DE29680627U1 - Non-steroidal anti-inflammatory drug for topical and systemic treatment of acute and chronic polypoid rhinosinusitis - Google Patents
Non-steroidal anti-inflammatory drug for topical and systemic treatment of acute and chronic polypoid rhinosinusitisInfo
- Publication number
- DE29680627U1 DE29680627U1 DE29680627U DE29680627U DE29680627U1 DE 29680627 U1 DE29680627 U1 DE 29680627U1 DE 29680627 U DE29680627 U DE 29680627U DE 29680627 U DE29680627 U DE 29680627U DE 29680627 U1 DE29680627 U1 DE 29680627U1
- Authority
- DE
- Germany
- Prior art keywords
- steroidal anti
- topical
- chronic
- acute
- inflammatory drug
- 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.)
- Expired - Lifetime
Links
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- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 title claims description 27
- 230000000699 topical effect Effects 0.000 title claims description 16
- 238000011282 treatment Methods 0.000 title claims description 12
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- 208000015768 polyposis Diseases 0.000 claims description 5
- 206010039083 rhinitis Diseases 0.000 claims description 5
- KWGRBVOPPLSCSI-WPRPVWTQSA-N (-)-ephedrine Chemical compound CN[C@@H](C)[C@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WPRPVWTQSA-N 0.000 claims description 4
- CNIIGCLFLJGOGP-UHFFFAOYSA-N 2-(1-naphthalenylmethyl)-4,5-dihydro-1H-imidazole Chemical compound C=1C=CC2=CC=CC=C2C=1CC1=NCCN1 CNIIGCLFLJGOGP-UHFFFAOYSA-N 0.000 claims description 4
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- 208000027157 chronic rhinosinusitis Diseases 0.000 claims description 4
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- ILYSAKHOYBPSPC-UHFFFAOYSA-N 2-phenylbenzoic acid Chemical class OC(=O)C1=CC=CC=C1C1=CC=CC=C1 ILYSAKHOYBPSPC-UHFFFAOYSA-N 0.000 claims description 2
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Classifications
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- 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
- A61K31/60—Salicylic acid; Derivatives thereof
- A61K31/612—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid
- A61K31/616—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid by carboxylic acids, e.g. acetylsalicylic acid
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- 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
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
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- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
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- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/196—Carboxylic acids, e.g. valproic acid having an amino group the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
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- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
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Description
Nicht-steroidales Antiphlogistikum zur topischen und systemischen Behandlung der akuten und chronischen polypoiden RhinosinusitisNon-steroidal anti-inflammatory drug for the topical and systemic treatment of acute and chronic polypoid rhinosinusitis
BeschreibungDescription
Die vorliegende Erfindung betrifft nicht-steroidale Antiphlogistika bei Erkrankungen der oberen und unteren Atemwege.The present invention relates to non-steroidal anti-inflammatory drugs for diseases of the upper and lower respiratory tract.
Es ist bekannt, nicht-steroidale Antiphlogistika (im folgenden als
NSAID abgekürzt: „non-steroidal anti inflammatory drugs") als Antiphlogistika,
Analgetika und Antipyretika einzusetzen. NSAID werden systemisch zur Behandlung von entzündlichen Gelenkserkrankungen
einschließlich der chronischen Polyarthritis, der Polyarthrose und bei schmerzhaften Zuständen nach Traumata, z.B. Muskelzerrung,
Gewebsverletzung, eingesetzt. Dabei handelt es sich um eine symptomatische Therapie, die bedarfsweise und zeitlich begrenzt verordnet
wird. Der entscheidende Nachteil einer Dauerverordnung systemisch wirksamer NSAID ist bekannterweise das Auftreten von Oberbauchbeschwerden,
wie bei der akuten Gastritis, Magen- und Zwölffingerdarmgeschwüre mit zusätzlicher Blutungskomplikation.
Darüber hinaus kann eine systemische Behandlung mit NSAID nur bis zu einem gewissen Schweregrad der Erkrankung angewendet werden;
darüber hinaus bleibt nur eine systemische Therapie mit Corticosteroiden übrig, deren schwere Nebenwirkungen allgemein bekannt sind.
Zu der Gruppe der NSAID gehören eine Vielzahl unterschiedlicher Substanzen, denen ein gemeinsames Wirkprinzip zugrunde liegt. Dieses
besteht in der Hemmung der sogenannten Cyclooxygenasen (PGH-Synteasen: PGHS-I, PGHS-2), die Arachidonsäure als das
Substrat für die Neusynthese von Prostaglandinen und Thromboxan in
diesem Stoffwechselweg metabolisieren.
