DD292137A5 - METHOD FOR PRODUCING A PLASTER - Google Patents

Abstract

The invention relates to a method for the production of a patch, which enables a controlled, electrophoretic medicament ligation. The patch is produced by coagulation of a latex. The latex contains an electrically conductive additive, for. B. graphite. The patch contains an electrode or it can be coupled with an electrode. The polarity and the strength of an electric field can be used to control the release of active substance. {Plaster; Skin; acrylate; iontophoresis; electrophoresis; Electrode; dispersion; Diffusion coefficient; copolymer; Latex}

Description

Field of application of the invention

The present invention relates to a process for the preparation of a medical patch, especially an adhesive active substance-containing patch, which is in medicine preferably for pain relief for addiction withdrawal or seizure prophylaxis and therapy is visible and can be easily, preferably by the patient handle.

Characteristic of the known state of the art

It is known that the diffusion of charged compounds through a DC electric field can be accelerated. In this context, the iontophoresis is beschiieben. Iontophoresis is a method which, when applied topically, can drive ionic drugs or drugs into the skin and through the skin by means of electricity. Thus, for example, DE-OS 3225748, EP 0058458, EP 0011813, EP 0058920, GB 1591817, DE-OS 2756460, EP 0147524, EP 0178601 and DE-PS 3139677 describe niotophoretic application systems which can be used in this sense. In addition, it has been demonstrated that electric fields can exert a positive influence on wound healing. This fact is taken into account in DE 1901605, DE 2757103, GB 2078514 and GB 1598817.

In other cases, the release of drugs from various forms of storage is controlled by electric or magnetic fields (electro-osmotic control valve - DE-AS 2626348, drug flow control - DE-PS 3218407) or the transdermal absorption of substances accelerated and amplified (transdermal application by permanently magnetizable and magnetized plastic films EP 0127174).

Often the principle of iontophoresis is associated with the simultaneous electrophoretic release of the active ingredients from a corresponding "reservoir".

Sibalis (EP 0178601) developed in 1985 z. B. a transdermal drug applicator, which allows a current-induced drug release from a porous material and at the same time a recovery of the released drug into the skin. In EP 0060451 elektrophoretischo electrodes are described, which u.a. Lidocaine dissolved in a gel containing various polyacrylates and methacrylates and are used to introduce the ionized substance into the body.

Also in EP 0058920, gels of various polymers (eg PVA, PVP, polyHEMA derivatives) serve as contact material to the human skin or as ion carriers. EP 0011813 describes a bioelectrode which serves to iontophoretically release ions or polar molecules into the skin. This electrode carries a solution of the substance to be released and is separated from the skin by a membrane.

Also Spevak, Lattin and Jerne describe in EP Ü060451 iontophoretically electrodes for introducing ionized substances into the body, wherein the substance to be driven, is present dissolved.

All descriptions are of the late-night nature that due to the more (solution) or less (gel) high water content of the reservoir, both chemical and microbiological stability problems are to be expected. In addition, especially in the devices containing the drug in a solution, there is a risk of unintentional. fall unloading "under mechanical stress (shock, pressure).

Thus, the previously known devices in the application are uncertain, they can not be stored long, their handling is complicated and can not be done by the patient.

Object of the invention

The aim of the invention is to avoid the disadvantages of the previously known devices and to develop a patch that can be produced inexpensively and easily, with known physiotherapeutic devices available to the patient or in medical institutions or a corresponding simple energy dispenser can be brought to action and characterized by an exact dosage of the active ingredient as well as its controllable release and a high storage stability.

Explanation of the essence of the invention

The invention is based on a method for the production of a plaster, which is characterized, carrier material with incorporated active ingredients, which consists of a coagulating latex, contains an electrically conductive additive and an electrode or can be coupled with an electrode. In conjunction with another electrode, a force field, preferably a DC electric field has been generated, the strength of which can be used to control the release of the incorporated active substance.

As the coagulable latex, an aqueous acrylate dispersion of a copolymer of acrylic / methacrylic acid and acrylic / methacrylic esters may be used in accordance with a conventional method for producing transdermal patches (e.g., DD-WP 217939). The latex is treated with active ingredients, eg. As local anesthetics, antihistamines, added in certain ionic strength and stirred until uniform. A certain mass of an electrically conductive substance, for example a metal, a carbon modification, preferably graphite, a carbide, etc., is suspended in this mixture. The average particle size of the suspended particles may not be 500μηι (they should preferably be between 50 ... δΟΟμηι).

The resulting mixture is poured out with frequent stirring immediately afterwards onto a surface (eg polyethylene film or aluminum foil) of defined area (eg 87 cm ³ ). The pad may be laid up as a "inner electrode" with a platinum wire mesh coextensive with the resulting patch The contact between the electrode and the patch may also be through the minor leaflet (eg aluminum foil) or later, eg electrically conductive It is also possible to combine the plaster with an electrode by forming an electrically conductive adhesive layer on the surface.

