WO1993015715A1 - Asthma or lung aerosol preparations containing lecithin - Google Patents

Asthma or lung aerosol preparations containing lecithin Download PDF

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Publication number
WO1993015715A1
WO1993015715A1 PCT/EP1993/000201 EP9300201W WO9315715A1 WO 1993015715 A1 WO1993015715 A1 WO 1993015715A1 EP 9300201 W EP9300201 W EP 9300201W WO 9315715 A1 WO9315715 A1 WO 9315715A1
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Prior art keywords
dncg
fenoterol
salbutamol
preparation according
reproterol
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PCT/EP1993/000201
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German (de)
French (fr)
Inventor
Kurt H. Bauer
Gieselher Warnke
Original Assignee
IG Sprühtechnik GmbH
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Publication of WO1993015715A1 publication Critical patent/WO1993015715A1/en

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    • 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
    • A61K9/007—Pulmonary tract; Aromatherapy
    • A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
    • A61K9/008—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy comprising drug dissolved or suspended in liquid propellant for inhalation via a pressurized metered dose inhaler [MDI]

Definitions

  • the present invention relates to an aerosol preparation which, in addition to the customary antiasthmatic active ingredients, contains lecithins or phospholipids as auxiliaries, a process for producing aerosol cans which contain such aerosol preparations, and the use of these spray aerosols.
  • spray aerosols has been found to be particularly beneficial in the treatment of asthma, allergic bronchitis and other respiratory diseases. They have proven particularly useful in the treatment of shortness of breath.
  • the patient With a spray directed into the mouth opening, the patient can administer a relatively precisely metered amount of the active substance (s), which is finely atomized as an aerosol, the active substances being held in the mouth and throat, or in the trachea, the bronchi, depending on the particle size and finally get into the alveoli.
  • active substance s
  • Anti-asthmatic aerosol preparations usually contain one or more active ingredients as a suspension in micronized form, but also in dissolved form. If lecithins are added to the aerosol preparations in addition to the active ingredients, liposomes which are friendly to lung tissue and mucous membranes and which contain the active ingredient are formed when sprayed. Various problems arise in aerosol preparations of this type which are formulated as propellants using the physiologically inert, non-flammable and therefore particularly preferred in such cases.
  • the aerosol preparation is in the form of a heterogeneous dispersion, for example suspension, emulsion or a mixture of these two systems, because of the poor water solubility of these propellant gases. If an active ingredient is neither soluble in water nor in the propellant gases, then it is emulsified or suspended in this preparation and not dissolved available. In order to prevent inhomogeneity in the application, sufficient shaking of the aerosol must be ensured by intensive shaking before each inhalation. The fineness of such emulsions or the suspensions or the suspended particles not only determines the dosing accuracy, but also the pulmonary gait and thus the therapeutic effectiveness to a decisive degree.
  • the object of the invention is to eliminate the disadvantages of these spray aerosols known from the prior art.
  • a practically clear, homogeneous, colloidal or molecularly disperse solution should therefore preferably be provided.
  • substances such as middle-chain triglycerides (eg miglyol, myritol), fatty acid esters of lower alcohols (eg isopropyl myristate, isopropyl stearate, ethyl oleate) and partially acetylated glycerides (eg lauryl acetylglyceride), preferably a lipophilic or castor oil or preferably a castor oil or castor oil, can also be used as absorption promoters and as lipophilic solvents Agent, for example Tween 80 (Polysorbate 80) or Tween 20 (Polysorbate 20), Span or Arlacel 20 (Sorbitan fatty acid ester), triacetin, DMSO, PEG, glycerol fatty acid ester or the like in
  • the aerosol preparations according to the invention can also contain cholesterol and / or tocopoferol.
  • Another advantage of the aerosol preparations according to the invention is that the use of dimethyl ether instead of the CFC propellants also improves the environmental compatibility of the sprays.
  • the aerosol preparations according to the invention can be composed, for example, as follows:
  • a typical preparation of the aerosol solution according to the invention is composed as follows:
  • beclo ethasone (0.1-1.0%), budesonide (0.1-1.0%), DNCG (1.0-5.0%), fenoterol (0 , 1-1.0%), ipratropium bromide (0.05-0.5%), salbutamol (0.2-1.0%), reproterol (0.5-2.5%) and terbutaline (1.0 -2.5%).
  • beclomethasone and salbutamol, DNCG and fenoterol, DNCG and reproterol, DNCG and salbutamol or fenoterol and ipratropium bromide can also be used advantageously.
  • difatty acid phosphatidylcholines difatty acid phosphatidylglycerol, dipalmitoylphosphatidylcholine and stearoylpalmitoylphosphatidylglycerol can also be used.
  • a predetermined fill weight e.g. 3 grams of this preparation (solution) are filled through the valve of an airtight sealed (crimped) aerosol can in compliance with the prescribed filling accuracy.
  • the liquefied dimethyl ether is then introduced through the valve under pressure.
  • the amount of dimethyl ether to be refilled depends on the target weight. It can be between 50 to 300 percent by weight of the amount of filler.
  • the amount of diethyl ether is advantageously between 100 and 200 percent by weight per amount of filler.
  • the weight ratio between active ingredient solution and dimethyl ether is consequently between 1: 0.5 and 1: 3, preferably between 1: 1 and 1: 2.