Die bekannten Wirkungen der Gruppe der nicht-steroidalen Antiphlogistika
wird nach dem Stand der Technik durch die Hemmung der Cyclooxygenase-Aktivität vermittelt. Glucocorticosteroide haben im
Vergleich zu den Cyclooxygenase-Hemmstoffen eine deutlich höhere anti-inflammatorische Wirkung bei nur unbedeutenden anti-pyretiIt is known that non-steroidal anti-inflammatory drugs (hereinafter abbreviated as NSAIDs) are used as anti-inflammatory drugs, analgesics and antipyretics. NSAIDs are used systemically to treat inflammatory joint diseases including chronic polyarthritis, polyarthrosis and painful conditions following trauma, e.g. muscle strains or tissue injuries. This is a symptomatic therapy that is prescribed as needed and for a limited period of time. The main disadvantage of a long-term prescription of systemically effective NSAIDs is the occurrence of upper abdominal complaints, as in acute gastritis, stomach and duodenal ulcers with additional bleeding complications.
In addition, systemic treatment with NSAIDs can only be used up to a certain degree of severity of the disease; beyond this, only systemic therapy with corticosteroids remains, the severe side effects of which are well known.
The group of NSAIDs includes a variety of different substances that share a common mode of action. This consists in the inhibition of the so-called cyclooxygenases (PGH synteases: PGHS-I, PGHS-2), which metabolize arachidonic acid as the substrate for the new synthesis of prostaglandins and thromboxane in this metabolic pathway.
The known effects of the group of non-steroidal anti-inflammatory drugs are mediated according to the state of the art by the inhibition of cyclooxygenase activity. Compared to cyclooxygenase inhibitors, glucocorticosteroids have a significantly higher anti-inflammatory effect with only insignificant anti-pyretic
sehen oder analgetischen Effekten. Die Ursache liegt in einer Hemmung der sogenannten Phospholipase-Aktivität im Bereich der Membran menschlicher Zellen, die Arachidonsäure aus den Phospholipidspeichern freisetzt und die schließlich über die Stoffwechselwege der Cyclooxygenasen und Lipoxygenasen zu verschiedenen Entzündungsmediatoren mit chemotaktischer Wirkung (Leukotrien B4) und bronchialkonstriktorischer Wirkung (Leukotrien C4, D4, E4) sowie zu Prostaglandinen und Thromboxan metabolisiert wird. Nach dem gegenwärtigen Kenntnisstand unterscheiden sich Glucocorticosteroide von den nicht-steroidalen Antiphlogistika durch die klinisch bekannte höhergradige Entzündungshemmung als Folge der starken Suppression der Leukotrien-Produktion. Jedoch wird durch Glucocorticosteroide infolge der Phospholipasehemmung der Arachidonsäuremetabolismus der Cyclooxygenase in deutlich vermindertem Maße gehemmt. Dadurch ist die steroid-induzierte Cyclooxygenase-Hemmung nie vollständig. Grundlage der neuentwickelten Therapie ist die steroidantagonistische Wirkung von Acetylsalicylsäure und vermutlich auch anderen nicht-steroidalen Antiphlogistika, wie z.B. von Diclofenac (Juergens et al.: Inhibition of moncyte leukotriene B4 production following aspirin desensitization. J. Allergy Clin. Immunol 1995; 96:148-156). Diese Untersuchungen zeigen, daß die A23187 stimulierte Produktion von LTB4 und LTC4 ex vivo mit der inflammatorischen Aktivität und dem systemischen Steroidbedarf der Atemwegserkfankung korreliert ist. Unter systemischer Dauertherapie mit Acetylsalicylsäure (1-2 &khgr; 650 mg) konnte eine signifikante Hemmung der monozytären LTB4-Produktion nachgewiesen werden. Diese Wirkung wird indirekt durch eine Stimulation der PGHS-2-Aktivität in Gegenwart einer Hemmung der PGHS-I vermittelt. Die nicht inhibierte PGHS-2 metabolisiert Arachidonsäure zu 15-HETE, das wiederum als Hemmstoff der 5-Lipoxygenaseaktivität bekannt ist. Die Hemmung der Leukotrienproduktion durch Acetylsalicylsäure und andere NSAIDs als neues antiphlogistisches Wirkungskonzept eröffnet neue Indikationen und Applikationsformen für den therapeutischen Einsatz von NSAIDs.or analgesic effects. The cause lies in an inhibition of the so-called phospholipase