EP1772395A1 - Protective packaging for pharmaceutical products - Google Patents

Protective packaging for pharmaceutical products Download PDF

Info

Publication number
EP1772395A1
EP1772395A1 EP05090280A EP05090280A EP1772395A1 EP 1772395 A1 EP1772395 A1 EP 1772395A1 EP 05090280 A EP05090280 A EP 05090280A EP 05090280 A EP05090280 A EP 05090280A EP 1772395 A1 EP1772395 A1 EP 1772395A1
Authority
EP
European Patent Office
Prior art keywords
oxygen
protective packaging
pharmaceutical
packaging according
packaging
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.)
Granted
Application number
EP05090280A
Other languages
German (de)
French (fr)
Other versions
EP1772395B1 (en
Inventor
Karsten Gröger
Reinhard Schmitz
Jens Flemming
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Berlin Chemie AG
Original Assignee
Berlin Chemie AG
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=36110769&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=EP1772395(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Berlin Chemie AG filed Critical Berlin Chemie AG
Priority to EP05090280A priority Critical patent/EP1772395B1/en
Priority to AT05090280T priority patent/ATE501059T1/en
Priority to DE502005011092T priority patent/DE502005011092D1/en
Publication of EP1772395A1 publication Critical patent/EP1772395A1/en
Application granted granted Critical
Publication of EP1772395B1 publication Critical patent/EP1772395B1/en
Revoked legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B65—CONVEYING; PACKING; STORING; HANDLING THIN OR FILAMENTARY MATERIAL
    • B65D—CONTAINERS FOR STORAGE OR TRANSPORT OF ARTICLES OR MATERIALS, e.g. BAGS, BARRELS, BOTTLES, BOXES, CANS, CARTONS, CRATES, DRUMS, JARS, TANKS, HOPPERS, FORWARDING CONTAINERS; ACCESSORIES, CLOSURES, OR FITTINGS THEREFOR; PACKAGING ELEMENTS; PACKAGES
    • B65D81/00—Containers, packaging elements, or packages, for contents presenting particular transport or storage problems, or adapted to be used for non-packaging purposes after removal of contents
    • B65D81/18—Containers, packaging elements, or packages, for contents presenting particular transport or storage problems, or adapted to be used for non-packaging purposes after removal of contents providing specific environment for contents, e.g. temperature above or below ambient
    • B65D81/20—Containers, packaging elements, or packages, for contents presenting particular transport or storage problems, or adapted to be used for non-packaging purposes after removal of contents providing specific environment for contents, e.g. temperature above or below ambient under vacuum or superatmospheric pressure, or in a special atmosphere, e.g. of inert gas
    • B65D81/2069—Containers, packaging elements, or packages, for contents presenting particular transport or storage problems, or adapted to be used for non-packaging purposes after removal of contents providing specific environment for contents, e.g. temperature above or below ambient under vacuum or superatmospheric pressure, or in a special atmosphere, e.g. of inert gas in a special atmosphere
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B65—CONVEYING; PACKING; STORING; HANDLING THIN OR FILAMENTARY MATERIAL
    • B65D—CONTAINERS FOR STORAGE OR TRANSPORT OF ARTICLES OR MATERIALS, e.g. BAGS, BARRELS, BOTTLES, BOXES, CANS, CARTONS, CRATES, DRUMS, JARS, TANKS, HOPPERS, FORWARDING CONTAINERS; ACCESSORIES, CLOSURES, OR FITTINGS THEREFOR; PACKAGING ELEMENTS; PACKAGES
    • B65D81/00—Containers, packaging elements, or packages, for contents presenting particular transport or storage problems, or adapted to be used for non-packaging purposes after removal of contents
    • B65D81/18—Containers, packaging elements, or packages, for contents presenting particular transport or storage problems, or adapted to be used for non-packaging purposes after removal of contents providing specific environment for contents, e.g. temperature above or below ambient
    • B65D81/20—Containers, packaging elements, or packages, for contents presenting particular transport or storage problems, or adapted to be used for non-packaging purposes after removal of contents providing specific environment for contents, e.g. temperature above or below ambient under vacuum or superatmospheric pressure, or in a special atmosphere, e.g. of inert gas
    • B65D81/2007—Containers, packaging elements, or packages, for contents presenting particular transport or storage problems, or adapted to be used for non-packaging purposes after removal of contents providing specific environment for contents, e.g. temperature above or below ambient under vacuum or superatmospheric pressure, or in a special atmosphere, e.g. of inert gas under vacuum
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B65—CONVEYING; PACKING; STORING; HANDLING THIN OR FILAMENTARY MATERIAL
    • B65D—CONTAINERS FOR STORAGE OR TRANSPORT OF ARTICLES OR MATERIALS, e.g. BAGS, BARRELS, BOTTLES, BOXES, CANS, CARTONS, CRATES, DRUMS, JARS, TANKS, HOPPERS, FORWARDING CONTAINERS; ACCESSORIES, CLOSURES, OR FITTINGS THEREFOR; PACKAGING ELEMENTS; PACKAGES
    • B65D81/00—Containers, packaging elements, or packages, for contents presenting particular transport or storage problems, or adapted to be used for non-packaging purposes after removal of contents
    • B65D81/24—Adaptations for preventing deterioration or decay of contents; Applications to the container or packaging material of food preservatives, fungicides, pesticides or animal repellants
    • B65D81/26—Adaptations for preventing deterioration or decay of contents; Applications to the container or packaging material of food preservatives, fungicides, pesticides or animal repellants with provision for draining away, or absorbing, or removing by ventilation, fluids, e.g. exuded by contents; Applications of corrosion inhibitors or desiccators
    • B65D81/266—Adaptations for preventing deterioration or decay of contents; Applications to the container or packaging material of food preservatives, fungicides, pesticides or animal repellants with provision for draining away, or absorbing, or removing by ventilation, fluids, e.g. exuded by contents; Applications of corrosion inhibitors or desiccators for absorbing gases, e.g. oxygen absorbers or desiccants