Abstract

The invention concerns an aerosol preparation which, in addition to the usual anti-asthmatic active substances, contains lecithins or phospholipids as additives. The invention also concerns a method of producing aerosol cans containing such preparations, and the use of these aerosols.

Description

Asthma oder Pulmonal-Aerosolzubereitungen mit Lecithin Asthma or pulmonary aerosol preparations with lecithin
Gegenstand der vorliegenden Erfindung ist eine Aerosolzubereitung, die neben den gebräuchlichen antiasthmatischen Wirkstoffen Lecithine oder Phospholipide als Hilfsstoffe enthält, ein Verfahren zur Herstellung von Aerosoldosen, die solche Aerosolzubereitungen enthalten, sowie die Verwendung dieser Sprühaerosole.The present invention relates to an aerosol preparation which, in addition to the customary antiasthmatic active ingredients, contains lecithins or phospholipids as auxiliaries, a process for producing aerosol cans which contain such aerosol preparations, and the use of these spray aerosols.
Die Verwendung von Sprühaerosolen hat sich bei der Behandlung von Asthma, allergischer Bronchitis und anderer Atemwegserkrankungen als besonders vorteilhaft erwiesen. Insbesondere bei der Behandlung von Atemnot haben sie sich bewährt. Durch einen in die Mundöffnung gerichteten Sprühstoß kann sich der Patient eine relativ genau dosierte und als Aerosol feinst zerstäubte Menge an Wirkstoff (en) verabreichen, wobei die Wirkstoffe je nach Teilchengröße in Mund- und Rachenraum festgehalten werden, bzw. in die Luftröhre, die Bronchien und schließlich in die Alveolen gelangen.The use of spray aerosols has been found to be particularly beneficial in the treatment of asthma, allergic bronchitis and other respiratory diseases. They have proven particularly useful in the treatment of shortness of breath. With a spray directed into the mouth opening, the patient can administer a relatively precisely metered amount of the active substance (s), which is finely atomized as an aerosol, the active substances being held in the mouth and throat, or in the trachea, the bronchi, depending on the particle size and finally get into the alveoli.
Antiasthmatische Aerosolzubereitungen enthalten in der Regel einen oder mehrere Wirkstoffe als Suspension in mikronisierter Form, aber auch in gelöster Form. Werden den Aerosolzubereitungen neben den Wirkstoffen noch Lecithine zugesetzt, so bilden sich beim Versprühen lungengewebε- und schleimhaut-freundliche Liposome, die den Wirkstoff enthalten. Bei derartigen Aerosolzubereitungen, die unter Verwendung der physiologisch inerten, nicht brennbaren und daher in solchen Fällen besonders bevorzugten Fluorkohlenwasseεtoffe als Treibmittel formuliert werden, treten verschiedene Probleme auf. Bei den üblicherweise als Treibgase verwendeten Fluorchlorkohlenwasserstoffen wie Trichlorfluormethan, Dichlor- tetrafluorethan und Dichlorfluormethan liegt die Aerosol¬ zubereitung wegen der schlechten Wasserlöslichkeit dieser Treibgase als heterogene Dispersion, z.B. Suspension, Emulsion oder einem Gemisch dieser beiden Systeme vor. Ist ein Wirkstoff weder in Wasser noch in den Treibgasen löslich, dann wird er in dieser Zubereitung emulgiert bzw. suspendiert und nicht gelöst vorliegen. Um einer Inhomogenität bei der Applikation vorzubeugen, muß durch intensives Schütteln