EP2079458A2 - Transdermales therapeutisches system mit zweiphasigem freisetzungsprofil - Google Patents
Transdermales therapeutisches system mit zweiphasigem freisetzungsprofilInfo
- Publication number
- EP2079458A2 EP2079458A2 EP07802907A EP07802907A EP2079458A2 EP 2079458 A2 EP2079458 A2 EP 2079458A2 EP 07802907 A EP07802907 A EP 07802907A EP 07802907 A EP07802907 A EP 07802907A EP 2079458 A2 EP2079458 A2 EP 2079458A2
- Authority
- EP
- European Patent Office
- Prior art keywords
- tts
- therapeutic system
- transdermal therapeutic
- hydrocarbon
- functional group
- 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.)
- Withdrawn
Links
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
- 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
-
- 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
- A61K31/48—Ergoline derivatives, e.g. lysergic acid, ergotamine
-
- 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
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
Definitions
- the present invention relates to a transdermal therapeutic system for ergoline compounds having a new two-phase release profile in which in a first phase (0-5 hours after administration) only 0-20% of the therapeutically desired steady state plasma concentration of the ergoline compound is achieved and then only in a second phase (5-20 hours after administration), the therapeutically desired steady state plasma concentration of the ergoline compound is achieved.
- dopaminergic therapies of Parkinson's disease and other conditions such as Restless Legs Syndrome and other neurological disorders associated with brain damage or injury, if fully effective, will be affected by a large number of side effects.
- the adjustment of oral dopaminergic therapies is either using levodopa alone or with the aid of enhancers (MAO inhibitors, COMT inhibitors) or dopamine agonists. It is based on the individual bioavailability and the therapeutic needs of a patient, ie, the therapy is titrated, so to speak. This titration may involve up to five different agents with unpredictable metabolism or other interactions.
- transdermal preparation of a dopamine agonist (Table 1; -3-), which is normally prepared to deliver the active ingredient persistently, is apparently not generally capable of significantly reducing peripheral accessory defects as compared to conventional immediate-release formulations.
- transdermal formulations can compensate for skin-binding effects of the active agent during the first phase of release, by overcharging the system, and / or introducing defined amounts of the drug into the outer adhesive layer. This is likely to indicate a more consistent delivery of the drug to the systemic circulation but, in the case of drugs with a narrow therapeutic range, is an inappropriate method of administration to prevent side effects.
- TTS transdermal therapeutic system
- transdermal therapeutic system for transdermal administration which comprises an impermeable covering layer, an ergoline compound of the formula (I),
- R 1 is an H atom or a halogen atom and R 2 is an alkyl group having 1 to 4 carbon atoms and a single or double bond, and a peelable protective layer, wherein the ergoline compound or whose physiologically acceptable salt or derivative is stabilized by an antioxidant and a basic polymer, wherein the TTS is characterized in that in the matrix at least one hydrocarbon having 8 to 18 carbon atoms in a straight or branched chain, which at the end of the alkyl chain is a functional Group wears and / or aloe vera oil are included.
- the TTS according to the invention is further characterized in that in a first phase (0-5 hours after administration) only 0-20% of the therapeutically aimed steady State plasma concentration of the ergoline compound can be achieved and then in a second phase (5-20 hours after application), the therapeutically desired steady state plasma concentration of the ergoline compound is achieved.
- steady state plasma concentration describes the concentration of lisuride in the blood plasma in which the absorbed amount of the active ingredient is equal to the amount eliminated, so that a constant plasma concentration over time is achieved.
- the blood samples taken over the period of application of the TTS patch were transformed into blood plasma and the content of lisuride determined by means of selective analysis methods (RIA or LC / MS / MS).
- RIA selective analysis methods
- LC / MS / MS selective analysis methods
- the target plasma concentration is 5 ⁇ g Lisuride per ml to 10 ng Lisuride per ml, preferably 50 to 500 ⁇ g Lisuride per ml. Highest preferred is a steady state plasma concentration of 100 to 200 pg lisuride per ml. All
- Concentration data refer to the amount of lisuride per ml blood plasma volume.