Definitions

  • the present invention relates to a pharmaceutical protective packaging and more particularly to a packaging for protection against oxygen.
  • antioxidants or free-radical scavengers such as ascorbic acid, tocopherol, butylhydroxyanisole or butylhydroxytoluene
  • antioxidants or free-radical scavengers such as ascorbic acid, tocopherol, butylhydroxyanisole or butylhydroxytoluene
  • inert gases protected fumigation
  • the object of the present invention is therefore to provide a pharmaceutical protective packaging which, independently of climatic external conditions, allows the storage of oxygen-sensitive medicaments over a relatively long period of time.
  • the object is achieved according to the invention by providing a pharmaceutical protective packaging in which the oxygen content within the packaging is less than 1% by volume.
  • Preferred according to the invention is a pharmaceutical protective packaging according to the invention, the oxygen content within the packaging being less than 0.5% by volume.
  • Particularly preferred according to the invention is a pharmaceutical protective packaging according to the invention, wherein the oxygen content within the packaging is less than 0.1% by volume.
  • the packing prefferably evacuated, the pressure being less than 50 mbar.
  • the packing contains a protective gas selected from argon, nitrogen or carbon dioxide.
  • the pack contains an oxygen absorber.
  • the pharmaceutical protective packaging is structurally designed in such a way that it consists of at least two interconnected spaces, wherein a moisture and / or gas absorbing substance is located in one of the spaces.
  • the pharmaceutical protective packaging according to the invention also contains an oxygen indicator.
  • the oxygen indicator is arranged in an externally visible region of the protective packaging.
  • Another object of the present invention is the use of a protective packaging according to the invention for oxygen-sensitive active ingredients.
  • the active substance contains at least one oxygen-sensitive group which is selected from alcohol, phenol, aldehyde, enol, ether, amine, ketol, aromatic, heteroaromatic, peptide, protein, amino acid, carboxylic acid, fatty acid, fatty acid ester, Sterol and steroid.
  • oxygen-sensitive group which is selected from alcohol, phenol, aldehyde, enol, ether, amine, ketol, aromatic, heteroaromatic, peptide, protein, amino acid, carboxylic acid, fatty acid, fatty acid ester, Sterol and steroid.
  • the active ingredient is selected from vitamins such as vitamins A, B and E group, ascorbic acid, antibiotics such as amphotericin B, thyroid hormones such as levothyroxine, liothyronine, cysteine, tryptophan, nepadutant, sorbic acid , omega-3 fatty acids, omega-4 fatty acids, lipids phospholipids, ethyl oleates, cholesterol
  • Suitable packaging is familiar to the person skilled in the art.
  • suitable packaging materials are also conventional blister pack, which are produced by deep drawing in a known manner.
  • aluminum foils are used, which are coated with conventional, heat-sealable plastics and also plastic films, which are suitable for the sealing process, as is known in the art.
  • aluminum-aluminum packaging which are also mechanically closed or heat-sealable equipped. These aluminum-aluminum packages can also be used as outer packaging for normal packaging, such as blister packs. Other suitable packages are readily known to those skilled in the art.
  • the package can be evacuated.
  • the ambient air is removed from the packaging and thus the harmful oxygen.
  • the oxygen content is only about 0.5% by volume.
  • the evacuation of the package can be done by, for example, blistering the packages in a vacuum. But it can also be a conventional blister pack placed in an outer packaging, such as an aluminum-aluminum packaging and then evacuated and sealed in the usual way.
  • the oxygen content can also be reduced by applying a protective gas to the packaging.
  • a protective gas for this purpose, it may be necessary to rinse the pack beforehand, if appropriate also several times with the protective gas, in order to lower the oxygen content in accordance with the invention.
  • an aluminum-aluminum outer packaging may be used, wherein the outer packaging may also be acted upon together with the inner packaging with the protective gas.
  • Suitable inert gases are inert gases which do not react with oxygen-sensitive groups of the active substances to be stored.
  • shielding gases include, but are not limited to, argon, nitrogen or carbon dioxide.
  • noble gases and inert gases are suitable. Of course, mixtures of these gases can also be used.
  • oxygen absorbers are known.
  • iron-containing absorbers may be used which may be suitably coated or coated.
  • oxygen absorbers are sold, for example, under the trademarks Ageless or Pharmakeep by Mitsubishi Gas Chemical Company, Inc.
  • the pharmaceutical protective packaging such that at least two interconnected spaces are present. These spaces are interconnected by channels or otherwise, so that there may be a pressure and / or gas exchange between these spaces. If one now fills one of the rooms with the medicament to be stored and the other room with the oxygen absorber, then the reduction of the content of oxygen within the protective packaging according to the invention occurs.
  • such an arrangement may be useful in the case of using a shielding gas or in evacuation.
  • an oxygen indicator can be added to the packaging.
  • These oxygen indicators are known and used in the form of tablets which show a color change at a certain oxygen content.
  • These oxygen indicators may contain substances that show a color change on the addition of oxygen. This is the case with pyrogallol, for example, with a color change to red.
  • other indicators may be used according to the invention.
  • it is therefore provided to add an indicator to the package, for example. If, as described above, the pharmaceutical protective package has, for example, several rooms, then the indicator can be placed in one of these rooms.
  • the indicator is placed in the outer packaging, for example in an aluminum-aluminum outer packaging, in which case advantageously the aluminum package may contain a viewing window through which the possible color change can be observed.
  • Such oxygen indicators are available, for example, under the trade designation Ageless-eye from Mitsubishi Gas Chemical Company, Inc.
  • the pharmaceutical protective packaging according to the invention can be used for drugs which tend to decompose on exposure to oxygen.
  • drugs usually contain a slightly reactive group, which is then altered by reaction with oxygen.
  • reactive groups include, for example, alcohols, phenols, aldehydes, enols, ethers, amines, ketols, aromatics, heteroaromatics, peptides, proteins, amino acids, carboxylic acids, fatty acids, fatty acid esters, sterols and steroids. This list is not exhaustive and can be extended by the expert without further ado.
  • drugs containing such reactive groups include, among others, vitamins such as ascorbic acid, tocopherols, vitamins of A, B and E groups, antibiotics such as amphotericin B, thyroid hormones such as levothyroxine, liothyronine, tryptophan , Sorbic acid, omega-3 fatty acids, omega-4 fatty acids, nepadutant, phospholipids, ethyl oleates, cholesterols, as well as other steroid hormones and the like.
  • vitamins such as ascorbic acid, tocopherols, vitamins of A, B and E groups
  • antibiotics such as amphotericin B
  • thyroid hormones such as levothyroxine, liothyronine, tryptophan , Sorbic acid, omega-3 fatty acids, omega-4 fatty acids, nepadutant, phospholipids, ethyl oleates, cholesterols, as well as other steroid hormones and the like.
  • Other suitable drugs
  • Tables 2 and 3 show the evaluation of an experiment at the storage condition 40 ° C / 75% rel.
  • F. Levothyroxine [%] was determined after a storage period of x months.
  • a conventional blister (Table 2) was used and stored in an aluminum transfer bag of the same blister in the presence of an oxygen absorber in the aluminum transfer bag.

Landscapes

  • Engineering & Computer Science (AREA)
  • Mechanical Engineering (AREA)
  • Food Science & Technology (AREA)
  • Packages (AREA)
  • Medical Preparation Storing Or Oral Administration Devices (AREA)
  • Apparatus For Radiation Diagnosis (AREA)
  • Glass Compositions (AREA)
  • Materials For Medical Uses (AREA)

Abstract

The pharmaceutical security packaging has an oxygen content within the package at a level of one percent by volume, to reduce the level of oxidation of the contents. The oxygen content can be approximately half a percent by volume or as low as point one percent. The package contents can be at a pressure of fifty millibars and the package can contain argon, nitrogen or carbon dioxide. The container can include an oxygen level indicator. Claims include uses for the packaging.

Description

Die vorliegende Erfindung betrifft eine pharmazeutische Schutzverpackung und insbesondere eine Verpackung zum Schutz vor Sauerstoff.The present invention relates to a pharmaceutical protective packaging and more particularly to a packaging for protection against oxygen.

