Probleme der Initiierung und Katalyse der Flüssigphasenoxidation von Cyclohexan und der Aldehyde

Die Flüssigphasenoxidation organischer Verbindungen mit Sauerstoffmolekülen ist ein wertvoller, eingehend untersuchter Prozeß mit Nebenprodukten, bei dem die Geschwindigkeit der Keimbildung im Anfangsabschnitt wesentlich geringer ist als die Geschwindigkeit von dem einen Zwischenprodukt zu den verschiedenen Produkten führenden Folgereaktionen. Zur Beschleunigung der Oxidationsreaktionen muß man deshalb zu Beginn des Prozesses freie Radikale mit einer hohen Reaktionsgeschwindigkeit erzeugen. Die jüngsten Erfolge auf dem Gebiet der Erzeugung von leistungsstarken Ultraschall-Wellen (US) ergeben Energiedichten von 10 hoch 3 - 10 hoch 6 W/qu.cm bei einer Intensität von 10 hoch 5 W/qu.cm. Diese Werte liegen um ein Vielfaches über den Energiedichten, die beim Einsatz anderer physikalischer Methoden zur Einwirkung auf Substanzen erzielt werden, wie etwa Radiolyse und Photolyse. Somit ist die Ultraschallkavitation eine der neuesten und vielversprechenden Methoden zur Initiierung der Oxidationsvorgänge organischer Verbindungen. Die hohe Initiierungsgeschwindigkeit, die zu Beginn des Prozesses erzeugt wird, stellt sicher, daß der Prozess im Gesamten schnell abläuft; der Ultraschalleinfluß wirkt sich jedoch im Wesentlichen auf das Initiierungsstadium aus und für die gewünschte Regulierung der Produktzusammensetzung und zur Steigerung der Selektivität des Prozesses muß man Katalysatoren und katalytische Systeme einsetzen. Am Beispiel der katalytischen Flüssigphasenoxidation der alpha-Alkylacroleine und von Cyclohexan wurde gezeigt, daß man in Gegenwart von Co(II)- und Ce(III)-Verbindungen, die sich in ihrer Aktivitität und ihren Koordinationseigenschaften stark unterscheiden, die Produktzusammensetzung durch Veränderung der Reaktionsweisen regulieren kann, was auch eines der Prinzipien zur Steigerung der Selektivität der Oxidationsvorgänge ist

Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes.

Abstract BACKGROUND: The cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown. METHODS: We randomly assigned patients with type 2 diabetes, with or without previous cardiovascular disease, to receive subcutaneous injections of extended-release exenatide at a dose of 2 mg or matching placebo once weekly. The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The coprimary hypotheses were that exenatide, administered once weekly, would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy. RESULTS: In all, 14,752 patients (of whom 10,782 [73.1%] had previous cardiovascular disease) were followed for a median of 3.2 years (interquartile range, 2.2 to 4.4). A primary composite outcome event occurred in 839 of 7356 patients (11.4%; 3.7 events per 100 person-years) in the exenatide group and in 905 of 7396 patients (12.2%; 4.0 events per 100 person-years) in the placebo group (hazard ratio, 0.91; 95% confidence interval [CI], 0.83 to 1.00), with the intention-to-treat analysis indicating that exenatide, administered once weekly, was noninferior to placebo with respect to safety (P<0.001 for noninferiority) but was not superior to placebo with respect to efficacy (P=0.06 for superiority). The rates of death from cardiovascular causes, fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, hospitalization for heart failure, and hospitalization for acute coronary syndrome, and the incidence of acute pancreatitis, pancreatic cancer, medullary thyroid carcinoma, and serious adverse events did not differ significantly between the two groups. CONCLUSIONS: Among patients with type 2 diabetes with or without previous cardiovascular disease, the incidence of major adverse cardiovascular events did not differ significantly between patients who received exenatide and those who received placebo. (Funded by Amylin Pharmaceuticals; EXSCEL ClinicalTrials.gov number, NCT01144338 .)

Edoxaban versus warfarin in patients with atrial fibrillation

Contains fulltext : 125374.pdf (publisher's version ) (Open Access)BACKGROUND: Edoxaban is a direct oral factor Xa inhibitor with proven antithrombotic effects. The long-term efficacy and safety of edoxaban as compared with warfarin in patients with atrial fibrillation is not known. METHODS: We conducted a randomized, double-blind, double-dummy trial comparing two once-daily regimens of edoxaban with warfarin in 21,105 patients with moderate-to-high-risk atrial fibrillation (median follow-up, 2.8 years). The primary efficacy end point was stroke or systemic embolism. Each edoxaban regimen was tested for noninferiority to warfarin during the treatment period. The principal safety end point was major bleeding. RESULTS: The annualized rate of the primary end point during treatment was 1.50% with warfarin (median time in the therapeutic range, 68.4%), as compared with 1.18% with high-dose edoxaban (hazard ratio, 0.79; 97.5% confidence interval [CI], 0.63 to 0.99; P<0.001 for noninferiority) and 1.61% with low-dose edoxaban (hazard ratio, 1.07; 97.5% CI, 0.87 to 1.31; P=0.005 for noninferiority). In the intention-to-treat analysis, there was a trend favoring high-dose edoxaban versus warfarin (hazard ratio, 0.87; 97.5% CI, 0.73 to 1.04; P=0.08) and an unfavorable trend with low-dose edoxaban versus warfarin (hazard ratio, 1.13; 97.5% CI, 0.96 to 1.34; P=0.10). The annualized rate of major bleeding was 3.43% with warfarin versus 2.75% with high-dose edoxaban (hazard ratio, 0.80; 95% CI, 0.71 to 0.91; P<0.001) and 1.61% with low-dose edoxaban (hazard ratio, 0.47; 95% CI, 0.41 to 0.55; P<0.001). The corresponding annualized rates of death from cardiovascular causes were 3.17% versus 2.74% (hazard ratio, 0.86; 95% CI, 0.77 to 0.97; P=0.01), and 2.71% (hazard ratio, 0.85; 95% CI, 0.76 to 0.96; P=0.008), and the corresponding rates of the key secondary end point (a composite of stroke, systemic embolism, or death from cardiovascular causes) were 4.43% versus 3.85% (hazard ratio, 0.87; 95% CI, 0.78 to 0.96; P=0.005), and 4.23% (hazard ratio, 0.95; 95% CI, 0.86 to 1.05; P=0.32). CONCLUSIONS: Both once-daily regimens of edoxaban were noninferior to warfarin with respect to the prevention of stroke or systemic embolism and were associated with significantly lower rates of bleeding and death from cardiovascular causes. (Funded by Daiichi Sankyo Pharma Development; ENGAGE AF-TIMI 48 ClinicalTrials.gov number, NCT00781391.)