Antithrombotic combination of di:hydro:ergotamine cpd. and heparin - administered using a two-chamber system syringe to avoid instability problems on prolonged storage

摘要

Use of a two-chamber system (esp. a 2-chamber syringe) for admin. of a cpd. of formula (I) or its salt and of heparin or its salt is new. R is H or 1-4C alkyl; R1 is Me, Et or isopropyl; R2 is isopropyl, sec. butyl, isobutyl or benzyl; and X is H or OMe. The pref. cpd. (I) is dihydroergotamine, pref. in the form of the methanesulphonate. Heparin is pref. in the form of the Na salt. Pref., one chamber of the 2-chamber system contains a soln. of 0.5 mg dihydroergotamine methanesulphonate in 0.3 ml of a mixt. of water and one or more polyalcohols while the second chamber contains 2500 or 5000 IU heparin sodium in 0.7 ml water. In a suitable syringe the two solns. are sepd. by a stopper. When the syringe piston is pressed in, the stopper is pushed forwards into a bypass section of the syringe, where the two solns. can mix. The combination of (I) and heparin has antithrombotic activity (cf. DE 2554533). Use of a 2-chamber system avoids pptn. arising from the insolubility of combinations of (I) and heparin on prolonged storage.