ELECTRICALLY-HEATABLE PLASTER

Abstract

The invention relates to electrically-heatable plasters which comprise a self-adhesive skin contact layer, an electrically-conductive textile fabric in which electrically-conductive fibres are in contact with one another, as a heating element, and optionally at least one active substance, as well as to a method for production and the use of same for local heat therapy and/or transdermal application of active substances.

Claims

1. (canceled)

2-14. (canceled)

15. A method comprising: utilizing an electrically conductive textile sheet comprising a fabric, a knitted structure, a crocheted structure, a braided structure, a bi-directional or multi-directional fabric, a felt, or a fleece of fibers, in which electrically conductive fibers are in contact with one another, the electrically conductive textile sheet being provided with electrical contacts to manufacture an electrically heatable plaster having a self-adhesive skin contact layer comprising at least one pharmaceutical active substance.

16. A method comprising: utilizing the electrically heatable plaster having a self-adhesive skin contact layer comprising at least one pharmaceutical active substance; an electrically conductive, textile sheet comprising a fabric, a knitted structure, a crocheted structure, a braided structure, a bi-directional or multi-directional fabric, a felt, or a fleece of fibers, in which electrically conductive fibers are in contact with one another; and wherein the electrically conductive textile sheet is provided with electrical contacts; and wherein the electrically conductive textile sheet constitutes a rear layer of the plaster, to deliver the at least one pharmaceutical active substance contained in the plaster to a patient.

17. (canceled)

18. A method comprising: applying an electrically heatable plaster having a self-adhesive skin contact layer comprising at least one pharmaceutical active substance; an electrically conductive, textile sheet comprising a fabric, a knitted structure, a crocheted structure, a braided structure, a bi-directional or multi-directional fabric, a felt, or a fleece of fibers, in which electrically conductive fibers are in contact with one another; and wherein the electrically conductive textile sheet is provided with electrical contacts; and wherein the electrically conductive textile sheet constitutes a rear layer of the plaster, to a patient and closing a circuit between a voltage source and the electrically conductive textile sheet.

19. The method as claimed in claim 18, wherein the electrically conductive sheet is embedded in a resin layer or polymer layer.

20. The method as claimed in claim 19, wherein the resin layer or polymer layer includes at least one electrically conductive filler.

21. The method as claimed in claim 18, wherein the textile sheet comprises: a) exclusively electrically conductive fibres; b) both electronically conductive fibres and electronically non-conductive fibers; or c) at least one electrically non-conductive textile sheet, which is equipped with adhesive, at least one electrically conductive binder, and electrically conductive particles that are fixed three-dimensionally and durably in the textile sheet.

22. The method as claimed in claim 18, wherein the voltage source is a direct current source.

23. The method as claimed in claim 18, wherein the pharmaceutical active substance comprises at least one substance selected from the group consisting of non-steroidal anti-inflammatory drugs (NSAIDs), anticholinergics, parasympatolytic agents, antimycotics, MAO-B inhibitors, serotonin antagonists, alpha2 receptor agonists, photosensitizers, hormones, and proteins.

Description

EXEMPLARY EMBODIMENTS

Example 1: Ibuprofen-Plaster with an Electrically Heatable Rear Layer

[0088] 174.32 g Durotak 387-2353 (solids content 37%) was diluted with 8.07 g ethylacetate and 31.6 g of a solution of 10% potassium hydroxide in methanol was added. After thorough mixing, 16.63 g oleic acid was added. 1.2 g aluminium acetyl acetonate and 1 g acetyl acetone were then added. After all the components were well mixed together, 16.63 g ibuprofen (racemate) was added. The composition was stirred at room temperature until all the components were completely dissolved. The adhesive composition was then spread out on a siliconized PET film 100 μm by means of a scraper so that a dry weight of 60 g/m.sup.2 was achieved. The solvents were evaporated at ca. 80° C. The laminate was then covered with the heatable fibre material which was a spun fleece with electrically conductive fibres.

Example 2: Diclofenac Plaster with an Electrically Heatable Rear Layer

[0089] 94.92 g Durotak 387-2287 (solids content 50%) was mixed with a solution of 0.72 g aluminium acetyl acetonate in 13 g ethyl acetate. 0.12 g α-tocopherol dissolved in 0.4 g ethyl acetate was added to this composition and homogeneously stirred. 2.4 g diclofenac-Na was dissolved in 5.4 g methanol and added to the composition. The composition was stirred at room temperature until the solids had completely dissolved. The adhesive composition was spread out onto a siliconized PET film 100 μm by means of a scraper such that a dry weight of 80 g/m.sup.2 was achieved. The solvents were evaporated at ca. 75° C. The laminate was then covered with the heatable fibre material which was a spun fleece with electrically conductive fibres.

