EP2135666B1 - Syringes for producing medicinal suspensions and related system - Google Patents

Syringes for producing medicinal suspensions and related system Download PDF

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Publication number
EP2135666B1
EP2135666B1 EP08011309A EP08011309A EP2135666B1 EP 2135666 B1 EP2135666 B1 EP 2135666B1 EP 08011309 A EP08011309 A EP 08011309A EP 08011309 A EP08011309 A EP 08011309A EP 2135666 B1 EP2135666 B1 EP 2135666B1
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EP
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Prior art keywords
syringe
medicament
ultrasonic bath
syringes
application
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German (de)
French (fr)
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EP2135666A1 (en
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Jürgen Göbel
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J7/00—Devices for administering medicines orally, e.g. spoons; Pill counting devices; Arrangements for time indication or reminder for taking medicine
    • A61J7/0015—Devices specially adapted for taking medicines
    • A61J7/0053—Syringes, pipettes or oral dispensers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F23/00—Mixing according to the phases to be mixed, e.g. dispersing or emulsifying
    • B01F23/50—Mixing liquids with solids
    • B01F23/55—Mixing liquids with solids the mixture being submitted to electrical, sonic or similar energy
    • B01F23/551—Mixing liquids with solids the mixture being submitted to electrical, sonic or similar energy using vibrations
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F31/00—Mixers with shaking, oscillating, or vibrating mechanisms
    • B01F31/80—Mixing by means of high-frequency vibrations above one kHz, e.g. ultrasonic vibrations
    • B01F31/87—Mixing by means of high-frequency vibrations above one kHz, e.g. ultrasonic vibrations transmitting the vibratory energy by means of a fluid, e.g. by means of air shock waves
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F33/00—Other mixers; Mixing plants; Combinations of mixers
    • B01F33/50—Movable or transportable mixing devices or plants
    • B01F33/501—Movable mixing devices, i.e. readily shifted or displaced from one place to another, e.g. portable during use
    • B01F33/5011—Movable mixing devices, i.e. readily shifted or displaced from one place to another, e.g. portable during use portable during use, e.g. hand-held
    • B01F33/50112—Movable mixing devices, i.e. readily shifted or displaced from one place to another, e.g. portable during use portable during use, e.g. hand-held of the syringe or cartridge type
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F33/00—Other mixers; Mixing plants; Combinations of mixers
    • B01F33/80—Mixing plants; Combinations of mixers
    • B01F33/836—Mixing plants; Combinations of mixers combining mixing with other treatments
    • B01F33/8361—Mixing plants; Combinations of mixers combining mixing with other treatments with disintegrating
    • B01F33/83612—Mixing plants; Combinations of mixers combining mixing with other treatments with disintegrating by crushing or breaking
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F2101/00—Mixing characterised by the nature of the mixed materials or by the application field
    • B01F2101/22—Mixing of ingredients for pharmaceutical or medical compositions
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F33/00—Other mixers; Mixing plants; Combinations of mixers
    • B01F33/50—Movable or transportable mixing devices or plants
    • B01F33/501—Movable mixing devices, i.e. readily shifted or displaced from one place to another, e.g. portable during use
    • B01F33/5011—Movable mixing devices, i.e. readily shifted or displaced from one place to another, e.g. portable during use portable during use, e.g. hand-held