After a drying process (eg 72 h at 20-25 ⁰ C) results from the poured mixture a film-shaped plaster. This is combined with another electrode during use. By connecting the two electrodes to a force such as a DC power source (eg 8V), an electric field can be generated. According to the polarity of the field (preferably: patch »anode (+) in drug anions or patch = cathode (-) in drug cations) and its strength, the Wirkstoffausstrom can be controlled.

embodiments

The following examples illustrate the invention in a non-limiting manner.

example 1

(Preparation of a procaine [1] plaster)

Step I: 5.00 ml of acrylate dispersion (40% solids content) are mixed with a solution of 1.00 ml of glycerol in 7.50 ml of water.

Preparation: 0.0940 g1 are dissolved to 12.50 ml in water (ionic strength I = 0.0251 mmol " ¹ ) After mixing the two mixtures, 1.00 g are added to the dispersion with stirring (magnetic stirrer, 5 min at the lowest level) Suspended graphite powder.

Table 1 Influence of an electric field and the composition of the patch on the diffusion coefficient D, _pp for the 1-Liberation from the respective patch

Film Composition Voltage U Current ID, _pp V mA 1Q- ¹⁰ Cm ² S- '

Approach I + 11 0 0 4.5

Approach I + 11+ Graphite 8 20 49.7

Example 2

(Preparation of a Cinchocaine [2] -Piaster) _:

Preparation I: 10.00 ml of acrylate dispersion (40% solids content) are mixed with a solution of 1.00 ml of glycerol in 2.50 ml

Water-mixed batch II: 0.1300 g 2 are dissolved to 12.50 ml in water.

After mixing the two batches, 1.00 g of carbide powder are suspended in the dispersion as indicated in Example 1. By simple in vitro testing it can be shown that by the electrically isitfähigon addition, z. B. graphite, the experimental diffusion coefficients for the liberation of the drug from the patch can be increased tenfold (Tab. 1)

 The polarity of the electric field influences the active substance outflow (Table 2). Boi 1 leads to a poling of the patch as an anode to increase, a polarity of the patch as a cathode to reduce dor apparent diffusion coefficient.

Table 2 Dependence of the diffusion coefficients D, _pp for the 1 -liberation from Pfiastorn according to the invention on the position of the plaster and the current intensity I dos of electrical feidos

Recipe of the plaster No. Polarity of the plaster Current I mA 10 ' ⁸ Cm ² S " ¹ 1 1 Anode (+) 0 10 4.5 71.8 2 2 Cathode (-) 0 10 61.7 59.1

A control of the active substance liberation can preferably take place via a variation of the strength of the electric field (Table 3).

Table 3: Dependence of the diffusion coefficient D, _pp for the 2-Liberation of patches according to the invention of the current intensity I of the electric Foldes

ImA D ₈ PpIO- ¹¹ Cm ² S- ¹ 0 0.02 10 8.22 25 17.40 40 55,80 60 73,50 75 137.00

Claims (6)

1. A process for the preparation of a plaster, characterized in that a carrier material is incorporated with incorporated active ingredients, which is produced from a coagulating latex on a base, so üb'jr the strength of an electric field between the pad or a paving-like Elektrorie and a outer electrode, the release of the drug can be controlled. 2. The method according to claim 1, gekannzeichnet characterized in that the latex is an aqueous polyacrylate dispersion, preferably a dispersion of a dermatologically indifferent, carboxyl-containing Copofymerisates of acrylic, methacrylic, itaconic, crotonic, maleic, fumaric acid with analogous esters of C ₁ -C ₈ -AlkOhOlBn is used, which is characterized by a maximum impurity content of 0.56Gew .-%. 3. The method according to claim 1 and 2, characterized in that the electrically conductive additive, for example a metal, a »carbon modification, preferably graphite, a carbide, etc., molecular, colloid to at most finely dispersed, preferably in'einer particle size between 50 and 500μηη, is distributed in the carrier material. 4. The method according to claim 1 to 3, characterized in that the patch on the side facing away from the skin additionally contains a le'tfähige adhesive layer, which allows coupling with an electrode. 5. The method according to claim 1 to 4, characterized in that the additional adhesive layer of a dispersion of a dermatologically indifferent, carboxyl-containing copolymer of acrylic, methacrylic, itaconic, crotonic, maleic, fumaric acid with analogous esters of C ₁ -C ₈ alcohols is produced, which is characterized by a foreign substance content of not more than 0.56 wt .-%. 6. The method according to claim 1 to 5, characterized in that for expelling the active ingredients known physiotherapeutic devices, preferably simple, stationable in the patient or combinable with the plaster power sources can be used.