vor jeder Inhalation für eine ausreichende Gleichmäßigkeit des Aerosols gesorgt werden. Die Feinheit solcher Emulsionen oder der Suspensionen bzw. der suspendierten Partikel bestimmt nämlich nicht nur die Dosiergenauigkeit, sondern auch die Lungengangigke.i und damit die therapeutische Wirksamkeit in entscheidendem Maße.Anti-asthmatic aerosol preparations usually contain one or more active ingredients as a suspension in micronized form, but also in dissolved form. If lecithins are added to the aerosol preparations in addition to the active ingredients, liposomes which are friendly to lung tissue and mucous membranes and which contain the active ingredient are formed when sprayed. Various problems arise in aerosol preparations of this type which are formulated as propellants using the physiologically inert, non-flammable and therefore particularly preferred in such cases. In the case of the chlorofluorocarbons usually used as propellant gases, such as trichlorofluoromethane, dichlorotetrafluoroethane and dichlorofluoromethane, the aerosol preparation is in the form of a heterogeneous dispersion, for example suspension, emulsion or a mixture of these two systems, because of the poor water solubility of these propellant gases. If an active ingredient is neither soluble in water nor in the propellant gases, then it is emulsified or suspended in this preparation and not dissolved available. In order to prevent inhomogeneity in the application, sufficient shaking of the aerosol must be ensured by intensive shaking before each inhalation. The fineness of such emulsions or the suspensions or the suspended particles not only determines the dosing accuracy, but also the pulmonary gait and thus the therapeutic effectiveness to a decisive degree.
Der Erfindung liegt die Aufgabe zugrunde, die Nachteile dieser aus dem Stand der Technik bekannten Sprühaerosole zu beseitigen. Es sollte deshalb vorzugsweise eine praktisch klare, homogene, kolloid- oder molekulardisperse Lösung bereitgestellt werden.The object of the invention is to eliminate the disadvantages of these spray aerosols known from the prior art. A practically clear, homogeneous, colloidal or molecularly disperse solution should therefore preferably be provided.
Es wurde überraschend gefunden, daß bei Ersatz der Fluorchlorkohlenwasserstoffe als Treibgas durch Dimethylether die Formulierungen praktisch als homogene, molekulardisperse Lösungen zu erhalten sind. Die obengenannten Nachteile entfallen. Von besonderer Bedeutung ist weiterhin, daß Dimethylether aufgrund seiner geringen Lipophilität bzw. wegen seiner Hydrophilität zu einer verbesserten Resorption des Wirkstoffs beiträgt. Eine weitere Verbesserung der erfindungsgemäßen Formulierungen wird durch den Zusatz von Wasser oder hydrophilen Lösungsmitteln, wie Alkoholen, beispielsweise Ethanol, erzielt. Ethanol kann aber auch ganz oder teilweise durch mehrwertige Alkohole wie Propylenglykol , Glycerol oder Etheralkohole, wie beispielsweise Polyethylenglykol , ersetzt werden. Diese Zusätze verbessern die physiologische Unbedenklichkeit und erhöhen darüberhinaus auch die Lungenverträglichkeit des Therapeutikums . Weiterhin können als Resorptionsförderer und als lipophile Lösungsmittel auch noch Stoffe wie ittelkettige Triglyceride , (z.B. Miglyol, Myritol) , Fettsäureester niederer