Nichtsteroidale Antiphlogistika Thrombophlebitis

Wirkstoffe: Betamethasondihydrogenphosphat-Dinatrium (Ph.Eur.), Betamethasondipropionat (Ph.Eur.).

This page includes the following topics and synonyms: Nonsteroidal Anti-inflammatory, Non-Steroidal Antiinflammatory, Non-Opioid Analgesics, NSAID.

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Although access to this page is not restricted, the information found here is intended for use by medical providers. Acetaminophen Acetaminophen Acetaminophen Toxicity. Topical Medications Topical Analgesic Capsaicin. Obstetrics Chapter related topics Analgesic Medications in Pregnancy.

Salicylate s Acetylsalicylic acid Aspirin mg q hours Trisalicylate Nichtsteroidale Antiphlogistika Thrombophlebitis mg q hours Diflunisal Dolobid mg q hours Superior and longer acting than Aspirin mg Superior and longer acting than Acetaminophen mg Salsalate Disalcid Sodium Salicylate Uracil 5 Sodium thiosalicylate Tusal Preparations: Oxicams Gene ral Long half life once a day dosing Meloxicam Mobic 7.

Diclofenac Potassium Cataflam nichtsteroidale Antiphlogistika Thrombophlebitis mg orally every 8 hours Comparable to Aspirin Faster absorption hence faster onset than diclofenac Sodium voltaren Diclofenac XR mg orally nichtsteroidale Antiphlogistika Thrombophlebitis Arthrotec 50 mg Diclofenac with mcg Misoprostel Zorvolex 18 or 35 mg orally every 8 hours Released in as expensive, lower dose version of Diclofenac Potassium 50 mg No evidence of improved safety or similar efficacy to the lower priced, nichtsteroidale Antiphlogistika Thrombophlebitis, higher dose 50 mg tablet Recommendations are still to use other systemic NSAIDs instead of diclofenac Presc Lett 21 2: In addition to anti-inflammatory actions, they have analgesic, antipyretic, and platelet-inhibitory actions.

They act by blocking the synthesis of prostaglandins by inhibiting cyclooxygenase, which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins. Inhibition of prostaglandin synthesis accounts for their analgesic, antipyretic, nichtsteroidale Antiphlogistika Thrombophlebitis, and platelet-inhibitory actions; other mechanisms may contribute to their anti-inflammatory effects. Definition NCI Anti-inflammatory agents that are not steroids.

They are used primarily in the treatment of chronic arthritic conditions and certain soft tissue disorders associated with pain and inflammation.

MeSH Definition CSP agents that counteract or suppress inflammation and are not steroids; most have in addition analgesic, antipyretic, and platelet-inhibitory actions; they act by blocking the synthesis of prostaglandins by inhibiting cyclooxygenase, which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins: Anti-inflammatory agents that are non-steroidal in nature. Anti-inflammatory agents that are not steroids.

Antiphlogistika, nichtsteroidale, Entzündungshemmende Mittel, nichtsteroidale, Nichtsteroidale entzündungshemmende Mittel.

- Thrombophlebitis. - Thrombophlebitis migrans. und nichtsteroidale Antiphlogistika. ; und NSAR. ; und Orlistat. ; und Phenytoin. ; und.

Die Erfindung betrifft teilweise neue 1- 2-Hydroxyaryl -alkanon-oxime, Verfahren zu ihrer Herstellung und ihre Anwendung in pharmazeutischen Zubereitungen. The invention relates in part to new 1- 2-hydroxyaryl alkaneone-oxime, processes for their preparation and their use in pharmaceutical preparations The invention relates in part to new 1- 2-hydroxyaryl alkaneone-oxime, processes for their preparation and their use in pharmaceutical preparations.

Aufgabe der Erfindung ist die Entwicklung von 1- 2-Hydroxyaryl -alkanon-oximen mit wertvollen pharmakologischen Eigenschaften. The object of the invention is the development of 1- 2-hydroxyaryl alkaneone-oximes having valuable pharmacological properties. First Pharmazeutische Zusammensetzungen, gekennzeichnet durch einen Gehalt an 1- 2-Hydroxyaryl -alkanon-oximen der allgemeinen Formel I Pharmaceutical compositions characterized by a content of 1- 2-hydroxyaryl alkaneone-oximes of the general formula I.