- the preferred plasma concentration depends on the potency of the compound.
- the transdermal therapeutic system (TTS) is further characterized in that the at least one hydrocarbon having 8 to 18 carbon atoms in straight or branched chain at the end of the alkyl ketone te as a functional group preferably carries a hydroxyl or amino group or a pyrrolidone ring or a -0OCCH 2 N (CH 3 ) 2 group.
- the at least one hydrocarbon having 8 to 18 carbon atoms in straight or branched chain at the end of the alkyl chain as a functional group carries a hydroxyl group (alcohol).
- the at least one functional group hydrocarbon at the end of the alkyl chain has from 10 to 14 carbon atoms in a straight or branched chain.
- the at least one functional group hydrocarbon at the end of the alkyl chain has 12 carbon atoms in a straight or branched chain.
- the at least one hydrocarbon having a functional group at the end of the alkyl chain is 1-dodecanol.
- the at least one hydrocarbon having a functional group at the end of the alkyl chain is contained in the transdermal therapeutic system of the present invention in 0.001 to 20.00% by weight. Preferably, it is present in 0.50 to 15.00 wt .-%, wherein it is contained in a very preferred embodiment in 1.00 to 10.00 wt .-%. Most preferably, the at least one hydrocarbon having a functional group is present at the end of the alkyl chain in 10.00% by weight.
- the transdermal therapeutic system according to the invention is further characterized in that the aloe vera oil contained in the matrix consists of a vegetable fatty oil, preferably peanut oil, almond oil, sesame oil or soybean oil was obtained. Particularly preferred is the extraction of soybean oil. The extraction was carried out from the fresh leaves of the plant.
- the aloe vera oil is contained in the matrix of the transdermal therapeutic system in 0.01 to 20.00% by weight.
- the aloe vera oil is in 0.5 to 10.00 wt .-% before.
- the transdermal therapeutic system comprises the aloe vera oil at 5.00% by weight.
- the ergoline compound contained in the transdermal therapeutic system according to the invention is preferably lisuride or proterguride or its physiologically acceptable salt or derivative.
- a particularly preferred embodiment of the transdermal therapeutic system contains as ergoline compound lisuride (see formula II) or proterguride (see formula III).
- the ergoline compound or its physiologically acceptable salt or derivative is contained in 0.50 to 20.00% by weight in the matrix of the transdermal therapeutic system.
- the transdermal therapeutic system comprises the ergoline compound or its phy- Socially acceptable salt or derivative in 3.00 to 6.00 wt .-% to.
- the TTS according to the invention is characterized in that the matrix can contain penetration-enhancing agents.
- the matrix may have a covering diffusion barrier and an adhesive layer permeable to the substances of the formula (I).
- the antioxidant contained in the TTS according to the invention is preferably selected from the group of di-tert-butylmethylphenole, tert. Butyl methoxyphenols, tocopherols and / or ubiquinones.
- the antioxidant is preferably present in amounts of 0.25 wt .-% to 5.00 wt .-% before.
- the basic polymer contained in the TTS according to the invention is preferably an acrylate (co) polymer, with a butyl methacrylate (2-diaminoethyl) methacrylate-methacrylate copolymer being particularly preferred.
- the basic polymer may be contained in the matrix or the adhesive layer.
- the basic polymer in the matrix or adhesive layer has an adhesion promoter.
- This adhesion promoter preferably contains resins (modified or unmodified) and / or neutral polyacrylates.
- the TTS according to the invention contains from 1 to 20% by weight of adhesive power. stronger, with a content of 2 to 10 wt .-% tackifier is most preferred.
- Placebo-controlled double-blind studies in 335 parkinsonism patients have confirmed that most or all of the common side effects that are common in all other dopamine-like therapeutic treatments and agents can be avoided (nausea, vomiting, orthostasis , Drowsiness).
