DE2332663C2 - Use of corticosteroid active ingredients for inhalation therapy - Google Patents
Use of corticosteroid active ingredients for inhalation therapyInfo
- Publication number
- DE2332663C2 DE2332663C2 DE2332663A DE2332663A DE2332663C2 DE 2332663 C2 DE2332663 C2 DE 2332663C2 DE 2332663 A DE2332663 A DE 2332663A DE 2332663 A DE2332663 A DE 2332663A DE 2332663 C2 DE2332663 C2 DE 2332663C2
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- Prior art keywords
- methyl
- pregnadiene
- dioxo
- acid
- hydroxy
- Prior art date
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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
- A61K9/0075—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
-
- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
-
- 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]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
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- Pharmacology & Pharmacy (AREA)
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- Otolaryngology (AREA)
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- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
COOR3 COOR 3
COCO
1515th
20 ι—Ri 20 ι— Ri
worinwherein
-B-A--B-A-
-B-A--B-A-
die Gruppierungen —CH^-CHi-,
-CH = CH-oder-CCl = CH-,
ein Wasserstoffatom, ein Fluoratom oder eine 25 worin Methylgruppe,the groupings —CH ^ -CHi-, -CH = CH- or -CCl = CH-,
a hydrogen atom, a fluorine atom or a 25 in which methyl group,
ein Wasserstoffatom, ein Fluoratom oder ein Chloratom,a hydrogen atom, a fluorine atom or a chlorine atom,
eine Methylengruppe, eine Hydroxymethylen- X gruppe, eine Fluormethylengruppe, eine Chlormethylengruppe oder eine Carbonylgruppe, Ya methylene group, a hydroxymethylene X group, a fluoromethylene group, a chloromethylene group or a carbonyl group, Y
ein Wasserstoffatom oder eine Methylgruppe und Zis a hydrogen atom or a methyl group and Z
ein Wassersloffatom oder R| und R2 gemeinsam eine Isopropylidendioxygruppe und ein Kohlenwasserstoffrest mit 1 bis 12 Kohlen- Ri Stoffatomen bedeuten, zusammen mit einem fe- R2 sten wasserlöslichen Träger zur Inhalationsthea hydrogen atom or R | and R2 together an isopropylidenedioxy group and a hydrocarbon radical with 1 to 12 carbon Ri Substance atoms mean, together with a solid, water-soluble carrier for inhalation
rapie.rapie.
die Gruppierungen —CH2—CH2—,
-CH =CH- oder -CCl = CH-,
ein Wasserstoffatom, ein Fluoratom oder eine Methylgruppe, the groups —CH2 — CH2—, -CH = CH- or -CCl = CH-,
a hydrogen atom, a fluorine atom or a methyl group,
ein Wasserstoffatom, ein Fluoratom oder ein Chloratom,a hydrogen atom, a fluorine atom or a chlorine atom,
eine Methylengruppe, eine Hydroxymethylertgruppe, eine Fluormethylengruppe, eine Chlormethylengruppe
oder eine Carbonylgruppe,
ein Wasserstoffatom oder eine Methylgruppe und ein Wasserstoffatom oder Ri und R2 gemeinsam
eine Isopropylidendioxygruppe und
ein Kohlenwasserstoffatom mit 1 bis 12 Kohlenstoffatomen bedeuten, zusammen mit einem festen,
wasserlöslichen Träger verwendet.a methylene group, a hydroxymethyl group, a fluoromethylene group, a chloromethylene group or a carbonyl group,
a hydrogen atom or a methyl group and a hydrogen atom or Ri and R2 together an isopropylidenedioxy group and
represents a hydrocarbon atom having 1 to 12 carbon atoms, used together with a solid, water-soluble carrier.
Die Erfindung betrifft die Verwendung von Kortikoid-Wirkstoffen zur Inhalationstherapie von vorzugsweise allergischen Erkrankungen der Atemwege.The invention relates to the use of corticosteroid active ingredients for inhalation therapy of preferably allergic respiratory diseases.