activity in the area of the membrane of human cells, which releases arachidonic acid from the phospholipid stores and which is finally metabolized via the metabolic pathways of the cyclooxygenases and lipoxygenases to various inflammatory mediators with chemotactic effects (leukotriene B4) and bronchial constrictor effects (leukotriene C4, D4, E4) as well as to prostaglandins and thromboxane. According to current knowledge, glucocorticosteroids differ from non-steroidal anti-inflammatory drugs in that they have a clinically known higher degree of inflammation inhibition as a result of the strong suppression of leukotriene production. However, glucocorticosteroids inhibit the arachidonic acid metabolism of the cyclooxygenase to a significantly lesser extent due to the phospholipase inhibition. As a result, the steroid-induced cyclooxygenase inhibition is never complete. The basis of the newly developed therapy is the steroid antagonistic effect of acetylsalicylic acid and presumably also other non-steroidal anti-inflammatory drugs, such as diclofenac (Juergens et al.: Inhibition of monocyte leukotriene B4 production following aspirin desensitization. J. Allergy Clin. Immunol 1995; 96:148-156). These studies show that the A23187-stimulated production of LTB4 and LTC4 ex vivo is correlated with the inflammatory activity and the systemic steroid requirement of the respiratory disease. A significant inhibition of monocyte LTB4 production was demonstrated under long-term systemic therapy with acetylsalicylic acid (1-2 x 650 mg). This effect is indirectly mediated by stimulation of PGHS-2 activity in the presence of inhibition of PGHS-I. The non-inhibited PGHS-2 metabolizes arachidonic acid to 15-HETE, which in turn is known to inhibitor 5-lipoxygenase activity. The inhibition of leukotriene production by acetylsalicylic acid and other NSAIDs as a new anti-inflammatory action concept opens up new indications and application forms for the therapeutic use of NSAIDs.
Der vorliegenden Erfindung liegt die Aufgabe zugrunde, ein Mittel zur Behandlung von chronischen, allergischen und infekt-exazerbierten Erkrankungen der oberen Atemwege bzw. steroid-pflichtigen Erkrankungen, bereitzustellen, bei dessen Verwendung weniger Neben-Wirkungen auftreten und das effektiver ist, als bei herkömmlichen Therapien.The present invention is based on the object of providing an agent for the treatment of chronic, allergic and infectious-exacerbated diseases of the upper respiratory tract or steroid-dependent diseases, the use of which has fewer side effects and is more effective than conventional therapies.
Die Aufgabe wird erfindungsgemäß durch ein topisches und systemisches
nicht-steroidales Antiphlogistikum (NSAID) zur Suppression der Leukotrien-Produktion, insbesondere des chemotaktisch
wirksamen Leukotrien B4, und der Prostaglandin- und/oder Thromboxanproduktion durch Inhibition der Enzymaktivitäten der
Phosphoslipasen, Lipoxygenasen und/oder Cyclooxygenasen gelöst.
Bei den nicht-steroidalen Antiphlogistika kann es sich erfindungsgernäß insbesondere um Essigsäure-, Propionsäure-, Fenaminsäure-,
Biphenylcarbonsäurederivate oder ein Oxicam handeln.
Besonders bevorzugt sind Acetylsalicylsäure, Diclofenac, Ibuprofen oder Indometazin.
Der wesentliche Vorteil dieser Verwendung eines NSAID besteht in einer überraschend hochgradigen anti-inflammatorischen Wirkung, die
insbesondere zur Hemmung lokaler Entzündungsprozesse führt.The object is achieved according to the invention by a topical and systemic non-steroidal anti-inflammatory drug (NSAID) for suppressing leukotriene production, in particular the chemotactically active leukotriene B4, and prostaglandin and/or thromboxane production by inhibiting the enzyme activities of phospholipases, lipoxygenases and/or cyclooxygenases.
According to the invention, the non-steroidal anti-inflammatory drugs can be, in particular, acetic acid, propionic acid, fenamic acid, biphenylcarboxylic acid derivatives or an oxicam.
Acetylsalicylic acid, diclofenac, ibuprofen or indomethacin are particularly preferred.
