EP0227656A1 - Pharmaceutical compositions containing gels - Google Patents

Pharmaceutical compositions containing gels

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Publication number
EP0227656A1
EP0227656A1 EP85903649A EP85903649A EP0227656A1 EP 0227656 A1 EP0227656 A1 EP 0227656A1 EP 85903649 A EP85903649 A EP 85903649A EP 85903649 A EP85903649 A EP 85903649A EP 0227656 A1 EP0227656 A1 EP 0227656A1
Authority
EP
European Patent Office
Prior art keywords
active ingredient
prostaglandin
pluronic
agents
agent
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP85903649A
Other languages
German (de)
French (fr)
Inventor
Bernhard Better
Evelyn Grosse
Ingfried Zimmermann
Johannes-Wilhelm Tack
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.)
Bayer Pharma AG
Original Assignee
Schering 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
Application filed by Schering AG filed Critical Schering AG
Publication of EP0227656A1 publication Critical patent/EP0227656A1/en
Withdrawn legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0034—Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/557—Eicosanoids, e.g. leukotrienes or prostaglandins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers

Definitions

  • the invention relates to new gel formulations for therapeutic and diagnostic purposes and to a method for producing these formulations.
  • DE-OS 30 01 454 discloses lyophilisate formulations of hydroxyl-containing films with prostaglandins, which are converted into ready-to-use viscous solutions before use. The disadvantage of these formulations is that they form lumps which complicate the release of the active ingredient or prevent it.
  • DE-OS 33 07 816 describes lyophilisates of alkali polyacrylates which are mixed with aqueous solutions of prostaglandins. Although the active ingredient is released better from this formulation, the partially inhomogeneous incorporation of the active ingredient into such gels with a consistently high viscosity and above all the applicability of these gels by the user remains unsatisfactory.
  • the invention was based on the object of developing gel formulations for active ingredients with limited stability which are to be used in body cavities or on body surfaces.
  • CA 1072-413 (Derwent Publication No. 18422C / 11) specifies the possible uses of polyoxyethylene-polyoxypropylene block copolymers as carriers for pharmaceuticals for therapeutic or prophylactic use on the body surface or in body cavities.
  • the weight percentage of gel fractions is given as 15-50%.
  • the preferred range emerges from the exemplary embodiment with 30% by weight: 20% Pluronic F 127 and 10% Pluronic L 44 in aqueous solution.
  • Pluronic F-127 preparations can only be found for ophthalmic practice (DE-OS 27 03 152). It has now been found that for the therapeutic and diagnostic use of Pluronic F-127 gel formulations in body cavities or on body areas, the proportion of 18 to 19 percent by weight of Pluronic F-127 proves to be particularly advantageous in these formulations.
  • the invention also relates to a method for producing Pluronic F-127 gel formulations for therapeutic and diagnostic use.
  • Aqueous Pluronic F-127 solutions with a Pluronic F-127 content of 18-19 percent by weight are easily movable liquids with low viscosity at low and high temperatures and only form medium viscosity (20-50 ° C) highly viscous gels.
  • This reversible sol-gel process allows the dissolved active ingredient to be easily incorporated homogeneously into a cooled Pluronic F-127 solution and drawn into a suitable application system (e.g. syringe with catheter tube).
  • a highly viscous gel forms at the application site during and immediately after application.
  • Figure 1 shows the temperature-dependent viscosity behavior of Pluronic F-127 solutions with different proportions of Pluronic F-127. It can be seen from this figure that an optimal viscosity for the body temperature range is achieved with solutions whose Pluronic F-127 content is between 13 and 19 percent by weight. A 20% Pluronic F-127 solution has to be cooled lower than a 13-19% solution in order to dissolve the active ingredient.
  • Figure 2 in which the percentage of Pluronic F-127 was plotted against temperature, also shows why the 18-19% range is a particularly preferred range for galenical preparations.
  • Pluronic F-127 formulations of the present invention have the advantage over the gels based on cellulose derivatives which have hitherto been customary in that the active ingredient in the cool state has no particular properties. Cooling can be incorporated, that Pluronic F-127 can be sterilized without changing its gel behavior and that the polymer in Pluronic F-127 solutions has short-term stability. All Pluronic F-127 formulations are easy to apply when cool and guarantee intensive fogging of the mucous membrane before they heat up and form gel. Pluronic F-127 is a good gel-forming agent that is compatible with the mucous membrane, is toxicologically harmless and is absorbed by the body after some time.
  • the invention relates both to gel formulations with prostaglandins, steroid hormones, antifungals and antibiotics for theraneutic purposes and to gel formulations with X-ray contrast agents, ultrasound contrast agents and NMR contrast agents for diagnostic purposes.
  • the invention also relates to a method for producing gel formulations with the substances mentioned above.
  • the gel formulations according to the invention contain the
  • Active ingredient in the therapeutically or diagnostically effective dose which is well known for the active ingredients under consideration. If necessary, known and customary auxiliaries are added to the new formulations in galenics.
  • Pluronic F-127 are completely dissolved in 6.4g water (for injections) at a temperature of around 15 ° C.
  • the solution cooled to 10 ° C., is filtered through a membrane filter with a pore size of 1.2 ⁇ m, filled into 10 ml vials and sterilized in an autoclave at 120 ° C. for 20 minutes.
  • the Pluronic F-127 solutions are stored at temperatures below 8 ° C.
  • the contents of an ampoule containing 100 pg of the active ingredient 16-phenoxyprostaglandin-E 2 -methanesulfonamide with 2.0 ml of water are taken up and added to the vial with the cooled Pluronic F-127 solution. After briefly shaking, a clear, homogeneous solution is formed which gels at temperatures above 18 ° C.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Gynecology & Obstetrics (AREA)
  • Urology & Nephrology (AREA)
  • Reproductive Health (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicinal Preparation (AREA)