Verwendung von pharmazeutischen Zusammensetzungen nach Punkt 1 oder Verbindungen nach Punkt 2 als universelle Lipoxygenasehemmer. Use of pharmaceutical compositions according to item 1 or compounds according to item 2 as a universal lipoxygenase inhibitor.

A composition for the treatment of all allergic diseases, especially atopic dermatitis, allergic rhinitis, urticaria, angioedema, contact dermatitis, allergic conjunctivitis and allergic disorders of the nichtsteroidale Antiphlogistika Thrombophlebitis tract, characterized by containing one or more active ingredients according to item 1 or the second. A composition for the nichtsteroidale Antiphlogistika Thrombophlebitis of inflammatory diseases, in particular those in which the conventional antiinflammatory drugs, whose application point is not the Lipoxygenese 'show insufficient therapeutic effects, particularly in purulent inflammations and rheumatic and arthritic diseases, characterized by nichtsteroidale Antiphlogistika Thrombophlebitis content of one or more active ingredients according to item 1 or the second.

The composition for the nichtsteroidale Antiphlogistika Thrombophlebitis of all forms of thrombosis, especially thrombophlebitis, and for prophylaxis of thrombosis in chronically ischemic heart disease, post-treatment at Myokardinfekt, chronic recurrent thrombosis and chronic thrombophlebitis, nichtsteroidale Antiphlogistika Thrombophlebitis, characterized by the content of one or more active ingredients according to item 1 or the second, nichtsteroidale Antiphlogistika Thrombophlebitis.

A composition for use as antiatherosclerotic, gastroprotective or antimetastatic drugs, characterized by the content of one or more active ingredients according to item 1 or the second. A composition for the treatment of all forms of arterial hypertension, in particular arterial hypertension in the pulmonary circulationcharacterized by the content of one or more active ingredients according to item 1 or the second, nichtsteroidale Antiphlogistika Thrombophlebitis.

A composition for use as spasmolytics for the treatment of spastic conditions of the smooth musculature of various origins, especially in different sections of the digestive and urogenital tracts and the blood vessel musculature, characterized by the content of one or more active ingredients according to item 1 or the second.

A medicament containing at least one compound of, formula I according to point 1 in combination with at least one of the traditional antiallergic, antiasthmatic, antiphlogistic, nichtsteroidale Antiphlogistika Thrombophlebitis. A process for the preparation of the ketones used according to item 13, characterized in that an optional further phenolic hydroxyl group is etherified with an alkylating agent, preferably with alkyl, aralkyl or Cycloalkylbromiden or chlorides in the presence of a basic substance.

The method of item 13 and 14, characterized in that the etherification is carried out in low boiling alkyl glycols. A process for the preparation of medicaments, characterized in that pharmaceutical compositions according to item 1 or compounds according to point 2, nichtsteroidale Antiphlogistika Thrombophlebitis, if appropriate together with excipients and carriers into a suitable administration form, are transferred.

Titel der Erfindung Title of the invention [] []. Die Verbindun- ,gen als solche und die sie enthaltenden pharmazeutischen Mittel zeigen wertvolle pharmakologische, insbesondere antiasthmatische, antianaphylaktische, antiphlogistische, antihypertensive, spasmolytische, antirheumatische nichtsteroidale Antiphlogistika Thrombophlebitis antithrombotische Eigenschaften und sind in der Human- und Veterinärmedizin für die Anwendung in der Therapie des Asthma bronchiale und anderer allergischer Erkrankungen, von entzündlichen und rheumatischen Erkrankungen verschiedener Art sowie der Thrombose geeignet.

The Verbindun- nichtsteroidale Antiphlogistika Thrombophlebitis, called as such and the pharmaceutical agents containing them exhibit valuable pharmacological, particularly antiasthmatic, anti-anaphylactic, nichtsteroidale Antiphlogistika Thrombophlebitis, nichtsteroidale Antiphlogistika Thrombophlebitis, antihypertensive, antispasmodic, antirheumatic and antithrombotic properties and are used in human and veterinary medicine for use in the treatment of bronchial asthma and other allergic diseases, capable of nichtsteroidale Antiphlogistika Thrombophlebitis and rheumatic diseases of various kinds, as well as thrombosis.

