutyl) indole acetate, tranquilizers such as reserpine, chlorpromazine hydrochloride, hormones such as adrenocorticosteroids such as 6- ⁇ -methylprednisolone, androgenic steroids such as methyltestosteroids, fluoxymester
- the transdermal system according to the invention is particularly suitable for the transdermal delivery of opioids, especially in the case of long-term pain relief.
- opioids are ⁇ -, K- or ⁇ -opioid receptor agonists, very particularly preferably ⁇ -opioid receptor agonists.
- opioids preferably at least one opioid selected from the group comprising codeine, dextropropoxyphene, dihydrocodeine, diphenoxylate, ethylmorphine, meptazinol, nalbuphine, pethidine, tilidine, viminol, butorphanol, dextromoramide, decocin, etorphine, hydrocodone, ketobemidone, levomethadone, levorphanol, nalorphine , Oxymorphone, pentazocine, diacetylmorphine, hydromorphone, morphine, oxycodone, alfentanil, fentanyl, carfentanil, lofentanil, remifentanyl, sulfentanil and buprenorphine.
- Particularly preferred opioid used is at least one compound selected from the group comprising sulfentanil, hydromorphone, carfentanil, lofentanil, fentanyl, morphine and buprenorphine, most preferably buprenorphine.
- the opioids if appropriate in the form of their ether, ester or acid derivatives, can in each case as pure stereoisomer, in particular enantiomer or diastereomer, racemate or in the form of a mixture of stereoisomers, in particular the enantiomers and / or diastereomers, in any mixing ratio, or each in the form of appropriate physiologically acceptable salts, or in each case in the form of corresponding solvates.
- physiologically acceptable salts are those which are prepared by reacting the free bases of the respective opioid with an inorganic or organic acid, preferably with hydrochloric, hydrobromic, sulfuric, phosphoric, methanesulfonic, p-toluenesulfonic, carbonic, formic, acetic, oxalic, succinic, Tartaric acid, mandelic acid, fumaric acid, lactic acid, citric acid, glutamic acid or aspartic acid obtained salts.
- physiologically acceptable salts which may be mentioned by way of example are the salts obtained by reacting the free acids of the particular opioid with a suitable base.
- the required dose of the opioid in the transdermal therapeutic system of the present invention will be determined by the skilled artisan based on the known factors such as sex, age or weight, the nature and severity of the pain, and the duration of use of the transdermal therapeutic system, usually the one for the corresponding opioid
- the opioid is present in the active substance-containing layer in its saturation concentration.
- the daily dose to be administered is preferably 400 to 1800 ⁇ g, more preferably 800 to 1700 ⁇ g, most preferably 1000 to 1200 ⁇ g.
- the transdermal system is preferably dosed so that it can be used for 3 to 5 days for pain relief.
- the pharmaceutical active substance preferably the opioid
- the pharmaceutical active substance can be distributed in a matrix or present in a reservoir. It is possible both in the matrix and in the reservoir embodiment to use the active ingredient liquid, semi-solid or solid or as appropriate drug formulation, so that the active ingredient over a certain period of time continuously and controlled by the skin to a human or animal organism is delivered.
- Preferred transdermal systems according to the invention are those described in WO 98/36728, WO 96/19975 or US Pat. No. 6,264,980 or EP 430 019 A2 or CA 2030178, the entire contents of these publications and the content of those cited therein Literature is part of the disclosure of this invention.
- the transdermal therapeutic system of the invention is in the form of a patch which
- a cover layer a an active substance-containing layer b), an adhesive layer c), a removable protective layer d).
- At least one pharmaceutical active substance is present in the matrix-containing layer b1) and / or in the adhesive layer c), the layer b1) and / or in the adhesive layer c) at least one perfume component may have encapsulated and optionally the matrix layer b1) and the adhesive layer c) are combined to form a layer.
- the encapsulated fragrance may also be arranged between the active substance-containing layer and the covering layer and / or the adhesive layer c) and / or between the layer c) and the detachable layer d).