Das Problem der Zersetzung von pharmazeutischen Wirkstoffen durch Luftsauerstoff ist seit langem bekannt. Dies findet seinen Ausdruck darin, dass Arzneimittel mit sauerstoffempfindlichen Wirkstoffen ein verkürztes Haltbarkeitsdatum aufweisen. Auch sind hohe Anforderungen an die Lagerung zu stellen, insbesondere müssen die Arzneimittel bei bestimmten Temperatur- und Luftfeuchtigkeitsbedingungen gelagert werden, um beispielsweise eine Mindesthaltbarkeit von 2 Jahren zu gewährleisten.The problem of the decomposition of pharmaceutical agents by atmospheric oxygen has long been known. This is expressed by the fact that drugs with oxygen-sensitive active ingredients have a shortened expiration date. In addition, high storage requirements must be imposed, in particular the pharmaceuticals must be stored under certain temperature and humidity conditions, for example to ensure a minimum shelf life of 2 years.

Das Problem der Zersetzung kommt nicht nur dadurch zum Ausdruck, dass der Gehalt an Wirkstoff abnimmt, oft entstehen auch Zersetzungsprodukte, welche neben sensorischen Beeinträchtigungen auch toxische Wirkungen haben können.The problem of decomposition is not only expressed by the fact that the content of active ingredient decreases, often also decomposition products, which in addition to sensory impairments can also have toxic effects.

Ein besonderes Problem der Lagerung von Arzneimitteln stellt sich außerhalb der gemäßigten klimatischen Zonen. In heißen und/oder feuchten Teilen der Welt stellen die Lagerungsbedingungen ganz besondere Herausforderungen dar. Zum einen ist in diesen Ländern der Standard der Versorgung mit Arzneimitteln im Allgemeinen recht niedrig, und besondere Lagerungsbedingungen zu schaffen, ist meist sehr kostenintensiv, da spezielle Vorrichtungen benötigt werden, zu deren Betrieb auch hohe Energiekosten hinzutreten.A particular problem of storage of medicines arises outside the temperate climatic zones. Storage conditions are particularly challenging in hot and / or humid parts of the world. Firstly, in these countries, the standard of drug supply is generally quite low and creating special storage conditions is usually very costly because special equipment is needed , to whose operation also high energy costs are added.

Es wurde nun gefunden, dass ein Lagerungs-Parameter für die Haltbarkeit von Arzneimitteln und anderen Wirkstoffen besonders wichtig ist. Die stark oxidative Wirkung von Sauerstoff wurde bei den bisherigen Verpackungen nahezu vollständig außer Betracht gelassen. Es konnte gezeigt werden, dass der Einfluss des in der Umgebungsluft enthaltenen Sauerstoffs für einen großen Teil der Verluste am Gehalt der Wirkstoffe verantwortlich ist.It has now been found that a storage parameter is particularly important for the shelf life of drugs and other drugs. The strong oxidative effect of Oxygen was almost completely disregarded in previous packaging. It could be shown that the influence of the oxygen contained in the ambient air is responsible for a large part of the losses in the content of the active ingredients.

Diesem negativen Einfluss des Sauerstoffs wurde bisher entgegnet, indem in die entsprechenden Rezepturen Antioxidantien oder Radikalfänger wie Ascorbinsäure, Tocopherol, Butylhydroxyanisol oder Butylhydroxytoluol eingearbeitet wurden, um oxidativen Abbau zu verhindern (vgl. Bauer, Frömming, Führer, Lehrbuch der Pharmazeutischen Technologie, WVG Stuttgart, 2002 ) bzw. durch die Anwendung von Inertgasen ("Schutzbegasung"), derzeit praktiziert bei Abfüllung von flüssigen Arzneimitteln.To date, this negative influence of the oxygen has been counteracted by incorporating antioxidants or free-radical scavengers such as ascorbic acid, tocopherol, butylhydroxyanisole or butylhydroxytoluene into the corresponding formulations in order to prevent oxidative degradation (cf. Bauer, Frömming, Führer, Textbook of Pharmaceutical Technology, WVG Stuttgart, 2002 ) or by the use of inert gases ("protective fumigation"), currently practiced in filling liquid medicines.

Aufgabe der vorliegenden Erfindung ist es daher, eine pharmazeutische Schutzverpackung zur Verfügung zu stellen, welche unabhängig von klimatischen äußeren Bedingungen die Lagerung von sauerstoffempfindlichen Arzneimitteln über einen längeren Zeitraum gestattet.The object of the present invention is therefore to provide a pharmaceutical protective packaging which, independently of climatic external conditions, allows the storage of oxygen-sensitive medicaments over a relatively long period of time.

Die Aufgabe wird erfindungsgemäß dadurch gelöst, dass eine pharmazeutische Schutzverpackung zur Verfügung gestellt wird, bei der der Sauerstoffgehalt innerhalb der Verpackung weniger als 1 Vol-% beträgt.The object is achieved according to the invention by providing a pharmaceutical protective packaging in which the oxygen content within the packaging is less than 1% by volume.

Erfindungsgemäß bevorzugt ist eine erfindungsgemäße pharmazeutische Schutzverpackung, wobei der Sauerstoffgehalt innerhalb der Verpackung weniger als 0,5 Vol-% beträgt.Preferred according to the invention is a pharmaceutical protective packaging according to the invention, the oxygen content within the packaging being less than 0.5% by volume.

Erfindungsgemäß besonders bevorzugt ist eine erfindungsgemäße pharmazeutische Schutzverpackung, wobei der Sauerstoffgehalt innerhalb der Verpackung weniger als 0,1 Vol-% beträgt.Particularly preferred according to the invention is a pharmaceutical protective packaging according to the invention, wherein the oxygen content within the packaging is less than 0.1% by volume.

Erfindungsgemäß bevorzugt ist es auch, dass die Packung evakuiert ist, wobei der Druck weniger als 50 mbar beträgt.It is also preferred according to the invention for the packing to be evacuated, the pressure being less than 50 mbar.

Erfindungsgemäß bevorzugt ist es ferner, dass die Packung ein Schutzgas ausgewählt aus Argon, Stickstoff oder Kohlendioxid, enthält.According to the invention it is further preferred that the packing contains a protective gas selected from argon, nitrogen or carbon dioxide.

Weiterhin ist auch bevorzugt, dass die Packung einen Sauerstoffabsorber enthält.Furthermore, it is also preferred that the pack contains an oxygen absorber.

Bevorzugt ist erfindungsgemäß auch, dass die pharmazeutische Schutzverpackung konstruktiv derart gestaltet ist, dass sie aus mindestens zwei miteinander verbundenen Räumen besteht, wobei sich in einem der Räume eine Feuchtigkeit und/oder Gas absorbierende Substanz befindet.According to the invention, it is also preferred that the pharmaceutical protective packaging is structurally designed in such a way that it consists of at least two interconnected spaces, wherein a moisture and / or gas absorbing substance is located in one of the spaces.