Abstract

On décrit des compositions pharmaceutiques ou des produits de diagnostic renfermant du Pluronic F-127 qui contiennent une quantité thérapeutique ou diagnostique active du principe actif et 18 à 19% pds de Pluronic F-127, formateur de gel ainsi qu'un procédé de préparation de ces produits.Disclosed are pharmaceutical compositions or diagnostic products comprising Pluronic F-127 which contain an active therapeutic or diagnostic amount of the active ingredient and 18 to 19 wt% of Pluronic F-127, gel former and a method of preparing these products.

Description

Gelhaltige pharmazeutische Zubereitungen Pharmaceutical preparations containing gel
Die Erfindung betrifft neue Gelformulierungen für therapeutische und diagnostische Zwecke sowie ein Verfahren zur Herstellung dieser Formulierungen.The invention relates to new gel formulations for therapeutic and diagnostic purposes and to a method for producing these formulations.
Aus der DE-OS 30 01 454 sind Lyophilisat-Formulierungen von Hydroxylgruppen-haltigen Folymeren mit Prostaglandinen bekannt, die vor der Applikation in gebrauchsfertige viskose Lösungen umgewandelt werden. Der Nachteil dieser Formulierungen ist, daß sich dabei Klürαpchen bilden, die die Freisetzung des Wirkstoffes erschweren oder sαgar verhindern. In der DE-OS 33 07 816 werden Lyophilisate von Alkalipolyacrylaten beschrieben, die mit wäßrigen Lösungen von Prostaglandinen versetzt werden. Aus dieser Formulierung wird der Wirkstoff zwar besser freigesetzt, unbefriedigend bleibt jedoch nach wie vor die zum Teil inhomogene Einarbeitung des Wirkstoffes in derartige Gele mit gleichbleibend hoher Yiskosität und vor allem die Applizierbarkeit dieser Gele durch den Anwender. Der Erfindung lag die Aufgabe zugrunde, Gelformulierungen für Wirkstoffe mit begrenzter Stabilität zu entwickeln, die in Körperhchlen oder an Körperflächen zur Anwendung kommen sollen.DE-OS 30 01 454 discloses lyophilisate formulations of hydroxyl-containing films with prostaglandins, which are converted into ready-to-use viscous solutions before use. The disadvantage of these formulations is that they form lumps which complicate the release of the active ingredient or prevent it. DE-OS 33 07 816 describes lyophilisates of alkali polyacrylates which are mixed with aqueous solutions of prostaglandins. Although the active ingredient is released better from this formulation, the partially inhomogeneous incorporation of the active ingredient into such gels with a consistently high viscosity and above all the applicability of these gels by the user remains unsatisfactory. The invention was based on the object of developing gel formulations for active ingredients with limited stability which are to be used in body cavities or on body surfaces.
In CA 1072-413 (Derwent-Publikations-Nr. 18422C/11) wird die Anwendungsmσglichkeit von Polyoxyethylen-Polyoxypropylen-Blockcopolymeren als Träger von Pharmazeutika für die therapeutische oder prophylaktische Anwendung an der Körperoberfläche oder in Körperhöhlen genannt. Der Gewichtsprozentanteil an Gel-Anteilen wird mit 15-50% angegeben. Der bevorzugte Bereich geht aus dem Ausführungsbeispiel mit 30- Gew.-% hervor: 20% Pluronic F 127 und 10% Pluronic L 44 in wäßriger Lösung.CA 1072-413 (Derwent Publication No. 18422C / 11) specifies the possible uses of polyoxyethylene-polyoxypropylene block copolymers as carriers for pharmaceuticals for therapeutic or prophylactic use on the body surface or in body cavities. The weight percentage of gel fractions is given as 15-50%. The preferred range emerges from the exemplary embodiment with 30% by weight: 20% Pluronic F 127 and 10% Pluronic L 44 in aqueous solution.