- pharmacokinetic data obtained from further clinical studies has a plasma concentration profile of the drug that lacks sharp peak levels.
- passage levels in the pharmacologically effective concentration range are maintained with repeated administration, with a favorable ratio of peak to passage concentration of about four.
- TTS time-sensitive titration
- active ingredients and side effects
- a very strong therapeutic effect can be achieved, which already within the first Days of therapy occurs.
- This effect can also be achieved in situations where impaired cognition and / or disturbed consciousness exist.
- active ingredient combinations there is no further need for active ingredient combinations.
- the treatment will be easy and patient-friendly, which is why the approval of patients and their quality of life are greatly improved.
- the TTS according to the invention is suitable for the treatment of neurodegenerative diseases, in particular Parkinson's disease and Parkinsonism (Parkinson's syndrome). Furthermore, the TTS according to the invention is suitable for the treatment of restless legs syndrome as well as for the treatment of other neurological damages which are accompanied by brain damage and injuries.
- Lisuride was dissolved in organic solvents and mixed with a pressure-sensitive polyacrylate adhesive, dodecanol, aloe extract, polyvinylpyrrolidone, butylhydroxytoluene and - if necessary - with other auxiliaries to the physical properties of the resulting lami- nats to modify.
- the mixture was applied to a fluoropolymerized release liner and dried to completely remove the organic solvent before laminating with a polyethylene (PE) back membrane.
- PE polyethylene
- the content of lisuride was 5% and the coating weight of the dry adhesive coating was determined to be 5 mg / cm 2 .
- Circular samples of 1.2 cm in diameter were punched out of this laminate by means of hanger perforations and glued onto the stratum corneum of the correspondingly prepared skin segments after removal of the release liner.
- the thus prepared skin segments were then introduced into classical, static diffusion cells, so that the underside of the skin was in direct contact with the acceptor medium used.
- the acceptor medium used was a modified phosphate-buffered solution of pH 7.4, which has sufficient solubility for the active ingredient to ensure "sink” conditions throughout the experiment
- the medium was permanently heated to 38 ° C., which resulted in a temperature of 32 0 C resulted in the diffusion region.
- TTS lisurid-containing TTS of up to 30 cm 2 .
- the TTS had an identical composition and was prepared under the same process conditions as the formulation of Example 1.
- the lisuride content was 0.25 mg / cm 2 and the weight of the dry coating was 5 mg / cm 2 .
- the period of use was 48 hours, after which the patches were removed and examined for their remaining active pharmaceutical ingredient content.
- Blood samples were taken at predetermined times and transformed into plasma.
- the measured concentrations were plotted against time for each application.
- the resulting curve shows a biphasic profile, with no permeation of the drug from the patch through the skin into the bloodstream in the first hours (about 0 to 3 hours) (or only in unquantifiable, negligible amounts).
- the transdermal throughput of the drug increases. This is followed by a second absorption phase at a significantly higher rate.
- the plateau is finally reached, which reflects the maximum and, in particular, the target plasma concentration for the therapy.
- a continuous release of the active substance from the applied TTS is assumed (see Fig. 2).
- Fig. 3 shows the plasma concentration profile after simulation of four consecutive applications of a 40 cm 2 Lisurid TTS.
- Profile shows no accumulation and no sharp peak concentrations. Furthermore, it has clinically effective concentrations at the time points of the transit levels.
- the simulation has a clinically useful ratio of peak to transit level of the lisuride of no more than three to five, which supports the avoidance of peak dose dyskinesias as well as passage-level akinesia in therapy of, in particular, advanced Parkinson's disease.
- Table 2 Pharmacokinetic parameters of lisuride after repeated application of a 20 cm 2 TTS.
- the double blind randomized clinical trial included patients with advanced Parkinson's Dyskinesia (PD) with only unsatisfactory therapeutic outcomes with oral therapies, such as ⁇ 2 hours "off” per day or a total of ⁇ 6 hours "off” within the last three days demonstrated, templates. Patients were trained to assess their condition themselves.