Es ist bekannt, daß man Kortikoid-Wirkstoffe enthaltende Arzneimittel zur Behandlung von allergischen Erkrankungen der Atemwege wie zum Beispiel der Rhinitis oder des Bronchialasthmas, verwenden kann. Die Anwendung dieser Arzneimittel zur Behandlung derartiger Erkrankungen ist aber trotz ihrer guten Wirksamkeit nicht unbedenklich, da die hierzu verwendeten Kortikoide in höherer Dosierung und bei langanhaltender Behandlung häufig schwere Nebenwirkungen, wie zum Beispiel das sogenannte Cushing Syndrom, verursachen (Brit. Med. J., 1966,2,796 und The Lancet 1970,733).It is known that medicaments containing corticosteroids are used for the treatment of allergic diseases the respiratory tract such as rhinitis or bronchial asthma. The application However, this drug for the treatment of such diseases is in spite of its good effectiveness not harmless, as the corticoids used for this purpose in higher doses and with longer lasting ones Treatment often causes serious side effects, such as what is known as Cushing's syndrome (Brit. Med. J., 1966,2,796 and The Lancet 1970,733).
Um die bei der Behandlung allergischer Erkrankungen der Atemwege mit Kortikoiden auftretenden Nebenwirkungen zu mindern, ging man dazu über, die Kortikoide nicht wie zuvor oral zu applizieren, sondern sie als Aerosole zu inhalieren (The Lancet, 1963,147; Arch. Intern. Med., 115 (1965) 602; Brit. Med. J., 1972, 1, 585). Mit Hilfe dieser Applikationsform war es möglich, die auftretenden Nebenwirkungen zu mindern; vermeiden konnte man die unerwünschten Nebenwirkungen schon deshalb nicht, weil bei der Inhalation stets ein Teil des Inhalationsmittels in den Magen-Darm-Trakt gelangt.To address the side effects associated with treating allergic respiratory diseases with corticosteroids In order to reduce the risk, it was decided not to apply the corticosteroids orally, as before, but to apply them to inhale as aerosols (The Lancet, 1963,147; Arch. Intern. Med., 115 (1965) 602; Brit. Med. J., 1972, 1, 585). With the help of this form of application it was possible to reduce the side effects occurring; avoid one could not have the undesirable side effects because of the inhalation always a part of the Inhalant enters the gastrointestinal tract.
Unter einem Kohlenwasserstoffrest R3 soll eine aliphatische, aromatische, cycloaliphatische, gesättigte oder ungesättigte Gruppe mit 1 bis 12 Kohlenstoffatomen verstanden werden.A hydrocarbon radical R3 should be an aliphatic, aromatic, cycloaliphatic, saturated or unsaturated group with 1 to 12 carbon atoms be understood.
Vorzugsweise soll unter dem Kohlenwasserstoffrest R3 eine Gruppe verstanden werden, die 1 bis 6 Kohlenstoffatome besitzt.The hydrocarbon radical R 3 is preferably to be understood as meaning a group which has 1 to 6 carbon atoms.
Als Gruppen R3 seien beispielsweise genannt:Examples of groups R 3 include:
5050
5555
60 der 6«-Fluor-l 60 of the 6 "fluorine-l
1,4-pregnadien-21 -säure-methylester,
der 6a-Fluor-1 l^-hydroxy-S^O-dioxo-16*-methyl-1,4-pregnadiene-21-acid methyl ester,
the 6a-fluoro-1 l ^ -hydroxy-S ^ O-dioxo-16 * -methyl-
1,4-pregnadien-21 -säure-äthylester,
der 6λ-Fluor-ll/i-hydroxy-S^O-dioxo-ie1,4-pregnadiene-21-acid ethyl ester,
the 6λ-fluoro-II / i-hydroxy-S ^ O-dioxo-ie
1,4-pregnadien-21 -säure-propylester.1,4-pregnadiene-21-acid propyl ester.
die Methyl-, Äthyl-, Propyl-, Allyl-, Cyclopropyl-, Isopropyl-, Propinyl-, Butyl-, sek.-Butyl-, teit.-Butyl-, Butyl-(2)-, Cyclobutyl-, Pentyl-, Isopentyl-, tert-Pentyl-, 2-Methylbutyl-, Cyclopentyl-, Hexyl-, Cyclohexyl-, Cyclohex-2-enyl-, Cyclopentylmethyl-, Heptyl-, Benzyl-, 2-Phenyläthyl-, Octyl-, Bornyl-, Isobornyl-, Menthyl-, Nonyl-, Decyl-, 3-Phenyl-propyl-, 3-Phenyl-prop-2-enyl- und Dodecylgruppe.the methyl, ethyl, propyl, allyl, cyclopropyl, isopropyl, propynyl, butyl, sec-butyl, partial butyl, Butyl (2), cyclobutyl, pentyl, isopentyl, tert-pentyl, 2-methylbutyl, cyclopentyl, hexyl, Cyclohexyl, cyclohex-2-enyl, cyclopentylmethyl, Heptyl, benzyl, 2-phenylethyl, octyl, bornyl, Isobornyl, menthyl, nonyl, decyl, 3-phenyl-propyl, 3-phenyl-prop-2-enyl and dodecyl groups.