The main advantage of this use of an NSAID is a surprisingly high anti-inflammatory effect, which particularly leads to the inhibition of local inflammatory processes.
In einer bevorzugten Ausführungsform betrifft die vorliegende Erfindung
die Verwendung eines nicht-steroidalen Antiphlogistikums zur topischen Behandlung von akuten, infekt-exazerbierten Erkrankungen,
von allergischen, infekt-exazerbierten Erkrankungen und von chronisch entzündlichen, infekt-exazerbierten Erkrankungen der oberen
Atemwege.
Unter einer „akuten, infekt-exazerbierten Erkrankung der oberen Atemwege" wird in der vorliegenden Erfindung z.B. eine akute Rhinitis,
Rhinosinusitis, Sinusitis und Polyposis nasi mit oder ohne nasale Kongestion verstanden; entsprechend wird mit dem Begriff
„allergische, infekt-exazerbierte Erkrankung der oberen Atemwege"In a preferred embodiment, the present invention relates to the use of a non-steroidal anti-inflammatory drug for the topical treatment of acute, infectious-exacerbated diseases, of allergic, infectious-exacerbated diseases and of chronic inflammatory, infectious-exacerbated diseases of the upper respiratory tract.
In the present invention, an "acute, infection-exacerbated disease of the upper respiratory tract" is understood to mean, for example, acute rhinitis, rhinosinusitis, sinusitis and nasal polyposis with or without nasal congestion; accordingly, the term "allergic, infection-exacerbated disease of the upper respiratory tract"
-A--A-
beispielsweise eine allergische Rhinitis, Rhinosinusitis, Sinusitis, mit oder ohne nasale Kongestion bzw. mit dem Begriff „chronisch entzündliche, infekt-exazerbierte Erkrankung der oberen Atemwege" beispielsweise eine chronische Rhinitis, Rhinosinusitis, Sinusitis, Polyposis nasi mit oder ohne nasale Kongestion oder Anosmie bezeichnet.for example, allergic rhinitis, rhinosinusitis, sinusitis, with or without nasal congestion or the term "chronic inflammatory, infection-exacerbated disease of the upper respiratory tract" for example, chronic rhinitis, rhinosinusitis, sinusitis, nasal polyposis with or without nasal congestion or anosmia.
Unter einer „topischen Behandlung" versteht man hier die örtliche, d.h. lokale Anwendung eines Heilmittels im Gegensatz zu einer „systemischen Therapie", die eine den gesamten Organismus betreffende Behandlung (auch generalisierende Behandlung), d.h. ausschließlich durch orale oder intravenöse Applikation betrifft.A "topical treatment" is understood here to mean the local, i.e. local application of a medicinal product, in contrast to a "systemic therapy", which concerns a treatment affecting the entire organism (also generalized treatment), i.e. exclusively through oral or intravenous application.
Die Steroidpflichtigkeit bedeutet hier eine zwingende Abhängigkeit von täglicher, langfristiger oraler Einnahme systemisch wirkender GIukocorticosteroide. The need for steroids here means a mandatory dependency on daily, long-term oral intake of systemically acting glucocorticosteroids.
Die Erfindung betrifft insbesondere die Verwendung von nicht-steroidalen
Antiphlogistica zur topischen Behandlung steroidsensitiver und steroidpflichtiger Erkrankungen, vorzugsweise bei Erkrankungen der
oberen Atemwege.
Ein wesentlicher Vorteil hierbei ist, daß insbesondere steroidsensitive obere Atemwegserkrankungen mit NSAID topisch und/oder systemisch
behandelt werden können. Es wurde überraschend gefunden, daß unter Therapie mit Acetysalicylsäure dauerhaft die akute, chronische
und allergische Rhinosinusitis mit Rückentwicklung von Nasenpolypen erfolgreich behandelt werden können. Die Therapie spricht
insbesondere gut an bei Patienten mit erhöhtem Eosinophilen Cationic Protein (ECP) mit und ohne bronchialer Hyperreaktivität.
Die Folge ist eine topische und systemische Corticosteroid-Einsparung, z.B. bei Erkrankungen der oberen Atemwege, wie z.B. typischerweise
bei der Rhinosinusitis mit dauerhafter Beseitigung von Nasenpolypen.The invention particularly relates to the use of non-steroidal anti-inflammatory drugs for the topical treatment of steroid-sensitive and steroid-dependent diseases, preferably diseases of the upper respiratory tract.