Weitere Angaben über die Verwendung von Pluronic F-127- Zubereitungen findet man nur noch für die ophthalmologische Praxis (DE-OS 27 03 152). Es wurde nun gefunden, daß sich für die therapeutische und diagnostische Anwendung von Pluronic F-127-Gelformulierungen in Körperhöhlen oder an Körperflächen der Anteil von 18 bis 19 Gewichtsprozente an Pluronic F-127 als besonders vorteilhaft in diesen Formulierungen erweist. Die Erfindung betrifft auch ein Verfahren zur Herstellung von Pluronic F-127-Gelformulierungen für die therapeutische und diagnostische Anwendung.Further information on the use of Pluronic F-127 preparations can only be found for ophthalmic practice (DE-OS 27 03 152). It has now been found that for the therapeutic and diagnostic use of Pluronic F-127 gel formulations in body cavities or on body areas, the proportion of 18 to 19 percent by weight of Pluronic F-127 proves to be particularly advantageous in these formulations. The invention also relates to a method for producing Pluronic F-127 gel formulations for therapeutic and diagnostic use.
Wäßrige Pluronic F-127-Lösungen mit einem Pluronic F-127-Anteil von 18-19 Gewichtsprozenten sind bei tiefen und hohen Temperaturen leicht bewegliche Flüssigkeiten mit niedriger Viskosität und nur bei mittleren Temperaturen (20-50°C) bilden sie hochviskose Gele. Dieses reversible Sol-Gel- Verhajfen erlaubt es, den gelösten Wirkstoff leicht in eine gekühlte Pluronic F-127-Lösung homogen einzuarbeiten und in ein geeignetes Applikationssystem aufzuziehen (z.B. Spritze mit Katheterschlauch). Während und unmittelbar nach der Anwendung bildet sich am Applikationsort ein hochviskoses Gel.Aqueous Pluronic F-127 solutions with a Pluronic F-127 content of 18-19 percent by weight are easily movable liquids with low viscosity at low and high temperatures and only form medium viscosity (20-50 ° C) highly viscous gels. This reversible sol-gel process allows the dissolved active ingredient to be easily incorporated homogeneously into a cooled Pluronic F-127 solution and drawn into a suitable application system (e.g. syringe with catheter tube). A highly viscous gel forms at the application site during and immediately after application.
In Abbildung 1 ist das Temperatur-abhängige Viskositätsverhalten von Pluronic F-127-Lösungen mit unterschiedlichen Anteilen an Pluronic F-127 graphisch dargestellt. Man erkennt aus dieser Abbildung, daß eine optimale Viskosität für den Körpertemperaturbereich mit Lösungen erreicht wird, deren Anteil an Pluronic F-127 zwischen 13 und 19 Gewichtsprozente liegt. Eine 20%ige Pluronic F-127-Lösung muß, um den Wirkstoff in Lösung zu bringen, bereits tiefer gekühlt werden als eine 13-19%ige Lösung. Abbildung 2, in der der prozentuale Anteil an Pluronic F-127 gegen die Temperatur aufgetragen wurde, verdeutlicht ebenfalls, warum der Bereich 18-19% ein besonders bevorzugter Bereich für galenische Zubereitungen ist. Alle Lösungen mit einem Anteil von 13-19% Pluronic F-127 liegen im Körpertemperaturbereich von 37°C als Gel vor und müssen zur Lösung des Wirkstoffes nicht unter 17°C gekühlt werden. Die Viskositäten wurden mittels eines Rotationsviskosimeters (Haake Viskotester VT02) gemessen.Figure 1 shows the temperature-dependent viscosity behavior of Pluronic F-127 solutions with different