- PD Parkinson's Dyskinesia
- Second efficacy endpoints are UPDRS (motor part and activities of daily living (ADL), alone or in combination) and general measurements (determination by physicians and patients, CGI, QoL scale) Adverse side-effects were noted in the usual way: concomitant anti-PD therapy did not allow oral dopamine agonists, and the dosing of all other anti-PD drugs had to be stable for at least four weeks before the study and 50% of the patients were lisuride An identical placebo patch was administered to the other half and the data are presented in Tables 3 and 4 and in FIG.
- dyskinesia Since the total daily “OFF” time decreases significantly, the entire “ON” time without cumbersome dyskinesia shows a corresponding increase. However, there is no increase in dyskinesia, as in the case of increasing daily levodopa dosage and frequency, or expected with levodopa enhancers (MAO-B or COMT inhibitors).
- Mean 53 were pooled in a double-blind comparison within the patients of oral lisuride and placebo.
- the dose of lisuride was increased to the maximum tolerance dose of 5 mg daily using a conventional immediate-release tablet formulation of lisuride (in vitro release of greater than 80% of the declared dose within 30 minutes, see Fig. 5).
- the dosage of other drugs was kept unchanged during the study. Lisurid was added to the existing therapy. Opposing reactions were evaluated by an uninvolved physician. In addition to the efficacy results of the treatment, particular attention was paid to gastrointestinal side effects. Gastrointestinal symptoms, especially nausea, were found in eight patients (40%).
- Succinic acid (5%) was dissolved in a mixture of acetone and 2-propanol, Eudragit E 100 polymer (43%) was added slowly and dissolved with stirring, dibutyl sebacate (19%) was added slowly and dissolved with stirring. Then lisuride (5%) was dissolved in acetone and added to the polymer mixture. Butylhydroxytoluene (1%), polyvinylidone 25 (10%), 1-dodecanol (10%), adhesion promoter (2%) and aloe vera oil (5%) were weighed in and added with stirring added to the polymer solution.
- the polymer mixture was coated on a siliconized Poylesterfolie and dried in ⁇ closing under controlled exposure to moderate heat and polyester film in a continuously operating installation to a dry Lisuridlami- nat of 50 g / cm 2 laminated.
- the finished laminate was rolled up in rolls.
- the laminate was stored as an intermediate in polyethylene film (PE film) until further processing.
- the final production of the TTS was carried out in a punching and packing machine with a multi-step process.
- a peelable layer was cut through the release ⁇ layer in the laminate, without cutting through the adhesive layer.
- the laminate was cut around the individual TTS 'in the longitudinal and transverse directions. Subsequently, the TDS was transferred through a suction head. A subsequent heat sealer sealed the films in bags, each containing a TTS.
- FIG. 1a Permeation profile of lisuride by excised hairless mouse skin, using acrylate-based transdermal systems without aloe vera oil and without 1-dodecanol.
- Fig. 2 Plasma concentration time profile after application of lisurid patch on elderly volunteers for 48 hours (values shown are mean values).
- Fig. 3 Simulation of lisurid plasma levels after transdermal application.
- Fig. 4 Primary efficacy endpoint.
- Fig. 5 In vitro delivery of lisuride from an oral immediately releasing tablet preparation in water.