Bevorzugt ist ferner insbesondere, dass die erfindungsgemäße pharmazeutische Schutzverpackung weiterhin einen Sauerstoffindikator enthält.It is furthermore preferred in particular that the pharmaceutical protective packaging according to the invention also contains an oxygen indicator.

Dabei ist besonders bevorzugt, dass der Sauerstoffindikator in einem von außen einsehbaren Bereich der Schutzverpackung angeordnet ist.It is particularly preferred that the oxygen indicator is arranged in an externally visible region of the protective packaging.

Ein weiterer Gegenstand der vorliegenden Erfindung ist die Verwendung einer erfindungsgemäßen Schutzverpackung für sauerstoffempfindliche Wirkstoffe.Another object of the present invention is the use of a protective packaging according to the invention for oxygen-sensitive active ingredients.

Besonders bevorzugt ist die erfindungsgemäße Verwendung, wenn der Wirkstoff mindestens eine sauerstoffempfindliche Gruppe enthält, welche ausgewählt ist aus Alkohol, Phenol, Aldehyd, Enol, Ether, Amin, Ketol, Aromat, Heteroaromat, Peptid, Protein, Aminosäure, Karbonsäure, Fettsäure, Fettsäureester, Sterol und Steroid.The use according to the invention is particularly preferred if the active substance contains at least one oxygen-sensitive group which is selected from alcohol, phenol, aldehyde, enol, ether, amine, ketol, aromatic, heteroaromatic, peptide, protein, amino acid, carboxylic acid, fatty acid, fatty acid ester, Sterol and steroid.

Ganz besonders bevorzugt ist die Verwendung, wobei der Wirkstoff ausgewählt ist aus Vitaminen, wie Vitaminen der A, B und E-Gruppe, Ascorbinsäure, Antibiotika, wie Amphotericin B, Thyroxid-Hormonen, wie Levothyroxin, Liothyronin, Cystein, Tryptophan, Nepadutant, Sorbinsäure, omega-3-Fettsäuren, omega-4-Fettsäuren, Lipiden Phospholipiden, Ethyloleaten, CholesterolMost preferred is the use wherein the active ingredient is selected from vitamins such as vitamins A, B and E group, ascorbic acid, antibiotics such as amphotericin B, thyroid hormones such as levothyroxine, liothyronine, cysteine, tryptophan, nepadutant, sorbic acid , omega-3 fatty acids, omega-4 fatty acids, lipids phospholipids, ethyl oleates, cholesterol

Um die erfindungsgemäße Lehre umzusetzen, sind verschiedene Maßnahmen möglich. Geeignete Verpackungen sind dem Fachmann geläufig. In Frage kommen unter anderem, ohne dass diese Aufzählung eine Beschränkung darstellen soll, Schraubdeckel-Gläser und -Flaschen, sowohl aus Glas als auch aus üblichen Kunststoffen, wie PVP, Polyethylen, HDPE, LDPE, Polypropylen und ähnliche. Geeignete Verpackungsmittel sind aber auch übliche Blisterpackung, welche durch Tiefziehen in bekannten Weise hergestellt werden. Dabei werden Aluminiumfolien verwendet, die mit üblichen, heißsiegelfähigen Kunststoffen beschichtet sind und auch Kunststofffolien, die für den Siegelvorgang geeignet sind, wie diese dem Fachmann bekannt ist. Geeignet sind auch Alu-Alu-Verpackungen, welche ebenfalls mechanisch verschließbar sind oder aber heißsiegelfähig ausgerüstet sind. Diese Alu-Alu-Verpackungen können auch als Umverpackungen für normale Verpackungen, wie Blisterpackungen verwendet werden. Weitere geeignete Verpackungen sind dem Fachmann ohne weiteres bekannt.To implement the teaching of the invention, various measures are possible. Suitable packaging is familiar to the person skilled in the art. In question, inter alia, without this listing is intended to be a limitation, screw cap glasses and bottles, both of glass and of conventional plastics, such as PVP, polyethylene, HDPE, LDPE, polypropylene and the like. However, suitable packaging materials are also conventional blister pack, which are produced by deep drawing in a known manner. In this case, aluminum foils are used, which are coated with conventional, heat-sealable plastics and also plastic films, which are suitable for the sealing process, as is known in the art. Also suitable are aluminum-aluminum packaging, which are also mechanically closed or heat-sealable equipped. These aluminum-aluminum packages can also be used as outer packaging for normal packaging, such as blister packs. Other suitable packages are readily known to those skilled in the art.

Um den Sauerstoffgehalt im Inneren der Verpackung zu verringern, kann die Verpackung evakuiert werden. Damit wird die Umgebungsluft aus der Verpackung entfernt und somit auch der schädliche Sauerstoff. Bei einem Druck von 50 mbar beträgt der Sauerstoffgehalt nur noch ca. 0,5 Vol-%. Das Evakuieren der Verpackung kann erfolgen, indem beispielsweise das Blistern der Packungen im Vakuum geschieht. Es kann aber auch eine herkömmliche Blisterpackung in eine Umverpackung, beispielsweise eine Alu-Alu-Verpackung eingelegt und dann in üblicher Weise evakuiert und versiegelt werden.To reduce the oxygen content inside the package, the package can be evacuated. Thus, the ambient air is removed from the packaging and thus the harmful oxygen. At a pressure of 50 mbar, the oxygen content is only about 0.5% by volume. The evacuation of the package can be done by, for example, blistering the packages in a vacuum. But it can also be a conventional blister pack placed in an outer packaging, such as an aluminum-aluminum packaging and then evacuated and sealed in the usual way.

Der Sauerstoffgehalt kann aber auch dadurch verringert werden, dass die Verpackung mit einem Schutzgas beaufschlagt wird. Dazu kann es erforderlich sein, die Packung zuvor, gegebenenfalls auch mehrfach mit dem Schutzgas zu Spülen, um den Sauerstoffgehalt entsprechend der Erfindung abzusenken. Auch in Falle eines Schutzgases kann eine Alu-Alu-Umverpackung verwendet werden, wobei die Umverpackung gegebenenfalls auch zusammen mit der inneren Verpackung mit dem Schutzgas beaufschlagt sind. Als Schutzgase geeignet sind inerte Gase, welche nicht mit sauerstoffempfindlichen Gruppen der zu lagernden Wirkstoffe reagieren. Derartige Schutzgase sind, ohne darauf beschränkt zu sein, Argon, Stickstoff oder Kohlendioxid. Auch andere Edelgase und inerte Gase sind geeignet. Natürlich können auch Mischungen dieser Gase verwendet werden.However, the oxygen content can also be reduced by applying a protective gas to the packaging. For this purpose, it may be necessary to rinse the pack beforehand, if appropriate also several times with the protective gas, in order to lower the oxygen content in accordance with the invention. Also in the case of a protective gas, an aluminum-aluminum outer packaging may be used, wherein the outer packaging may also be acted upon together with the inner packaging with the protective gas. Suitable inert gases are inert gases which do not react with oxygen-sensitive groups of the active substances to be stored. Such shielding gases include, but are not limited to, argon, nitrogen or carbon dioxide. Other noble gases and inert gases are suitable. Of course, mixtures of these gases can also be used.