- transdermal therapeutic system is designed as a reservoir patch.
- this embodiment may encapsulate not only the pharmaceutical agent but also a perfume component, preferably in microcapsules, in the reservoir.
- the transdermal, therapeutic system in the adhesive layer c) and / or on the matrix layer b1) and / or on the adhesive layer c) and / or on the cover layer a) and / or on the removable protective layer d ) an encapsulated perfume.
- Encapsulated according to the invention preferably means microencapsulated.
- the cover layer a) is impermeable to the pharmaceutical active substance.
- Impermeable means that the cover layer a) is impermeable to the active substance at least in the region in which an active substance-containing matrix layer b1) is present. If the cover layer a) itself is not impermeable to active substances, then a barrier layer may preferably be present between the active substance-containing matrix layer b1) or the reservoir b2) and the cover layer a).
- the cover layer a) is preferably made of a flexible, stretchable, breathable, durable material and may be colored, for example skin color, his.
- the cover layer a) preferably has a thickness such that the transdermal therapeutic system has sufficient stability.
- the cover layer a) is preferably based on at least one material selected from the group comprising polyesters, particularly preferably polyethylene terephthalates; Polyolefins, more preferably polyethylenes, polypropylenes or polybutylenes; polycarbonates; Polyethylene oxides; polyurethanes; polystyrenes; polyamides; polyimides; polyvinyl acetates; polyvinyl chlorides; polyvinylidene; Copolymers of acrylonitrile and / or butadiene and / or styrene, more preferably acrylonitrile-butadiene-styrene terpolymer; Paper; Textiles and their mixtures.
- the cover layer a) can also be
- the matrix layer b1) is preferably based on lipophilic or hydrophilic polymers. Hydrophilic matrix-forming layers can be hydrous, in which case they are preferably gels.
- the matrix layer b1) is preferably based on at least one polymer selected from the group comprising cellulose derivatives, particularly preferably hydroxypropylcellulose, carboxymethylcellulose, ethylcellulose and cellulose ethers; Polyethylene; polyvinyl chlorides; polyvinylidene; Polypropylene; polyurethanes; polycarbonates; polyacrylate; polyacrylates; polymethacrylates; polyvinyl alcohols; polyvinylpyrrolidones; Polyethylene terephthalate; polytetrafluoroethylene; Ethylene-propylene copolymers; Ethylene-ethyl acrylate copolymers; Ethylene-vinyl acetate copolymers; Ethylene-vinyl alcohol copolymers; Ethylene-vinyloxyethanol cop
- the matrix layer b1) and / or the adhesive layer c) comprise at least one pressure-sensitive adhesive.
- This adhesive is preferably skin compatible and hypoallergenic. Preferably, it provides sufficient adhesion of the transdermal therapeutic system to the skin of the patient for a period of up to 8 days, more preferably up to 5 Days.
- the pressure-sensitive adhesive is an adhesive selected from the group consisting of polyacrylates, polyvinyl ethers, polyisobutylenes, polyurethanes, styrene-isoprene copolymers, butadiene-styrene copolymers, silicones, rubbers and resins.
- suitable polyacrylates are polymers of acrylates, methacrylates, alkyl acrylates and / or alkyl methacrylates, which are optionally copolymerized with further unsaturated monomers such as acrylamide, dimethylacrylamide, dimethylaminoethyl acrylate, hydroxyethyl acrylate, hydroxypropyl acrylate, methoxyethyl acrylate, methoxyethyl methacrylate, acrylonitrile and / or vinyl acetate.
- the pressure-sensitive adhesive is present in the matrix layer b1).
- the pressure-sensitive adhesive is preferably mixed with the abovementioned materials in known amounts and admixed with at least one pharmaceutical active substance and optionally at least one encapsulated perfume to produce the active substance-containing matrix layer region.
- the matrix layer b1) can also be crosslinked if necessary.
- the active substance present in the matrix layer b1) can be present in the liquid, semi-solid or solid, dispersed state or can be incorporated as a corresponding formulation with the addition of the customary auxiliaries as active substance formulation.
