NZ503643A

NZ503643A - Method for preventing the misuse of a transdermal therapeutic system

Info

Publication number: NZ503643A
Application number: NZ503643A
Authority: NZ
Inventors: Frank Becher; Ann-Katrin Klink
Original assignee: Lohmann Therapie Syst Lts
Priority date: 1997-10-01
Filing date: 1998-09-18
Publication date: 2003-05-30
Also published as: EP1019032B1; NO20001691L; AU759609B2; JP2001517695A; ATE228356T1; PL339736A1; HUP0003476A3; ID24333A; HU226644B1; ES2188021T3; NO20001492D0; TW431894B; CA2305432C; KR20010030886A; SK3332000A3; HK1029919A1; TR200000461T2; PL193066B1; NO319163B1; HUP0003476A2

Abstract

Transdermal therapeutic patches comprising of at least one active substance containing layer and at least one further active substance impermeable backing layer wherein the active substance containing layer is denatured with a therapeutically neutral, inert substance with an unpleasant taste to guard against oral ingestion of active ingredients.

Description

<div class="application article clearfix" id="description"> New Zealand Paient Spedficaiion for Paient Number 503643 I 2 8 FEB 2003 I RECEIVED METHOD FOR PREVENTING THE MISUSE OF A TRANSDERMAL THERAPEUTIC SYSTEM The invention relates to a process for the protection of a person against contamination as a result of improper, i.e. oral, application of toxic components of a transdermal therapeutic system (TTS), comprising at least one active substance-containing, especially pressure-sensitive adhesive layer and at least one further, active substance-impermeable backing layer, as well as a TTS containing a denaturant. A series of TTS present an acute danger of undesired side effects if administered orally by a person in order to extract a soluble active agent - either from a new system or a used one. Infants, for example, have a tendency to stick anything interesting into their mouth and to at least suck or chew on it. This cannot be avoided especially if children happen to attain access to such systems by chance, especially systems without a release liner. Such incidents have not yet been known to occur, but the pharmaceutical authorities increasingly fear that they might and have therefore, in various instances, demanded childproof packages. Such childproof packages have, in fact, been developed in various embodiments. However, they do not protect a child from putting a TTS in its mouth once the package has been opened or if the child somehow gets hold of a used patch. Especially in the case of TTS with active substances such as anesthetics, analgesics, tranquilizers or psychopharmacological agents, an oral abuse can lead to serious health impairments. On the other hand, addicts could be tempted to extract such, active agents from transdermal therapeutic systems by means of sucking of chewing. It is known that drinkable ethyl alcohol can be denatured and then put on the market as methylated spirit. A denaturing of pharmaceutical active agents, on the other hand, has not yet been published. Xt is the object of the invention to develop a process for the protection of a person of the kind mentioned in the introductory part of Claim 1 in a way that makes an oral abuse of the kind mentioned above impossible, at the same time, however, avoiding a disadvantageous change in the system's therapeutic active agent and also ruling out an impairment of health in the case of improper, i.e. oral, application, or to at least provide a useful alternative. To achieve this object, the process according to the invention proposes the addition of a therapeutically neutral, non-interacting substance with a disgusting taste. Because this substance causes extremely unpleasant and -unexpected experiences with respect to taste, a first oral contact with the TTS according to the invention or with one of its denatured layers is sufficient for achieving a spontaneous reaction with the effect of immediately spitting out the corresponding patch and thus for preventing children or drug addicts from an improper, i.e. oral, application of the active substance contained in the patch. One embodiment provides that a substance is used for the denaturation of a TTS which causes nausea and thus spoils the temptation of oral application for the person concerned. INTELLECTUAL PROPERTY OFFICE OF N.Z. 1 3 JUN 2001 received 3 Another embodiment of the process according to the invention provides that the substance is applied on top of the active substance-containing layer in a separate, extremely thin layer which does not prevent the permeation of the active substance. This has the benefit that the experiencing of an extremely disgusting taste directly upon first contact of the TTS with the oral mucosa or the tongue will dissuade further oral contact before a contamination through the active substance-containing layer can occur. As a further measure, the substance can additionally be applied to the backing layer in a separate, preferably very thin layer, thus safely achieving a further intensification of the effect of denaturation. In this case, the separate substance layer is to be applied in a thickness of between 10 and 100 |im, preferably between 5 and 2 0 jam. An especially advantageous embodiment of the invention further provides for the use of a substance which causes an irritation such as a burning of the oral mucosa and the tongue. One such negative experience should suffice to lastingly dissuade a child or an addict from further attempts at oral contact with a TTS. A similar effect can also be achieved if a substance is used which causes an intensely bitter taste and especially aftertaste. An effective embodiment of the process according to the invention provides for the use of gallic acid, quinine, tannin, angostura, (pure) caffeine, lobeline, tea tree oil, certain hyphomycete cultures, denatured or coagulated substances, turpentine or ammonia as amaroids or substances </div>