Definitions

  • Food probes can become clogged by particles that are too large. This may lead to the need for hospitalization and replacement of the probe. When given orally, the risk of aspiration of particles and / or mucosal irritation is given. Micropellet-based tablets must not be rubbed, as this may lead to rapid release or loss of efficacy.
  • the present invention seeks to provide a syringe, which improves and accelerates the comminution process for the drug.
  • the drug to be applied and the application liquid or a part thereof are exposed to an ultrasonic bath in a syringe whose walls are permeable to ultrasonic waves.
  • a syringe whose walls are permeable to ultrasonic waves.
  • commercial syringes esp. Luer-lock syringes.
  • Usually a capacity of 10 to 20 ml is used.
  • the soft plastic wall of commercial syringes allows the effective in the ultrasonic bath Waves through. They are transferred from the liquid contained therein to the drug so that it is gently crushed and suspended in the application liquid.
  • the method is suitable for those drugs which are pressed or granulated from fine-grained or powdery starting material (tablets).
  • the effect of the ultrasound triggers the bond between the particles - if necessary promoted by the dissolving forces of the liquid.
  • unsuitable are soft gelatin capsules; Hard gelatin capsules must be opened.
  • syringes are particularly advantageous because if desired they can be connected directly to a feeding probe. They are always cost-effective in the field of application with the required closures available, and the staff has practice in dealing with it.
  • the tablet to be applied is filled into a disposable syringe.
  • the syringe plunger is then replaced and the syringe is vented, ie the plunger is pushed in as far as the size of the medicament permits. The amount of trapped air is thus reduced (reduction of oxidation and humidity).
  • the syringe is closed with a commercially available combination stopper. It can then be easily stored for long periods, for example, for the daily or weekly needs ("drug centers"). Physical or chemical properties of the medicinal product may be taken into account, for example storage until application in the absence of light or air (shielding gas).
  • the syringes can be labeled patient specific or drug specific.
  • a spike stopper This consists of a commercially available combination stopper, in which a stainless steel mandrel or impact body is used, the bottom of which has the same diameter as the inner diameter of the combination stopper opening.
  • the stainless steel mandrel has the diameter of the syringe opening and protrudes depending on the make about 5 mm into the syringe chamber.
  • the protruding part is edged and acts as a mechanical impact surface, which improves and accelerates the crushing process.
  • the spike may also be used as a means that couples the ultrasonic vibration into the syringe space.
  • the mandrel closes off the syringe opening from the syringe space and thus prevents sedimentation of the drug in the syringe opening.
  • the syringe After insertion of the spike stopper, the syringe is filled to 30 to 50% with application liquid and sealed with the syringe plunger. Full filling is possible but inconvenient for shaking up the resulting suspension.
  • the medicine should be at least covered.
  • the application liquid is usually water, but can also be, for example, artificial gastric or intestinal juice.
  • the pH can be adjusted depending on the site of application or the drug.
  • the syringe is then immersed in an ultrasonic bath.
  • Commercially available equipment with water can be used. The most suitable one can easily be determined by trial and error. Successfully used was a commercial device with a frequency of 25 kHz, as it is also used by opticians to clean glasses.
  • the water level of the device should be higher than the area occupied by the drug in the syringe so that it is fully detected by the vibration transmitted by the ultrasonic bath. in the In general, this means that the water level in the device is at least as high as the liquid level in the syringe, better higher than this.
  • a holding device To hold the syringe or multiple syringes in the ultrasonic bath is conveniently used a holding device.
  • This may be formed by the lid of the ultrasonic bath, which has a corresponding number of holes for receiving a number of syringes whose diameter is slightly larger than that of the syringes so that they are guided.
  • the holes are inclined according to the invention with respect to the vertical direction, usefully with an inclination angle of 25 - 40 °, esp. 30 °. As a result, the syringes tilt in the holes and do not float on.
  • the lid is suitably locked in relation to the vessel of the ultrasonic bath.
  • the syringe By commissioning the ultrasound machine, a gentle wet grinding is performed. A possible second grinding is possible without refilling.
  • the syringe is removed from the holding device and shaken vigorously. The obtained suspension can now be applied directly to the feeding probe after removal of the plug. Alternatively, the suspension can be filled into a collection tube. The syringe is rinsed again with liquid in order to quantitatively remove any residues of the drug and to apply them as well. At the same time the food probe is rinsed.
  • the use of a syringe has decisive advantages: The preparation of the suspension takes place directly in the dispersion medium. The mechanical and thermal load on the drug is low. A quantitative application is possible. Contamination by other drugs does not occur. Micropellets are preserved. The grind takes place in a closed system without endangering the nursing staff. The galenics of the finished drug does not matter (exception: soft gelatin capsule). The dispersant can be chosen freely. Physical and chemical properties of the drug can be taken into account. Since the syringe opening in the diameter is much smaller than the feeding tube, the latter can not clog. The procedure is simple and can also be done by laymen. It is much more economical than the traditional one; the required working time is at least halved.
  • the attached drawing shows schematically a section through an ultrasound device with lid and inserted syringe.
  • the device 1 forms a vessel for a water bath 2, whose wall is equipped with an ultrasonic sonotrode, not shown.
  • the bath is closed with a removable lid 3, which is fixed by a bordering in the edge of the bath rim 4. It contains a series of bores 5, which are inclined at an angle of 30 ° with respect to the vertical direction and whose diameter is adapted to the outer diameter of the syringes to be absorbed by them.
  • a syringe is shown, which is secured by the tendency to float in the water bath.
  • syringe body 6 and a piston 7 and is closed by a combination stopper 8, the opening channel of which is filled by a removable pin 9 whose angular end projects into the interior of the syringe.
  • a tablet 10 is located together with an application liquid 11 in the interior of the syringe.
  • the water level of the bath 2 is higher than that in the interior of the syringe.