- the matrix layer b1) may comprise at least one solvent selected from the group comprising water, optionally short-chain alcohols, such as ethanol, n-propanol, isopropanol, propylene glycol, glycerol.
- the transdermal therapeutic system can also be designed so that the pressure-sensitive adhesive is present only in the edge zones of the active substance-containing layer b), which preferably contain no active ingredient.
- the transdermal therapeutic system according to the invention may have at least one skin permeation-promoting substance in the matrix layer b1) and / or the adhesive layer c) and / or in the reservoir. These substances enhance or facilitate the transport of the drug through the Skin and may be mixed with these or in a separate layer.
- polyethylene glycols As skin permeation promoting substances, polyethylene glycols, surfactants, laurocapram (Azone), longer-chain aliphatic alcohols, such as dedecanol, undecanol and octanol, esters of aliphatic carboxylic acids with polyethoxylated alcohols, diesters of aliphatic dicarboxylic acids, such as adipic acid, medium chain triglycerides of caprylic and / or capric acid, coconut oil, polyhydric alcohols such as 1, 2-propanediol, esters of polyhydric alcohols such as glycerol with levulinic acid or caprylic acid, aliphatic carboxylic acids, such as levulinic acid, and etherified polyhydric alcohols may be used.
- longer-chain aliphatic alcohols such as dedecanol, undecanol and octanol
- the transdermal therapeutic system according to the invention may contain preservatives and / or antioxidants.
- Suitable antioxidants are preferably vitamin E, butylhydroxytoluene, butylated hydroxyanisole, ascorbic acid, ascorbyl palmitate, potassium and sodium citrate, and disodium ethylenediaminetetraacetic acid as chelating agent.
- the transdermal therapeutic system of the invention may contain solvents.
- solvents are preferably surfactants, detergents, N-methyl-2-pyrrolidone, laurylpyrrolidone, triethanolamine, triacetin, diethylene glycol monomethyl ether, derivatives of fatty acids or fatty alcohols, for example oleyl oleate, and low molecular weight, polyhydric alcohols, for example propylene glycol and glycerol.
- the adhesive matrix layer b1) or the adhesive layer c) is preferably covered over the entire adhesive range with a removable protective layer d).
- the removable protective layer d) is preferably based on at least one material selected from the group consisting of polyester, polypropylenes, polyvinyl chlorides, aluminum and paper and has on the inside a coating based on silicones and / or polyethylene and / or fluorosilicone and / or polytetrafluoroethylene to be easily removable.
- stabilizers emulsifiers, thickeners and / or customary membrane system or reservoir plaster adjuvants can additionally be contained in the reservoir.
- Emulsifiers and thickeners are used the auxiliaries known to the expert.
- Preferred thickeners are vaseline, oleic acid oleate (Cetiol®), complex emulsifier gels (Lanette wax ASS, Lanette® N), semi-synthetic fats (softisan), fumed silica (Aerosil®) and / or bentonite (Veegum®, Volclay®, Ben-A-Gel ).
- Methylcellulose (Methocel.RTM., Tylose.RTM. MW, Tylose.RTM. MB), hydroxypropylcellulose (Klucel), hydroxyethylcellulose (ethoxose), hydroxypropylmethylcellulose (Methocel.RTM. E, Methocel.RTM. K), polyacrylic acid (Carbopol.RTM.), Carboxyvinyl polymer, can be used as gelling agents and thickeners. Carbomer copolymer, sodium plyoxilate, carboxymethyl cellulose or a mixture of at least two of said compounds. As auxiliaries, skin permeation-promoting substances may also be present in the reservoir. If necessary, the reservoir can also be designed as a fleece, woven fabric or the like impregnated with the active ingredient formulation.
- the reservoir is preferably enclosed by a membrane which is preferably based on at least one polymer selected from the group consisting of polyethylenes, polypropylenes, polyvinyl acetates, polyamides, ethylene-vinyl acetate copolymers, polyethylene terephthalates and silicones.