Als mögliche Wirkstoffe seien beispielsweise genannt:Possible active ingredients are, for example:
der ΟΛ-Fluor-l 1/?-hydroxy-3,20-dioxo-16*-methyl-the ΟΛ-fluorine-l 1 /? - hydroxy-3,20-dioxo-16 * -methyl-
l,4-pregnadien-21-säure-isopropylester, der θΛ-Fluor-l l/?-hydroxy-3,20-dioxo-l 6ar-methyl-l, 4-pregnadiene-21-acid isopropyl ester, the θΛ-fluorine-l l /? - hydroxy-3,20-dioxo-l 6ar-methyl-
l,4-pregnadien-21-säure-butylester, der 6λ-Fluor-1 l/y-hydroxy-ß^O-dioxo-16«-methyl-1,4-pregnadiene-21-acid butyl ester, the 6λ-fluoro-1 l / y-hydroxy-ß ^ O-dioxo-16 «-methyl-
l,4-pregnadien-21-säure-pentylester, der ÖA-Fluor-l l/?-hydroxy-3,20-dioxo-16«-methyl-1,4-pregnadiene-21-acid-pentylester, the ÖA-fluoro-1 l /? - hydroxy-3,20-dioxo-16 «-methyl-
1,4-pregnadien-21 -säure-hexylester, der δΛ-FIuor-l l/j'-hydroxy-S^O-dioxo-lÖÄ-methyl-1,4-pregnadiene-21-hexyl ester, the δΛ-fluorine-l l / j'-hydroxy-S ^ O-dioxo-lÖÄ-methyl-
l,4-pregnadien-21-säure-decylester, der δΛ-Fluor-l l^-hydroxy-S^O-dioxo-lÖÄ-methyl-1,4-pregnadiene-21-acid decyl ester, the δΛ-fluoro-l l ^ -hydroxy-S ^ O-dioxo-lÖÄ-methyl-
l,4-pregnadien-21-säure-tert.-butylester, der βΛ-Fluor-l l/?-hydroxy-3,20-dioxo-16^-methyl-1,4-pregnadiene-21-acid-tert-butyl ester, the βΛ-fluoro-l l /? - hydroxy-3,20-dioxo-16 ^ -methyl-
1,4-pregnadien-21 -säure-cyclobutylester, der 6«-Fluor-1 l/?-hydroxy-3,20-dioxo-16«-methyl-1,4-pregnadiene-21-acid cyclobutyl ester, the 6 "-fluoro-1 l /? - hydroxy-3,20-dioxo-16" -methyl-
l,4-pregnadien-21-säure-cyclohexylester, der βΛ-FIuor-l l/y-hydroxy-S^O-dioxo-iel, 4-pregnadiene-21-acid cyclohexyl ester, the βΛ-fluorine-l l / y-hydroxy-S ^ O-dioxo-ie
l,4-pregnadien-21-säure-benzylester, der δΛ-Fluor-i i^-hydroxy-S^O-dioxo-lÖ1,4-pregnadiene-21-acid benzyl ester, the δΛ-fluoro-i i ^ -hydroxy-S ^ O-dioxo-lÖ
1,4-pregnadien-21 -säure-2'-propenylester, der 6a- Fluor-1 i/i-hydroxy-S^O-dioxo-1 öar-methyl-1,4-pregnadiene-21-acid-2'-propenyl ester, the 6a- fluoro-1 i / i-hydroxy-S ^ O-dioxo-1 öar-methyl-
1,4-pregnadien-21 -säure-2'-propinylester, der 6λ-Fluor-1 l/?-hydroxy-3,20-dioxo-16«-methyl-1,4-pregnadiene-21-acid-2'-propynyl ester, the 6λ-fluoro-1 l /? - hydroxy-3,20-dioxo-16 «-methyl-
1,4-pregnadien-21 -säure-S'-butenylester, der6*-Fluor-11^-hydroxy-3,20-dioxo-16Ä-methyl-1,4-pregnadiene-21-acid-S'-butenyl ester, der6 * -Fluor-11 ^ -hydroxy-3,20-dioxo-16Ä-methyl-
1,4-pregnadien-21 -säure-S'-butinylester, der 6λ- Fluor-1 l/#-hydroxy-3,20-dioxo-16«-methyl-1,4-pregnadiene-21-acid-S'-butynyl ester, the 6λ- fluoro-1 l / # - hydroxy-3,20-dioxo-16 «-methyl-
