Formulations and Dosage Forms of Oxidized Phospholipids

Abstract

The current disclosure provides pharmaceutical compositions containing an oxidized phospholipid, such as 1-hexadecyl-2-(4′-carboxybutyl)-glycero-3-phosphocholine (VB-201) and a thermosoftening carrier, e.g., a poloxamer. The pharmaceutical compositions may further comprise an anti-adherent agent, such as talc and/or a thixotropic agent. The current disclosure further provides processes for preparing the pharmaceutical compositions. The disclosure further provides capsules containing the pharmaceutical compositions. Uses of such pharmaceutical compositions and capsules in treating inflammatory disorders are also disclosed.

1 - 122 . (canceled) 
     
     
         123 . A pharmaceutical composition comprising an oxidized phospholipid, a thermosoftening carrier, and an anti-adherent agent,
 wherein the weight ratio of said anti-adherent agent to said oxidized phospholipid is about 1:5 to about 5:1, and   wherein the oxidized phospholipid is 1-hexadecyl-2-(4′-carboxybutyl)-glycero-3-phosphocholine (VB-201).   
     
     
         124 . The pharmaceutical composition of  claim 123 , wherein said thermosoftening carrier is selected from the group consisting of a polyalkylene glycol, a polyalkylene glycol derivative, a wax, and combinations thereof. 
     
     
         125 . The pharmaceutical composition of  claim 124 , wherein said thermosoftening carrier is a poloxamer. 
     
     
         126 . The pharmaceutical composition of  claim 125 , wherein said poloxamer has a molecular weight from about 7000 to 10000 daltons. 
     
     
         127 . The pharmaceutical composition of  claim 125 , wherein said poloxamer is poloxamer 188. 
     
     
         128 . The pharmaceutical composition of  claim 124 , wherein said thermosoftening carrier is a polyethylene glycol, a polypropylene glycol, or a co-polymer thereof. 
     
     
         129 . The pharmaceutical composition of  claim 123 , wherein said anti-adherent agent is selected from the group consisting of talc, magnesium stearate, cellulose, cellulose derivatives, lactose, gelatin, alginates, aluminium hydroxide, magnesium oxide, clays, attapulgite, bentonite, carrageenan, copovidone, hectorite, polymethacrylates, sodium docusate, erythritol, povidones, croscarmellose sodium, dextrates, starches, iron oxide, kaolin, silicates, corn flour, sugars, calcium carbonate, magnesium carbonate, calcium phosphate, calcium sulfate, bicarbonates, citrate salts, and titanium dioxide. 
     
     
         130 . The pharmaceutical composition of  claim 129 , wherein said anti-adherent agent is talc. 
     
     
         131 . The pharmaceutical composition of  claim 123 , wherein said weight ratio of said anti-adherent agent to said oxidized phospholipid is from about 1:4 to about 1:1. 
     
     
         132 . The pharmaceutical composition of  claim 123 , further comprising a thixotropic agent. 
     
     
         133 . The pharmaceutical composition of  claim 132 , wherein said thixotropic agent is selected from the group consisting of fumed silica, kieselguhr, gums, cellulose derivatives, starches, polymers, emulsifiers, and clay derivatives, attapulgite, mica, synthetic magnesium phyllosilicates, layered silicates, modified smectites, hectorite, and sepiolite. 
     
     
         134 . The pharmaceutical composition of  claim 133 , wherein said thixotropic agent is a fumed silica. 
     
     
         135 . The pharmaceutical composition of  claim 134 , wherein said thermosoftening carrier is poloxamer 188 and said anti-adherent agent is talc. 
     
     
         136 . The pharmaceutical composition of  claim 123 , wherein said pharmaceutical composition is a liquid-fill composition. 
     
     
         137 . A method of treating cancer comprising administering to a human in need thereof a therapeutically effective amount of the pharmaceutical composition of  claim 123 . 
     
     
         138 . The method of  claim 137 , wherein said thermosoftening carrier is a poloxamer or a polyethylene glycol. 
     
     
         139 . The method of  claim 138 , wherein said anti-adherent agent is selected from the group consisting of talc, magnesium stearate, cellulose, cellulose derivatives, lactose, gelatin, alginates, aluminium hydroxide, magnesium oxide, clays, attapulgite, bentonite, carrageenan, copovidone, hectorite, polymethacrylates, sodium docusate, erythritol, povidones, croscarmellose sodium, dextrates, starches, iron oxide, kaolin, silicates, corn flour, sugars, calcium carbonate, magnesium carbonate, calcium phosphate, calcium sulfate, bicarbonates, citrate salts, and titanium dioxide. 
     
     
         140 . A method of treating a tumor comprising administering to a human in need thereof a therapeutically effective amount of the pharmaceutical composition of  claim 123 , wherein the tumor is selected from the group consisting of a malignant tumor, a benign tumor, a solid tumor, a metastatic tumor, and a non-solid tumor. 
     
     
         141 . The method of  claim 140 , wherein said thermosoftening carrier is a poloxamer or a polyethylene glycol. 
     
     
         142 . The method of  claim 141 , wherein said anti-adherent agent is selected from the group consisting of talc, magnesium stearate, cellulose, cellulose derivatives, lactose, gelatin, alginates, aluminium hydroxide, magnesium oxide, clays, attapulgite, bentonite, carrageenan, copovidone, hectorite, polymethacrylates, sodium docusate, erythritol, povidones, croscarmellose sodium, dextrates, starches, iron oxide, kaolin, silicates, corn flour, sugars, calcium carbonate, magnesium carbonate, calcium phosphate, calcium sulfate, bicarbonates, citrate salts, and titanium dioxide. 
     
     
         143 . A method of treating hepatic cirrhosis comprising administering to a human in need thereof a therapeutically effective amount of the pharmaceutical composition of  claim 123 . 
     
     
         144 . The method of  claim 143 , wherein said thermosoftening carrier is a poloxamer or a polyethylene glycol. 
     
     
         145 . The method of  claim 144 , wherein said anti-adherent agent is selected from the group consisting of talc, magnesium stearate, cellulose, cellulose derivatives, lactose, gelatin, alginates, aluminium hydroxide, magnesium oxide, clays, attapulgite, bentonite, carrageenan, copovidone, hectorite, polymethacrylates, sodium docusate, erythritol, povidones, croscarmellose sodium, dextrates, starches, iron oxide, kaolin, silicates, corn flour, sugars, calcium carbonate, magnesium carbonate, calcium phosphate, calcium sulfate, bicarbonates, citrate salts, and titanium dioxide.