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 addition it is provided a method for preparing the pharmaceutical composition.

1 .- 16 . (canceled) 
     
     
         17 . A pharmaceutical composition, comprising:
 3-beta-hydroxy-5-alpha-pregnan-20-one;   a sterol or an ester thereof; and   a mixture of acylglycerols;   and   wherein at room temperature the composition is a liquid oil composition.   
     
     
         18 . The pharmaceutical composition according to  claim 17 , wherein 3-beta-hydroxy-5-alpha-pregnan-20-one is present in an amount of up to 75 mg/g of the composition. 
     
     
         19 . The pharmaceutical composition according to  claim 17 , wherein 3-beta-hydroxy-5-alpha-pregnan-20-one is present in an amount of up to 50 mg/g of the composition. 
     
     
         20 . The pharmaceutical composition according to  claim 17 , wherein a weight ratio of said sterol or ester thereof to said 3-beta-hydroxy-5-alpha-pregnan-20-one is 1:10 to 10:1. 
     
     
         21 . The pharmaceutical composition according to  claim 20 , wherein a weight ratio of said sterol or ester thereof to said 3-beta-hydroxy-5-alpha-pregnan-20-one is 1:5 to 5:1. 
     
     
         22 . The pharmaceutical composition according to  claim 21 , wherein a weight ratio of said sterol or ester thereof to said 3-beta-hydroxy-5-alpha-pregnan-20-one is 1:3 to 3:1. 
     
     
         23 . The pharmaceutical composition according to  claim 17 , wherein the weight ratio of said sterol or ester thereof to said 3-beta-hydroxy-5-alpha-pregnan-20-one is 1:5 to 2:1. 
     
     
         24 . The pharmaceutical composition according to  claim 17 , wherein the sterol or ester thereof is cholesterol or an ester thereof. 
     
     
         25 . The pharmaceutical composition according to  claim 17 , wherein the concentration of said cholesterol or ester thereof is no more than about 30 mg/ml. 
     
     
         26 . The pharmaceutical composition according to  claim 17 , wherein the mixture of acylglycerols has a total combined percentage of (i) fatty acids with eight carbon atoms and (ii) fatty acids with ten carbon atoms of at least 95%. 
     
     
         27 . The pharmaceutical composition according to  claim 17 , wherein the mixture of acylglycerols comprises a medium-chain acylglycerol. 
     
     
         28 . The pharmaceutical composition according to  claim 17 , wherein the mixture of acylglycerols comprises medium-chain triacylglycerol (MCT). 
     
     
         29 . The pharmaceutical composition according to  claim 25 , wherein said medium-chain acylglycerol comprises at least about 95% triacylglycerols. 
     
     
         30 . The pharmaceutical composition according to  claim 17 , wherein the mixture of acylglycerols comprises sesame oil. 
     
     
         31 . The pharmaceutical composition according to  claim 27 , wherein the mixture of acylglycerols, in addition to the medium-chain acylglycerol, further comprises a vegetable oil. 
     
     
         32 . The pharmaceutical composition according to  claim 31 , wherein the vegetable oil is selected from the group consisting of sesame oil, peanut oil, olive oil and castor oil. 
     
     
         33 . The pharmaceutical composition according to  claim 17 , wherein the 3-beta-hydroxy-5-alpha-pregnan-20-one is suspended in a solution comprising the sterol or ester thereof and the mixture of acylglycerols. 
     
     
         34 . The pharmaceutical composition according to  claim 17 , wherein at least some of the 3-beta-hydroxy-5-alpha-pregnan-20-one is dissolved in a solution comprising the sterol or ester thereof and the mixture of acylglycerols. 
     
     
         35 . The pharmaceutical composition according to  claim 17 , wherein said composition is formulated for parenteral administration. 
     
     
         36 . A method of treating a condition of the central nervous system, comprising: administering the pharmaceutical composition according to  claim 17  to a subject in need thereof. 
     
     
         37 . The method according to  claim 36 , wherein the condition of the central nervous system is selected from the group consisting of epilepsy, menstruation cycle dependent 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. 
     
     
         38 . A method of terminating steroid induced anesthesia, comprising: administering the pharmaceutical composition according to  claim 17  to a subject in need thereof.