1,4-pregnadien-21 -säure-menthylester, der 6iv-Fluor-2-chlor-1 l/?-hydroxy-3,20-dioxo-16/x- 1,4-pregnadiene-21-acid menthyl ester, the 6iv-fluoro-2-chloro-1 l /? - hydroxy-3,20-dioxo-1 6 / x-
methyl-1,4-pregnadien-21 -säure-methylester, der 6«-Fluor-9«-chlor-l l^-hydroxy-S^O-dioxo-löa:-methyl-1,4-pregnadiene-21-acid methyl ester, der 6 "-Fluor-9" -chlor-l l ^ -hydroxy-S ^ O-dioxo-löa: -
methyl-1,4-pregnadien-21 -säure-methylester, der 6*-Fluor-9*-chlor-l l/?-hydroxy-3,20-dioxo-16«- methyl-1,4-pregnadien-21 -säure-butylester,methyl-1,4-pregnadiene-21-acid methyl ester, the 6 * -Fluor-9 * -chlor-l l /? - hydroxy-3,20-dioxo-16 «- methyl-1,4-pregnadiene-21-acid butyl ester,
methyl-1,4-pregnadien-21 -säure-isobutylester, re^a-Difluor-ll^-hydroxy-S^O-dio 1,4-pregnadien-21 -säure-methylester,methyl-1,4-pregnadiene-21-acid-isobutyl ester, re ^ a-Difluoro-ll ^ -hydroxy-S ^ O-dio 1,4-pregnadiene-21-acid methyl ester,
1,4-pregnadien-21 -säure-äthylester.1,4-pregnadiene-21-acid ethyl ester.
1,4-pregnadien-21-säure-butylester, der 6λ,1 l/y-Difluor-gÄ-chlor-S^O-dioxo-i 1,4-pregnadien-21 -säure-methylester,1,4-pregnadiene-21-acid butyl ester, the 6λ, 1 l / y-difluoro-gÄ-chloro-S ^ O-dioxo-i 1,4-pregnadiene-21-acid methyl ester,
l,4-pregnadien-21-säure-butylester, der 6«-Fluor-9«,l l/?-dichlor-3,20-dioxo-16*-methyl-1,4-pregnadiene-21-acid butyl ester, the 6 "-fluoro-9", l l /? - dichloro-3,20-dioxo-16 * -methyl-
l,4-pregnadien-21-säure-methylester, der 6«-Fluor-9«,l l/?-dichlor-3,20-dioxo-16«-methyl-1,4-pregnadiene-21-acid methyl ester, the 6 "-fluoro-9", l l /? - dichloro-3,20-dioxo-16 "-methyl-
1,4-pregnadien-21-säure-butylester, der 9*-Fluor-1 l/?-hydroxy-3,20-dioxo-16<*-methyl-1,4-1,4-pregnadiene-21-acid butyl ester, the 9 * -fluoro-1 l /? - hydroxy-3,20-dioxo-16 <* - methyl-1,4-
pregnadien-21-säure-methylester, der 9λ-Fluor-1 l^-hydroxy-S^O-dioxo-16«-methyl-1,4-Pregnadiene-21-acid methyl ester, the 9λ-fluoro-1 l ^ -hydroxy-S ^ O-dioxo-16 «-methyl-1,4-
pregnadien-21 -säure-butylester, der 1 l/f-Hydroxy-S^O-dioxo-löic-methyl-l^-pregna dien-butyl pregnadiene-21 acid ester, the 1 l / f-hydroxy-S ^ O-dioxo-löic-methyl-l ^ -pregna serving
21-säure-butylester,
der 1 l/^-Hydroxy-S^O-dioxo-l^-pregnadien-21-acid butyl ester,
der 1 l / ^ - Hydroxy-S ^ O-dioxo-l ^ -pregnadiene-
21 -säure-methylester,
der 1 l^-Hydroxy-S^O-dioxo-M-pregnadien-21-acid methyl ester,
the 1 l ^ -hydroxy-S ^ O-dioxo-M-pregnadiene-
21 -säure-butylester,
der6*-Fluor-ll/?-hydroxy-3,20-dioxo-16*-methyl-4-21-acid butyl ester,
der6 * -Fluor-II /? - hydroxy-3,20-dioxo-16 * -methyl-4-
pregnen-21-säure-butylester,
der 6ii-Fluor-3,20-dioxo-16*-methyl-4-pregnen-21 säure-butylester,