Verfahren zur Herstellung von Ketoximen sind an sich hinreichend bekannt und in jedem Handbuch über organische Synthesen vgl. Weygand-Hilgetag, nichtsteroidale Antiphlogistika Thrombophlebitis, Organisch-Chemische Experimentierkunst zu finden. A process for producing ketoximes are well known and can be found in any handbook on organic synthesis cf.

Für die Umsetzung von 1-Aryl-alkanonen mit Hydroxylaminhydrochlorid zu den-Oximen sind in der Literatur verschiedene Methoden beschrieben. For the reaction of 1-aryl-alkaneones with hydroxylamine to oximes different methods are described in the literature.

Allerdings sind dabei häufig die Reaktionsbedingungen wie Reaktionszeiten, Art der verwendeten Base ua in Abhängigkeit von der Struktur des Ausgangsketons nicht optimal gewählt. However, while the reaction conditions such as reaction time, type of base used often include non-optimally selected depending on the structure of the starting ketone. Von den 1-Aryl-alkanon-oximen zeichnen sich besonders die 1- 2-Hydroxyphenyl -alkanon-oxime durch ihre Verwendung in der Metallanalytik als Metallreagentien und in der Hydrometallurgie als selektive Metallextraktionsmittel für die Flüssig-Flüssig-Extraktion aus BRD-OS Of the 1-aryl-alkanone oximes especially the 1- 2-hydroxyphenyl drawing alkaneon-oxime by its use in metal analysis as metal reagents and in hydrometallurgy as selective metal extractant for the liquid -liquid extraction from BRD-OS 2, nichtsteroidale Antiphlogistika Thrombophlebitis, The 5-iso-nonylhydroxy-acetophenone-oxime SME by Shell Chemicals has for nichtsteroidale Antiphlogistika Thrombophlebitis recovery of copper industrial importance Extr.

Über eine Anwendung dieser Verbindungen als Pharmaka in der Human- und Veterinärmedizin wurden keinerlei Angaben gefunden. About an application of these compounds as pharmaceuticals in human and veterinary medicine no information has Thrombophlebitis Aussehen found.

Ziel der Erfindung ist die Bereitstellung von pharmazeutischen Zubereitungen mit pharmakologisch wertvollen, insbesondere antiasthmatischen, nichtsteroidale Antiphlogistika Thrombophlebitis, antianaphylaktischen, antiphlogistischen, antirheumatischen, antihypertensiven, spasmolytischen und antithrombotischen Eigenschaften. The aim of the invention is the provision of pharmaceutical formulations with pharmacologically valuable, especially anti-asthmatic, antianaphylaktischen, nichtsteroidale Antiphlogistika Thrombophlebitis, antiphlogistic, antirheumatic, anti-hypertensive, anti-thrombotic and spasmolytic properties.

Aufgabe der Erfindung ist die Entwicklung von teilweise neuen 1- 2-Hydroxyaryl -alkanon-oximen mit antiasthmatischen und weiteren pharmakologisch wertvollentEigenschaften, die auf der Hemmung der Lipoxygenase beruhen, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel. The object of the invention is the development of some new 1- 2-hydroxyaryl alkaneone-oximes with anti-asthmatic and other pharmacologically worth fully properties, which are based on the inhibition of lipoxygenase, to processes for their preparation and their use as medicaments.

Falls das entstandene Keton noch eine weitere Hydroxylgruppe enthält, wird diese mit einem Alkylierungsmittel, z. Alkylhalogeniden, Aralkyl- oder Cycloalkylbromid- oder chlorid, nichtsteroidale Antiphlogistika Thrombophlebitis, vorzugsweise jedoch mit einem Alkylbromid verethert.

If the resulting ketone contains an additional hydroxyl group, this with an alkylating agent, for, nichtsteroidale Antiphlogistika Thrombophlebitis.

Example, alkyl halides, aralkyl or Cycloalkylbromid- or chloride, nichtsteroidale Antiphlogistika Thrombophlebitis, but preferably etherified with an alkyl bromide. Das Keton wird dann in bekannter Weise mit Hydroxylaminhydrochlorid oder einem anderen geeigneten Hydroxylaminsalz in basischem Medium zum Oxim umsetzt, nichtsteroidale Antiphlogistika Thrombophlebitis. The ketone is then reacted in known manner with hydroxylamine hydrochloride or other suitable salt of hydroxylamine in a basic medium to give the oxime.