Example 3: Diclofenac Plaster with an Electrically Heatable Rear Layer

[0090] 118.57 g Durotak 387-2051 (solids content 50%) was neutralised with 24 g of a solution of 2.4 g potassium hydroxi9de in 21.6 g methanol. 90.66 g of the thus neutralised adhesive solution was mixed with 2.26 g of a solution of 0.3 g aluminium acetyl acetonate in 1.75 g methanol and 0.3 g ethyl acetate. 7.5 g oleic acid and 0.25 g α-tocopherol were added and stirred to complete dissolution. 6.38 g of the solution of 2.0 g diclofenac-Na in 4.38 g methanol was added to it. The composition was stirred at room temperature until all the solids completely dissolved. The adhesive composition was spread onto a siliconized PET film 100 μm by means of the scraper so that a dry weight of 80 g/m.sup.2 was achieved. The solvents were firstly flashed off for ca. 10 minutes at room temperature and then evaporated at ca. 60° C. The laminate was then covered with the heatable fibre material, which was a spun fleece with electrically conductive fibres.

Example 4: Conduct of the Skin Permeation Experiments

[0091] For the conduct of the in-vitro permeation tests, a modified diffusion cell in accordance with Keshary-Chien was used. The cell consists of two horizontally divided regions, the donor region and the acceptor region. The temperature of the diffusion cell was maintained at 32° C. by means of a water bath. The acceptor medium (phosphate buffer, pH 5.5) was constantly stirred during the test by means of a magnetic stirrer.

[0092] The skin was clamped between the two regions, whereby the stratum corneum of the skin pointed upwardly towards the donor region. The plaster was positioned on the skin sample with the adhesive layer towards the stratum corneum of the skin.

[0093] The acceptor medium was completely removed from the acceptor region at the specified removal times and kept for the subsequent quantitative determination of the active substance dissolved in it. The same amount of fresh acceptor medium was then added. It was thus ensured that the permeation kinetics are not influenced by potentially reaching the saturation solubility in the acceptor medium.

[0094] Dermatomised human skin (800 μm) was used for all the skin permeation experiments. The area of the opening in the cell was 1.54 cm.sup.2.

[0095] The quantitative determination of the active substances permeated into the acceptor medium was effected by means of high performance liquid chromatography (HPLC).

[0096] For the analysis of diclofenac, a mixture of acetonitrile and 0.025 m KH.sub.2PO.sub.4 (50:50, v/v) was used as the mobile phase. The pH value was set to 3.0. A 150×4.6 mm separation column packed with Zorbax SB C8 80 A 5 μm, was used as the stationary phase. The flow rate was 1.5 ml/min, the column temperature was 30° C. The injection volume was 50 μl, the detector wavelength was set to 225 nm.

[0097] For the analysis of ibuprofen, a 150×4.0 mm separation column packed with Novapack C18 5 μm was used. A mixture of acetonitrile:water-tetramethyl:ammonium hydroxide in a mixing ratio of 55:45:1.5 was used as the mobile phase. The pH value was set to 3.0. The flow rate was 1.0 ml/min., the column temperature was 25° C. The injection volume was 50 μl, the detection wavelength was set to 214 nm.

[0098] The calculation was effected by means of the External Standard Method using certified reference substances.

[0099] The plasters were manufactured so large that their edges projected significantly out of the diffusion cells. The contact to the heatable rear layer was effected by sewn on electrically conductive textile sheets. Direct current (POWER SUPPLY HM 7042-5, from the company HAMEG) was applied to them by means of crocodile clips. In order to achieve a surface temperature of 42° C., the voltage was set to 3V. In order to achieve a 50° C. surface temperature, the voltage was set to 6 V. The resulting current strength was ca. 200 Ma for 3 V and 42° C. and ca. 50 mA for 6V and 50° C.

[0100] A parallel measurement without the application of power was effected as a reference.

[0101] The results of the skin permeation experiments for the diclofenac plastics described in Example 2 are shown graphically in FIG. 1. It is apparent from this illustration that heating the rear layer of the diciofenac plaster to a temperature of about 42° C. or about 50° C. results in a significantly improved permeation of the diclofenac contained in the plaster over the skin compared to the reference referred to as “passive”, with which no direct current was applied.