- the reservoir may preferably be arranged between the cover layer a) and the adhesive layer c) or embedded in the adhesive layer c), which constitutes therein the active substance-containing layer.
- Suitable adhesives are the pressure-sensitive adhesives listed above.
- the reservoir contains at least one pharmaceutical agent, preferably as a solution, which can freely diffuse through the membrane surrounding the reservoir.
- Suitable solvents are suitable solvents in which the active ingredient dissolves sufficiently, thereby precipitation of the active ingredients is avoided.
- the optionally active substance-containing adhesive layer c) comprises 5 to 15% by weight, preferably 8 to 12% by weight, of at least one pharmaceutical active substance, preferably if this corresponds to the saturation concentration.
- the reservoir comprises 5 to 15% by weight, preferably 8 to 12% by weight, of at least one pharmaceutical active substance, preferably if this corresponds to the saturation concentration.
- weights are in each case based on the total weight of the system, the layer or the reservoir, depending on the reference.
- the perfume is preferably included, such as. B. in microcapsules and / or cyclodextrins or on the layers mentioned above or attached.
- a portion of the perfume or a mixture can also optionally mixed with other excipients and optionally diluted with a preferably readily volatile solvent selected from the group comprising ethanol, isopropanol, diethylene glycol monomethyl ether and ethyl acetate and applied as a layer.
- the cover layer comprises a) and / or the matrix layer b1) and / or the reservoir and / or the adhesive layer c) and / or the releasable protective layer d) and / or an optionally present, detachable application aid and / or the packaging, preferably on its inner wall, 0.5 to 40% by weight, preferably 0.5 to 20 wt .-%, particularly preferably 0.5 to 10 wt .-%, most preferably 0.5 to 5 Wt .-%, of the encapsulated perfume.
- 0.1 to 20 g / m 2 in addition to the encapsulated fragrance on the outer surface of the protective layer d) 0.1 to 20 g / m 2 , preferably 0.1 to 12 g / m 2 , particularly preferably 0.1 to 6 g / m 2 , of the fragrance, preferably dissolved and mixed with viscosity-increasing auxiliaries, mixed.
- Such layers may also be applied to the inner wall of the transdermal system package, as well as perfume-containing microcapsules or cyclodextrins, which may be fixed to the inner wall by conventional adhesives such as adhesives.
- Such microcapsules or cyclodextrins may also be present loosely in the packaging, wherein preferably the packaging for a separate device, such. A sachet.
- the transdermal therapeutic system according to the invention does not require a change in the layer structure compared to a fragrance-free system.
- the intrinsic odor of the transdermal therapeutic system is at least applied to the patient, advantageously already during opening of the package and during use over a period of at least 4 days, preferably of at least 3 days, more preferably at least 2 days imperceptible, so that the acceptance is given to the patient. This is preferably achieved through the use of microencapsulated perfume.
- the transdermal therapeutic system according to the invention is preferably packaged.
- the system according to the invention is present in a sealed, preferably sterile, packaging, which is preferably sealed. Therefore, it is possible to add so much perfume, preferably volatile perfume, to the gas atmosphere inside the package that a pleasant odor escapes when the package is opened to apply the system.
- a solvent selected from the group comprising ethanol, isopropanol, diethylene glycol monomethyl ether, dipropyl glycol and ethyl acetate.
- a perfume component is present not only in the gaseous atmosphere inside the package and / or on the wall of the package in a perfume chamber and / or an enclosed separate perfume bag, preferably encapsulated, but at least the packaged transdermal system also equipped with an encapsulated fragrance after one of the above options.
- the resultant mixture was uniformly coated on a polyester film having a thickness of 15 ⁇ m in a width of 100 mm so that the basis weight of the dried matrix layer was 80 g / m 2 and the solvents were removed by heating up to 60 ° C.
- the dried layer 5 g / m 2 lemongrass oil was sprayed.