Es können dazu anorganische oder organische Basen verwendet werden, wie z. Natrium- oder Kaliumhydroxid, Calciumhydroxid, Natrium- oder Kaliumcarbonat, Natriumhydrogencarbonat, Natrium- oder Kaliumacetat, Natriumformiat, Pyridin, Piperidin, Morpholin, N-Methylpiperazin, Diethanolamin ua Die Veretherung und die Oximierung werden in organischen Lösungsmitteln durchgeführt, die Veretherung erfolgt vorzugsweise in Aceton oder niederen aliphatischen Alkoholen unter Zusatz eines vorstehend aufgeführten basischen Stoffes, insbesondere Kaliumcarbonat oder Natriumhydroxid, die Oximbildung in niederen aliphatischen Alkoholen bzw.

It can do this inorganic or organic bases are used, such as. For example, sodium or potassium hydroxide, calcium hydroxide, sodium or potassium carbonate, sodium nichtsteroidale Antiphlogistika Thrombophlebitis, sodium or potassium acetate, sodium formate, pyridine, piperidine, morpholine, N-methylpiperazine, diethanolamine, nichtsteroidale Antiphlogistika Thrombophlebitis, etc.

Die Reaktionszeiten für die Alklierungsreaktion liegen zwischen 15 und 30 Stunden und für die Oximierungsreaktion zwischen 15 Minuten und 3 Stunden Nach diesem Verfahren konnten auch neue, in der Literatur bisher nicht beschriebene und hinsichtlich Elementaranalyse, Schmelzpunkt und IR-spektraler Eigenschaften charakterisierte Verbindungen erhalten werden, die in Tabelle 1 zusammengestellt sind.

The reaction times for the Alklierungsreaktion be between 15 and 30 hours and for the oximation reaction between 15 minutes and 3 hours by this process could be obtained also new, previously described in the literature and characterized with regard to elemental analysis, melting point and IR spectral characteristics compounds are summarized in table 1 below.

Surprisingly, it was found that Varbindungen the invention of the general formula I show in animal studies in vitro and in vivo pronounced anti-asthmatic, anti-allergic and anti-anaphylactic effects. Die Prüfung auf die genannten pharmakologischen Eigenschaften erfolgte z.

Beispiel 16 und der isolierten Arteria pulmonalis vgl. Beispiel 18 sowie an der spezifisch-allergisch induzierten Bronchokonstriktion an Ovalbumin-sensibilisierten narkotisierten und künstlich beatmeten Meerschweinchen "Meerschweinchenasthma" bzw. The check for the above-mentioned pharmacological properties were z. Diamantis, JL Melton; W, nichtsteroidale Antiphlogistika Thrombophlebitis.

Diamantis, JL Ob Strumpfhosen Hilfe von Krampfadern D.

The compounds of general formula I according to the invention lead to a complete inhibition of ovalbumin-induced asthma response in ovalbumin-sensitized guinea pigs. This effect in allergic asthma is similar to ketotifen, a modern anti-asthmatic whose molecular Wirkungsmechaniamus but different from that of the compounds of the invention is different see below.

Weiterhin belegt die Hemmung der arachidonsäure-induzierten Kontraktion an der isolierten Arteria pulmonalis vom Kaninchen Beispiel 18 die antihypertensive und spasmolytische Wirkung. Furthermore, nichtsteroidale Antiphlogistika Thrombophlebitis, the inhibition of arachidonic acid-induced contraction on the isolated pulmonary artery of rabbit Example 18 occupies the antihypertensive and spasmolytic effect.

Therefore, it was concluded-that compounds of the invention of general formula I also have to have pronounced anti-inflammatory properties. Cremes Salben Gele von Krampfadern conclusion could in a suitable animal model of inflammation in vivo, the carrageenin-induced edema of the rat paw, according to the method of Winter nichtsteroidale Antiphlogistika Thrombophlebitis al.

As a molecular target for the pharmacological effects of the compounds of the invention, the inhibition of lipoxygenase has been identified.

It is known that the metabolites of arachidonic acid formed by the enzyme lipoxygenase are involved in the development of inflammatory and allergic processes [see. Pharmacol, 32, nichtsteroidale Antiphlogistika Thrombophlebitis, ; J. Pharmacol, 32, ; B. Nichtsteroidale Antiphlogistika Thrombophlebitis, Trends in Pharmacol: Sci, Mai; B, nichtsteroidale Antiphlogistika Thrombophlebitis.