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  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Dispersion Chemistry (AREA)
  • Infusion, Injection, And Reservoir Apparatuses (AREA)
  • Media Introduction/Drainage Providing Device (AREA)
  • Medical Preparation Storing Or Oral Administration Devices (AREA)

Abstract

Pharmaceutical product administration involves subjecting pharmaceutical product and a portion of application liquid-contained container (1), preferably syringe, particularly Luer-lock syringe to an ultrasonic bath. The container walls are permeable for ultrasonic sound. The syringe has a volume of 10-20 ml. Independent claims are included for: (1) a syringe for administering pharmaceutical product, which comprises an impact body; and (2) a container for the ultrasonic bath, which comprises a cover having multiple insertion holes.

Description

Patienten mit Kau- und/oder Schluckstörungen oder Patienten, die über eine Sonde ernährt werden, benötigen die für sie notwendigen festen oralen Arzneimittel in Form einer Lösung oder Suspension. Üblich ist es, die Arzneimittel hierzu im Mörser oder in ähnlich wirkenden Werkzeugen zu Pulver zu zerreiben, in Einnahmegefäße, Löffel oder Einmalspritzen umzufüllen und mit Flüssigkeit zu suspendieren. Dies hat entscheidende Nachteile. Das Arzneimittel wird hoher mechanischer und teilweise thermischer Belastung ausgesetzt. Das gilt besonders bei der häufigen Praxis, aus Zeitersparnis mehrere Tabletten gleichzeitig zu zerreiben. Durch im Mörser verbleibende Reste und beim Umfüllen entstehende Verluste erfolgt die Arzneimittelgabe nicht quantitativ. Durch Verwendung eines Mörsers für mehrere verschiedene Arzneimittel kann es zu Cross-Kontamination mit anderen Arzneimitteln kommen. Im Trockenmahlprozess variiert die Korngröße und es kann zu Pulveraggregationen kommen. Nahrungssonden können durch zu große Partikeln verstopfen. Das kann zur Notwendigkeit der Klinikeinweisung und des Austauschs der Sonde führen. Bei oraler Gabe ist die Gefahr der Aspiration von Partikeln und/oder Schleimhautreizungen gegeben. Tabletten auf Mikropelletbasis dürfen nicht zerrieben werden, weil dies zu schneller Freisetzung oder zum Wirkungsverlust führen kann.Patients with chewing and / or swallowing disorders or patients who are fed via a probe need the solid oral drugs necessary for them in the form of a solution or suspension. It is customary to grind the drug into powder in a mortar or in similar-acting tools, to fill in receptacles, spoons or disposable syringes and to suspend with liquid. This has significant disadvantages. The drug is exposed to high mechanical and partial thermal stress. This is especially true in the frequent practice of simultaneously grinding several tablets out of time savings. Due to residues remaining in the mortar and losses incurred during transfer, drug administration is not quantitative. Using a mortar for several different medicines may result in cross-contamination with other medicines. In the dry grinding process, the grain size varies and it can lead to powder aggregation. Food probes can become clogged by particles that are too large. This may lead to the need for hospitalization and replacement of the probe. When given orally, the risk of aspiration of particles and / or mucosal irritation is given. Micropellet-based tablets must not be rubbed, as this may lead to rapid release or loss of efficacy.

Aufgrund der Umständlichkeit der Zubereitung kommt es vor, dass Arzneimittel nicht oder nur unregelmäßig genommen werden. Für das Pflegepersonal besteht die Gefahr des Einatmens von Arzneimittelstaub. Bei hochwirksamen Arzneistoffgruppen, z.B. Zytostatika, Corticoide, müssten entsprechend der Klassifizierung in der Gefahrstoffverordnung umfangreiche Sicherungsmaßnahmen getroffen werden, die in der Praxis häufig unbeachtet bleiben. Die herkömmliche Arbeitsweise ist zeitraubend und unwirtschaftlich.Due to the complexity of the preparation, it can happen that medicines are not taken or only taken irregularly. For the nursing staff, there is a risk of inhaling drug dust. For highly effective drug groups, e.g. Cytostatic agents, corticoids, would have to be taken in accordance with the classification in the Hazardous Substances Regulation extensive safeguards that often remain unnoticed in practice. The conventional way of working is time consuming and uneconomical.

