CA2305432C - Method for preventing the misuse of a transdermal therapeutic system - Google Patents
Method for preventing the misuse of a transdermal therapeutic system Download PDFInfo
- Publication number
- CA2305432C CA2305432C CA002305432A CA2305432A CA2305432C CA 2305432 C CA2305432 C CA 2305432C CA 002305432 A CA002305432 A CA 002305432A CA 2305432 A CA2305432 A CA 2305432A CA 2305432 C CA2305432 C CA 2305432C
- Authority
- CA
- Canada
- Prior art keywords
- substance
- transdermal therapeutic
- therapeutic system
- layer
- active substance
- 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.)
- Expired - Lifetime
Links
- 230000001225 therapeutic effect Effects 0.000 title claims abstract description 25
- 238000000034 method Methods 0.000 title description 9
- 239000010410 layer Substances 0.000 claims description 32
- 239000000126 substance Substances 0.000 claims description 28
- 239000013543 active substance Substances 0.000 claims description 23
- 235000019640 taste Nutrition 0.000 claims description 11
- 238000004925 denaturation Methods 0.000 claims description 5
- 230000036425 denaturation Effects 0.000 claims description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 4
- 239000004820 Pressure-sensitive adhesive Substances 0.000 claims description 4
- LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 claims description 4
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 claims description 4
- LNTHITQWFMADLM-UHFFFAOYSA-N gallic acid Chemical compound OC(=O)C1=CC(O)=C(O)C(O)=C1 LNTHITQWFMADLM-UHFFFAOYSA-N 0.000 claims description 4
- 235000019658 bitter taste Nutrition 0.000 claims description 3
- 230000007794 irritation Effects 0.000 claims description 3
- 230000007935 neutral effect Effects 0.000 claims description 3
- MXYUKLILVYORSK-UHFFFAOYSA-N (+/-)-allo-lobeline Natural products C1CCC(CC(=O)C=2C=CC=CC=2)N(C)C1CC(O)C1=CC=CC=C1 MXYUKLILVYORSK-UHFFFAOYSA-N 0.000 claims description 2
- MXYUKLILVYORSK-HBMCJLEFSA-N (-)-lobeline Chemical compound C1([C@@H](O)C[C@H]2N([C@H](CCC2)CC(=O)C=2C=CC=CC=2)C)=CC=CC=C1 MXYUKLILVYORSK-HBMCJLEFSA-N 0.000 claims description 2
- 241000189429 Angostura Species 0.000 claims description 2
- 235000001258 Cinchona calisaya Nutrition 0.000 claims description 2
- 206010013911 Dysgeusia Diseases 0.000 claims description 2
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 claims description 2
- 206010028813 Nausea Diseases 0.000 claims description 2
- 241000779819 Syncarpia glomulifera Species 0.000 claims description 2
- 229910021529 ammonia Inorganic materials 0.000 claims description 2
- 229960001948 caffeine Drugs 0.000 claims description 2
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 claims description 2
- LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 claims description 2
- 229940074391 gallic acid Drugs 0.000 claims description 2
- 235000004515 gallic acid Nutrition 0.000 claims description 2
- 229960002339 lobeline Drugs 0.000 claims description 2
- 229930013610 lobeline Natural products 0.000 claims description 2
- 230000008693 nausea Effects 0.000 claims description 2
- 239000001739 pinus spp. Substances 0.000 claims description 2
- 229960000948 quinine Drugs 0.000 claims description 2
- 235000018553 tannin Nutrition 0.000 claims description 2
- 229920001864 tannin Polymers 0.000 claims description 2
- 239000001648 tannin Substances 0.000 claims description 2
- 229940111630 tea tree oil Drugs 0.000 claims description 2
- 239000010677 tea tree oil Substances 0.000 claims description 2
- 229940036248 turpentine Drugs 0.000 claims description 2
- 239000011247 coating layer Substances 0.000 claims 1
- 239000012530 fluid Substances 0.000 claims 1
- 210000000214 mouth Anatomy 0.000 claims 1
- 239000003398 denaturant Substances 0.000 abstract description 2
- 230000000694 effects Effects 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 238000011109 contamination Methods 0.000 description 3
- 231100000331 toxic Toxicity 0.000 description 3
- 230000002588 toxic effect Effects 0.000 description 3
- 230000006735 deficit Effects 0.000 description 2
- 210000002200 mouth mucosa Anatomy 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 229940035674 anesthetics Drugs 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000001055 chewing effect Effects 0.000 description 1
- 239000011928 denatured alcohol Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- 239000003193 general anesthetic agent Substances 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000001003 psychopharmacologic effect Effects 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 239000003204 tranquilizing agent Substances 0.000 description 1