proportions of Pluronic F-127. It can be seen from this figure that an optimal viscosity for the body temperature range is achieved with solutions whose Pluronic F-127 content is between 13 and 19 percent by weight. A 20% Pluronic F-127 solution has to be cooled lower than a 13-19% solution in order to dissolve the active ingredient. Figure 2, in which the percentage of Pluronic F-127 was plotted against temperature, also shows why the 18-19% range is a particularly preferred range for galenical preparations. All solutions with a share of 13-19% Pluronic F-127 are in the body temperature range of 37 ° C as a gel and do not need to be cooled below 17 ° C to dissolve the active ingredient. The viscosities were measured using a rotary viscometer (Haake Viskotester VT02).
Pluronic F-127-Formulierungen der vorliegenden Erfindung haben gegenüber den bisher üblichen Gelen auf der Basis von Zellulosederivaten den Vorteil, daß der Wirkstoff in kühlem Zustand ohne besondere. Kühlung eingearbeitet werden kann, daß Pluronic F-127 sterilisiert werden kann, ohne sein Gel-Verhalten zu verändern und daß der V/irkstoff in Pluronic F-127-Lösungen eine Kurzzeitstabilität besitzt. Alle Pluronic F-127-Formulierungen sind in kühlem Zustand leicht applizierbar und garantieren vor ihrer Erwärmung und Gelbildung einen intensiven Schleimhautkontrast- Beschlag. Pluronic F-127 stellt einen guten Schleimhautverträglichen Gelbildner dar, der toxilogisch unbedenklich ist und vom Körper nach einiger Zeit resorbiert wird.Pluronic F-127 formulations of the present invention have the advantage over the gels based on cellulose derivatives which have hitherto been customary in that the active ingredient in the cool state has no particular properties. Cooling can be incorporated, that Pluronic F-127 can be sterilized without changing its gel behavior and that the polymer in Pluronic F-127 solutions has short-term stability. All Pluronic F-127 formulations are easy to apply when cool and guarantee intensive fogging of the mucous membrane before they heat up and form gel. Pluronic F-127 is a good gel-forming agent that is compatible with the mucous membrane, is toxicologically harmless and is absorbed by the body after some time.
Die Erfindung betrifft sowohl Gelformulierungen mit Prostaglandinen, Steroidhormonen, Antimykotika und Antibiotika für theraneutische Zwecke als auch Gelformulierungen mit Röntgenkontrastmitteln, Ultraschallkontrastmitteln und NMR-Kontrastmitteln für diagnostische Zwecke. Die Erfindung betrifft ebenso ein Verfahren zur Herstellung von Gelformulierungen mit den oben genannten Substanzen. Die erfindungsgemäßen Gelformulierungen enthalten denThe invention relates both to gel formulations with prostaglandins, steroid hormones, antifungals and antibiotics for theraneutic purposes and to gel formulations with X-ray contrast agents, ultrasound contrast agents and NMR contrast agents for diagnostic purposes. The invention also relates to a method for producing gel formulations with the substances mentioned above. The gel formulations according to the invention contain the
Wirkstoff in der therapeutisch oder diagnostisch wirksamen Dosis, die für die in Betracht kommenden Wirkstoffe hinlänglich bekannt ist. Gegebenfalls werden den neuen Formulierungen in der Galenik bekannte und übliche Hilfsstoffe hinzugefügt.Active ingredient in the therapeutically or diagnostically effective dose, which is well known for the active ingredients under consideration. If necessary, known and customary auxiliaries are added to the new formulations in galenics.
