Phospholipid compositions

Abstract

Compositions involving a modified egg yolk extract for use as an effective anti-cancer agent are described. The modified egg yolk extract involves specific fractions of phosphatidylcholines and sphingomyelins modified and produced from a chemical synthesis applied to the extract that produce a beneficial effect on the inhibition of cancerous cell growth. Methods of administering these compositions are also described.

1 . A pharmaceutical composition comprising an effective amount of a plurality of bioactive phospholipids derived from hen egg yolk and one or more pharmaceutically acceptable diluents, excipients and/or carriers, wherein said plurality of bioactive phospholipids is substantially free of N-acyl ether phosphatidylethanolamines (NAEPE). 
     
     
         2 . The pharmaceutical composition according to  claim 1 , wherein said plurality of bioactive phospholipids is substantially free of phosphatidylethanolamines (PE). 
     
     
         3 . The pharmaceutical composition of  claim 1 , wherein said plurality of bioactive phospholipids is substantially free of lysophosphatidylcholines (LPC). 
     
     
         4 . The pharmaceutical composition according to  claim 1 , wherein said plurality of bioactive phospholipids is substantially free of glycerophosphocholine. 
     
     
         5 . The pharmaceutical composition according to  claim 1  wherein said plurality of phospholipids is enriched in one or more lipids selected from the group consisting of:
 (i) one or more phosphatidylcholine (PC) derivatives having the structure: 
 
       
         
           
           
               
               
           
         
       
       where R 1  or R 2  are independently selected from the group consisting of palmitoyl (C16:0), hexadecenoyl (C16:1), palmitoleoyl (C16:1), stearoyl (C18:0), octadecenoyl (C18:1), oleoyl (C18:1), octadecadienoyl (C18:2), linoleoyl (C18:2), α-linolenoyl (C18:3), octadecatrienoyl (C18:3), arachidonoyl (C20:4), eicosatetraenoyl (C20:4), docosapentaenoyl (C22:5), and docosahexaenoyl (C22:6) radicals; and/or
 (ii) one or more sphingomyelin (SPH) derivatives having the structure 
 
       
         
           
           
               
               
           
         
       
       wherein R 6  is palmitoyl (C16:0), stearoyl (C18:0), oleoyl (C18:1), tetradecanoyl (C14:0), heptadecanoyl (C17:0), nonadecanoyl (C19:0), eicosanoyl (C20:0), docosanoyl (C22:0), docosenoyl (C22:1), henicosanoyl (C23:0), tetracosadienoic (C24:2), or tetracosanoyl (C14:0); and pharmaceutically acceptable salts thereof. 
     
     
         6 . The pharmaceutical composition according to  claim 5 , wherein R 1  is selected from, palmitoyl (C16:0), palmitoleoyl (C16:1), stearoyl (C18:0), oleoyl (C18:1), and linoleoyl (C18:2). 
     
     
         7 . The pharmaceutical composition according to  claim 5 , wherein R 2  is selected from linoleoyl (C18:2), oleoyl (C18:1), eicosatetraenoyl (C20:4), and docosahexaenoyl (C22:6). 
     
     
         8 . The pharmaceutical composition according to  claim 5 , wherein R 6  is palmitoyl (C16:0). 
     
     
         9 . The pharmaceutical composition according to  claim 5 , wherein said one or more phosphatidylcholine (PC) derivatives collectively comprise at least about 70% (w/w) of said plurality of phospholipids. 
     
     
         10 . The pharmaceutical composition according to  claim 5 , wherein said one or more sphingomyelin (SPH) derivatives collectively comprise between about 0.1% and 25% (w/w) of said plurality of phospholipids. 
     
     
         11 . The pharmaceutical composition according to  claim 5 , wherein said plurality of phospholipids consists of one or more phosphatidylcholine (PC) derivatives and one or more sphingomyelin (SPH) derivatives; wherein said one or more phosphatidylcholine (PC) derivatives collectively comprise at least about 70% (w/w) of said plurality of phospholipids and said one or more sphingomyelin (SPH) derivatives collectively comprise between about 0.1% and 25% (w/w) of said plurality of phospholipids. 
     
     
         12 . The pharmaceutical composition according to  claim 5 , wherein said plurality of phospholipids is enriched in one or more phosphatidylcholine (PC) compounds and one or more sphingomyelin (SPH) compounds. 
     
     
         13 . The pharmaceutical composition according to  claim 5 , wherein said plurality of phospholipids is enriched in
 a) (R)-2-(((9Z,12Z)-octadeca-9,12-dienoyl)oxy)-3-(palmitoyloxy)propyl (2-(trimethylammonio)ethyl) phosphate and   b) (R)-2-(((9Z,12Z)-octadeca-9,12-dienoyl)oxy)-3-(oleoyloxy)propyl (2-(trimethylammonio)ethyl) phosphate.   
     
     
         14 . The pharmaceutical composition according to  claim 13 , wherein said plurality of phospholipids is enriched in (2S,3R,E)-2-heptadecanamido-3-hydroxyoctadec-4-en-1-yl (2-(trimethylammonio)ethyl) phosphate. 
     
