EP0839031A1 - Utilisation d'un medicament anti-inflammatoire non-steroidien pour le traitement topique et general de la rhino-sinusite polypoide aigüe et chronique - Google Patents

Utilisation d'un medicament anti-inflammatoire non-steroidien pour le traitement topique et general de la rhino-sinusite polypoide aigüe et chronique

Info

Publication number
EP0839031A1
EP0839031A1 EP96924744A EP96924744A EP0839031A1 EP 0839031 A1 EP0839031 A1 EP 0839031A1 EP 96924744 A EP96924744 A EP 96924744A EP 96924744 A EP96924744 A EP 96924744A EP 0839031 A1 EP0839031 A1 EP 0839031A1
Authority
EP
European Patent Office
Prior art keywords
steroidal anti
inflammatory drug
topical
inflammatory
chronic
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP96924744A
Other languages
German (de)
English (en)
Inventor
Uwe R. Juergens
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Individual
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Individual filed Critical Individual
Publication of EP0839031A1 publication Critical patent/EP0839031A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • 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
    • 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
    • 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 
    • 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
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—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
    • 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
    • A61K31/404—Indoles, e.g. pindolol
    • A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca

Definitions

  • the present invention relates to the use of non-steroidal anti-inflammatory drugs in diseases of the upper and lower respiratory tract.
  • non-steroidal anti-inflammatory drugs hereinafter abbreviated as NSAID: "non-steroidal anti inflammatory drugs”
  • NSAIDs are used systemically for the treatment of inflammatory joint diseases including chronic polyarthritis, polyarthrosis and used for painful conditions after trauma, eg muscle strain, tissue injury .. This is a symptomatic therapy that is prescribed as needed and for a limited time.
  • the decisive disadvantage of a permanent prescription of systemically effective NSAID is known to be the occurrence of Ober ⁇ abdominal discomfort, such as acute gastritis, gastric and duodenal ulcers with additional bleeding complications, in addition, systemic treatment with NSAID can only be used up to a certain severity of the disease, and only systemic therapy with corticosterois remains the rest whose serious side effects are well known.
  • the NSAID group includes a large number of different substances that are based on a common principle of action.
  • 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 ultimately leads via the metabolic pathways of the cyclooxygenases and lipoxygenases to various inflammation mediators with a chemotactic effect ( Leukotriene B4) and bronchial constrictive effects (leukotriene C4, D4, E4) as well as to prostaglandins and thromboxane is metabolized.
  • glucocorticosteroids differ from the non-steroidal anti-inflammatory drugs by the clinically known higher-level anti-inflammatory effect as a result of the strong suppression of leukotriene production.
  • Leukotriene production by acetylsalicylic acid and other NSAIDs as a new anti-inflammatory concept of action opens up new indications and forms of application for the therapeutic use of NSAIDs. It is the object of the present invention to provide a means for the treatment of chronic, allergic and infection-exacerbated diseases of the upper respiratory tract or diseases requiring steroids, the use of which results in fewer side effects and which is more effective than in the case of usual
  • the object is achieved according to the invention by the topical and systematic use of a non-steroidal anti-inflammatory drug (NSAID) for the suppression of the leukotriene production, in particular the chemotactically active leukotriene B4, and the prostaglandin and / or thromboxane production by inhibiting the enzyme activities of the phosphoslipases , Lipoxygenases and / or cyclooxygenases dissolved.
  • the non-steroidal anti-inflammatory agents can be, in particular, acetic acid, propionic acid, fenamic acid, biphenylcarboxylic acid derivatives or an oxicam.
  • Acetylsalicylic acid, diclofenac, ibuprofen or indometazine are particularly preferred.
  • the main advantage of using an NSAID is a surprisingly high level of anti-inflammatory activity, which leads in particular to the inhibition of local inflammatory processes.
  • the present invention relates to the use of a non-steroidal anti-inflammatory drug for the topical treatment of acute, infection-exacerbated diseases, of allergic, infection-exacerbated diseases and of chronic inflammatory, infection-exacerbated diseases of the upper respiratory tract. Under an "acute, infection-exacerbated disease of the upper respiratory tract
  • Respiratory tract in the present invention is understood to mean, for example, acute rhinitis, rhinosinusitis, sinusitis and polyposis nasi with or without nasal congestion.
