Pharmaceutical composition comprising 3-beta-hydroxy-5-alpha-pregnan-20-one with improved storage and solubility properties

Abstract

It is provided a pharmaceutical composition comprising 3-beta-hydroxy-5-alpha-pregnan-20-one, at least one sterol or an ester thereof and a mixture of acylglycerols with a solid fat content of less than 25% at 25° C. and 0% at 37° C. In addtion it is provided a method for preparing the pharmaceutical composition.

1 . A pharmaceutical composition comprising 3-beta-hydroxy-5-alpha-pregnan-20-one, at least one sterol or an ester thereof and a mixture of acylglycerols with a solid fat content of less than about 25% at 25° C. and about 0% at 37° C. 
     
     
         2 . The pharmaceutical composition according to  claim 1  wherein the sterol is selected from the group consisting of cholesterol, beta-sitosterol, stigmasterol, brassicasterol and avenasterol. 
     
     
         3 . The pharmaceutical composition according to  claim 2  wherein the sterol is cholesterol. 
     
     
         4 . The pharmaceutical composition according to  claim 1  wherein the mixture of acylglycerols is a vegetable oil. 
     
     
         5 . The pharmaceutical composition according to  claim 4  where the vegetable oil is selected from the group consisting of sesame oil, peanut oil, olive oil, and castor oil. 
     
     
         6 . The pharmaceutical composition according to  claim 1  wherein the mixture of acylglycerols is a medium-chain acylglycerol. 
     
     
         7 . The pharmaceutical composition according to  claim 1  in which 3-beta-hydroxy-5-alpha-pregnan-20-one is essentially dissolved. 
     
     
         8 . The pharmaceutical composition according to  claim 1  comprising a suspension of 3-beta-hydroxy-5-alpha-pregnan-20-one. 
     
     
         9 . A pharmaceutical composition for parenteral administration according to  claim 1 . 
     
     
         10 . A pharmaceutical composition for oral administration according to  claim 1 . 
     
     
         11 . A pharmaceutical composition for vaginal administration according to  claim 1 . 
     
     
         12 . A pharmaceutical composition for nasal administration according to  claim 1 . 
     
     
         13 . A method for preparing a pharmaceutical composition according to  claim 7  comprising the steps of
 a) dissolving 3-beta-hydroxy-5-alpha-pregnan-20-one in ethanol, 
 b) adding a mixture of acylglycerols with a solid fat content of less than about 25% at 25° C. and about 0% at 37° C. and a sterol or an ester thereof, 
 c) mixing until a homogeneous liquid is obtained and 
 d) evaporating the ethanol. 
 
     
     
         14 . A pharmaceutical composition obtainable by the method according to  claim 13 . 
     
     
         15 . Use of a pharmaceutical composition according to  claim 1  for the treatment or prevention of conditions of the central nervous system. 
     
     
         16 . The use according to  claim 15  where the condition of the central nervous system is selected from the group consisting of epilepsy, menstruation cycle dependant epilepsy, depression, stress related depression, migraine, tiredness and in particular stress related tiredness, premenstrual syndrome, premenstrual dysphoric disorder, menstrual cycle linked mood changes, stress related memory changes, menstrual cycle linked memory changes, Alzheimer's dementia, menstrual cycle linked difficulties in concentration, menstrual cycle linked sleep disorders and tiredness, substance abuse, menstrual cycle linked alcoholism, side effects of oral contraceptives and postmenopausal therapy or combinations thereof. 
     
     
         17 . Use of the pharmaceutical composition according to  claim 1  for the termination of steroid induced anaesthesia.