Pharmaceutical composition for the parenteral administration of ultrashort-effective beta-adrenoreceptor antagonists

Abstract

The present invention relates to a pharmaceutical composition in the form of a storage-stable solution for the parenteral administration of ultrashort-effective β-adrenoreceptor antagonists, comprising a) an ultrashort-effective β-adrenoreceptor antagonist and/or a pharmaceutically acceptable salt thereof, b) water, and c) a cyclodextrin and/or a functional cyclodextrin derivative. The composition according to the invention has high stability, even without the presence of additional adjuvants.

What is claimed: 
     
         1 . A pharmaceutical composition comprising:
 a) an ultrashort-effective β-adrenoreceptor antagonist or a pharmaceutically acceptable salt thereof;   b) water; and   c) a cyclodextrin or a functional cyclodextrin derivative.   
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein the pH value of the composition is 3 to 7.5. 
     
     
         3 . The pharmaceutical composition of  claim 2 , wherein the pH value of the composition is 5 to 7. 
     
     
         4 . The pharmaceutical composition of  claim 1 , wherein the concentration of the cyclodextrin or the functional derivative thereof is 0.1% to 20% (w/v). 
     
     
         5 . The pharmaceutical composition of  claim 4 , wherein, the concentration of the cyclodextrin or the functional derivative thereof is 0.25% to 7% (w/v). 
     
     
         6 . The pharmaceutical composition of  claim 5 , wherein the concentration of the cyclodextrin or the functional derivative thereof is 0.5% to 4%. 
     
     
         7 . The pharmaceutical composition of  claim 1 , wherein the cyclodextrin is selected from the group consisting of α-cyclodextrin, β-cyclodextrin, and γ-cyclodextrin. 
     
     
         8 . The pharmaceutical composition of  claim 1 , wherein the functional cyclodextrin derivative is selected from the group consisting of (2-hydroxypropyl)-β-cyclodextrin and (sulfobutylether)-7β-cyclodextrin. 
     
     
         9 . The pharmaceutical composition of  claim 1 , wherein the ultrashort-effective β-adrenoreceptor antagonist is selected from the group consisting of esmolol, landiolol, and flestolol. 
     
     
         19 . The pharmaceutical composition of  claim 1 , wherein the concentration of the ultrashort-effective β-adrenoreceptor antagonist or salt thereof is 0.1% to 30%. 
     
     
         11 . The pharmaceutical composition of  claim 1 , wherein the composition has an osmolarity of 270 mosmol/l to 310 mosmol/l. 
     
     
         12 . The pharmaceutical composition of  claim 11 , wherein the composition has an osmolarity of 280 mosmol/l to 300 mosmol/l. 
     
     
         13 . The pharmaceutical composition of  claim 1 , wherein the ultrashort-effective (3-adrenoreceptor antagonist is esmolol or a salt thereof, and further wherein the composition is present in the form of a sales unit selected from the group consisting of:
 1 ml solution containing 10-20 mg esmolol or a salt thereof,   2 ml solution containing 10-100 mg esmolol or a salt thereof,   5 ml solution containing 50-500 mg esmolol or a salt thereof,   10 ml solution containing 50-5000 mg esmolol or a salt thereof,   10 ml solution containing 2500 mg esmolol or a salt thereof,   50 ml solution containing 50-5000 mg esmolol or a salt thereof,   100 ml solution containing 50-5000 mg esmolol or a salt thereof, and   250 ml solution containing 50-5000 mg esmolol or a salt thereof.   
     
     
         14 . The pharmaceutical composition of  claim 1 , wherein the ultrashort-effective β-adrenoreceptor antagonist is landiolol or festolol or a salt thereof, and further wherein the composition is present in the form of a sales unit selected from the group consisting of:
 1 ml solution containing 5-20 mg landiolol or festolol or a salt thereof, 
 2 ml solution containing 5-100 mg landiolol or festolol or a salt thereof, 
 5 ml solution containing 10-500 mg landiolol or festolol or a salt thereof, 
 10 ml solution containing 10-5000 mg landiolol or festolol or a salt thereof, 
 25 ml solution containing 25-2500 mg landiolol or festolol or a salt thereof, 
 50 ml solution containing 50-5000 mg landiolol or festolol or a salt thereof, 
 100 ml solution containing 50-5000 mg landiolol or festolol or a salt thereof, and 
 250 ml solution containing 50-5000 mg landiolol or festolol or a salt thereof. 
 
     
     
         15 . A method of reducing heart beat frequency in a patient comprising administering a composition of  claim 1  to a patient, whereby the heart beat frequency in the patient is reduced. 
     
     
         16 . The method of  claim 15 , wherein the patient has atrial fibrillation, atrial flutter, sinus tachycardia, atrioventricular tachycardia, AV node tachycardia, supraventricular tachycardia, ventricular arrhythmias, perioperative ischaemia, unstable angina pectoris, or acute myocardial infarction.