- 230000002936 tranquilizing effect Effects 0.000 description 1
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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P23/00—Anaesthetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
Landscapes
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Dermatology (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biomedical Technology (AREA)
- Anesthesiology (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Neurology (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Electrotherapy Devices (AREA)
- Medicines Containing Plant Substances (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Saccharide Compounds (AREA)
- Radiation-Therapy Devices (AREA)
- Electrolytic Production Of Non-Metals, Compounds, Apparatuses Therefor (AREA)
Abstract
Denaturants are added to a transdermal therapeutic system to prevent an improper, i.e. oral, application.
Description
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 2 i i hand, addicts could be tempted to extract such active agents from transdermal therapeutic systems by means of sucking or chewing.
~t is knovun 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.
It is the object of the invention to develop a process for the protection o~ a person against contamination as a result of improper, i.e. oral, application Of toxic camponents Of a transdermal therapeutic System (TTS) 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.
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 br drug addicts from an improper, i.e. oral, application of the active subetas:e" ""ntaiaed~ :~:~ w a ;,at~'~
One embodiment provides that a substance is used for the denaturation of a TT5 which causes nausea and thus spoils the temptation of oral applicatibn for the person concerned.
x1736814.1 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 dim, preferably between and 2 0 E lm .
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 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 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.
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 2 i i hand, addicts could be tempted to extract such active agents from transdermal therapeutic systems by means of sucking or chewing.
~t is knovun 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.
It is the object of the invention to develop a process for the protection o~ a person against contamination as a result of improper, i.e. oral, application Of toxic camponents Of a transdermal therapeutic System (TTS) 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.
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 br drug addicts from an improper, i.e. oral, application of the active subetas:e" ""ntaiaed~ :~:~ w a ;,at~'~
One embodiment provides that a substance is used for the denaturation of a TT5 which causes nausea and thus spoils the temptation of oral applicatibn for the person concerned.
x1736814.1 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 dim, preferably between and 2 0 E lm .
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 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 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.
Claims (17)
1. A transdermal therapeutic system comprising at least one active substance-containing layer, as well as at least one further backing layer impermeable to the active substance, wherein the transdermal therapeutic system contains a substance for denaturing which is therapeutically neutral and does not interact with the active substance and which has a disgusting taste.
2. The transdermal therapeutic system according to claim 1, wherein the substance of disgusting taste is contained at least in the active substance-containing layer.
3. The transdermal therapeutic system according to claim 1 or 2, wherein the substance used for denaturing are incorporated in a coat layer with which the active substance-containing layer and, as the case may be, the cover layer are coated.
4. The transdermal therapeutic system according to claim 3, wherein the coating layer is soluble in the oral fluid.
5. The transdermal therapeutic system according to any one of claims 1 to 4, wherein the substance for denaturing is a substance causing nausea.
6. The transdermal therapeutic system according to any one of claims 1 to 5, wherein the substance for denaturing is applied to the active substance-containing layer in a separate, extremely thin layer not impairing the permeation of the active substance.
7. The transdermal therapeutic system according to any one of claims 1 to 6, wherein the substance for denaturing is additionally applied to the backing layer, in a separate, extremely thin layer.