pregnen-21-acid butyl ester,
the 6ii-fluoro-3,20-dioxo-16 * -methyl-4-pregnen-21 acid butyl ester,
der 3,20-dioxo-16«-methyl-4-pregnen-21 -säurebutylester,
der 6«-Fluor-3,l 1,20-trioxo-16*-methyl-the 3,20-dioxo-16 «-methyl-4-pregnen-21-acid butyl ester,
the 6 "-fluoro-3, l 1,20-trioxo-16 * -methyl-
l,4-pregnadien-21-säure-methylester,
der6«-F!uor-3,ll,20-trioxo-16a:-methyl-l, 4-pregnadiene-21-acid methyl ester,
der6 "-F! uor-3, ll, 20-trioxo-16a: -methyl-
l,4-pregnadien-21-säure-butylester,
der 1 l/o'-Hydroxy-3,20-dioxo-4-pregnen-?l-säuremethylesier,
1,4-pregnadiene-21-acid butyl ester,
the 1 l / o'-hydroxy-3,20-dioxo-4-pregnen-? l-acid methylier,
der 6*-Fluof-3,l l,20-trioxo-16a-methyl-4-pregnen-the 6 * -Fluof-3, l, 20-trioxo-16a-methyl-4-pregnen-
21 -säure-butylester,
der 9«-Fluor-l l^-hydroxy^O-dioxo-16«,! Tx- 21-acid butyl ester,
the 9 "-fluoro-1 l ^ -hydroxy ^ O-dioxo-16",! Tx-
isopropyliden-dioxy-1,4-pregnadien-21 säure-methylester, isopropylidene-dioxy-1,4-pregnadiene-21 acid methyl ester,
der9«-Fluor-ll/?-hydroxy-3,20-dioxo-16«,17«-der9 "-Fluor-II /? - hydroxy-3,20-dioxo-16", 17 "-
isopropyliden-dioxy-1,4-pregnadien-21 -isopropylidene-dioxy-1,4-pregnadiene-21 -
säure-äthylester,acid ethyl ester,
der θΛ-Fluor-l l/?-hydroxy-3,20-dioxo-loÄ,17*-
isopropyliden-dioxy-1,4-pregnadien-21 -the θΛ-fluorine-l l /? - hydroxy-3,20-dioxo-loÄ, 17 * -
isopropylidene-dioxy-1,4-pregnadiene-21 -
säure-butylester und
der 1 l/?-Hydroxy-3,20-dioxo-6Ä,16a:-dimethyl-acid butyl ester and
der 1 l /? - hydroxy-3,20-dioxo-6Ä, 16a: -dimethyl-
l,4-pregnadien-21-säure-butylester.1,4-pregnadiene-21-acid butyl ester.
Die verwendeten Kortikoid-Wirkstoffe sind in den deutschen Patentmeldungen P 21 50 268, P 22 04 361, P 22 64 003, P 23 19 478 und 23 19 479 sowie in der belgischen Patentschrift 7 79 869 beschrieben. Diese Verbindungen können beispielsweise mit Hilfe des Verfahrens hergestellt werden, welches in der belgischen Patentschrift 7 79 869 beschrieben ist.The corticosteroid active ingredients used are in German patent applications P 21 50 268, P 22 04 361, P 22 64 003, P 23 19 478 and 23 19 479 as well as in the Belgian Patent 7 79 869 described. These compounds can, for example, with the aid of the method which is described in Belgian patent 7 79 869.
Zur Herstellung der Inhalationsmittel ist es besonders vorteilhaft, die Kcrtikoid-Wirkstoffe durch Mikronisieren oder Ausfällen auf eine mittlere Korngröße von 0,01 bis 20 μ zu bringen.It is special for the manufacture of inhalants Advantageously, the corticoid active ingredients by micronizing or precipitating to a mean grain size of 0.01 to bring up to 20 μ.