Bekannt ist der Vorschlag ( US-A-5376072 ), in einer Spritze durch einen mittels Gewinde vorschraubbaren Stempel, dessen Stirnseite ebenso wie der Boden der Spritze mit Aufrauung versehen ist, ein Arzneimittel zu zerquetschen und/oder zu zerreiben. In der Praxis wird die bekannte Anordnung jedoch höchstens den von den Zähnen erreichbaren Teil des Medikaments zerreiben und im übrigen bestenfalls eine Zerstückelung erreichen können, wenn nicht sogar durch die Pressung zwischen Spritzenboden und Stempel eine Verdichtung geschieht.The proposal is known ( US-A-5376072 ), in a syringe by means of a screw-threadable punch, the front side is provided as well as the bottom of the syringe with roughening, to crush a medicine and / or to grind. In practice, however, the known arrangement will grind at most the part of the drug which can be reached by the teeth and, moreover, at best can achieve fragmentation, if compression does not occur even through the pressure between the syringe base and the punch.

Ferner ist es bekannt ( US 2004/191275 A1 ), ein zu zerkleinerndes Arzneimittel und eine Applikationsflüssigkeit innerhalb eines Behälters, dessen Wände für Ultraschallwellen durchlässig sind, einem Ultraschallbad auszusetzen und dadurch die Zerkleinerung zusammen mit der Dispergierung vorzunehmen. Dadurch werden die mit der Trockenzerkleinerung verbundenen Nachteile vermieden.Furthermore, it is known ( US 2004/191275 A1 ), to suspend a drug to be crushed and an application liquid within a container whose walls are permeable to ultrasonic waves, to suspend an ultrasonic bath and thereby carry out the comminution together with the dispersion. As a result, the disadvantages associated with dry comminution are avoided.

Aus der US 2006/0093644 A1 ist es bekannt, eine Spritze, die Arzneimittel und eine Applikationsflüssigkeit enthält, einer Ultraschallquelle auszusetzen.From the US 2006/0093644 A1 It is known to expose a syringe containing drugs and an application liquid to an ultrasound source.

Ausgehend von diesem Stand der Technik liegt der Erfindung die Aufgabe zugrunde, eine Spritze anzugeben, die den Zerkleinerungsvorgang für das Arzneimittel verbessert und beschleunigt.Based on this prior art, the present invention seeks to provide a syringe, which improves and accelerates the comminution process for the drug.

Diese Aufgabe wird durch eine Spritze mit den Merkmalen der Patentansprüche 1 bzw. 2 und durch ein System zur Herstellung von Arzneimittelsuspensionen gemäß Anspruch 8 gelöst ; die abhängigen Ansprüche betreffen vorteilhafte Weiterentwicklungen der Erfindung.This object is achieved by a syringe with the features of claims 1 and 2 and by a system for the preparation of drug suspensions according to claim 8; the dependent claims relate to advantageous developments of the invention.

Demnach werden das zu applizierende Arzneimittel und die Applikationsflüssigkeit oder ein Teil derselben in einer Spritze, derren Wände für Ultraschallwellen durchlässig sind, einem Ultraschallbad ausgesetzt. Besonders geeignet dafür sind handelsübliche Spritzen, insb. Luer-Lock-Spritzen. Meist wird ein Fassungsvermögen von 10 bis 20 ml verwendet. Abhängig von der Größe der Tabletten bzw. der Art und Menge der Applikationsflüssigkeit können aber auch größere oder kleinere Spritzen Verwendung finden. Die weiche Kunststoffwand handelsüblicher Spritzen lässt die im Ultraschallbad wirksamen Wellen durch. Sie werden von der darin befindlichen Flüssigkeit auf das Arzneimittel übertragen, so dass dieses schonend zerkleinert und in der Applikationsflüssigkeit suspendiert wird. In erster Linie ist das Verfahren für solche Arzneimittel geeignet, die aus feinkörnigem oder pulvrigem Vormaterial verpresst oder granuliert sind (Tabletten). Die Ultraschalleinwirkung löst die Bindung zwischen den Partikeln - ggf. gefördert durch die Lösekräfte der Flüssigkeit. Ungeeignet sind Weichgelatinekapseln; Hartgelatinekapseln müssen geöffnet werden.Accordingly, the drug to be applied and the application liquid or a part thereof are exposed to an ultrasonic bath in a syringe whose walls are permeable to ultrasonic waves. Particularly suitable for this are commercial syringes, esp. Luer-lock syringes. Mostly a capacity of 10 to 20 ml is used. Depending on the size of the tablets or the type and amount of the application liquid but larger or smaller syringes can be used. The soft plastic wall of commercial syringes allows the effective in the ultrasonic bath Waves through. They are transferred from the liquid contained therein to the drug so that it is gently crushed and suspended in the application liquid. First and foremost, the method is suitable for those drugs which are pressed or granulated from fine-grained or powdery starting material (tablets). The effect of the ultrasound triggers the bond between the particles - if necessary promoted by the dissolving forces of the liquid. Unsuitable are soft gelatin capsules; Hard gelatin capsules must be opened.