Claims

<div class="application article clearfix printTableText" id="claims"> 4 .with a disgusting taste for the denaturation of at least one layer of a TSS. For the implementation of one embodiment of the process, the invention provides for the incorporation of the substances used for denaturation in a film layer with which the active substance-containing layer and, depending on the case, also the backing layer are coated. An especially advantageous solution provides for the use of a film layer soluble in saliva. The use of the term "disgusting taste", is used to define any substance that when included in a TTS, the resulting taste is sufficient to deter any oral application of the TTS. The process is uncomplicated and effective and protects children and/or addicts against improper, i.e. oral, application of toxic components of a transdermal therapeutic system. Thus, the process and the TTS according to the invention present an ideal means of achieving the object as mentioned above. INTELLECTUAL PROPERTY OFFICE OF N.Z. 1 3 JUN 2001 received What We Claim Is: w "* ^ ^ ^

1. Transdermal therapeutic system (TTS), comprising at least one active substance-containing layer and at least one further, active substance-impermeable backing layer, wherein the active substance-containing layer is denatured with a denaturant which is therapeutically neutral, does not interact with the active substance and has a disgusting taste.

2. TTS according to claim 1, wherein the active substance-containing layer is a pressure-sensitive adhesive layer.

3. TTS according to claim 1 or 2, wherein the denaturant is contained at least in the active substance-containing layer.

4. TTS according to any one of the claims 1 to 3, wherein the denaturant is incorporated in a film layer with which the active substance-containing layer or the active substance-containing layer and the backing layer are coated.

5. TTS according to claim 4, wherein the film layer is soluble in saliva.

6. TTS according to any one of claims 1 to 5, wherein the denaturant causes nausea.

7. TTS according to any one of the claims 1 to 6, wherein said denaturant is applied on top of the active substance-containing layer in a separate film layer which does not prevent the permeation of the active substance.

8. TTS according to any one of the claims 1 to 7, wherein said denaturant is applied to the backing layer in the form of an additional separate film layer.

9. TTS according claim 7 or 8, wherein the separate film layer is applied in a thickness of between 10 to 100 jam. INTELLECTUAL PROPERTY OFFICE OF N.Z. 2 7 NOV 2002 received

10. TTS according to claim 7 or 8, wherein the separate film layer is applied in a thickness of between 5 and 20 fjm.

11. TTS according to any one of the claims 1 to 10, wherein the denaturant causes an irritation such as burning of the mucosa of the oral cavity and the tongue.

12. TTS according to any one of the claims 1 to 11, wherein the denaturant causes an intensely bitter taste.

13. TTS according claim 12, wherein the intensely bitter taste is also an aftertaste.

14. TTS according to any one of the claims 1 to 13, wherein the denaturant is gallic acid, quinine, tannin, angostura, (pure) caffeine, lobeline, tea tree oil, hyphomycete cultures, denatured or coagulated substances, turpentine or ammonia as amaroids or substances with a disgusting taste.

15. Process for the protection of a person against contamination as a result of improper oral application of a TTS, which comprises denaturing at least the active substance-containing layer of said denaturant, said TTS comprising at least one active substance containing layer and at least one further active substance-impermeable backing layer.

16. A TTS according to any one of claims 1 to 14, substantially as herein described.

17. A process according to claim 15, substantially as herein described. LTS LOHMANN THERAPIE-SYSTEME GHBH INTELLECTUAL PROPERTY OFFICE OF N.Z. 2 7 NOV 2002 received </div>