Alkohole (z.B. Isopropylmyristat , Isopropylstearat , Ethyloleat) und teilacetylierte Glyceride (z.B. Laurylacetylglycerid) , vorzugsweise Rizinusöl bzw. ein lipophiles oder a phiphiles Agenz, beispielsweise Tween 80 (Polysorbat 80) oder Tween 20 (Polysorbat 20) , Span oder Arlacel 20 (Sorbitan-Fettsäureester) , Triacetin, DMSO, PEG, Glycerol-fettsaurerester oder ähnliches inIt has surprisingly been found that when the chlorofluorocarbons are replaced as propellant by dimethyl ether, the formulations can be obtained practically as homogeneous, molecularly disperse solutions. The disadvantages mentioned above are eliminated. It is also of particular importance that dimethyl ether, because of its low lipophilicity or because of its hydrophilicity, contributes to an improved absorption of the active ingredient. A further improvement of the formulations according to the invention is achieved by adding water or hydrophilic solvents, such as alcohols, for example ethanol. However, ethanol can also be wholly or partly replaced by polyhydric alcohols such as propylene glycol, glycerol or ether alcohols such as polyethylene glycol. These additives improve the physiological safety and also increase the lung tolerance of the therapeutic agent. Furthermore, substances such as middle-chain triglycerides (eg miglyol, myritol), fatty acid esters of lower alcohols (eg isopropyl myristate, isopropyl stearate, ethyl oleate) and partially acetylated glycerides (eg lauryl acetylglyceride), preferably a lipophilic or castor oil or preferably a castor oil or castor oil, can also be used as absorption promoters and as lipophilic solvents Agent, for example Tween 80 (Polysorbate 80) or Tween 20 (Polysorbate 20), Span or Arlacel 20 (Sorbitan fatty acid ester), triacetin, DMSO, PEG, glycerol fatty acid ester or the like in
ERSATZBLATT Mengen von etwa 5-20% bezogen auf die Wirkstoffdosis, eingesetzt werden. Zusätzlich können die erfindungsgemäßen Aerosolzubereitungen noch Choleεterol und/oder Tocoferol enthalten.REPLACEMENT LEAF Amounts of about 5-20% based on the dose of active ingredient are used. In addition, the aerosol preparations according to the invention can also contain cholesterol and / or tocopoferol.
Ein weiterer Vorteil der erfindungsgemäßen Aerosolzubereitungen besteht darin, daß durch die Verwendung des Dimethylethers anstelle der FCKW-Treibmittel auch die Umweltverträglichkeit der Sprays verbessert wird.Another advantage of the aerosol preparations according to the invention is that the use of dimethyl ether instead of the CFC propellants also improves the environmental compatibility of the sprays.
Die erfindungsgemäßen Aerosolzubereitungen können beispielsweise folgendermaßen zusammengesetzt sein:The aerosol preparations according to the invention can be composed, for example, as follows:
Wirkstoffactive substance
Sojalecithin S 100 (Lipoid)Soy Lecithin S 100 (Lipoid)
CholesterolCholesterol
Tocoferol
Figure imgf000005_0001
Tocoferol
Figure imgf000005_0001
Wasser ad 100,0 %Water ad 100.0%
Ethanol (96 %ig) 26,0 - 42,0 %;Ethanol (96%) 26.0-42.0%;
Wirkstoffactive substance
EilecithinEgg lecithin
CholesterolCholesterol
TocoferolTocoferol
Wasserwater
EthanolEthanol
Rizinusölcastor oil
Wirkstoffactive substance
LecithinLecithin
Tocoferol
Figure imgf000005_0002
Tocoferol
Figure imgf000005_0002