- the sprayed, dried surface was covered with a polyester film with a silicone coating.
- the thickness of the film was 75 ⁇ m. Patches of 25 cm 2 were cut out.
- a suspension of lemongrass oil-containing microcapsules having a size of 10 microns was applied and dried.
- the resulting mixture was uniformly coated on a polyester film whose thickness was 15 ⁇ m and the width thereof 100 mm so that the basis weight of the dried matrix layer was 80 g / m 2 and the solvents were removed by heating up to 60 ° C.
- This surface was covered with a polyester film with a silicone coating. The thickness of the film was 75 ⁇ m. Patches of 25 cm 2 were cut out.
- a matrix patch is prepared as indicated in Example 2 under a).
- the cut patches prepared according to a) were each introduced into a packaging bag with the dimensions length ⁇ width 10 ⁇ 10 cm, which consists of a ready-to-dry packaging material.
- a pouch of dimensions length x width 3x3 cm encapsulated 50 ⁇ l of mint oil which had already been completely sealed was placed in the packaging bag so that one side seam of the perfume pouch is located parallel to the still to be closed opening of the packaging pouch and the next Closing the packaging bag by sealing in the sealed seam area is thereby fixed. Below this sealed seam area, a cutting line is marked, on the outer wall of the packaging bag and parallel to the sealing seam sealing this opening, so that when the packaging bag is cut open, the fragrance bag is opened and the fragrance is thus released.
- microcapsules with 50 .mu.l of mint oil it is also possible to apply microcapsules with 50 .mu.l of mint oil to the inner wall along the outer marked cutting line, at least the cutting process being used to open and remove the Plaster the microcapsules containing the fragrance are destroyed and thereby the fragrance is released.
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Abstract
L'invention concerne un système thérapeutique transdermique destiné à délivrer au moins un principe actif pharmaceutique, présentant au moins une matière odoriférante incorporée, de préférence encapsulée, qui est libérée ultérieurement lors de l'application du système.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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DE200510033543 DE102005033543A1 (de) | 2005-07-14 | 2005-07-14 | Ein einen Duftstoff aufweisendes transdermales therapeutisches System |
DE102005033543.8 | 2005-07-14 |
Publications (1)
Publication Number | Publication Date |
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WO2007006529A1 true WO2007006529A1 (fr) | 2007-01-18 |
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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PCT/EP2006/006728 WO2007006529A1 (fr) | 2005-07-14 | 2006-07-10 | Systeme therapeutique transdermique presentant une matiere odoriferante |
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DE (1) | DE102005033543A1 (fr) |
WO (1) | WO2007006529A1 (fr) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
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EP2946775A1 (fr) | 2014-05-20 | 2015-11-25 | LTS LOHMANN Therapie-Systeme AG | Système thérapeutique transdermique contenant de l'huile de lavande |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE102007021549A1 (de) * | 2007-05-08 | 2008-11-13 | Novosis Ag | Transdermales therapeutisches System enthaltend mindestens zwei Opioide |
DE102008059727B4 (de) * | 2008-12-01 | 2012-03-22 | Lts Lohmann Therapie-Systeme Ag | Duftendes Tattoo-Pflaster. Verfahren zu seiner Herstellung und seine Verwendung |
WO2019174713A1 (fr) * | 2018-03-12 | 2019-09-19 | Symrise Ag | Film adhésif de substance active |
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US5399404A (en) * | 1991-12-19 | 1995-03-21 | Schering-Plough Healthcare Products | Foot and shoe deodorizer patch |
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DE19701059A1 (de) * | 1997-01-15 | 1998-07-16 | Lohmann Therapie Syst Lts | Acetylsalicylsäure enthaltendes transdermales therapeutisches System mit Resorptionsverstärkung |
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EP2946775A1 (fr) | 2014-05-20 | 2015-11-25 | LTS LOHMANN Therapie-Systeme AG | Système thérapeutique transdermique contenant de l'huile de lavande |
Also Published As
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DE102005033543A1 (de) | 2007-01-18 |
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