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Neurosurgery (AREA)
- Dermatology (AREA)
- Neurology (AREA)
- Epidemiology (AREA)
- Biomedical Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
Description
Claims
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE102006048130A DE102006048130A1 (de) | 2006-10-06 | 2006-10-06 | Transdermales therapeutisches System mit zweiphasigem Freisetzungsprofil |
PCT/EP2007/058867 WO2008043601A2 (de) | 2006-10-06 | 2007-08-27 | Transdermales therapeutisches system mit zweiphasigem freisetzungsprofil |
Publications (1)
Publication Number | Publication Date |
---|---|
EP2079458A2 true EP2079458A2 (de) | 2009-07-22 |
Family
ID=38704689
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP07802907A Withdrawn EP2079458A2 (de) | 2006-10-06 | 2007-08-27 | Transdermales therapeutisches system mit zweiphasigem freisetzungsprofil |
Country Status (7)
Country | Link |
---|---|
US (1) | US20100143475A1 (de) |
EP (1) | EP2079458A2 (de) |
JP (1) | JP2010505786A (de) |
AU (1) | AU2007306582A1 (de) |
DE (1) | DE102006048130A1 (de) |
WO (1) | WO2008043601A2 (de) |
ZA (1) | ZA200901959B (de) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2023107931A1 (en) * | 2021-12-06 | 2023-06-15 | Terran Biosciences, Inc. | Salt and solid forms of indole analogs and methods of use thereof |
Family Cites Families (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE4116912A1 (de) * | 1991-05-18 | 1992-11-26 | Schering Ag | Mittel zur transdermalen applikation enthaltend ergolin-derivate |
US5229130A (en) * | 1991-12-20 | 1993-07-20 | Cygnus Therapeutics Systems | Vegetable oil-based skin permeation enhancer compositions, and associated methods and systems |
DE19911262C2 (de) * | 1999-03-13 | 2003-04-10 | Scs Skin Care Systems Gmbh | Vorrichtung zur Abgabe kosmetischer Wirkstoffe |
US6455066B1 (en) * | 2000-03-10 | 2002-09-24 | Epicept Corporation | Intradermal-penetration agents for topical local anesthetic administration |
DE10341317B4 (de) * | 2003-09-03 | 2008-10-23 | Axxonis Pharma Ag | Transdermales therapeutisches System (TTS) zur Verabreichung von Ergolinverbindungen ausgenommen Pergolid |
DE10043321B4 (de) * | 2000-08-24 | 2005-07-28 | Neurobiotec Gmbh | Verwendung eines transdermalen therapeutischen Systems zur Behandlung der Parkinsonschen Krankheit, zur Behandlung und Prävention des prämenstruellen Syndroms und zur Lactationshemmung |
US20070243240A9 (en) * | 2000-08-24 | 2007-10-18 | Fred Windt-Hanke | Transdermal therapeutic system |
US20040001882A1 (en) * | 2002-03-06 | 2004-01-01 | Hexal Ag | Transdermal system with fentanyl |
CA2529528A1 (en) * | 2003-06-20 | 2004-12-29 | Ronald Aung-Din | Topical therapy for the treatment of migraines, muscle sprains, muscle spasm, spasticity and related conditions |
DE102004009903A1 (de) * | 2004-02-26 | 2005-09-22 | Grünenthal GmbH | Pflaster mit reduzierter Hautirritation |
-
2006
- 2006-10-06 DE DE102006048130A patent/DE102006048130A1/de not_active Withdrawn
-
2007
- 2007-08-27 JP JP2009530821A patent/JP2010505786A/ja not_active Withdrawn
- 2007-08-27 WO PCT/EP2007/058867 patent/WO2008043601A2/de active Application Filing
- 2007-08-27 EP EP07802907A patent/EP2079458A2/de not_active Withdrawn
- 2007-08-27 US US12/311,305 patent/US20100143475A1/en not_active Abandoned
- 2007-08-27 AU AU2007306582A patent/AU2007306582A1/en not_active Abandoned
-
2009
- 2009-03-20 ZA ZA2009/01959A patent/ZA200901959B/en unknown
Non-Patent Citations (1)
Title |
---|
See references of WO2008043601A2 * |
Also Published As
Publication number | Publication date |
---|---|
US20100143475A1 (en) | 2010-06-10 |
WO2008043601A2 (de) | 2008-04-17 |
AU2007306582A1 (en) | 2008-04-17 |
