Pharmaceutical compositions

Abstract

A process for preparing an emulsion composition comprising a cyclosporin, a rapamycin or an ascomycin or a derivative thereof as active agent, which process comprises the step of admixing to a placebo fat emulsion a concentrate comprising a) the active agent, b) a stabiliser selected from a phospholipid, a glycolipid, a sphingolipid, a diacylphosphatidyl glycerol, an egg-phosphatidylglycerol, a soy-phosphatidylglycerol, a diacylphosphatidylglycerol, or a salt thereof; or a saturated, mono- or di-unsaturated (C 12-24 ) fatty acid, or a salt thereof, and c) an organic solvent, wherein the weight ratio of active agent to stabiliser is between 400:1 and 0.5:1. The invention also provides ready-to-use emulsions, e.g. for intravenous administration, prepared using the above process.

1. A concentrate  An emulsion for intravenous administration comprising
 a) [3′-desoxy-3-oxo-MeBmc t] 1 -[Val] 2 -Ciclosporin as active agent,  
 b) a stabiliser selected from oleic acid or a salt thereof, or palmitoyl oleoyl phosphatidylglycerol (POPG) or a salt thereof as a stabiliser, and  
 c) ethanol, and 
   d) a placebo fat emulsion    
 
       which concentratewherein the emulsion is free of poly(oxyethylene)-40-castor oil and wherein the weight ratio of active agent to stabiliszer is from 400:1 to 10:1. 
     
     
       2. A concentrate  An emulsion a claimed in  claim 1  which further comprises propylene glycol. 
     
     
       3. A concentrate  An emulsion as claimed in  claim 1  wherein the stabiliser comprises sodium oleate. 
     
     
       4. A concentrate  An emulsion as claimed in  claim 1  wherein the stabiliser comprises sodium POPG. 
     
     
       5. An emulsion for intravenous administration comprising the concentrate of  claim 1  and a placebo fat emulsion. 
     
     
       6. A method of treatment and prevention of transplant rejection, autoimmune disease and of inflammatory conditions which method comprises administering an effective amount a concentrate of  claim 1  to a subject in need of such treatment. 
     
     
       7. A concentrate consisting essentially of
 a) a[3′-desoxy-3-oxo-MeBmt] 1 -[Val] 2 -Cicolosporin as active agent,    b) oleic acid or salt thereof, or palmitoyl oleoyl phosphatidylglycerol (POPG) or a salt thereof as a stabiliser, and    c) ethanol    
       wherein the weight ratio of active agent to stabiliser is from 400:1 to 10:1. 
     
     
       8. A method for treating keratoconjunctivitis sicca in a patient in need of such treatment comprising administering an effective amount of  33 - epi - chloro -   33   - desoxy - ascomycin for treating keratoconjunctivitis sicca to the patient.   
     
     
       9. The method of  claim 8 , wherein  33 - epi - chloro -   33   - desoxy - ascomycin is administered to the patient in the form of a pharmaceutical concentrate containing a stabilizer in a weight ratio of  33   - epi - chloro -   33   - desoxy - ascomycin to stabilizer of from  400 : 1  to  0 . 5 : 1 .   
     
     
       10. The method of  claim 9 , wherein the stabiliser is selected from the group consisting of a phospholipid, a glycolipid, a sphingolipid, a diacylphosphatidyl glycerol, an egg- phosphatidyl glycerol, a soy - phosphatidylglycerol, a saturated, mono -  or di - unsaturated  ( C   12-24 )  fatty acid and a salt thereof.