Wasser 30,0 - 60,0 %Water 30.0 - 60.0%
Ethanol 20,0 - 40,0 %, Eine typische Zubereitung der erfindungsgemäßen Aerosollösung setzt sich folgendermaßen zusammen:Ethanol 20.0 - 40.0%, A typical preparation of the aerosol solution according to the invention is composed as follows:
Wirkstoff 0,05-5 %Active substance 0.05-5%
Sojalecithin S 100 (Lipoid) 11,630 %Soy Lecithin S 100 (Lipoid) 11.630%
Cholesterol 1,163 %Cholesterol 1.163%
Tocoferol 0,581 %Tocoferol 0.581%
Wasser ad 100 %Water ad 100%
Ethanol (96 %ig) 36,047 %Ethanol (96%) 36.047%
Als Wirkstoffe können in den erfindungsgemäßen Zubereitungen eingesetzt werden: Beclo ethason (0,1-1,0%) , Budesonid (0,1- 1,0%) , DNCG (1,0-5,0%) , Fenoterol (0,1-1,0%) , Ipratropiumbromid (0,05-0,5%) , Salbutamol (0,2-1,0%) , Reproterol (0,5-2,5%) und Terbutalin (1,0-2,5%) . Auch Mischungen aus Beclomethason und Salbutamol, DNCG und Fenoterol, DNCG und Reproterol, DNCG und Salbutamol oder Fenoterol und Ipratropiumbromid können vorteilhafterweise eingesetzt werden.The following can be used as active ingredients in the preparations according to the invention: beclo ethasone (0.1-1.0%), budesonide (0.1-1.0%), DNCG (1.0-5.0%), fenoterol (0 , 1-1.0%), ipratropium bromide (0.05-0.5%), salbutamol (0.2-1.0%), reproterol (0.5-2.5%) and terbutaline (1.0 -2.5%). Mixtures of beclomethasone and salbutamol, DNCG and fenoterol, DNCG and reproterol, DNCG and salbutamol or fenoterol and ipratropium bromide can also be used advantageously.
Als Lecithine bzw. Phospholipide können außer den obengenannten weiterhin Difettsäurephosphatidylcholine, Difettεäurephospha- tidylglycerol , Dipalmitoylphosphatidylcholin und Stearoylpal- mitoylphosphatidylglycerol eingesetzt werden.As lecithins or phospholipids, in addition to the abovementioned, difatty acid phosphatidylcholines, difatty acid phosphatidylglycerol, dipalmitoylphosphatidylcholine and stearoylpalmitoylphosphatidylglycerol can also be used.
Ein vorgegebenes Füllgewicht, z.B. 3 Gramm dieser Zubereitung (Lösung) werden unter Einhaltung der vorgeschriebenen Füllgenauigkeit durch das Ventil einer luftdicht verschlossenen (vercrimpten) Aerosoldose eingefüllt. Anschließend wird unter Druck der verflüssigte Dimethylether durch das Ventil eingebracht. Die Menge an nachzufüllendem Dimethylether richtet sich nach dem Sollgewicht. Sie kann zwischen 50 bis 300 Gewichtsprozenten der Füllstoffmenge betragen. Vorteil¬ hafterweise liegt die Di ethylethermenge zwischen 100 und 200 Gewichtsprozente pro Füllstoffmenge. Das Gewichtsverhältnis zwischen Wirkstofflösung und Dimethylether beträgt folglich zwischen 1:0,5 und 1:3, vorzugsweise zwischen 1:1 und 1:2. A predetermined fill weight, e.g. 3 grams of this preparation (solution) are filled through the valve of an airtight sealed (crimped) aerosol can in compliance with the prescribed filling accuracy. The liquefied dimethyl ether is then introduced through the valve under pressure. The amount of dimethyl ether to be refilled depends on the target weight. It can be between 50 to 300 percent by weight of the amount of filler. The amount of diethyl ether is advantageously between 100 and 200 percent by weight per amount of filler. The weight ratio between active ingredient solution and dimethyl ether is consequently between 1: 0.5 and 1: 3, preferably between 1: 1 and 1: 2.