Die Verwendung von Spritzen ist deshalb besonders vorteilhaft, weil sie falls gewünscht unmittelbar an eine Nahrungssonde angeschlossen werden können. Sie sind im Anwendungsbereich stets kostengünstig mit den erforderlichen Verschlüssen verfügbar, und das Personal hat Übung im Umgang damit.The use of syringes is particularly advantageous because if desired they can be connected directly to a feeding probe. They are always cost-effective in the field of application with the required closures available, and the staff has practice in dealing with it.

Nach dem Entfernen des Spritzenkolbens wird die zu applizierende Tablette in eine Einmalspritze gefüllt. Der Spritzenkolben wird in der Regel anschließend wieder eingesetzt und die Spritze entlüftet, d.h. der Kolben wird so weit eingeschoben, wie es die Größe des Arzneimittels gestattet. Die Menge der eingeschlossenen Luft wird so vermindert (Verminderung von Oxydation und Luftfeuchtigkeit). Die Spritze wird mit einem handelsüblichen Kombistopfen verschlossen. Sie kann dann problemlos für längere Zeitgelagert werden, beispielsweise für den Tages- oder Wochenbedarf ("Arzneimittelstellen"). Physikalische oder chemische Eigenschaften des Arzneimittels können berücksichtigt werden, zum Beispiel Lagerung bis zur Anwendung unter Licht- oder Luftausschluss (Schutzgas). Die Spritzen können patientenspezifisch oder arzneimittelspezifisch gekennzeichnet werden.After removing the syringe plunger, the tablet to be applied is filled into a disposable syringe. As a rule, the syringe plunger is then replaced and the syringe is vented, ie the plunger is pushed in as far as the size of the medicament permits. The amount of trapped air is thus reduced (reduction of oxidation and humidity). The syringe is closed with a commercially available combination stopper. It can then be easily stored for long periods, for example, for the daily or weekly needs ("drug centers"). Physical or chemical properties of the medicinal product may be taken into account, for example storage until application in the absence of light or air (shielding gas). The syringes can be labeled patient specific or drug specific.

Zur Vorbereitung der Suspensionsherstellung wird der Spritzenkolben entfernt und der Kombistopfen durch einen Dornstopfen ersetzt. Dieser besteht aus einem handelsüblichen Kombistopfen, in den ein Edelstahldorn bzw. Prallkörper eingesetzt ist, dessen Boden denselben Durchmesser hat wie der Innendurchmesser der Kombistopfenöffnung. Der Edelstahldorn hat den Durchmesser der Spritzenöffnung und ragt je nach Fabrikat etwa 5 mm in den Spritzenraum hinein. Der hineinragende Teil ist kantig ausgebildet und wirkt als mechanische Prallfläche, die den Zerkleinerungsvorgang verbessert und beschleunigt. Der Dorn bzw. Prallkörper kann auch als Mittel verwendet werden, das die Ultraschallschwingung in den Spritzenraum einkoppelt. Der Dorn schließt die Spritzenöffnung gegenüber dem Spritzenraum ab und verhindert so eine Sedimentierung des Arzneimittels in der Spritzenöffnung.To prepare the suspension preparation, remove the syringe plunger and replace the combination stopper with a spike stopper. This consists of a commercially available combination stopper, in which a stainless steel mandrel or impact body is used, the bottom of which has the same diameter as the inner diameter of the combination stopper opening. The stainless steel mandrel has the diameter of the syringe opening and protrudes depending on the make about 5 mm into the syringe chamber. The protruding part is edged and acts as a mechanical impact surface, which improves and accelerates the crushing process. The spike may also be used as a means that couples the ultrasonic vibration into the syringe space. The mandrel closes off the syringe opening from the syringe space and thus prevents sedimentation of the drug in the syringe opening.