Die vaginale Anwendung von Sulproston (16-Phenoxy-prosta- glandin-E2-methansulfonamid)-haltigem Pluronic F-127-Gel bei graviden Meerschweinchen führte stets zu einem raschen Einsetzen von Uteruskontraktionen. Die überwiegende Zahl der behandelten Tiere abortierte. Die vorliegende Erfindung wird durch die folgenden Beisυiele verdeutlicht, ohne dadurch begrenzt zu werden.The vaginal application of Pluronic F-127 gel containing Sulproston (16-phenoxy-prostaglandin-E 2 -methanesulfonamide) to gravid guinea pigs always led to a rapid onset of uterine contractions. The majority of the animals treated aborted. The present invention is illustrated by the following examples, without being limited thereby.
Beispiel 1example 1
1,9g Pluronic F-127 werden bei einer Temperatur von etwa 15°C in 6,4g Wasser (für Injektionszwecke) vollständig gelöst. Die auf 10°C gekühlte Lösung wird über ein Membranfilter mit 1,2 Um Porenweite filtriert, in 10 ml Vials abgefüllt und bei 120°C 20 Minuten im Autoklaven sterilisiert. Die Pluronic F-127-Lösungen werden bei Temperaturen unter 8°C gelagert. Zur Herstellung der Wirkstoffhaltigen gebrauchsfertigen Formulierung wird der Inhalt einer Ampulle mit 100 pg des Wirkstoffes 16-Phenoxyprostaglandin-E2-methansulfonamid mit 2,0 ml Wasser (für Injektionszwecke) aufgenommen und in das Vial mit der gekühlten Pluronic F-127-Lösung gegeben. Nach kurzem Schütteln entsteht eine klare homogene Lösung, die bei Temperaturen oberhalb 18°C geliert.1.9g Pluronic F-127 are completely dissolved in 6.4g water (for injections) at a temperature of around 15 ° C. The solution, cooled to 10 ° C., is filtered through a membrane filter with a pore size of 1.2 μm, filled into 10 ml vials and sterilized in an autoclave at 120 ° C. for 20 minutes. The Pluronic F-127 solutions are stored at temperatures below 8 ° C. To prepare the ready-to-use formulation containing the active ingredient, the contents of an ampoule containing 100 pg of the active ingredient 16-phenoxyprostaglandin-E 2 -methanesulfonamide with 2.0 ml of water (for injection purposes) are taken up and added to the vial with the cooled Pluronic F-127 solution. After briefly shaking, a clear, homogeneous solution is formed which gels at temperatures above 18 ° C.
Beispiel 2Example 2
64,6 g demineralisiertes Wasser werden auf 45 bis 50°C erwärmt, darauf nacheinander 29,9 g Amidotrizoesäure, 8,0g Keglumin, 0,32 g Natriumhydroxid und 0,04 g Dinatriummedetat eingebracht und unter Konstanthaltung der Temperatur (45-50°C) gelöst. In die auf etwa 10°C abgekühlte Lösung wird 23,1 g Pluronic F-127 eingetragen und unter gelegentlichem Umrühren bis zur vollständigen Lösung des Gelbildners bei KühlSchranktemperatur gelagert. Nach dem Filtrieren entsteht eine klare farblose bis schwach gelbe Lösung, die bei Temperaturen oberhalb 18°C geliert. 64.6 g of demineralized water are heated to 45 to 50 ° C., then 29.9 g of amidotrizoic acid, 8.0 g of keglumine, 0.32 g of sodium hydroxide and 0.04 g of disodium medate are introduced in succession and the temperature is kept constant (45-50 ° C) solved. 23.1 g of Pluronic F-127 are introduced into the solution, which has cooled to about 10 ° C., and are stored with occasional stirring until the gel former has completely dissolved at the refrigerator temperature. After filtering, a clear colorless to pale yellow solution is formed, which gels at temperatures above 18 ° C.