A significant advantage here is that steroid-sensitive upper respiratory tract diseases in particular can be treated topically and/or systemically with NSAIDs. Surprisingly, it was found that acute, chronic and allergic rhinosinusitis with regression of nasal polyps can be successfully treated with acetylsalicylic acid. The therapy responds particularly well to patients with elevated eosinophil cationic protein (ECP) with and without bronchial hyperreactivity. The result is a reduction in topical and systemic corticosteroids, eg in upper respiratory tract diseases, such as rhinosinusitis with permanent elimination of nasal polyps.
Die Dosis einer erfindungsgemäßen topischen NSAID-Therapie kann beispielsweise bei der allergischen bzw. chronischen Rhinosinusitis ca. 50 bis 4000 pg/die pro Nasenloch, aufgeteilt in zwei Tagesdosen in einer Durchschnittsdosis von ca. 2 &khgr; 250 bis 1000 pg/die pro Nasenloch, betragen. In einer weiteren, ebenfalls bevorzugten Ausführungs-The dose of a topical NSAID therapy according to the invention can, for example, be about 50 to 4000 pg/day per nostril in allergic or chronic rhinosinusitis, divided into two daily doses in an average dose of about 2 x 250 to 1000 pg/day per nostril. In a further, also preferred embodiment,
form ■wird das NSAID in Form eines Nasensprays lokal applizieit. Das Polypenwachstum der Nase und wesentlich auch des Darms wird durch eine systemische Therapie und NSAIDs, wie z.B. Acetylsalicylsäure in dünndarmlöslichen Filmtabletten in einer Dosis von 300-900 mg/Tag, bevorzugt 600 mg/Tag, verhindert.form ■the NSAID is applied locally in the form of a nasal spray. The growth of polyps in the nose and, to a large extent, in the intestine is prevented by systemic therapy and NSAIDs, such as acetylsalicylic acid in intestinal-soluble film-coated tablets in a dose of 300-900 mg/day, preferably 600 mg/day.
Die Erfindung betrifft desweiteren die Verwendung eines nicht-steroidalen Antiphlogistikums zur topischen Therapie und Prophylaxe der Nasenpolypbildung und der topischen, prophylaktischen Behandlung der akuten, allergischen und chronischen Rhinosinusitis.The invention further relates to the use of a non-steroidal anti-inflammatory drug for the topical therapy and prophylaxis of nasal polyp formation and the topical, prophylactic treatment of acute, allergic and chronic rhinosinusitis.
Die systemische Verwendung hat in der Initialphase der Therapie den
Vorteil, daß höhere Plasmaspiegel erreicht werden und durch den systemischen Einsatz die entzündliche Infiltration verschiedener
Mediator produzierender Zellen in den oberen und unteren Atemwegen
durch die verminderte Produktion von chemotaktischen Faktoren (Leukotrien B4) reduziert bzw. verhindert wird. Die Folge ist eine
schnelle Abheilung der Nasenpolypen und Rhinosinusitis in Fällen mit schwerer klinischer Symptomatik, die schließlich topisch zur Rezidivprophylaxe
weitergeführt werden kann. Leichte und mittelschwere Fälle können dagegen sofort ohne vorhergehenden systemischen Einsatz
nicht-steroidaler Antiphlogistica primär topisch behandelt werden.
Bereits nach zwei- bis ca. achtwöchiger topischer Therapie mit Aspirin bis 2x1 mg/die ist die nasale Kongestion rückläufig und das Riech-
und Geschmacksvermögen wieder hergestellt. Die Behandlung der mit Anosmie assoziierten Polyposis nasi und Rhinosinusitis stellt daher
eine besondere Indikation für die erfindungsgemäße Verwendung der gesamten Stoffgruppe dar. Bei der akuten Rhinitis ist eine Rückbildung
der nasalen Kongestion nach 10-15 Minuten spürbar.