8. The transdermal therapeutic system according to any one of claims 1 to 7, wherein the separate layer of the said substance is applied in a thickness of between 10 and 100 µm.
9. The transdermal therapeutic system according to claim 8 wherein the separate layer of the said substance is applied in a thickness of between 5 and 20 µm.
10. The transdermal therapeutic system according to any one of claims 1 to 9, wherein the substance of disgusting taste is a substance causing an irritation
11. The transdermal therapeutic system according to claim 10 wherein the irritation is burning of the mucosae of the oral cavity and the tongue.
12. The transdermal therapeutic system according to any one of claims 1 to 11, wherein the substance of disgusting taste is a substance causing an intensely bitter taste.
13. The transdermal therapeutic system according to claim 12 wherein the intensely bitter taste is an aftertaste.
14. The transdermal therapeutic system according to any one of claims 1 to 13, wherein, for denaturation or producing a disgusting taste, at least one layer of the transdermal therapeutic system contains gallic acid, quinine, tannin, angostura, caffeine (pure), lobeline, tea tree oil, mould cultures, denatured or coagulated substances, turpentine or ammonia as amaroids or, respectively, substances having a disgusting taste.
15. The transdermal therapeutic system according to claim 1, wherein the at least one active substance-containing layer has been rendered pressure-sensitive adhesive.
16. Use of a therapeutically neutral substance of disgusting taste for preparing a transdermal therapeutic system which is thereby protected against impermissible oral application, said system comprising at least one active substance-containing layer, wherein said active substance-containing layer has been rendered pressure-sensitive adhesive, as well as at least one further backing layer impermeable to the active substance, and with said substance not interacting with the active substance.
17. The use according to claim 16, wherein said at least one active substance containing layer comprises a pressure-sensitive adhesive.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19743484A DE19743484C1 (en) | 1997-10-01 | 1997-10-01 | Transdermal patches containing substance with unpleasant taste |
| DE19743484.3 | 1997-10-01 | ||
| PCT/EP1998/005955 WO1999016428A1 (en) | 1997-10-01 | 1998-09-18 | Method for preventing the misuse of a transdermal therapeutic system |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2305432A1 CA2305432A1 (en) | 1999-04-08 |
| CA2305432C true CA2305432C (en) | 2007-04-03 |
Family
ID=7844345
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002305432A Expired - Lifetime CA2305432C (en) | 1997-10-01 | 1998-09-18 | Method for preventing the misuse of a transdermal therapeutic system |
Country Status (22)
| Country | Link |
|---|---|
| EP (1) | EP1019032B1 (en) |
| JP (2) | JP4755338B2 (en) |
| KR (1) | KR100552102B1 (en) |
| AT (1) | ATE228356T1 (en) |
| AU (1) | AU759609B2 (en) |
| CA (1) | CA2305432C (en) |
| DE (2) | DE19743484C1 (en) |
| DK (1) | DK1019032T3 (en) |
| ES (1) | ES2188021T3 (en) |
| HU (1) | HU226644B1 (en) |
| ID (1) | ID24333A (en) |
| IL (1) | IL134479A (en) |
| MY (1) | MY116425A (en) |
| NO (2) | NO319163B1 (en) |
| NZ (1) | NZ503643A (en) |
| PL (1) | PL193066B1 (en) |
| PT (1) | PT1019032E (en) |
| SK (1) | SK3332000A3 (en) |
| TR (1) | TR200000461T2 (en) |
| TW (1) | TW431894B (en) |