Claims

PatentansprücheClaims
1) Pluronic F-127-haltige Arzneimittel oder diagnostische Mittel, enthaltend eine therapeutisch oder diagnostisch wirksame Menge eines Wirkstoffes und 18-19 Gewichtsprozente des Gelbildners Pluronic F-127.1) Pluronic F-127-containing medicinal product or diagnostic agent, containing a therapeutically or diagnostically effective amount of an active ingredient and 18-19 percent by weight of the gelling agent Pluronic F-127.
2) Arzneimittel für intravaginale und/oder intrazervikale Anwendung gemäß Anspruch 1, dadurch gekennzeichnet, daß der Wirkstoff ein Prostaglandin darstellt.2) Medicament for intravaginal and / or intracervical use according to claim 1, characterized in that the active ingredient is a prostaglandin.
3) Arzneimittel gemäß Anspruch 2, dadurch gekennzeichnet, daß das Prostaglandin Prostaglandin-E2 oder ein Derivat davon darstellt3) Medicament according to claim 2, characterized in that the prostaglandin is prostaglandin E 2 or a derivative thereof
4) Arzneimittel gemäß Anspruch 3, dadurch gekennzeichnet, daß das Prostaglandin-E2-Derivat 16-Phenoxy-prostaglandin-E2-N-methansulfonamid darstellt.4) Medicament according to claim 3, characterized in that the prostaglandin E2 derivative is 16-phenoxy-prostaglandin E 2 -N-methanesulfonamide.
5) Diagnostisches Mittel gemäß Anspruch 1, dadurch gekennzeichnet, daß der Wirkstoff ein Kontrastmittel ist.5) Diagnostic agent according to claim 1, characterized in that the active ingredient is a contrast agent.
6) Diagnostisches Mittel gemäß Anspruch 1, dadurch gekennzeichnet, daß der Wirkstoff ein jodhaltiges Röntgenkontrastmittel ist.6) Diagnostic agent according to claim 1, characterized in that the active ingredient is an iodine-containing X-ray contrast agent.
7) Diagnostisches Mittel gemäß Anspruch 1, dadurch gekennzeichnet, daß der Wirkstoff ein Ultraschall- oder NMR- Kontrastmittel ist.7) Diagnostic agent according to claim 1, characterized in that the active ingredient is an ultrasound or NMR contrast agent.
8) Arzneimittel gemäß Anspruch 1, dadurch gekennzeichnet, daß der Wirkstoff ein Antibiotikum oder Antimykotikkm ist. 9) Arzneimittel gemäß Anspruch 1, dadurch gekennzeichnet, daß der Wirkstoff ein δstrogenes Steroidhormon ist.8) Medicament according to claim 1, characterized in that the active ingredient is an antibiotic or antifungal km. 9) Medicament according to claim 1, characterized in that the active substance is a δstrogenes steroid hormone.
10) Verwendung von Mitteln, enthaltend Pluronic F-127 und Prostaglandin E2-Derivatεn, zur Abortvorbereitung.10) Use of agents containing Pluronic F-127 and prostaglandin E 2 derivatives to prepare for abortion.
11) Verwendung eines Mittels, bestehend aus Pluronic F-127 und Prostaglandin E2 zur Geburtseinleitung.11) Use of an agent consisting of Pluronic F-127 and prostaglandin E 2 for induction of labor.
12) Verwendung von Mitteln, bestehend aus Pluronic F-127 und einem Kontrastmittel, für Diagnoseverfahren.12) Use of agents consisting of Pluronic F-127 and a contrast agent for diagnostic procedures.