Claims

PATENTANSPRÜCHE PATENT CLAIMS
1. Aerosolzubereitung bestehend aus einem oder mehreren antiasthmatischen Wirkstoffen, sowie Lecithinen bzw. Phospholipiden als Surfactant, dadurch gekennzeichnet, daß es als Treibmittel Dimethylether und gegebenenfalls noch Zuεatzεtoffe enthält.1. Aerosol preparation consisting of one or more anti-asthmatic active ingredients, and lecithins or phospholipids as surfactants, characterized in that it contains dimethyl ether and, if appropriate, additional additives.
2. Aeroεolzubereitung gemäß Anεpruch 1, dadurch gekennzeichnet, daß alε Zuεatzεtoffe Löεungεmittel wie Waεεer und/oder Alkohol zugegeben werden.2. Aerosol preparation according to Claim 1, characterized in that solvents such as water and / or alcohol are added as additives.
3. Aeroεolzubereitung gemäß einem der Anεprüche 1 oder 2, dadurch gekennzeichnet, daß alε Alkohol Ethanol und/oder Propylenglykol, Glycerol oder Polyethylenglykol zugegeben wird.3. Aeroεol preparation according to one of claims 1 or 2, characterized in that ethanol and / or propylene glycol, glycerol or polyethylene glycol is added as alcohol.
4. Aerosolzubereitung gemäß einem der Ansprüche 1 bis 3, dadurch gekennzeichnet, daß zusätzlich ein Reεorptionεförderer, vorzugεweiεe Rizinuεöl oder ein lipophileε oder amphiphiles Agenz, beispielsweiεe Tween 80 (Polysorbat 80) oder Tween 204. Aerosol preparation according to one of claims 1 to 3, characterized in that in addition a Reεorptionεförderer, vorzugεweiεe castor oil or a lipophilic or amphiphilic agent, for example Tween 80 (Polysorbate 80) or Tween 20
(Polysorbat 20) , Span oder Arlacel 20 (Sorbitan-Fettsäureester) , Triacetin, DMSO, PEG oder Glycerol-fettsaurerester zugegeben wird.(Polysorbate 20), Span or Arlacel 20 (sorbitan fatty acid ester), triacetin, DMSO, PEG or glycerol fatty acid ester is added.
5. Aerosolzubereitung gemäß einem der Ansprüche 1 bis 4, dadurch gekennzeichnet, daß das Gewichtsverhältnis von Wirkstofflöεung zum Treibmittel Dimethylether zwischen 1:0,5 und 1:3, vorzugεweise zwischen 1:1 und 1:2 beträgt.5. Aerosol preparation according to one of claims 1 to 4, characterized in that the weight ratio of active ingredient solution to the propellant dimethyl ether is between 1: 0.5 and 1: 3, preferably between 1: 1 and 1: 2.
6. Aerosolzubereitung gemäß Anspruch 1, dadurch gekennzeichnet, daß es folgender Rezeptur entspricht: Wirkstoff6. Aerosol preparation according to claim 1, characterized in that it corresponds to the following recipe: Active ingredient
Sojalecithin S 100 (Lipoid)Soy Lecithin S 100 (Lipoid)
CholesterolCholesterol
TocoferolTocoferol
Wasserwater
Ethanol (96 %ig)
Figure imgf000008_0001
Ethanol (96%)
Figure imgf000008_0001
wobei als Wirkstoff Beclomethason, Budeεonid, DNCG, Fenoterol, Ipratropiumbromid, Salbutamol, Reproterol und Terbutalin oder auch eine Miεchung aus Beclomethason und Salbutamol, DNCG und Fenoterol, DNCG und Reproterol, DNCG und Salbutamol oder Fenoterol und Ipratropiumbromid eingesetzt werden kann.beclomethasone, Budeεonid, DNCG, fenoterol, ipratropium bromide, salbutamol, reproterol and terbutaline or a mixture of beclomethasone and salbutamol, DNCG and fenoterol, DNCG and reproterol, DNCG and salbutampr and fenropol can be used as the active ingredient.
7. Aerosolzubereitung gemäß Anspruch 1, dadurch gekennzeichnet, daß es folgender Rezeptur entspricht:7. Aerosol preparation according to claim 1, characterized in that it corresponds to the following recipe:
Wirkstoffactive substance
EilecithinEgg lecithin
CholesterolCholesterol
TocoferolTocoferol
Wasserwater
EthanolEthanol
Rizinusöl
Figure imgf000008_0002
castor oil
Figure imgf000008_0002
wobei als Wirkstoff Beclomethason, Budesonid, DNCG, Fenoterol, Ipratropiumbromid, Salbutamol, Reproterol und Terbutalin oder auch eine Miεchung aus Beclomethason und Salbutamol, DNCG und Fenoterol, DNCG und Reproterol, DNCG und Salbutamol oder Fenoterol und Ipratropiumbromid eingesetzt werden kann.where as the active ingredient beclomethasone, budesonide, DNCG, fenoterol, ipratropium bromide, salbutamol, reproterol and terbutaline or also a mixture of beclomethasone and salbutamol, DNCG and fenoterol, DNCG and reproterol, DNCG and salbutidolate or fenoterol and can be used.
8. Aerosolzubereitung gemäß Anspruch 1, dadurch gekennzeichnet, daß es folgender Rezeptur entspricht: Wirkεtoff 0,05 - 5,0 %8. Aerosol preparation according to claim 1, characterized in that it corresponds to the following recipe: Active ingredient 0.05 - 5.0%
Lecithin 0,5 - 2,0 %Lecithin 0.5 - 2.0%
Tocoferol 0,2 - 1,0 %Tocoferol 0.2 - 1.0%
Waεεer 30,0 - 60,0 %Water 30.0 - 60.0%
Ethanol 20,0 - 40,0 %Ethanol 20.0 - 40.0%
wobei als Wirkstoff Beclomethason, Budeεonid, DNCG, Fenoterol, Ipratropiumbromid, Salbutamol, Reproterol und Terbutalin oder auch eine Miεchung auε Beclomethason und Salbutamol, DNCG und Fenoterol, DNCG und Reproterol, DNCG und Salbutamol oder Fenoterol und Ipratropiumbromid eingesetzt werden kann.Beclomethasone, Budeεonid, DNCG, fenoterol, ipratropium bromide, salbutamol, reproterol and terbutaline or a mixture of beclomethasone and salbutamol, DNCG and fenoterol, DNCG and reproterol, DNCG and salbutomide or fenoterol can be used as the active ingredient.
9. Aerosolzubereitung gemäß Anspruch 1, dadurch gekennzeichnet, daß es folgender Rezeptur entεpricht:9. Aerosol preparation according to claim 1, characterized in that it corresponds to the following formulation:
Wirkεtoff 0,05-5 %Active substance 0.05-5%
Sojalecithin S 100 (Lipoid) 11,630 %Soy Lecithin S 100 (Lipoid) 11.630%
Choleεterol 1,163 %Choleεterol 1.163%
Tocoferol 0,581 %Tocoferol 0.581%
Wasser ad 100 %Water ad 100%
Ethanol (96 %ig) 36,047 %Ethanol (96%) 36.047%
wobei als Wirkstoff Beclomethason, Budesonid, DNCG, Fenoterol, Ipratropiumbromid, Salbutamol, Reproterol und Terbutalin oder auch eine Mischung auε Beclomethaεon und Salbutamol, DNCG und Fenoterol, DNCG und Reproterol, DNCG und Salbutamol oder Fenoterol und Ipratropiumbromid eingesetzt werden kann.beclomethasone, budesonide, DNCG, fenoterol, ipratropium bromide, salbutamol, reproterol and terbutaline or a mixture of beclomethasone and salbutamol, DNCG and fenoterol, DNCG and reproterol, DNCG and salbutamol or fenoterol and I can be used as the active ingredient.
10. Aeroεolzubereitung gemäß einem der Anεprüche 1 biε 9 zur Behandlung von Atemwegserkrankungen.10. Aerosol preparation according to one of claims 1 to 9 for the treatment of respiratory diseases.
11. Aeroεolzubereitung gemäß einem der Anεprüche 1 bis 9 zur Behandlung und Prophylaxe von Atemnot bei Atemwegserkrankungen wie Asthma oder allergiεcher Bronchitis. 11. Aerosol preparation according to one of claims 1 to 9 for the treatment and prophylaxis of shortness of breath in respiratory diseases such as asthma or allergic bronchitis.
PCT/EP1993/000201 1992-02-06 1993-01-29 Asthma or lung aerosol preparations containing lecithin WO1993015715A1 (en)