Zur Erhöhung der Lagerfähigkeit und zur Erleichterung der Aerosolbildung setzt man diesen Kortikoid-Pulvern noch zusätzlich einen festen, pharmakologisch unwirksamen wasserlöslichen pulverförmigen Träger mit einer mittleren Korngröße von 20 bis 200 μ zu. Als Träger eignen sich beispielsweise Dextran, Mannit, Glucose oder Laktose. Diese pulverförmigen Inhalationsmittel, welchen zusätzlich noch weitere Zusätze, wie zum Beispiel Geschmackskorregentien (zum Beispiel Saccharin) oder Antibiotika (zum Beispiel ein Penicillin, ein Tetracyclin oder ein Erythromycin) zugefügt werden können, enthalten üblicherweise ab 0,1% Kortikoid-Wirkstoff. Die Herstellung von pulverförmigen Inhalationsmitteln und ihre Anwendung ist in den deutschen Offenlegungsschriften 17 92 207 und 22 29 981 beschrieben. These corticosteroid powders are used to increase the shelf life and to facilitate aerosol formation additionally a solid, pharmacologically inactive, water-soluble powdery carrier with an average grain size of 20 to 200 μ. Examples of suitable carriers are dextran, mannitol and glucose or lactose. These powdery inhalants, which also have other additives, such as for example taste correctors (for example saccharin) or antibiotics (for example a penicillin, a tetracycline or an erythromycin) can be added, usually contain from 0.1% corticosteroid active ingredient. The manufacture of powdered inhalants and their application is in the German Offenlegungsschriften 17 92 207 and 22 29 981 described.
Die Inhalationsmittel werden, wie bereits erv/ähnt, vorzugsweise zur Behandlung von allergischen Erkrankungen der Atemwege, wie zum Beispiel rhinitische Erkrankungen, Heuschnupfen oder Bronchialasthma, verwendet. As already mentioned, the inhalants are preferably used for the treatment of allergic diseases respiratory tract, such as rhinitis, hay fever or bronchial asthma.
Die Menge des Inhalationsmittels, welches pro Inhalation und pro Tag zu applizieren ist, variiert nach der Schwere der Erkrankung und der Konstitution des zu - 55 Behandelnden. Üblicherweise wird man pro Inhalation etwa 0,01 bis 100 mg und vorzugsweise 0,1 bis 10 mg Kortikoid-Wirkstoff applizieren. Die erforderliche Tagesdosis beträgt üblicherweise 0,02 bis 1000 mg und vorzugsweise 0,1 bis 50 mg.The amount of inhalant to be administered per inhalation and per day varies according to the Severity of the illness and the constitution of the person to be treated. Usually one will per inhalation Apply about 0.01 to 100 mg and preferably 0.1 to 10 mg of corticosteroid active ingredient. The required daily dose is usually 0.02 to 1000 mg, and preferably 0.1 to 50 mg.
Die nachfolgenden Beispiele dienen zur weiteren Erläuterung der Erfindung:The following examples serve to further illustrate the invention:
1,000 g mikronisierter 6*-Fluor-ll/?-hydroxy-3,20-dioxo-16<*-methyl-l,4-pregnadien-21 -säure-butylester (mittlere Korngröße: kleiner als 7 μ) und 39,000 g vermahlene Lactose werden gemischt. Je 40 mg der Mi-1,000 g of micronized 6 * -fluoro-II /? - hydroxy-3,20-dioxo-16 <* - methyl-l, 4-pregnadiene-21 -butyl ester (mean grain size: less than 7 μ) and 39,000 g of ground lactose are mixed. 40 mg each of the mini
schung werden in Steckkapseln abgefüllt.are filled into push-fit capsules.
Zur Applikation des Inhalationsmittels verwendet man einen Spinhaler®.A Spinhaler® is used to apply the inhalant.
Beispi el 2 5Example 2 5
1,000 g mikronisierter 6*-Fluor-9Ä,1 l/?-dichlor-3,20-dioxo-16a:-methyl-1,4-pregnaüien-21 -säure-butylester (mittlere Korngröße: kleiner als 7 μ) und 39,000 g vermahlene Lactose werden gemischt. Je 40 mg der Mi- 10 schung werden in Steckkapseln abgefüllt1,000 g of micronized 6 * -Fluor-9Ä, 1 l /? - dichloro-3,20-dioxo-16a: -methyl-1,4-pregnaüien-21 -butyl ester (mean grain size: less than 7 μ) and 39,000 g milled lactose are mixed. 40 mg each of the mixture are filled into push-fit capsules
Zur Applikation des Inhalationsmitiels verwendet man einen Spinhaler®.Used to apply the inhalant a Spinhaler®.