  • allergic, infection-exacerbated disease of the upper respiratory tract for example allergic rhinitis, rhinosinusitis, sinusitis, with or without nasal congestion or with the term "chronically inflammatory, infection-exacerbated disease of the upper respiratory tract", for example chronic rhinitis, rhinosinusitis, sinusitis, nasal polyposis with or without nasal Congestion or anosmia.
  • a “topical treatment” here means the local, i.e. local application of a remedy in contrast to a “systemic therapy”, which is a treatment that affects the entire organism (also generalizing treatment), i.e. only affected by oral or intravenous administration.
  • the invention relates in particular to the use of non-steroidal anti-inflammatory agents for the topical treatment of steroid-sensitive and steroid-requiring diseases, preferably in diseases of the upper respiratory tract.
  • An important advantage here is that in particular steroid-sensitive upper respiratory diseases can be treated topically and / or systemically with NSAID. It was surprisingly found that acute, chronic and allergic rhinosinusitis with regression of nasal polyps can be successfully treated under therapy with acetysalicylic acid. The therapy responds particularly well in patients with increased eosinophil cationic
  • a topical NSAID therapy can, for example in the case of allergic or chronic rhinosinusitis, approximately 50 to 4000 ⁇ g / die per nostril, divided into two daily doses in an average dose of approx , amount.
  • the NSAID is applied locally in the form of a nasal spray.
  • NSAIDs such as, for example, acetylsalicylic acid in small intestine-soluble film tablets in a dose of 300-900 mg / day, preferably 600 mg / day.
  • the invention further relates to the use of a non-steroidal anti-inflammatory for topical therapy and prophylaxis of nasal polyp formation and topical, prophylactic treatment of acute, allergic and chronic rhinosinusitis.
  • the systemic use in the initial phase of the therapy has the advantage that higher plasma levels are achieved and, through the systemic use, the inflammatory infiltration of various mediator-producing cells in the upper and lower respiratory tract due to the reduced production of chemotactic factors (leukotriene B4) is reduced or prevented.
  • the result is a rapid healing of the nasal polyps and rhinosinusitis in cases with severe clinical symptoms, which can ultimately be continued topically for the prevention of recurrence.
  • mild and moderate cases can be treated topically immediately without prior systemic use of non-steroidal anti-inflammatory drugs.
  • topical therapy with aspirin up to 2 x 1 mg / day, the nasal congestion has decreased and the smell and taste have been restored.
  • the treatment of the polyposis nasi and rhinosinusitis associated with anosmia therefore represents a special indication for the use according to the invention of the entire group of substances.
  • acute rhinitis the nasal congestion regresses after 10-15 minutes.
  • the growth of nasal polyps was successfully treated by topical aspirin therapy with initially 2 x 1 mg / over two months and then reducing the dose to aspirin 1 mg / until the nasal polyps and rhinosinusitis disappeared.
  • the systemic treatment for polyptherapy 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.
  • a non-steroidal anti-inflammatory agent for the symptomatic treatment of acute and chronic rhinosinusitis, allergic rhinosinusitis, allergic rhinitis, nasal polyposis and anosmia and e.g. for headaches and nasal congestion.
  • the invention not only relates to the use of NSAID as
  • topical steroid preferably with at least one topical steroid (budesonide, flunisolide, beclomethasone, fluticasone), an essential oil (1,8-cineol, menthol), an antihistamine, an ⁇ -sympathomimetic or an additional 5-lipoxygenase inhibitor.
  • the NSAID used according to the invention can be used with various sympathomimetics for swelling of the nasal mucosa (ephedrine, phenylephedrine, phenylpropanolamine, pseudoephedrine,
  • 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 anti-congestive or anti-allergic effects, strong anti-inflammatory effect is achieved with regression of the cells infiltrating the nasal mucosa, so that the previously symptomatic therapy can be decisively improved by a causal therapy approach (Preventer + Reliever).
  • a particularly preferred form of the invention relates to the above uses in the form of continuous topical therapy.
  • a major effect here is that, despite long-term therapy, fewer side effects occurred than with systemic long-term therapy.
  • systemic long-term therapy with non-steroidal anti-inflammatory drugs also prevented prophylactically the regrowth of the nasal polyps and ensured the healing of the rhinosinusitis and is also suitable for the postoperative prevention of recurrence of nasal polyps.
  • Systemic therapy with NSAID is very likely also suitable for the treatment of intestinal polyps and should help explain the results available on the effect of aspirin on colon carcinoma, which can result from degenerate polyps. In this respect it can be assumed that the proven NSAID effect will also significantly reduce the polyps in the intestine and the risk of precancerosis and colon carcinoma.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pain & Pain Management (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