| WO (1) | WO1999016428A1 (en) |
| ZA (1) | ZA988904B (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19743484C1 (en) * | 1997-10-01 | 1999-01-28 | Lohmann Therapie Syst Lts | Transdermal patches containing substance with unpleasant taste |
| GB0026137D0 (en) * | 2000-10-25 | 2000-12-13 | Euro Celtique Sa | Transdermal dosage form |
| US7867511B2 (en) * | 2004-01-23 | 2011-01-11 | Travanti Pharma Inc. | Abuse potential reduction in abusable substance dosage form |
| DE102004019916A1 (en) * | 2004-04-21 | 2005-11-17 | Grünenthal GmbH | Anti-abuse drug-containing patch |
| JP7329857B2 (en) * | 2018-10-17 | 2023-08-21 | 日榮新化株式会社 | Adhesive sheet and its manufacturing method |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8804164D0 (en) * | 1988-02-23 | 1988-03-23 | Tucker J M | Bandage for administering physiologically active compound |
| US5236714A (en) * | 1988-11-01 | 1993-08-17 | Alza Corporation | Abusable substance dosage form having reduced abuse potential |
| US5149538A (en) * | 1991-06-14 | 1992-09-22 | Warner-Lambert Company | Misuse-resistive transdermal opioid dosage form |
| DE4342174C1 (en) * | 1993-12-10 | 1995-05-11 | Lohmann Therapie Syst Lts | Transdermal therapeutic system and a method for producing a transdermal therapeutic system for the combined transdermal application of physostigmine and scopolamine for the prophylaxis and pretreatment of poisoning by highly toxic organophosphorus neurotoxins, in particular Soman and its use |
| DE19743484C1 (en) * | 1997-10-01 | 1999-01-28 | Lohmann Therapie Syst Lts | Transdermal patches containing substance with unpleasant taste |
-
1997
- 1997-10-01 DE DE19743484A patent/DE19743484C1/en not_active Expired - Fee Related
-
1998
- 1998-09-18 AU AU96265/98A patent/AU759609B2/en not_active Ceased
- 1998-09-18 KR KR1020007003579A patent/KR100552102B1/en not_active Expired - Lifetime
- 1998-09-18 NZ NZ503643A patent/NZ503643A/en not_active IP Right Cessation
- 1998-09-18 ES ES98950053T patent/ES2188021T3/en not_active Expired - Lifetime
- 1998-09-18 IL IL13447998A patent/IL134479A/en not_active IP Right Cessation
- 1998-09-18 AT AT98950053T patent/ATE228356T1/en active
- 1998-09-18 DE DE59806468T patent/DE59806468D1/en not_active Expired - Lifetime
- 1998-09-18 PT PT98950053T patent/PT1019032E/en unknown
- 1998-09-18 ID IDW20000399A patent/ID24333A/en unknown
- 1998-09-18 JP JP2000513566A patent/JP4755338B2/en not_active Expired - Lifetime
- 1998-09-18 WO PCT/EP1998/005955 patent/WO1999016428A1/en not_active Ceased
- 1998-09-18 EP EP98950053A patent/EP1019032B1/en not_active Expired - Lifetime
- 1998-09-18 SK SK333-2000A patent/SK3332000A3/en unknown
- 1998-09-18 DK DK98950053T patent/DK1019032T3/en active
- 1998-09-18 CA CA002305432A patent/CA2305432C/en not_active Expired - Lifetime
- 1998-09-18 PL PL339736A patent/PL193066B1/en not_active IP Right Cessation
- 1998-09-18 TR TR2000/00461T patent/TR200000461T2/en unknown
- 1998-09-18 HU HU0003476A patent/HU226644B1/en not_active IP Right Cessation
- 1998-09-25 TW TW087115939A patent/TW431894B/en not_active IP Right Cessation
- 1998-09-29 MY MYPI98004449A patent/MY116425A/en unknown
- 1998-09-30 ZA ZA988904A patent/ZA988904B/en unknown
-
2000
- 2000-03-22 NO NO20001492A patent/NO319163B1/en not_active IP Right Cessation
- 2000-03-31 NO NO20001691A patent/NO20001691D0/en not_active Application Discontinuation
-
2008
- 2008-08-20 JP JP2008212077A patent/JP2009035561A/en active Pending
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