Beispiel 3 15Example 3 15
1,000 g mikronisierter 6«-Fluor-9*-chlor-ll/?-hydroxy-3,20-dioxo-16a:-methyl-1,4-pregnadien-21 -säureisobutylester (mittlere Korngröße: kleiner als 7 μ) und 39,000 g vermahlene Lactose werden gemischt. Je 40 mg 20 der Mischung werden in Steckkapseln abgefüllt.1,000 g of micronized 6 "-fluoro-9 * -chlor-II /? -Hydroxy-3,20-dioxo-16a: -methyl-1,4-pregnadiene-21 Isobutyl acid ester (mean particle size: less than 7 μ) and 39,000 g of ground lactose are mixed. 40 mg each 20 the mixture are filled into push-fit capsules.
Zur Applikation des Inhalationsmittels verwendet man einen Spinhaler®.A Spinhaler® is used to apply the inhalant.
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Claims (1)
Priority Applications (15)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE2332663A DE2332663C2 (en) | 1973-06-23 | 1973-06-23 | Use of corticosteroid active ingredients for inhalation therapy |
| SE7408091A SE7408091L (en) | 1973-06-23 | 1974-06-19 | |
| ES427480A ES427480A1 (en) | 1973-06-23 | 1974-06-20 | Corticoid-containing inhalant preparations |
| IE1292/74A IE39516B1 (en) | 1973-06-23 | 1974-06-20 | Corticoid-containing inhalant preparations |
| NLAANVRAGE7408421,A NL184724C (en) | 1973-06-23 | 1974-06-21 | PROCESS FOR PREPARING A PHARMACEUTICAL PREPARATION CONTAINING A CORTICOID. |
| BE145751A BE816709A (en) | 1973-06-23 | 1974-06-21 | INHALATION PRODUCTS |
| IL45087A IL45087A (en) | 1973-06-23 | 1974-06-21 | Inhalant preparations containing 3,20-dioxo-pregn-4-enoic acid derivatives |
| ZA00744022A ZA744022B (en) | 1973-06-23 | 1974-06-21 | Corticoid-containing inhalant preparations corticoid-containing inhalant preparations |
| FR7421859A FR2233987B1 (en) | 1973-06-23 | 1974-06-24 | |
| DD179417A DD112437A5 (en) | 1973-06-23 | 1974-06-24 | |
| JP49072169A JPS6245846B2 (en) | 1973-06-23 | 1974-06-24 | |
| AU70421/74A AU493830B2 (en) | 1974-06-24 | Corticoid-containing inhalant preparations | |
| GB27902/74A GB1479488A (en) | 1973-06-23 | 1974-06-24 | Corticoid-containing inhalant preparations |
| DK337574A DK337574A (en) | 1973-06-23 | 1974-06-24 | |
| US05/714,668 US4039668A (en) | 1973-06-23 | 1976-08-16 | Corticoid-containing inhalants |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE2332663A DE2332663C2 (en) | 1973-06-23 | 1973-06-23 | Use of corticosteroid active ingredients for inhalation therapy |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE2332663A1 DE2332663A1 (en) | 1975-01-16 |
| DE2332663C2 true DE2332663C2 (en) | 1986-07-31 |
Family
ID=5885228
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE2332663A Expired DE2332663C2 (en) | 1973-06-23 | 1973-06-23 | Use of corticosteroid active ingredients for inhalation therapy |
Country Status (13)
| Country | Link |
|---|---|
| JP (1) | JPS6245846B2 (en) |
| BE (1) | BE816709A (en) |
| DD (1) | DD112437A5 (en) |
| DE (1) | DE2332663C2 (en) |
| DK (1) | DK337574A (en) |
| ES (1) | ES427480A1 (en) |
| FR (1) | FR2233987B1 (en) |
| GB (1) | GB1479488A (en) |
| IE (1) | IE39516B1 (en) |
| IL (1) | IL45087A (en) |
| NL (1) | NL184724C (en) |
| SE (1) | SE7408091L (en) |
| ZA (1) | ZA744022B (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MX3864E (en) * | 1975-05-27 | 1981-08-26 | Syntex Corp | A PROCESS TO PREPARE THE CRYSTALLINE COMPOUND 6-FLUIRO-11B 21-DIHIROXI-16 17-ISOPROPILIDENDIOXIPREGNA-1 4-DIEN-3 20-DIONA |