Eine weitere Möglichkeit den Sauerstoffgehalt in den pharmazeutischen Verpackungen zu verringern, welche gleichfalls zum Umfang der Erfindung gehört, ist es, der Verpackung einen Sauerstoffabsorber beizugeben. Derartige Sauerstoffabsorber sind bekannt. Beispielsweise können Eisen enthaltende Absorber verwendet werden, welche gegebenenfalls in geeigneter Weise beschichtet oder überzogen sind. Solcherart Sauerstoffabsorber werden zum Beispiel unter den Warenzeichen Ageless oder Pharmakeep durch die Firma Mitsubishi Gas Chemical Company, Inc. vertrieben.Another way to reduce the oxygen content in the pharmaceutical packaging, which is also within the scope of the invention, is to add an oxygen scavenger to the package. Such oxygen absorbers are known. For example, iron-containing absorbers may be used which may be suitably coated or coated. Such oxygen absorbers are sold, for example, under the trademarks Ageless or Pharmakeep by Mitsubishi Gas Chemical Company, Inc.

Auch hierbei ist es möglich, den Sauerstoffabsorber direkt der Primärpackung oder aber auch der Umverpackung oder beiden beizugeben.Here, too, it is possible to add the oxygen absorber directly to the primary pack or else to the outer pack or both.

Insbesondere kann es vorteilhaft sein, die pharmazeutische Schutzverpackung derart zu gestalten, dass mindestens zwei miteinander verbundene Räume vorhanden sind. Diese Räume sind mittels Kanälen oder in anderer Weise miteinander verbunden, so dass es zu einem Druck- und/oder Gasaustausch zwischen diesen Räumen kommen kann. Befüllt man nun einen der Räume mit dem aufzubewahrenden Arzneimittel und den anderen Raum mit dem Sauerstoffabsorber, so kommt es zur erfindungsgemäßen Verringerung des Gehalts an Sauerstoff innerhalb der Schutzverpackung. Eine derartige Anordnung kann aber im Falle der Verwendung eines Schutzgases oder bei der Evakuierung nützlich sein.In particular, it may be advantageous to design the pharmaceutical protective packaging such that at least two interconnected spaces are present. These spaces are interconnected by channels or otherwise, so that there may be a pressure and / or gas exchange between these spaces. If one now fills one of the rooms with the medicament to be stored and the other room with the oxygen absorber, then the reduction of the content of oxygen within the protective packaging according to the invention occurs. However, such an arrangement may be useful in the case of using a shielding gas or in evacuation.

Um sicher zu stellen, dass der Sauerstoffgehalt während der Lagerungsdauer nicht über den erfindungsgemäßen Wert steigt, kann der Verpackung ein Sauerstoffindikator beigegeben werden. Diese Sauerstoffindikatoren sind bekannt und werden in Form von Tabletten verwendet, die einen Farbumschlag bei einem bestimmten Sauerstoffgehalt zeigen. Diese Sauerstoffindikatoren können Stoffe enthalten, die beim Hinzutreten von Sauerstoff einen Farbumschlag zeigen. Dies ist beispielsweise bei Pyrogallol der Fall, wobei ein Farbumschlag nach rot erfolgt. Andere Indikatoren können natürlich erfindungsgemäß verwendet werden. Erfindungsgemäß ist deshalb vorgesehen, der Packung beispielsweise einen Indikator beizugeben. Hat die pharmazeutische Schutzpackung, wie oben beschrieben, beispielsweise mehrere Räume, so kann der Indikator in einem dieser Räume platziert werden. Es ist aber auch erfindungsgemäß, wenn der Indikator in die Umverpackung, beispielsweise in eine Alu-Alu-Umverpackung eingelegt wird, wobei dann vorteilhafter Weise die Alu-Packung ein Sichtfenster enthalten kann, durch welche der etwaige Farbumschlag beobachtet werden kann.In order to ensure that the oxygen content does not rise above the value according to the invention during the storage period, an oxygen indicator can be added to the packaging. These oxygen indicators are known and used in the form of tablets which show a color change at a certain oxygen content. These oxygen indicators may contain substances that show a color change on the addition of oxygen. This is the case with pyrogallol, for example, with a color change to red. Of course, other indicators may be used according to the invention. According to the invention, it is therefore provided to add an indicator to the package, for example. If, as described above, the pharmaceutical protective package has, for example, several rooms, then the indicator can be placed in one of these rooms. However, it is also according to the invention when the indicator is placed in the outer packaging, for example in an aluminum-aluminum outer packaging, in which case advantageously the aluminum package may contain a viewing window through which the possible color change can be observed.

Solcherart Sauerstoffindikatoren sind zum Beispiel unter der Warenbezeichnung Ageless-eye von der Firma Mitsubishi Gas Chemical Company, Inc. erhältlich.Such oxygen indicators are available, for example, under the trade designation Ageless-eye from Mitsubishi Gas Chemical Company, Inc.

Die erfindungsgemäße pharmazeutische Schutzverpackung kann für Arzneimittel verwendet werden, die unter Sauerstoffzutritt zur Zersetzung neigen. Derartige Arzneimittel enthalten meist eine leicht reaktive Gruppe, welche dann durch Reaktion mit Sauerstoff verändert wird. Derartige reaktive Gruppen sind beispielsweise Alkohole, Phenole, Aldehyde, Enole, Ether, Amine, Ketole, Aromaten, Heteroaromaten, Peptide, Proteine, Aminosäuren, Karbonsäure, Fettsäuren, Fettsäureester, Sterole und Steroide. Diese Aufzählung ist nicht abschließend und kann vom Fachmann ohne weiteres beliebig erweitert werden.The pharmaceutical protective packaging according to the invention can be used for drugs which tend to decompose on exposure to oxygen. Such drugs usually contain a slightly reactive group, which is then altered by reaction with oxygen. Such reactive groups include, for example, alcohols, phenols, aldehydes, enols, ethers, amines, ketols, aromatics, heteroaromatics, peptides, proteins, amino acids, carboxylic acids, fatty acids, fatty acid esters, sterols and steroids. This list is not exhaustive and can be extended by the expert without further ado.

Beispiele für Arzneistoffe, welche derartige reaktive Gruppen enthalten, sind, neben anderen, Vitamine, wie Ascorbinsäure, Tocopherole, Vitamine der A-, B- und E-Gruppen, Antibiotika, wie Amphotericin B, Thyroxid-Hormone, wie Levothyroxin, Liothyronin, Tryptophan, Sorbinsäure, omega-3-Fettsäuren, omega-4-Fettsäuren, Nepadutant, Phospholipiden, Ethyloleate, Cholesterole, wie auch andere Steroidhormone und dergleichen. Weitere geeignete Arzneimittel erschließen sich dem Fachmann ohne weiteres.Examples of drugs containing such reactive groups include, among others, vitamins such as ascorbic acid, tocopherols, vitamins of A, B and E groups, antibiotics such as amphotericin B, thyroid hormones such as levothyroxine, liothyronine, tryptophan , Sorbic acid, omega-3 fatty acids, omega-4 fatty acids, nepadutant, phospholipids, ethyl oleates, cholesterols, as well as other steroid hormones and the like. Other suitable drugs are readily apparent to those skilled in the art.