Nach dem Einsetzen des Dornstopfens wird die Spritze zu 30 bis 50% mit Applikationsflüssigkeit gefüllt und mit dem Spritzenkolben verschlossen. Das vollständige Füllen ist möglich, aber unzweckmäßig, damit die sich ergebende Suspension aufgeschüttelt werden kann. Das Arzneimittel sollte mindestens bedeckt sein. Die Applikationsflüssigkeit ist meist Wasser, kann aber beispielsweise auch künstlicher Magen- oder Darmsaft sein. Der pH-Wert kann je nach Applikationsort oder Arzneimittel eingestellt werden.After insertion of the spike stopper, the syringe is filled to 30 to 50% with application liquid and sealed with the syringe plunger. Full filling is possible but inconvenient for shaking up the resulting suspension. The medicine should be at least covered. The application liquid is usually water, but can also be, for example, artificial gastric or intestinal juice. The pH can be adjusted depending on the site of application or the drug.

Die Spritze wird sodann in ein Ultraschallbad getaucht. Handelsübliche Geräte mit Wasser sind verwendbar. Das bestgeeignete kann leicht durch Probieren ermittelt werden. Erfolgreich verwendet wurde ein handelsübliches Gerät mit einer Frequenz von 25 kHz, wie es auch von Optikern zum Reinigen von Brillen verwendet wird. Der Wasserspiegel des Geräts soll höher sein als der vom Arzneimittel in der Spritze eingenommene Bereich, damit dies voll von der vom Ultraschallbad übertragenen Schwingung erfasst wird. Im Allgemeinen bedeutet dies, dass der Wasserspiegel im Gerät mindestens ebenso hoch ist wie der Flüssigkeitsstand in der Spritze, besser höher als dieser.The syringe is then immersed in an ultrasonic bath. Commercially available equipment with water can be used. The most suitable one can easily be determined by trial and error. Successfully used was a commercial device with a frequency of 25 kHz, as it is also used by opticians to clean glasses. The water level of the device should be higher than the area occupied by the drug in the syringe so that it is fully detected by the vibration transmitted by the ultrasonic bath. in the In general, this means that the water level in the device is at least as high as the liquid level in the syringe, better higher than this.

Zum Halten der Spritze oder mehrerer Spritzen im Ultraschallbad verwendet man zweckmäßigerweise eine Haltevorrichtung. Diese kann von dem Deckel des Ultraschallbads gebildet sein, der zur Aufnahme einer Anzahl von Spritzen eine entsprechende Anzahl von Bohrungen aufweist, deren Durchmesser wenig größer ist als derjenige der Spritzen, so dass diese geführt sind. Die Bohrungen sind nach der Erfindung geneigt gegenüber der Vertikalrichtung, sinnvollerweise mit einem Neigungswinkel von 25 - 40°, insb. 30°. Dadurch verkanten sich die Spritzen in den Bohrungen und schwimmen nicht auf. Der Deckel ist in geeigneter Weise im Verhältnis zum Gefäß des Ultraschallbads arretiert.To hold the syringe or multiple syringes in the ultrasonic bath is conveniently used a holding device. This may be formed by the lid of the ultrasonic bath, which has a corresponding number of holes for receiving a number of syringes whose diameter is slightly larger than that of the syringes so that they are guided. The holes are inclined according to the invention with respect to the vertical direction, usefully with an inclination angle of 25 - 40 °, esp. 30 °. As a result, the syringes tilt in the holes and do not float on. The lid is suitably locked in relation to the vessel of the ultrasonic bath.

Durch die Inbetriebnahme des Ultraschallgeräts wird eine schonende Nassmahlung durchgeführt. Eine eventuelle Zweitmahlung ist ohne Umfüllen möglich. Nach Beendung des Mahlvorgangs wird die Spritze aus der Haltevorrichtung entnommen und kräftig aufgeschüttelt. Die gewonnene Suspension kann nun nach Abnahme des Stopfens direkt in die Nahrungssonde appliziert werden. Alternativ kann die Suspension in ein Einnahmeglas gefüllt werden. Die Spritze wird nochmals mit Flüssigkeit gespült, um etwaige Reste des Arzneimittels quantitativ zu entfernen und diese ebenfalls zu applizieren. Dabei wird gleichzeitig die Nahrungssonde gespült.By commissioning the ultrasound machine, a gentle wet grinding is performed. A possible second grinding is possible without refilling. After completion of the grinding process, the syringe is removed from the holding device and shaken vigorously. The obtained suspension can now be applied directly to the feeding probe after removal of the plug. Alternatively, the suspension can be filled into a collection tube. The syringe is rinsed again with liquid in order to quantitatively remove any residues of the drug and to apply them as well. At the same time the food probe is rinsed.