| DE2829953A1 (en) * | 1978-07-03 | 1980-01-24 | Schering Ag | PHARMACEUTICAL PREPARATION FOR TREATING THE KOLITIS ULCEROSA AND KOLITIS GRANULOMATOSA |
| US5215979A (en) * | 1985-12-19 | 1993-06-01 | Aktiebolaget Draco | 16,17-acetalsubstituted pregnane 21-oic acid derivatives |
| US7858650B2 (en) | 2004-10-22 | 2010-12-28 | Ono Pharmaceutical Co., Ltd. | Medicinal composition for inhalation |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB799902A (en) * | 1954-08-11 | 1958-08-13 | Merck & Co Inc | Therapeutic preparations |
| US3320125A (en) * | 1964-04-28 | 1967-05-16 | Merck & Co Inc | Inhalation aerosol composition |
| GB1242211A (en) * | 1967-08-08 | 1971-08-11 | Fisons Pharmaceuticals Ltd | Pharmaceutical composition |
| GB1381872A (en) * | 1971-06-22 | 1975-01-29 | Fisons Ltd | Pharmaceutical compositions for inhalation |
| BE787100A (en) * | 1971-08-06 | 1973-02-02 | Beecham Group Ltd | COMPOSITION FOR THE TREATMENT OF ASTHMA |
| DD95565B1 (en) * | 1971-10-04 | 1986-10-29 | Schering Ag | PROCESS FOR PREPARING NEW PREGNANEANEUREDERIVATE |
| DE2150268C3 (en) * | 1971-10-04 | 1980-11-06 | Schering Ag, 1000 Berlin Und 4619 Bergkamen | Pregnanic acid derivatives, processes for their preparation and pharmaceuticals containing them |
| DE2264003C2 (en) * | 1972-12-22 | 1982-11-04 | Schering Ag, 1000 Berlin Und 4619 Bergkamen | New pregnanic acid derivatives, processes for their production and pharmaceutical preparations containing them |
| DE2319479C2 (en) * | 1973-04-14 | 1982-10-28 | Schering Ag, 1000 Berlin Und 4619 Bergkamen | Pregnanic acid derivatives, processes for their production and pharmaceutical preparations containing them |
-
1973
- 1973-06-23 DE DE2332663A patent/DE2332663C2/en not_active Expired
-
1974
- 1974-06-19 SE SE7408091A patent/SE7408091L/ not_active Application Discontinuation
- 1974-06-20 ES ES427480A patent/ES427480A1/en not_active Expired
- 1974-06-20 IE IE1292/74A patent/IE39516B1/en unknown
- 1974-06-21 IL IL45087A patent/IL45087A/en unknown
- 1974-06-21 NL NLAANVRAGE7408421,A patent/NL184724C/en not_active IP Right Cessation
- 1974-06-21 BE BE145751A patent/BE816709A/en not_active IP Right Cessation
- 1974-06-21 ZA ZA00744022A patent/ZA744022B/en unknown
- 1974-06-24 FR FR7421859A patent/FR2233987B1/fr not_active Expired
- 1974-06-24 GB GB27902/74A patent/GB1479488A/en not_active Expired
- 1974-06-24 DD DD179417A patent/DD112437A5/xx unknown
- 1974-06-24 DK DK337574A patent/DK337574A/da unknown
- 1974-06-24 JP JP49072169A patent/JPS6245846B2/ja not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| BE816709A (en) | 1974-12-23 |
| SE7408091L (en) | 1974-12-23 |
| IE39516B1 (en) | 1978-10-25 |
| NL7408421A (en) | 1974-12-30 |
| DK337574A (en) | 1975-03-17 |
| ES427480A1 (en) | 1976-07-16 |
| DE2332663A1 (en) | 1975-01-16 |
| NL184724B (en) | 1989-05-16 |
| IE39516L (en) | 1974-12-23 |
| JPS5047967A (en) | 1975-04-28 |
| GB1479488A (en) | 1977-07-13 |
| NL184724C (en) | 1989-10-16 |
| JPS6245846B2 (en) | 1987-09-29 |
| AU7042174A (en) | 1976-01-08 |
| ZA744022B (en) | 1975-06-25 |
| FR2233987A1 (en) | 1975-01-17 |
| IL45087A (en) | 1978-04-30 |
| FR2233987B1 (en) | 1977-07-08 |
| DD112437A5 (en) | 1975-04-12 |
| IL45087A0 (en) | 1974-09-10 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| OD | Request for examination | ||
| D2 | Grant after examination | ||
| 8364 | No opposition during term of opposition |