Die nachfolgenden Beispiele erläutern die Erfindung.The following examples illustrate the invention.

Beispiel 1example 1 Abbau von Levothyroxin-NatriumDegradation of levothyroxine sodium

In der Tabelle 1 ist der Abbau von Levothyroxin-Natrium 50 µg Tabletten der Charge #22002 nach 2 Wochen Lagerung bei 60 °C / 80 % rel. F. angegeben. Es zeigt sich, dass bei der Verwendung eines Sauerstoffabsorbers unter den Stress-Lagerungsbedingungen im Vergleich zu der herkömmlichen Lagerung nur ein sehr geringer Abbau des Wirkstoffes beobachtet werden konnte. Der Abbau betrug höchstens 0,8 % der Deklaration des Gehalts an Wirkstoff. Tabelle 1 Packmittel Ausgangswert Gehalt in [% d. D.] nach 2 Wochen Lagerung Gehalt in [% d. D.] Abnahme Gehalt in [%] Glasverpackung, geschlossen (Referenz) 93,6 78,7 14,9 Glasverpackung, geschlossen, mit Sauerstoffabsorber 93,6 92,8 0,8 Alu-Alu-Verpackung, mit Sauerstoffabsorber 93,6 92,9 0,7 In Table 1, the degradation of levothyroxine sodium is 50 μg tablets of lot # 22002 after 2 weeks of storage at 60 ° C / 80% rel. F. indicated. It turns out that when using an oxygen absorber under the stress storage conditions compared to the conventional Storage only a very small degradation of the drug could be observed. The degradation was at most 0.8% of the declaration of the content of active substance. <u> Table 1 </ u> packaging Initial value content in [% d. D.] after 2 weeks storage content in [% d. D.] Decrease in salary in [%] Glass packaging, closed (reference) 93.6 78.7 14.9 Glass packaging, closed, with oxygen absorber 93.6 92.8 0.8 Aluminum-aluminum packaging, with oxygen absorber 93.6 92.9 0.7

Beispiel 2Example 2 Langzeitlagerung von LevothyroxinLong-term storage of levothyroxine

Die Tabellen 2 und 3 zeigen die Auswertung eines Versuchs bei den Lagerungsbedingung 40 °C / 75 % rel. F. Bestimmt wurde der Gehalt Levothyroxin [%] nach einer Lagerzeit von x Monaten. Verwendet wurde ein herkömmliches Blister (Tabelle 2) und eine Lagerung in einem Alu-Umbeutel des gleichen Blisters in Anwesenheit eines Sauerstoffabsorbers in dem Alu-Umbeutel.Tables 2 and 3 show the evaluation of an experiment at the storage condition 40 ° C / 75% rel. F. Levothyroxine [%] was determined after a storage period of x months. A conventional blister (Table 2) was used and stored in an aluminum transfer bag of the same blister in the presence of an oxygen absorber in the aluminum transfer bag.

Auch unter diesen relativ scharfen Lagerungsbedingungen zeigt sich, dass die Verminderung des Sauerstoffs in der pharmazeutischen Verpackung zu einer dramatischen Verbesserung der Haltbarkeit führt. Gemäß den gesetzlichen Bestimmungen darf der Gehalt an Wirkstoff innerhalb der Lagerungszeit nicht unter 90 % der Deklaration absinken. Im vorliegenden Fall sind die nicht in der Schutzpackung gelagerten Arzneimittel bereits nach 3 Monaten verfallen (Tabelle 2). Tabelle 2 Alu-Alu-Blister Lagerzeit Charge 44003 Charge 44004 0 97,3 95,6 3 89,9 89,6 6 87,3 86,8 Tabelle 3 Alu-Beutel mit Sauerstoffabsorber Lagerzeit Charge 44003 Charge 44004 0 97,9 97,3 3 94,0 92,5 6 94,9 93,8 Even under these relatively harsh storage conditions, it can be seen that the reduction of oxygen in the pharmaceutical packaging leads to a dramatic improvement in shelf life. According to the legal regulations, the content of active substance must not fall below 90% of the declaration within the storage period. In the present case, the medicines not stored in the protective package have already expired after 3 months (Table 2). <u> Table 2 </ u> Alu-Alu blisters storage time Lot 44003 Lot 44004 0 97.3 95.6 3 89.9 89.6 6 87.3 86.8 Aluminum bag with oxygen absorber storage time Lot 44003 Lot 44004 0 97.9 97.3 3 94.0 92.5 6 94.9 93.8

Claims (12)