Der Einsatz einer Spritze hat entscheidende Vorteile: Die Herstellung der Suspension erfolgt direkt im Dispersionsmittel. Die mechanische und thermische Belastung für den Arzneistoff ist gering. Eine quantitative Applikation ist möglich. Verunreinigung durch andere Arzneimittel findet nicht statt. Mikropellets bleiben erhalten. Die Mahlung erfolgt im geschlossenen System ohne Gefährdung des Pflegepersonals. Die Galenik des Fertigarzneimittels spielt keine Rolle (Ausnahme Weichgelatinekapsel). Das Dispersionsmittel kann frei gewählt werden. Physikalische und chemische Eigenschaften des Arzneimittels können berücksichtigt werden. Da die Spritzenöffnung im Durchmesser wesentlich kleiner ist als die Ernährungssonde, kann letztere nicht verstopfen. Das Verfahren ist einfach und kann auch von Laien durchgeführt werden. Es ist wesentlich wirtschaftlicher als das herkömmliche; die benötigte Arbeitszeit wird mindestens halbiert.The use of a syringe has decisive advantages: The preparation of the suspension takes place directly in the dispersion medium. The mechanical and thermal load on the drug is low. A quantitative application is possible. Contamination by other drugs does not occur. Micropellets are preserved. The grind takes place in a closed system without endangering the nursing staff. The galenics of the finished drug does not matter (exception: soft gelatin capsule). The dispersant can be chosen freely. Physical and chemical properties of the drug can be taken into account. Since the syringe opening in the diameter is much smaller than the feeding tube, the latter can not clog. The procedure is simple and can also be done by laymen. It is much more economical than the traditional one; the required working time is at least halved.

Die beigefügte Zeichnung zeigt schematisch einen Schnitt durch ein Ultraschallgerät mit Deckel und eingesetzter Spritze.The attached drawing shows schematically a section through an ultrasound device with lid and inserted syringe.

Das Gerät 1 bildet ein Gefäß für ein Wasserbad 2, dessen Wand mit einer nicht gezeigten Ultraschall-Sonotrode ausgerüstet ist. Das Bad ist mit einem abnehmbaren Deckel 3 verschlossen, der durch eine in den Rand des Bades fassende Randleiste 4 fixiert ist. Er enthält eine Reihe von Bohrungen 5, die unter einem Winkel von 30° gegenüber der Vertikalrichtung geneigt sind und deren Durchmesser dem Außendurchmesser der von ihnen aufzunehmenden Spritzen angepasst ist. In einer der Bohrungen ist eine Spritze gezeigt, die durch die Neigung gegen Aufschwimmen in dem Wasserbad gesichert ist. Sie umfasst einen Spritzenkörper 6 und einen Kolben 7 und ist von einem Kombistopfen 8 verschlossen, dessen Öffnungskanal durch einen herausnehmbaren Stift 9 ausgefüllt ist, dessen kantiges Ende in den Innenraum der Spritze ragt. Eine Tablette 10 befindet sich zusammen mit einer Applikationsflüssigkeit 11 in dem Innenraum der Spritze. Der Wasserspiegel des Bades 2 ist höher als der im Innenraum der Spritze. Sobald die Ultraschallerzeugung eingeschaltet ist, gelangen Ultraschallwellen zu dem Spritzeninhalt, zerstören den Zusammenhalt der die Tablette bildenden Partikeln und dispergieren sie.The device 1 forms a vessel for a water bath 2, whose wall is equipped with an ultrasonic sonotrode, not shown. The bath is closed with a removable lid 3, which is fixed by a bordering in the edge of the bath rim 4. It contains a series of bores 5, which are inclined at an angle of 30 ° with respect to the vertical direction and whose diameter is adapted to the outer diameter of the syringes to be absorbed by them. In one of the holes, a syringe is shown, which is secured by the tendency to float in the water bath. It comprises a syringe body 6 and a piston 7 and is closed by a combination stopper 8, the opening channel of which is filled by a removable pin 9 whose angular end projects into the interior of the syringe. A tablet 10 is located together with an application liquid 11 in the interior of the syringe. The water level of the bath 2 is higher than that in the interior of the syringe. As soon as the ultrasound generation is switched on, ultrasonic waves reach the syringe contents, destroy the syringe Cohesion of the particles forming the tablet and disperse them.