Die Hemmung der Lipoxygenase wurde überzeugend an einer geeigneten tierischen Lipoxygenase nachgewiesen, die nach dem Verfahren von Rapoport und Mitarb. The inhibition of lipoxygenase was convincingly demonstrated in a suitable animal lipoxygenase according to the procedure of Rapoport et al.

The powerful inhibitions were detectable for a part of the inventive compounds also at a final concentration of 0. Durch Variation der Substanzkonzentration konnten die Titrationskurven der Hemmung und daraus die Halbhemmungskonzentrationen I 50 -Werte ermittelt werden. By varying the substance concentration in the titration curves of the inhibition nichtsteroidale Antiphlogistika Thrombophlebitis from this the half inhibition concentrations I 50 values were determined.

It was for the highly effective anti-asthmatic 5-methylhydrox y laurophenone oxime 7 uM. The suitability of Zipoxygenase from rabbit as a model for the molecular-pharmacological site of action of the compounds of the invention was demonstrated by the fact that other known from the literature such as lipoxygenase inhibitors.

The previously known Lipogygenasehemmer not achieve the anti-asthmatic nichtsteroidale Antiphlogistika Thrombophlebitis of the compounds of the invention, nichtsteroidale Antiphlogistika Thrombophlebitis.

Beispiel 20 und die Lipoxygenase aus Erbsen. The inventive compounds also inhibit all investigated isolated from plant sources lipoxygenases, including the soybean lipoxygenase-1 see.

Example 20 and the lipoxygenase from peas. From these and other studies, the reasoning ring revealed that the inventive compounds represent inhibitors of lipoxygenases universal regardless of its origin and position specificity, resulting in a number of valuable pharmacological properties Golf mit Krampfadern obtained.

Buytenhek, Methods in Enzymology 86, 60isoliert wurde, bis zu einer Endkonzentration von 1 mM nicht nennenswert gehemmt wird. Of special interest is the observation that the other important enzyme of Arachidonsäureksakade, cyclooxygenase, which was prepared from the seminal vesicles of cattle by the method of FJG van der Ouderaa and M. Buytenhek, Methods in Enzymology 86, 60isolated, nichtsteroidale Antiphlogistika Thrombophlebitis added to a final Seife mit trophischen Geschwüren of 1 mM is not significantly inhibited.

Acetylsalicylsäure, Indometacin ua oder sowohl die Lipoxygenase als auch die Cyclooxygenase z, nichtsteroidale Antiphlogistika Thrombophlebitis. Phenidon hemmen, woraus sich bei diesen bekannten Verbindungen unerwünschte pharmakologische Nebenwirkungen ergeben zB ulcerogene, gastrotoxische und nichtsteroidale Antiphlogistika Thrombophlebitis Wirkungen der Acetylsalicylsäure.

In this respect, compounds of the invention are superior to many previously known anti-inflammatory drugs that either inhibit only the cyclooxygenase eg. As aspirin, indomethacin, etc. Since inhibition of lipoxygenase was identified as a molecular target for new drugs, including their effect on platelet aggregation was investigated, nichtsteroidale Antiphlogistika Thrombophlebitis.

The essential role of the lipoxygenase pathway for the irreversibility of platelet aggregation nichtsteroidale Antiphlogistika Thrombophlebitis known today [CE Dutilh et al. Prostaglandins and Medicine 6, ]. Der Irreversibilität der Thrombozytenaggregation wird bei der Pathogenese thrombotischer Erkrankungen eine Schlüsselrolle zugeschrieben.

Nichtsteroidale Antiphlogistika Thrombophlebitis irreversibility of platelet aggregation is attributed a key role in the pathogenesis of thrombotic disorders. In den-Experimenten wurde die Thrombozytenaggregation entweder. In the experiments, the platelet aggregation was triggered entweder. Die genannten Experimente belegen an geeigneten biologischen Modellen die antiasthmatischen, antiallergischen, antithrombotischen und antiinflammatorischen Effekte.

The experiments referred to demonstrate the anti-asthmatic, nichtsteroidale Antiphlogistika Thrombophlebitis, anti-allergic, anti-thrombotic and anti-inflammatory effects at suitable biological models.

Als Indikationsgebiete in der Human- und Veterinärmedizin können beispielsweise genannt werden: Indication areas in human and veterinary medicine can be, for example: The classification of allergic reactions responsible for clinical hypersensitivity and disease.

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