Pharmazeutische Schutzverpackung, dadurch gekennzeichnet, dass der Sauerstoffgehalt innerhalb der Verpackung weniger als 1 Vol-% beträgt.Pharmaceutical protective packaging, characterized in that the oxygen content within the packaging is less than 1% by volume. Pharmazeutische Schutzverpackung gemäß Anspruch 1, dadurch gekennzeichnet, dass der Sauerstoffgehalt innerhalb der Verpackung weniger als 0,5 Vol-% beträgt.Pharmaceutical protective packaging according to claim 1, characterized in that the oxygen content within the packaging is less than 0.5% by volume. Pharmazeutische Schutzverpackung gemäß Anspruch 1, dadurch gekennzeichnet, dass der Sauerstoffgehalt innerhalb der Verpackung weniger als 0,1 Vol-% beträgt.Pharmaceutical protective packaging according to claim 1, characterized in that the oxygen content within the packaging is less than 0.1% by volume. Pharmazeutische Schutzverpackung gemäß Anspruch 1, dadurch gekennzeichnet, dass die Packung evakuiert ist, wobei der Druck weniger als 50 mbar beträgt.Pharmaceutical protective packaging according to claim 1, characterized in that the packing is evacuated, the pressure being less than 50 mbar. Pharmazeutische Schutzverpackung gemäß Anspruch 1, dadurch gekennzeichnet, dass die Packung ein Schutzgas ausgewählt aus Argon, Stickstoff oder Kohlendioxid, enthält.Pharmaceutical protective packaging according to claim 1, characterized in that the package contains a protective gas selected from argon, nitrogen or carbon dioxide. Pharmazeutische Schutzverpackung gemäß Anspruch 1, dadurch gekennzeichnet, dass die Packung einen Sauerstoffabsorber enthält.Pharmaceutical protective packaging according to claim 1, characterized in that the pack contains an oxygen absorber. Pharmazeutische Schutzverpackung gemäß Anspruch 1, dadurch gekennzeichnet, dass sie aus mindestens zwei miteinander verbundenen Räumen besteht, wobei sich in einem der Räume eine Feuchtigkeit und/oder Gas absorbierende Substanz befindet.Pharmaceutical protective packaging according to claim 1, characterized in that it consists of at least two interconnected spaces, wherein in one of the spaces is a moisture and / or gas absorbing substance. Pharmazeutische Schutzverpackung gemäß Anspruch 1, dadurch gekennzeichnet, dass sie weiterhin einen Sauerstoffindikator enthält.Pharmaceutical protective packaging according to claim 1, characterized in that it further contains an oxygen indicator . Pharmazeutische Schutzverpackung gemäß Anspruch 8, dadurch gekennzeichnet, dass der Sauerstoffindikator in einem von außen einsehbaren Bereich der Schutzverpackung angeordnet ist.Pharmaceutical protective packaging according to claim 8, characterized in that the oxygen indicator is arranged in an externally visible region of the protective packaging. Verwendung einer Schutzverpackung gemäß einem der Ansprüche 1 bis 9 für sauerstoffempfindliche Wirkstoffe.Use of a protective packaging according to any one of claims 1 to 9 for oxygen-sensitive active ingredients. Verwendung gemäß Anspruch 10, dadurch gekennzeichnet, dass der Wirkstoff mindestens eine sauerstoffempfindliche Gruppe enthält, welche ausgewählt ist aus Alkohol, Phenol, Aldehyd, Enol, Ether, Amin, Ketol, Aromat, Heteroaromat, Peptid, Protein, Aminosäure, Karbonsäure, Fettsäure, Fettsäureester, Sterol und Steroid.Use according to claim 10, characterized in that the active substance contains at least one oxygen-sensitive group which is selected from alcohol, phenol, aldehyde, enol, ether, amine, ketol, aromatic, heteroaromatic, peptide, protein, amino acid, carboxylic acid, fatty acid, fatty acid ester , Sterol and steroid. Verwendung gemäß Anspruch 11, dadurch gekennzeichnet, dass der Wirkstoff ausgewählt ist aus Vitaminen, Vitaminen der A, B und E-Gruppe, Ascorbinsäure, Antibiotika, Amphotericin B, Thyroxid-Hormonen, Levothyroxin, Liothyronin, Cystein, Tryptophan, Nepadutant, Sorbinsäure, omega-3-Fettsäuren, omega-4-Fettsäuren, Lipiden, Phospholipiden, Ethyloleaten, Cholesterol.Use according to claim 11, characterized in that the active ingredient is selected from vitamins, vitamins A, B and E group, ascorbic acid, antibiotics, amphotericin B, thyroid hormones, levothyroxine, liothyronine, cysteine, tryptophan, neepadutant, sorbic acid, omega -3 fatty acids, omega-4 fatty acids, lipids, phospholipids, ethyl oleates, cholesterol.
EP05090280A 2005-10-05 2005-10-05 Protective packaging for pharmaceutical products Revoked EP1772395B1 (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
EP05090280A EP1772395B1 (en) 2005-10-05 2005-10-05 Protective packaging for pharmaceutical products
AT05090280T ATE501059T1 (en) 2005-10-05 2005-10-05 PHARMACEUTICAL PROTECTIVE PACKAGING
DE502005011092T DE502005011092D1 (en) 2005-10-05 2005-10-05 Pharmaceutical protective packaging

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
EP05090280A EP1772395B1 (en) 2005-10-05 2005-10-05 Protective packaging for pharmaceutical products

Publications (2)

Publication Number Publication Date
EP1772395A1 true EP1772395A1 (en) 2007-04-11
EP1772395B1 EP1772395B1 (en) 2011-03-09

Family

ID=36110769

Family Applications (1)

Application Number Title Priority Date Filing Date
EP05090280A Revoked EP1772395B1 (en) 2005-10-05 2005-10-05 Protective packaging for pharmaceutical products

Country Status (3)

Country Link
EP (1) EP1772395B1 (en)
AT (1) ATE501059T1 (en)
DE (1) DE502005011092D1 (en)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008152347A2 (en) * 2007-06-13 2008-12-18 Reckitt Benckiser Healthcare (Uk) Limited Pack of medicinal tablets
AT509424A3 (en) * 2009-09-29 2013-01-15 Messer Austria Gmbh DEVICE AND METHOD FOR TRANSPORTING MOISTURE-SENSITIVE PRODUCTS
WO2018141938A1 (en) 2017-02-03 2018-08-09 Berlin-Chemie Ag Oral thyroid therapeutic agent
DE102017122807A1 (en) 2017-09-29 2019-04-04 Berlin-Chemie Ag Oral thyroid therapy

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0541183A1 (en) * 1991-11-07 1993-05-12 Sara Lee/DE N.V. Method and apparatus for making a filled and closed vacuum pack
US5293996A (en) * 1992-05-14 1994-03-15 Motorola, Inc. Container having an observation window
EP0810163A1 (en) * 1996-05-28 1997-12-03 Mitsubishi Gas Chemical Company, Inc. Method for preservation of article
WO1998003866A1 (en) * 1996-07-19 1998-01-29 Pharmacia & Upjohn Ab Color composition comprising an agent containing pyrogallol entities, a salt of iron (ii) and an organic acid
US20040188304A1 (en) * 2002-12-31 2004-09-30 Bonnette Michael J. Packaging system with oxygen sensor

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0541183A1 (en) * 1991-11-07 1993-05-12 Sara Lee/DE N.V. Method and apparatus for making a filled and closed vacuum pack
US5293996A (en) * 1992-05-14 1994-03-15 Motorola, Inc. Container having an observation window
EP0810163A1 (en) * 1996-05-28 1997-12-03 Mitsubishi Gas Chemical Company, Inc. Method for preservation of article
WO1998003866A1 (en) * 1996-07-19 1998-01-29 Pharmacia & Upjohn Ab Color composition comprising an agent containing pyrogallol entities, a salt of iron (ii) and an organic acid
US20040188304A1 (en) * 2002-12-31 2004-09-30 Bonnette Michael J. Packaging system with oxygen sensor

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
BAUER; FRÖMMING; FÜHRER: "LEHRBUCH DER PHARMAZEUTISCHEN TECHNOLOGIE", 2002, WVG

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008152347A2 (en) * 2007-06-13 2008-12-18 Reckitt Benckiser Healthcare (Uk) Limited Pack of medicinal tablets
WO2008152347A3 (en) * 2007-06-13 2009-04-23 Reckitt Benckiser Healthcare Pack of medicinal tablets
AU2014203766B2 (en) * 2007-06-13 2016-06-09 Indivior Uk Limited Pack of medicinal tablets
AT509424A3 (en) * 2009-09-29 2013-01-15 Messer Austria Gmbh DEVICE AND METHOD FOR TRANSPORTING MOISTURE-SENSITIVE PRODUCTS
AT509424B1 (en) * 2009-09-29 2013-01-15 Messer Austria Gmbh DEVICE AND METHOD FOR TRANSPORTING MOISTURE-SENSITIVE PRODUCTS
WO2018141938A1 (en) 2017-02-03 2018-08-09 Berlin-Chemie Ag Oral thyroid therapeutic agent
DE102017122807A1 (en) 2017-09-29 2019-04-04 Berlin-Chemie Ag Oral thyroid therapy
DE102017122807B4 (en) 2017-09-29 2023-02-09 Berlin-Chemie Ag Oral thyroid therapeutic