L'invention concerne l'utilisation de médicaments anti-inflammatoires pour traiter des maladies des voies respiratoires supérieures et la polypose, spécialement pour supprimer la production de leucotriène, principalement de LTB4 chimiotactiquement actif, ainsi que la production de prostaglandine et de thromboxane par inhibition de l'activité enzymatique des phospholipases, les lipoxygénases et/ou des cyclo-oxygénases.
EP96924744A 1995-07-20 1996-07-18 Utilisation d'un medicament anti-inflammatoire non-steroidien pour le traitement topique et general de la rhino-sinusite polypoide aigüe et chronique Withdrawn EP0839031A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE19526425 1995-07-20
DE19526425 1995-07-20
PCT/DE1996/001304 WO1997003659A1 (fr) 1995-07-20 1996-07-18 Utilisation d'un medicament anti-inflammatoire non-steroidien pour le traitement topique et general de la rhino-sinusite polypoide aigüe et chronique

Publications (1)

Publication Number Publication Date
EP0839031A1 true EP0839031A1 (fr) 1998-05-06

Family

ID=7767281

Family Applications (1)

Application Number Title Priority Date Filing Date
EP96924744A Withdrawn EP0839031A1 (fr) 1995-07-20 1996-07-18 Utilisation d'un medicament anti-inflammatoire non-steroidien pour le traitement topique et general de la rhino-sinusite polypoide aigüe et chronique

Country Status (4)

Country Link
EP (1) EP0839031A1 (fr)
AU (1) AU6512296A (fr)
DE (2) DE19680594D2 (fr)
WO (1) WO1997003659A1 (fr)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
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
US6599927B2 (en) 1996-10-11 2003-07-29 Astrazeneca Ab Use of an H+, K+-ATPase inhibitor in the treatment of Widal's Syndrome
US6632451B2 (en) 1999-06-04 2003-10-14 Dexcel Pharma Technologies Ltd. Delayed total release two pulse gastrointestinal drug delivery system
US20020147216A1 (en) * 2000-01-31 2002-10-10 Yuhong Zhou Mucin synthesis inhibitors
US7345051B2 (en) 2000-01-31 2008-03-18 Genaera Corporation Mucin synthesis inhibitors
DK1255544T3 (da) * 2000-01-31 2007-09-17 Genaera Corp Mucin-syntese-inhibitorer
EA033355B1 (ru) * 2015-08-18 2019-10-31 State Institution The Republican Center For Res And Practice In Otorhinolaryngology Rnpc Otorinolari Способ лечения хронического полипозного риносинусита у пациента с аспириновой триадой
DE102015119541A1 (de) * 2015-10-23 2017-04-27 Maria Clementine Martin Klosterfrau Vertriebsgesellschaft Mbh Monoterpenhaltige Zusammensetzung zur Behandlung von Erkrankungen der Nase
WO2019190503A1 (fr) * 2018-03-28 2019-10-03 Cove Bio Llc Procédés et compositions pour le traitement de la maladie de parkinson

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4933365A (en) * 1989-01-25 1990-06-12 American Home Products Corporation Phospholipase A2 inhibitors
DE59108814D1 (de) * 1990-09-05 1997-09-11 Ciba Geigy Ag Arachidonsäurestoffwechselhemmende Diphenylverbindungen und ihre Verwendung in pharmazeutischen Zusammensetzungen
DE69232706T2 (de) * 1991-05-01 2002-11-28 Jackson H M Found Military Med Verfahren zur behandlung infektiöser respiratorischer erkrankungen
DE4333794A1 (de) * 1993-10-04 1995-04-06 Carl Heinrich Dr Weischer Neue Acetyl-Salicylsäure-Derivate zur Bekämpfung von Entzündungs- und Schmerzzuständen sowie zur Thromboseprophylaxe und -terapie

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9703659A1 *

Also Published As

Publication number Publication date
DE19680594D2 (de) 1997-09-18
WO1997003659A1 (fr) 1997-02-06
AU6512296A (en) 1997-02-18
DE29680627U1 (de) 1999-06-02

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