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DEP4203306.3 1992-02-06

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WO1995024892A1 (en) * 1994-03-14 1995-09-21 Abbott Laboratories Aerosol drug formulations containing vitamin e
EP0959874A1 (en) * 1996-07-03 1999-12-01 Research Development Foundation High dose liposomal aerosol formulations
US6491897B1 (en) 1995-06-27 2002-12-10 Boehringer Ingelheim Kg Stable pharmaceutical budesonide preparation for producing propellant-free aerosols
EP1438955A1 (en) * 1996-07-03 2004-07-21 Research Development Foundation High dose liposomal aerosol formulations
KR100497564B1 (en) * 1996-07-03 2005-11-28 리써치 디벨롭먼트 파운데이션 High Dose Liposome Aerosols

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DE10062712A1 (en) * 2000-12-15 2002-06-20 Boehringer Ingelheim Pharma New drug compositions based on anticholinergics and corticosteroids
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US7776315B2 (en) 2000-10-31 2010-08-17 Boehringer Ingelheim Pharma Gmbh & Co. Kg Pharmaceutical compositions based on anticholinergics and additional active ingredients
US20020137764A1 (en) 2000-10-31 2002-09-26 Karin Drechsel Inhalable formulation of a solution containing a tiotropium salt
DE10347994A1 (en) 2003-10-15 2005-06-16 Pari GmbH Spezialisten für effektive Inhalation Aqueous aerosol preparation
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GB2196254A (en) * 1984-04-13 1988-04-27 Fisons Plc Nedocromil sodium formation
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Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995024892A1 (en) * 1994-03-14 1995-09-21 Abbott Laboratories Aerosol drug formulations containing vitamin e
US6491897B1 (en) 1995-06-27 2002-12-10 Boehringer Ingelheim Kg Stable pharmaceutical budesonide preparation for producing propellant-free aerosols
US8062626B2 (en) 1995-06-27 2011-11-22 Boehringer Ingelheim Kg Stable pharmaceutical budesonide preparation for producing propellant-free aerosols
EP0959874A1 (en) * 1996-07-03 1999-12-01 Research Development Foundation High dose liposomal aerosol formulations
EP0959874A4 (en) * 1996-07-03 1999-12-22
EP1438955A1 (en) * 1996-07-03 2004-07-21 Research Development Foundation High dose liposomal aerosol formulations
KR100497564B1 (en) * 1996-07-03 2005-11-28 리써치 디벨롭먼트 파운데이션 High Dose Liposome Aerosols

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