     
         15 . The pharmaceutical composition according to  claim 5 , wherein said plurality of phospholipids is enriched in
 a) (R)-2-(((9Z,12Z)-octadeca-9,12-dienoyl)oxy)-3-(palmitoyloxy)propyl (2-(trimethylammonio)ethyl) phosphate and   b) (R)-2-(((9Z,12Z)-octadeca-9,12-dienoyl)oxy)-3-(oleoyloxy)propyl (2-(trimethylammonio)ethyl) phosphate,   c) (R)-2-(((4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoyl)oxy)-3-(palmitoyloxy)propyl (2-(trimethylammonio)ethyl) phosphate,   d) (R)-2((5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenoyl)oxy)-3-(palmitoyloxy)propyl (2-(trimethylammonio)ethyl) phosphate, and   e) (2S,3R,E)-2-heptadecanamido-3-hydroxyoctadec-4-en-1-yl (2-(trimethylammonio)ethyl) phosphate.   
     
     
         16 . The pharmaceutical composition according to  claim 5 , wherein said plurality of phospholipids is enriched in
 a) (R)-2-(((4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoyl)oxy)-3-(palmitoyloxy)propyl (2-(trimethylammonio)ethyl) phosphate,   b) (R)-2-(((9Z,12Z)-octadeca-9,12-dienoyl)oxy)-3-((Z)-hexadec-9-enoyl)oxy)propyl (2-(trimethylammonio)ethyl) phosphate,   c) (R)-2((9Z,12Z,15Z)-octadeca-9,12,15-trienoyl)oxy)-3-((Z)-hexadec-9-enoyl)oxy)propyl (2-(trimethylammonio)ethyl) phosphate,   d) (R)-2,3-bis(((9Z,12Z)-octadeca-9,12-dienoyl)oxy)propyl (2-(trimethylammonio)ethyl) phosphate,   e) (R)-2-(((9Z,12Z,15Z)-octadeca-9,12,15-trienoyl)oxy)-3-(oleoyloxy)propyl (2-(trimethylammonio)ethyl) phosphate,   f) (R)-2((5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenoyl)oxy)-3-(palmitoyloxy)propyl (2-(trimethylammonio)ethyl) phosphate,   g) (R)-2((7Z,10Z,13Z,16Z,19Z)-docosa-7,10,13,16,19-pentaenoyl)oxy)-3-(palmitoyloxy)propyl (2-(trimethylammonio)ethyl) phosphate,   h) (R)-2((5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenoyl)oxy)oxy)-3-(oleoyloxy)propyl (2-(trimethylammonio)ethyl) phosphate,   i) (R)-2-(((9Z,12Z)-octadeca-9,12-dienoyl)oxy)-3-(palmitoyloxy)propyl (2-(trimethylammonio)ethyl) phosphate,   j) (R)-2-((Z)-octadeca-9-enoyl)oxy)-3-((Z)-hexadec-9-enoyl)oxy)propyl (2-(trimethylammonio)ethyl) phosphate,   k) (R)-2-(((9Z,12Z)-octadeca-9,12-dienoyl)oxy)-3-(oleoyloxy)propyl (2-(trimethylammonio)ethyl) phosphate,   l) (R)-2-(((4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoyl)oxy)-3-(stearoyloxy)propyl (2-(trimethylammonio)ethyl) phosphate,   m) (R)-2-(((5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenoyl)oxy)-3-(stearoyloxy)propyl (2-(trimethylammonio)ethyl) phosphate,   n) (R)-2-(((9Z,12Z)-octadeca-9,12-dienoyl)oxy)-3-(stearoyloxy)propyl (2-(trimethylammonio)ethyl) phosphate, and   o) (2 S,3R,E)-2-heptadecanamido-3-hydroxyoctadec-4-en-1-yl (2-(trimethylammonio)ethyl) phosphate.   
     
     
         17 . The pharmaceutical composition according to  claim 16 , wherein said plurality of phospholipids is further enriched in
 p) (R)-2-(oleoyloxy)-3-(palmitoyloxy)propyl (2-(trimethylammonio)ethyl) phosphate,   q) (R)-2,3-bis(oleoyloxy)propyl (2-(trimethylammonio)ethyl) phosphate, and   r) (R)-2-(oleoyloxy)-3-(stearoyloxy)propyl (2-(trimethylammonio)ethyl) phosphate.   
     
     
         18 . The pharmaceutical composition according to  claim 1 , wherein said effective amount is from about 1 mg to about 2000 mg. 
     
     
         19 . The pharmaceutical composition according to  claim 1 , wherein said effective amount is from about 10 mg to about 1200 mg. 
     
     
         20 . The pharmaceutical composition according to  claim 1 , wherein said effective amount is from about 100 mg to about 1000 mg. 
     
     
         21 . The pharmaceutical composition according to  claim 1 , wherein said hen egg is of the genus  Gallus.    
     
     
         22 . The pharmaceutical composition according to  claim 1 , wherein said hen egg is from the species  Gallus gallus domesticus.