Also Published As

Publication number Publication date
ATE501059T1 (en) 2011-03-15
DE502005011092D1 (en) 2011-04-21
EP1772395B1 (en) 2011-03-09

Similar Documents

Publication Publication Date Title
DE69720978T2 (en) TOPICAL AGENTS CONTAINING AN OIL-IN-WATER EMULSION AND RETINOID
EP1007060B1 (en) Stable extract of hypericum perforatum l., a method for producing the same, and corresponding pharmaceutical preparations
EP0368103B1 (en) Method of filling and closing of containers with pharmaceutically pure contents
US20030042166A1 (en) Pharmaceutical kit for oxygen-sensitive drugs
EP0857064B1 (en) Stabilised pharmaceutical preparations containing thyroid hormone
DE19847968A1 (en) Separate storage of an active material and a solvent comprises a closure cap and a container, with a chamber attached to the unit.
DE19646977A1 (en) Stable dry extract of Hypericum perforatum L., Saint John&#39;s wort
DE60129597T2 (en) METHOD FOR IMPROVING THE STABILITY OF PHARMACEUTICAL PREPARATION
EP1772395B1 (en) Protective packaging for pharmaceutical products
WO1995000180A1 (en) Process for producing sterile packings of ready-for-use articles and container for such packings
DE69014691T2 (en) Process for the preparation of bromocriptine-containing pharmaceutical preparations with high stability and related products.
EP0096286A2 (en) Storage-stable tablets containing a hydrolysis-sensitive active agent
EP0471161B1 (en) Spray container containing nitroglycerin in a hydrophilic aqueous composition
EP2594283B1 (en) Aprotinin-based aerosol preparation for the treatment of viral respiratory infections
DE602004010817T2 (en) METHOD FOR STABILIZING ATORVASTATIN
EP2068842B2 (en) Active ingredient and trimagnesiumdicitrate as desiccant containing stabilised solid medicinal forms and method for the production thereof
DE202009019152U1 (en) A stable packaged dosage form of a combination preparation comprising a pharmaceutical composition containing amlodipine besylate and bisoprolol fumarate
DE2608314A1 (en) PACKING OF LIQUID, VESSEL AND CASING
EP3419598B1 (en) Fosfomycin formulation for parenteral administration
DE202016009131U1 (en) Ready-to-use bortezomib solution
EP0461505B1 (en) Spray containing nitroglycerin
DE10303229B4 (en) Ambroxol and Angiotensin Converting Enzyme (ACE) inhibitors Drugs and their use in the treatment of neurodegenerative diseases
EP2288326B1 (en) Pharmaceutical preparation in water vapour enclosures with improved stability
EP2643363B1 (en) Process for the preparation of low-peroxide crosslinked vinyllactam polymer
AT409484B (en) SEALED MULTIPLE DOSE DISPENSER

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

AK Designated contracting states

Kind code of ref document: A1

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 NL PL PT RO SE SI SK TR

AX Request for extension of the european patent

Extension state: AL BA HR MK YU

RIN1 Information on inventor provided before grant (corrected)

Inventor name: FLEMMING, JENS

Inventor name: SCHMITZ, REINHARD

Inventor name: GROEGER, KARSTEN

17P Request for examination filed

Effective date: 20070914

17Q First examination report despatched

Effective date: 20071107

AKX Designation fees paid

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 NL PL PT RO SE SI SK TR

GRAP Despatch of communication of intention to grant a patent

Free format text: ORIGINAL CODE: EPIDOSNIGR1

GRAS Grant fee paid

Free format text: ORIGINAL CODE: EPIDOSNIGR3

GRAA (expected) grant

Free format text: ORIGINAL CODE: 0009210

AK Designated contracting states

Kind code of ref document: B1

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 NL PL PT RO SE SI SK TR

REG Reference to a national code

Ref country code: GB

Ref legal event code: FG4D

Free format text: NOT ENGLISH

REG Reference to a national code

Ref country code: CH

Ref legal event code: EP

REG Reference to a national code

Ref country code: IE

Ref legal event code: FG4D

Free format text: LANGUAGE OF EP DOCUMENT: GERMAN

REF Corresponds to:

Ref document number: 502005011092

Country of ref document: DE

Date of ref document: 20110421

Kind code of ref document: P

REG Reference to a national code

Ref country code: DE

Ref legal event code: R096

Ref document number: 502005011092

Country of ref document: DE

Effective date: 20110421

REG Reference to a national code

Ref country code: NL

Ref legal event code: VDEP

Effective date: 20110309

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: LT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20110309

Ref country code: SE

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20110309

Ref country code: GR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20110610

Ref country code: LV

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20110309

Ref country code: ES

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20110620

LTIE Lt: invalidation of european patent or patent extension

Effective date: 20110309

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: BG

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20110609

Ref country code: SI

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20110309

Ref country code: CY

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20110309

Ref country code: NL

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20110309

Ref country code: FI

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20110309

REG Reference to a national code

Ref country code: IE

Ref legal event code: FD4D

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: PT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20110711

Ref country code: IE

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20110309

Ref country code: EE

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20110309

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: SK

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20110309

Ref country code: RO

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20110309

Ref country code: IS

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20110709

Ref country code: CZ

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20110309

PLBI Opposition filed

Free format text: ORIGINAL CODE: 0009260

PLAX Notice of opposition and request to file observation + time limit sent

Free format text: ORIGINAL CODE: EPIDOSNOBS2

26 Opposition filed

Opponent name: MITSUBISHI GAS CHEMICAL COMPANY, INC.

Effective date: 20111209

RDAF Communication despatched that patent is revoked

Free format text: ORIGINAL CODE: EPIDOSNREV1

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: PL

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20110309

REG Reference to a national code

Ref country code: DE

Ref legal event code: R026

Ref document number: 502005011092

Country of ref document: DE

Effective date: 20111209

RDAG Patent revoked

Free format text: ORIGINAL CODE: 0009271

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: PATENT REVOKED

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: MC

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20111031

Ref country code: IT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20110309

REG Reference to a national code

Ref country code: CH

Ref legal event code: PL

27W Patent revoked

Effective date: 20120218

GBPR Gb: patent revoked under art. 102 of the ep convention designating the uk as contracting state

Effective date: 20120218

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: LI

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20110309

Ref country code: CH

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20110309

REG Reference to a national code

Ref country code: DE

Ref legal event code: R119

Ref document number: 502005011092

Country of ref document: DE

Effective date: 20120501

REG Reference to a national code

Ref country code: AT

Ref legal event code: MM01

Ref document number: 501059

Country of ref document: AT

Kind code of ref document: T

Effective date: 20111005

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: AT

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20111005