Das Wachstum von Nasenpolypen konnte durch eine topische Aspirin-Therapie
mit anfangs 2x1 mg/die über zwei Monate und anschließender Dosisreduktion auf Aspirin 1 mg/die bis zum Verschwinden
der Nasenpolypen und der Rhinosinusitis erfolgreich behandelt werden. Die systemische Behandlung zur PolyptherapieSystemic use in the initial phase of therapy has the advantage that higher plasma levels are achieved and the inflammatory infiltration of various mediator-producing cells in the upper and lower respiratory tract is reduced or prevented by systemic use through reduced production of chemotactic factors (leukotriene B4). The result is rapid healing of nasal polyps and rhinosinusitis in cases with severe clinical symptoms, which can then be continued topically to prevent recurrence. Mild and moderate cases, on the other hand, can be treated primarily topically immediately without prior systemic use of non-steroidal anti-inflammatory drugs. After just two to eight weeks of topical therapy with aspirin up to 2x1 mg/day, nasal congestion has subsided and the sense of smell and taste has been restored. The treatment of nasal polyposis and rhinosinusitis associated with anosmia therefore represents a special indication for the use of the entire group of substances according to the invention. In acute rhinitis, a regression of nasal congestion is noticeable after 10-15 minutes.
The growth of nasal polyps could be successfully treated with topical aspirin therapy, initially with 2x1 mg/day for two months and then a dose reduction to aspirin 1 mg/day until the nasal polyps and rhinosinusitis disappeared. Systemic treatment for polyp therapy
wird mit einer Tagesdosis von 900 mg (aufgeteilt in 600mg - 300 mg 0) über 3 Monate eingeleitet und mit 300-600 mg/Tag weitergeführt.is initiated with a daily dose of 900 mg (divided into 600 mg - 300 mg 0) over 3 months and continued with 300-600 mg/day.
In einer weiteren Ausführungsform wird erfindungsgemäß die Ver-Wendung eines nicht-steroidalen Antiphlogistikums zur symptomatischen Behandlung von akuter und chronischer Rhinosinusitis, allergischer Rhinosinusitis, allergischer Rhinitis, Polyposis nasi und Anosmie sowie z.B. bei Kopfschmerzen und nasaler Kongestion, beansprucht.In a further embodiment, the invention claims the use of a non-steroidal anti-inflammatory drug for the symptomatic treatment of acute and chronic rhinosinusitis, allergic rhinosinusitis, allergic rhinitis, nasal polyposis and anosmia, as well as, for example, headaches and nasal congestion.
Die Erfindung betrifft aber nicht nur die Verwendung von NSAID als Monosubstanz sondern insbesondere auch in Kombination mit mindestens einem Steroid, vorzugsweise mit mindestens einem topischen Steroid (Budesonid, Flunisolid, Beclomethason, Fluticason), einem etherischem Öl (1,8-Cineol, Menthol), einem Antihistaminicum, einem a-Sympathomimetikum oder einem zusätzlichen 5-Lipoxygenaseinhibitor. However, the invention relates not only to the use of NSAID as a monosubstance but also in particular in combination with at least one steroid, preferably with at least one topical steroid (budesonide, flunisolide, beclomethasone, fluticasone), an essential oil (1,8-cineole, menthol), an antihistamine, an α-sympathomimetic or an additional 5-lipoxygenase inhibitor.
Diese Kombination hat den entscheidenden Vorteil, daß hierdurch die anti-inflammatorische Wirkungen der NSAID verstärkt werden und die Kombination, z.B. mit einem a-Sympathomimetikum (= Reliever) und einem NSAID (= Preventer) ein sinnvolles und OTC-fähiges Therapiekonzept darstellen.This combination has the decisive advantage that the anti-inflammatory effects of the NSAID are enhanced and the combination, e.g. with an a-sympathomimetic (= reliever) and an NSAID (= preventer), represents a sensible and OTC-compatible therapy concept.
Ebenso können die erfindungsgemäß verwendeten NSAID mit verschiedenen Sympathomimetika zur Nasenschleimhautabschwellung (Ephedrin, Phenylephedrin, Phenylpropanolamin, Pseudoephedrin, Zylometazolin, Tramazolin, Petryzolin, Naphazolin, Oxymetazolin, Indanazolin u.a.), in Kombination mit Antiallergika (Cromoglycinsäure, Nedocromil, Cetirizin, Terfenadin, Oxatomid, Astemizol u.a.), in Kombination mit Antibiotika (Tetracyclin, Neomycin, Bacitracen u.a.), sowie in Kombination mit elektrolythaltigen Lösungen (z.B. EMSA-SoIe) kombiniert werden.The NSAIDs used according to the invention can also be combined with various sympathomimetics for reducing swelling of the nasal mucosa (ephedrine, phenylephedrine, phenylpropanolamine, pseudoephedrine, zylometazoline, tramazoline, petryzoline, naphazoline, oxymetazoline, indanazoline, etc.), in combination with antiallergics (cromoglycic acid, nedocromil, cetirizine, terfenadine, oxatomide, astemizole, etc.), in combination with antibiotics (tetracycline, neomycin, bacitracene, etc.), as well as in combination with electrolyte-containing solutions (e.g. EMSA soda).
