Abstract Die außerordentlich schonende Umsetzung von Acetobromglucose (I) mit Alkoholen wie Cholesterin (II) zu Glucosiden wie (III) kann zweckmäßig in Gegenwart des Ag‐ Salzes eines Copolymerisats (Ag‐Pol.) aus Maleinsäure (IV) und dem Bis‐äther (V), der als säurebindendes Reagenz fungiert, durchgeführt werden.
The effect of recombinant hirudin (r-hir), unfractionated heparin (UFH) and acetylsalicylic acid (ASA) on the incidence of reocclusion after thrombolysis with plasminogen activator (rt-PA) was evaluated in anaesthetized rabbits. Formation of a platelet rich thrombus was achieved by implantation of a copper coil into the iliac artery. The occluded artery was recanalized in six of ten animals by intravenous administration of rt-PA given as a bolus injection of 0.1 mg/kg followed by infusion of 0.5 mg/kg/h. Within 1 h after termination of rt-PA infusion rethrombosis was observed in 100% of recanalized vessels. The incidence of reocclusion was diminished by r-hir in a dose-dependent manner to 50% after infusion of 0.05 mg/kg/h and to 25% after 0.1 mg/kg/h. No effect on APTT was detectable in this dosage after 3 h infusion. UFH in a dosage increasing APTT two-fold (35 U/kg/h) did not reduce the reocclusion rate. 100 U/kg/h UFH increased APTT to greater than 3 min and reduced reocclusion rates to 50%. ASA showed a minor effect on the incidence of restenosis whereas the combination of 0.1 mg/kg/h r-hir plus bolus injection of 10 mg/kg ASA led to a further reduction in reocclusion rates to only 11% and an increase in reperfusion rates from 60 to 90%. Our experiments indicate that the combination of plasminogen activator with r-hir may be a useful approach for the prophylaxis of early reocclusion.
The introduction of low-molecular-mass heparins (LMMHs) has added a new dimension to the prophylactic and therapeutic management of thromboembolic disorders. These agents are now globally accepted as drugs of choice for postsurgical prophylaxis of deep vein thrombosis (DVT). Currently, the LMMHs are being developed for various therapeutic and cardiovascular indications. Reviparin is an optimized LMMH prepared by controlled nitrous acid digestion of porcine mucosal heparin. This drug has been developed utilizing validated procedures and exhibits a relatively narrow molecular mass distribution in contrast to most other commercially available LMMHs. The specific activity in the anticoagulant assays is approximately 40 U/mg whereas the specific activity in amidolytic anti-Xa assays is approximately 100 anti-Xa U/mg. Reviparin is capable of producing dose- and time-dependent antithrombotic effects in animal models of thrombosis. Although ex vivo anticoagulant effects are initially observed at dosages that are antithrombotic, this agent has been found to produce sustained antithrombotic effects when ex vivo anticoagulant actions are not measurable. Repeated administration of this LMMH induces progressively stronger antithrombotic effects. This drug has also been found to release tissue factor pathway inhibitor (TFPI) following both intravenous (IV) and subcutaneous (SC) administration. The studies included in this article are designed to provide additional data on the molecular profile using new calibration methods and additional results on pharmacologic studies. In particular, the release of TFPI following IV and SC administration to nonhuman primates is described. The effect of repeated administration of Reviparin mimicking the postsurgical prophylaxis of DVT is also reported in terms of any augmentation of the antithrombotic or hemorrhagic effects of this agent.
Reviparin is a low-molecular-weight heparin (LMWH) prepared by controlled nitrous acid digestion of porcine mucosal heparin. The trade name designation for this agent is Clivarin. This agent has been released in Germany and France for the prophylaxis of deep venous thrombosis (DVT) in surgical patients. This agent is developed utilizing optimized procedures and exhibits a uniform, narrow-molecular-weight distribution in comparison to the other commercially available LMWHs. The specific activity in the anticoagulant assays is approximated to be 32 U/mg whereas the specific activity in terms of anti-Xa units is designated 120 aXa U/mg. Reviparin is capable of producing a dose- and time-dependent antithrombotic effect in animal models of thrombosis. While the ex vivo effects are initially presented at antithrombotically active dosages, this agent has been found to produce antithrombotic effects without any detectable ex vivo actions. This agent is also known to release tissue factor pathway inhibitor (TFPI) after both intravenous (IV) and subcutaneous (SC) administration. Repeated administration of Reviparin produces progressively stronger antithrombotic effects. Similarly, the bleeding as measured by rabbit ear blood loss is also progressively increased. However, the ratio between the dosage producing these effects is quite large. The current studies are designed to provide additional data on the molecular profile using new calibration methods and additional results on the pharmacologic studies in a dose-dependent manner. In particular, the release of TFPI following IV and SC administration in a primate model is described. The effect of repeated administration mimicking the post-surgical prophylaxis of DVT is also reported in terms of any augmentation of the antithrombotic or hemorrhagic effects of these agents.
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