Lipid composition

Abstract

We describe lipid based pharmaceutical compositions adapted for oral delivery and optionally delivery in accordance with a circadian rhythm.

1 . A pharmaceutical composition adapted for oral delivery of an effective amount of a steroid, comprising:
 a steroid;   a lipid based carrier wherein said carrier includes at least one triglyceride fatty acid wherein the fatty acid is at least 10 carbon atoms in length; and   at least one agent that enhances the solubility and bioavailability of said steroid when administered to a subject.   
     
     
         2 . The composition according to  claim 1 , wherein said steroid is: native testosterone, testosterone propionate, testosterone enanthate, testosterone cypionate, testosterone undecanoate, testosterone buciciate, methyltestosterone, fluoxymesterone or mesterolone. 
     
     
         3 . The composition according to  claim 1 , wherein said fatty acid chain length is 10-22 carbon atoms or 14-18 carbon atoms. 
     
     
         4 . The composition of  claim 1 , wherein composition has a ratio of unsaturated fatty acid to saturated fatty acid of at least or greater than 3. 
     
     
         5 . The composition of  claim 1 , wherein said fatty acid is monosaturated. 
     
     
         6 . The composition according to  claim 5 , wherein said monosaturated fatty acid is at least 30% of the lipid content of the composition. 
     
     
         7 . The composition of  claim 1 , wherein said fatty acid is polysaturated. 
     
     
         8 . The composition according to  claim 7 , wherein said polysaturated fatty acid is at least 30% of the lipid content of the composition. 
     
     
         9 . The composition of  claim 1 , wherein said fatty acid is an essential fatty acid. 
     
     
         10 . The composition of  claim 1 , wherein said lipid based carrier is oil. 
     
     
         11 . The composition of  claim 1 , wherein said lipid based carrier includes at least one or a combination of fatty acids selected from the group consisting of: caprylic/capric triglycerides, caprylic/capric/linoleic triglycerides, caprylic/capric/myristic/stearic fatty acid triglycerides, capylic/capric/succinic fatty acid triglycerides, caprylic/capric triglycerides with stearalkonium benonite and propylene carbonate, caprylic/capric triglycerides with stearalkonium hectorite and propylene carbonate. 
     
     
         12 . The composition of  claim 1 , wherein said at least one agent that enhances the solubility and bioavailability of said steroid is ethanol, benzyl alcohol, glycerol, propylene glycol, propylene carbonate, diethylene glycol monoethyl ether, cremaphor, polysorbate (Tween 80), or combinations thereof. 
     
     
         13 . The composition of  claim 1 , wherein said composition comprises: a steroid, sesame oil, lauroglycol, ethanol and benzyl alcohol. 
     
     
         14 . The composition according to  claim 18 , wherein said composition consists essentially of:
 2.5-7.5% w/w steroid;   at least 40% w/w sesame oil;   at least 30% w/w lauroglycol;   at least 5% w/w ethanol; and   at least 15% w/w benzyl alcohol.   
     
     
         15 . A method to treat a condition that would benefit from steroid replacement therapy comprising:
 administering an effective amount of the composition of  claim 1  to a subject in need of steroid replacement wherein the composition is administered in accordance with the circadian secretion of a steroid to provide physiological replacement of said steroid.   
     
     
         16 . The method according to  claim 15 , wherein said composition is administered prior to sleep. 
     
     
         17 . The method according to  claim 16 , wherein said composition is administered between 20:00 hours and 24:00 hours. 
     
     
         18 . The method of  claim 15 , wherein steroid replacement therapy is the treatment of primary male hypogonadism. 
     
     
         19 . The method of  claim 15 , wherein steroid replacement therapy is the treatment of secondary male hypogonadism. 
     
     
         20 . A pharmaceutical composition adapted for oral delivery of an effective amount of testosterone undecanoate, comprising:
 2.5-7.5% w/w testosterone undecanoate;   at least 40% w/w sesame oil;   at least 30% w/w lauroglycol;   at least 5% w/w ethanol;   at least 15% w/w benzyl alcohol; and   a pharmaceutically acceptable carrier, wherein the combination of ethanol and benzyl alcohol increases the solubility and bioavailability of testosterone undecanoate when administered to a subject.