13) Verfahren zur Herstellung von Pluronic F-127-haltigen Mitteln, enthaltend eine therapeutisch oder diagnostisch wirksame Menge eines Wirkstoffes und 18-19 Gewichtsprozente des Gelbildners Pluronic F-127.13) Process for the preparation of Pluronic F-127-containing agents, containing a therapeutically or diagnostically effective amount of an active ingredient and 18-19 percent by weight of the gelling agent Pluronic F-127.
14) Verfahren zur Herstellung von Mitteln für intravaginale und/oder intrazervikale Anwendung gemäß Anspruch 1, dadurch gekennzeichnet, daß der Wirkstoff ein Prostaglandin darstellt.14) Process for the preparation of agents for intravaginal and / or intracervical use according to claim 1, characterized in that the active ingredient is a prostaglandin.
15) Verfahren zur Herstellung von Mitteln gemäß Anspruch 2, dadurch gekennzeichnet, daß das Prostaglandin Prostaglandin-E2 oder ein Derivat davon darstellt.15) Process for the preparation of agents according to claim 2, characterized in that the prostaglandin is prostaglandin E 2 or a derivative thereof.
16) Verfahren zur Herstellung von Mitteln gemäß Anspruch 3, dadurch gekennzeichnet, daß das Prostaglandin-E2-Derivat16) Process for the preparation of agents according to claim 3, characterized in that the prostaglandin E 2 derivative
16-Phenoxy-prostaglandin-E2-N-methansulfonamid darstellt.16-Phenoxy-prostaglandin-E 2 -N-methanesulfonamide.
17) Verfahren zur Herstellung eines diagnostischen Mittels gemäß Anspruch 1, dadurch gekennzeichnet, daß der Wirkstoff ein Kontrastmittel ist. 18) Verfahren zur Herstellung eines diagnostischen Mittels gemäß Anspruch 1, dadurch gekennzeichnet, daß der Wirkstoff ein jodhaltiges Röntgenkontrastmittel ist.17) Method for producing a diagnostic agent according to claim 1, characterized in that the active ingredient is a contrast agent. 18) Method for producing a diagnostic agent according to claim 1, characterized in that the active ingredient is an iodine-containing X-ray contrast agent.
19) Verfahren zur Herstellung eines diagnostrischen Mittels gemäß Anspruch 1, dadurch gekennzeichnet, daß der Wirkstoff ein Ultraschall- oder NMR-Kontrastmittel ist.19) Method for producing a diagnostic agent according to claim 1, characterized in that the active ingredient is an ultrasound or NMR contrast agent.
20) Verfahren zur Herstllung von Mitteln gemäß Anspruch 1, dadurch gekennzeichnet, daß der Wirkstoff ein Antibiotikum oder Antimykotikum ist.20) Process for the preparation of agents according to claim 1, characterized in that the active ingredient is an antibiotic or antifungal.
21) Verfahren zur Herstellung von Mitteln gemäß Anspruch 1, dadurch gekennzeichnet, daß der Wirkstoff ein östrogenes Steroidhormon ist. 21) Process for the preparation of agents according to claim 1, characterized in that the active ingredient is an estrogenic steroid hormone.
EP85903649A 1984-07-27 1985-07-18 Pharmaceutical compositions containing gels Withdrawn EP0227656A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE3428264 1984-07-27
DE19843428264 DE3428264A1 (en) 1984-07-27 1984-07-27 VALID PHARMACEUTICAL PREPARATIONS