Claims (9)

  1. A syringe with a flexible wall for carrying out a method for the preparation of medicament suspensions for oral administration or for tube application, in which the medicament (10) is crushed in the syringe and is dispersed in an application fluid (11) in that the syringe, which contains the medicament (10) and at least part of the application fluid (11) and the walls of which are permeable to ultrasound, is exposed to an ultrasonic bath (2), characterised in that syringe contains an impact body (9).
  2. A syringe with a flexible wall for carrying out a method for the preparation of medicament suspensions for oral administration or for tube application, in which the medicament (10) is crushed in the syringe and is dispersed in an application fluid (11) in that the syringe, which contains the medicament and at least part of the application fluid (11) and the walls of which are permeable to ultrasound, is exposed to an ultrasonic bath (2), characterised in that the syringe lock contains a pin consisting of hard material as a vibration coupler between the ultrasonically moved part of the bath wall and the interior of the syringe, wherein the pin is in the form of an impact body (9).
  3. A syringe according to Claim 1 or 2, characterised in that it is a Luer-Lock syringe.
  4. A syringe according to any one of Claims 1 to 3, characterised in that it is a disposable syringe with a volume of 10 to 20 ml.
  5. A syringe according to any one of Claims 1 to 4, characterised in that the solid medicament (10) can be stored in the syringe.
  6. A syringe according to Claim 5, characterised in that the syringe is wholly or partly vented before closure.
  7. A syringe according to any one of Claims 1 to 6, characterised in that the syringe can be filled with application fluid (11) to 30 to 50 % of the syringe volume.
  8. A system for the preparation of medicament suspensions with an ultrasonic bath and a syringe according to any one of Claims 1 to 7, characterised in that the ultrasonic bath (2) has a cover (3) with a plurality of insertion holes (5) for the syringes, which are in the form of guides inclined to the vertical.
  9. A system according to Claim 8, characterised in that the ultrasonic bath (2) can be filled to a water level which is higher than that in the syringe used.
EP08011309A 2008-06-21 2008-06-21 Syringes for producing medicinal suspensions and related system Active EP2135666B1 (en)

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AT08011309T ATE547167T1 (en) 2008-06-21 2008-06-21 SYRINGES FOR PRODUCING MEDICINAL SUSPENSIONS AND SYSTEM RELATED THEREOF
EP08011309A EP2135666B1 (en) 2008-06-21 2008-06-21 Syringes for producing medicinal suspensions and related system

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EP08011309A EP2135666B1 (en) 2008-06-21 2008-06-21 Syringes for producing medicinal suspensions and related system

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Citations (1)

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US20060093644A1 (en) * 2004-08-20 2006-05-04 Gerhard Quelle Methods of administering microparticles combined with autologous body components

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DE935726C (en) * 1942-04-23 1955-11-24 Siemens Ag Process for dissolving substances in liquids using ultrasound
US5376072A (en) 1993-12-15 1994-12-27 Lake Medical Products, Inc. Apparatus for and method of, crushing a pill and administering the pill ingredients
ZA9811087B (en) * 1997-12-04 1999-06-03 Bracco Research Sa Automatic liquid injection system and method
DE60138934D1 (en) * 2000-02-25 2009-07-23 Hitachi Ltd Mixing device for automatic analyzer
JP3642713B2 (en) * 2000-02-29 2005-04-27 株式会社日立製作所 Automatic analyzer
US20040054286A1 (en) * 2001-11-05 2004-03-18 Audain Vaughn A Ultrasonic transducing probe with liquid flow-through capability and related automated workstation and methods of using same
US9174176B2 (en) 2003-01-09 2015-11-03 Disperse Systems, Inc. Ultrasonic dispersion apparatus, system, and method

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Publication number Priority date Publication date Assignee Title
US20060093644A1 (en) * 2004-08-20 2006-05-04 Gerhard Quelle Methods of administering microparticles combined with autologous body components

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