Die Kombination nicht-steroidaler Antiphlogistica mit diesen Stoffen hat z.B. bei Erkrankungen der oberen Atemwege den Vorteil, das neben der antikongestiven oder antiallergischen Wirkung eine zusatz-The combination of non-steroidal anti-inflammatory drugs with these substances has the advantage, for example in diseases of the upper respiratory tract, that in addition to the anticongestive or antiallergic effect, an additional
liche stark anti-inflammatorische Wirkung mit Rückbildung der die Nasenschleimhaut infiltrierenden Zellen nachhaltig erreicht wird, so daß die bisher symptomatische Therapie durch einen kausalen Therapieansatz entscheidend gebessert werden kann (Preventer + Reliever).A strong anti-inflammatory effect with regression of the cells infiltrating the nasal mucosa is achieved in the long term, so that the previously symptomatic therapy can be significantly improved by a causal therapeutic approach (preventer + reliever).
Eine besonders bevorzugte Erfindungsform betrifft die obigen Verwendungen in Form einer topischen Dauertherapie. Ein wesentlicher Effekt hierbei ist der, daß trotz Dauertherapie wesentlich weniger Nebenwirkungen auftraten, als bei einer systemischen Dauertherapie. Außerdem ist eine deutlich bessere Wirkung durch die höhere lokale Wirkstoffkonzentration zu erwarten.A particularly preferred form of the invention relates to the above uses in the form of a long-term topical therapy. A significant effect here is that, despite long-term therapy, significantly fewer side effects occurred than with long-term systemic therapy. In addition, a significantly better effect can be expected due to the higher local active ingredient concentration.
Die systemische Dauertherapie mit nicht-steroidalen Antiphlogistica verhinderte außerdem prophylaktisch ein Nachwachsen der Nasenpolypen und sicherte die Ausheilung der Rhinosinusitis und ist zudem geeignet zur postoperativen Rezidivprophylaxe von Nasenpolypen. Die systemische Therapie mit NSAID ist sehr wahrscheinlich auch zur Behandlung von Darmpolypen geeignet und dürfte die vorliegenden Ergebnisse zur Wirkung von Aspirin auf das Coloncarcinom, das aus entarteten Polypen hervorgehen kann, erklären helfen. Insofern ist zu vermuten, daß die nachgewiesene NSAID-Wirkung auch die Polypen im Darm und das Risiko der Präcancerose und des Coloncarcinoms signifikant vermindern wird.Long-term systemic therapy with non-steroidal anti-inflammatory drugs also prevented the nasal polyps from growing back and ensured that the rhinosinusitis healed. It is also suitable for postoperative prophylaxis against the recurrence of nasal polyps. Systemic therapy with NSAIDs is very likely also suitable for treating intestinal polyps and may help to explain the current results on the effect of aspirin on colon carcinoma, which can arise from degenerated polyps. It can therefore be assumed that the proven NSAID effect will also significantly reduce polyps in the intestine and the risk of precancerous lesions and colon carcinoma.