WO2008043601A3 (de) | 2008-06-12 |
DE102006048130A1 (de) | 2008-04-10 |
ZA200901959B (en) | 2010-02-24 |
JP2010505786A (ja) | 2010-02-25 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
DE69822199T2 (de) | Arzneimittel und verfahren zur behandlung von aufmerksamkeitsstörungen und aufmerksamkeits-/hyperaktivitätsstörungen mit methylphenidat | |
EP1178782B1 (de) | Transdermales therapeutisches system (tts) tolterodin enthaltend | |
EP2582364B1 (de) | Transdermale verabreichung von memantin | |
DE60304477T2 (de) | Verbessertes transdermales abgabesystem für die verabreichung von rotigotin | |
EP1178783B1 (de) | Vorrichtung und verwendung zur steigerung der transdermalen permeation von arzneistoffen | |
DE69916492T3 (de) | Pflaster zur transdermalen applikation von flüchtigen, flüssigen wirkstoffen | |
EP1501499B1 (de) | Transepikutane darreichungsform zur behandlung des restless leg syndroms | |
DE19923551A1 (de) | Pharmazeutisches Präparat mit dem Wirkstoff Diamorphin und seine Verwendung in einem Verfahren zur Behandlung der Opiatsucht | |
EP1347749A2 (de) | Transdermales therapeutisches system mit dem wirkstoff oxybutynin | |
DE60311449T2 (de) | Transdermales therapeutisches system mit zwei übereinanderliegenden matrixschichten, die verschiedene affinitäten zum enthaltenen wirkstoff ausweisen | |
DE69731882T2 (de) | Transdermal verabreichtes dextromethorphan als hustenmittel | |
EP1480625B1 (de) | Transdermalsystem mit fentanyl | |
EP1094797A1 (de) | Transdermales pflaster, enthaltend mindestens einen die blutfettwerte beeinflussenden wirkstoff | |
EP1251853B1 (de) | Transdermales therapeutisches system zur verabreichung von zaleplon | |
EP2079458A2 (de) | Transdermales therapeutisches system mit zweiphasigem freisetzungsprofil | |
EP1171105B1 (de) | Transdermales therapeutisches system mit einem stark wirksamen neuroleptikum | |
EP0742716B1 (de) | Pharmazeutische zusammensetzung zur systemischen transdermalen verabreichung mit dem wirkstoff morphin-6-glucuronid | |
DE10340428A1 (de) | Opioides Analgetikum enthaltende transdermale Formulierung | |
EP2366388A1 (de) | Nicht-okklusives transdermales therapeutisches System zur Verabreichung von Buprenorphin | |
EP1368008A1 (de) | Transdermales therapeutisches system zur verabreichung von partiellen dopamin-d2-agonisten | |
DE10341317B4 (de) | Transdermales therapeutisches System (TTS) zur Verabreichung von Ergolinverbindungen ausgenommen Pergolid | |
WO2019077116A1 (de) | Transdermales darreichungssystem enthaltend einen dopaminagonisten | |
EP0659079B1 (de) | Transdermales therapeutisches system mit pentylentetrazol als wirkstoff | |
WO2020025695A1 (de) | Transdermales therapeutisches system zur abgabe von scopolamin ohne membran |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
17P | Request for examination filed |
Effective date: 20090423 |
|
AK | Designated contracting states |
Kind code of ref document: A2 Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LI LT LU LV MC MT NL PL PT RO SE SI SK TR |
|
RIN1 | Information on inventor provided before grant (corrected) |
Inventor name: HOROWSKI, REINHARD Inventor name: SCHURAD, BJOERN Inventor name: TACK, JOHANNES Inventor name: MUELLER-SCHUBERT, ANTJE |
|
REG | Reference to a national code |
Ref country code: HK Ref legal event code: DE Ref document number: 1129569 Country of ref document: HK |
|
DAX | Request for extension of the european patent (deleted) | ||
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN |
|
18D | Application deemed to be withdrawn |
Effective date: 20110301 |
|
REG | Reference to a national code |
Ref country code: HK Ref legal event code: WD Ref document number: 1129569 Country of ref document: HK |