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EP0227656A1 true EP0227656A1 (en) 1987-07-08

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Application Number Title Priority Date Filing Date
EP85903649A Withdrawn EP0227656A1 (en) 1984-07-27 1985-07-18 Pharmaceutical compositions containing gels

Country Status (8)

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EP (1) EP0227656A1 (en)
JP (1) JPS61502817A (en)
AU (1) AU4672385A (en)
DE (1) DE3428264A1 (en)
DK (1) DK111686A (en)
ES (1) ES8705763A1 (en)
IL (1) IL75921A0 (en)
WO (1) WO1986000813A1 (en)

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CA2011423A1 (en) * 1989-03-07 1990-09-07 Peter M. Taylor Pharmaceutical compositions useful as drug delivery vehicles and/or as wound dressings
JP2926749B2 (en) * 1989-04-25 1999-07-28 吉富製薬株式会社 Prostaglandin-containing liquid composition
CA2040460C (en) * 1990-05-01 1997-06-10 Tacey X. Viegas Drug delivery with thermoreversible gels
US5593683A (en) * 1990-05-01 1997-01-14 Mdv Technologies, Inc. Method of making thermoreversible polyoxyalkylene gels
US5948387A (en) * 1990-06-01 1999-09-07 Imarx Pharmaceutical Corp. Contrast media for ultrasonic imaging
WO1994028872A1 (en) * 1993-06-04 1994-12-22 Warner-Lambert Company Non-alcoholic cold and sinus medication
JP2909876B2 (en) * 1994-01-24 1999-06-23 恭弘 小川 Contrast agent
US6312667B1 (en) 1998-11-12 2001-11-06 3M Innovative Properties Company Methods of etching hard tissue in the oral environment
US6669927B2 (en) 1998-11-12 2003-12-30 3M Innovative Properties Company Dental compositions
US6312666B1 (en) 1998-11-12 2001-11-06 3M Innovative Properties Company Methods of whitening teeth
US6620405B2 (en) 2001-11-01 2003-09-16 3M Innovative Properties Company Delivery of hydrogel compositions as a fine mist
US11383870B2 (en) * 2018-07-12 2022-07-12 Elena Valentinovna ARSHINTSEVA Thermal method for sterilizing poloxamer comprising liquid drugs

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US3852210A (en) * 1972-08-11 1974-12-03 Flow Pharma Inc Stable liquid detergent concentrates containing active oxygen
CA1051776A (en) * 1974-08-09 1979-04-03 Murray W. Winicov Poloxamer-iodine gel
US4100271A (en) * 1976-02-26 1978-07-11 Cooper Laboratories, Inc. Clear, water-miscible, liquid pharmaceutical vehicles and compositions which gel at body temperature for drug delivery to mucous membranes
CA1072413A (en) * 1976-07-13 1980-02-26 West Laboratories Poloxamer gel systems with gelling temperatures higher than room temperature
US4365516A (en) * 1978-01-06 1982-12-28 Rockwell International Corporation Ultrasonic couplant gel compositions and method for employing same
DE2966768D1 (en) * 1978-12-19 1984-04-12 Byk Gulden Lomberg Chem Fab Solutions of x-ray contrast agents
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Non-Patent Citations (1)

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See references of WO8600813A1 *

Also Published As

Publication number Publication date
IL75921A0 (en) 1985-12-31
ES8705763A1 (en) 1987-06-01
JPS61502817A (en) 1986-12-04
DK111686D0 (en) 1986-03-11
WO1986000813A1 (en) 1986-02-13
DK111686A (en) 1986-03-11
AU4672385A (en) 1986-02-25
ES545616A0 (en) 1987-06-01
DE3428264A1 (en) 1986-03-06

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