Claims (5)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE29680627U DE29680627U1 (en) | 1995-07-20 | 1996-07-18 | Non-steroidal anti-inflammatory drug for topical and systemic treatment of acute and chronic polypoid rhinosinusitis |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19526425 | 1995-07-20 | ||
| PCT/DE1996/001304 WO1997003659A1 (en) | 1995-07-20 | 1996-07-18 | Use of a non-steroidal anti-inflammatory drug for topical and systemic treatment of acute and chronic polypoid rhinosinusitis |
| DE29680627U DE29680627U1 (en) | 1995-07-20 | 1996-07-18 | Non-steroidal anti-inflammatory drug for topical and systemic treatment of acute and chronic polypoid rhinosinusitis |
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| DE29680627U1 true DE29680627U1 (en) | 1999-06-02 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE29680627U Expired - Lifetime DE29680627U1 (en) | 1995-07-20 | 1996-07-18 | Non-steroidal anti-inflammatory drug for topical and systemic treatment of acute and chronic polypoid rhinosinusitis |
| DE19680594T Expired - Fee Related DE19680594D2 (en) | 1995-07-20 | 1996-07-18 | Use of a non-steroidal anti-inflammatory drug for topical and systemic treatment of acute and chronic polypoid rhinosinusitis |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19680594T Expired - Fee Related DE19680594D2 (en) | 1995-07-20 | 1996-07-18 | Use of a non-steroidal anti-inflammatory drug for topical and systemic treatment of acute and chronic polypoid rhinosinusitis |
Country Status (4)
| Country | Link |
|---|---|
| EP (1) | EP0839031A1 (en) |
| AU (1) | AU6512296A (en) |
| DE (2) | DE29680627U1 (en) |
| WO (1) | WO1997003659A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE102015119541A1 (en) * | 2015-10-23 | 2017-04-27 | Maria Clementine Martin Klosterfrau Vertriebsgesellschaft Mbh | Monoterpene-containing composition for the treatment of diseases of the nose |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6231888B1 (en) | 1996-01-18 | 2001-05-15 | Perio Products Ltd. | Local delivery of non steroidal anti inflammatory drugs (NSAIDS) to the colon as a treatment for colonic polyps |
| US6380222B2 (en) | 1996-10-11 | 2002-04-30 | Astrazeneca Ab | Use of an H+, K+-atpase inhibitor in the treatment of nasal polyps |
| US6632451B2 (en) | 1999-06-04 | 2003-10-14 | Dexcel Pharma Technologies Ltd. | Delayed total release two pulse gastrointestinal drug delivery system |
| CA2398642A1 (en) * | 2000-01-31 | 2001-08-02 | Yuhong Zhou | Mucin synthesis inhibitors |
| US7345051B2 (en) | 2000-01-31 | 2008-03-18 | Genaera Corporation | Mucin synthesis inhibitors |
| US20020147216A1 (en) * | 2000-01-31 | 2002-10-10 | Yuhong Zhou | Mucin synthesis inhibitors |
| EA033355B1 (en) * | 2015-08-18 | 2019-10-31 | State Institution The Republican Center For Res And Practice In Otorhinolaryngology Rnpc Otorinolari | Method of treating chronic polypoid rhinosinusitis in a patient with aspirin triad |
| WO2019190503A1 (en) * | 2018-03-28 | 2019-10-03 | Cove Bio Llc | Methods and compositions for treating parkinson's disease |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4933365A (en) * | 1989-01-25 | 1990-06-12 | American Home Products Corporation | Phospholipase A2 inhibitors |
| DE59108814D1 (en) * | 1990-09-05 | 1997-09-11 | Ciba Geigy Ag | Diphenyl compounds inhibiting arachidonic acid metabolism and their use in pharmaceutical compositions |
| AU666852B2 (en) * | 1991-05-01 | 1996-02-29 | Henry M. Jackson Foundation For The Advancement Of Military Medicine | A method for treating infectious respiratory diseases |
| DE4333794A1 (en) * | 1993-10-04 | 1995-04-06 | Carl Heinrich Dr Weischer | Acetylsalicylic acid derivatives for controlling states of inflammation and pain and for the prophylaxis and therapy of thrombosis |
-
1996
- 1996-07-18 DE DE29680627U patent/DE29680627U1/en not_active Expired - Lifetime
- 1996-07-18 EP EP96924744A patent/EP0839031A1/en not_active Withdrawn
- 1996-07-18 DE DE19680594T patent/DE19680594D2/en not_active Expired - Fee Related
- 1996-07-18 WO PCT/DE1996/001304 patent/WO1997003659A1/en not_active Application Discontinuation
- 1996-07-18 AU AU65122/96A patent/AU6512296A/en not_active Abandoned
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE102015119541A1 (en) * | 2015-10-23 | 2017-04-27 | Maria Clementine Martin Klosterfrau Vertriebsgesellschaft Mbh | Monoterpene-containing composition for the treatment of diseases of the nose |
Also Published As
| Publication number | Publication date |
|---|---|
| AU6512296A (en) | 1997-02-18 |
| WO1997003659A1 (en) | 1997-02-06 |
| DE19680594D2 (en) | 1997-09-18 |
| EP0839031A1 (en) | 1998-05-06 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| R163 | Identified publications notified | ||
| R409 | Internal rectification of the legal status completed | ||
| R207 | Utility model specification |
Effective date: 19990715 |
|
| R156 | Lapse of ip right after 3 years |
Effective date: 20000503 |
|
| R156 | Lapse of ip right after 3 years |
Effective date: 20020501 |