Transplantation Therapies

Abstract

Embodiments of the present invention are directed to methods and dosage forms for treating inflammation and rejection in transplantation injuries with Bryostatin-1, Bryostatin-1 analogs and pharmaceutically acceptable salts thereof.

1 - 2 . (canceled) 
     
     
         3 . The method of  claim 43  wherein said effective amount of Bryostatin-1, Bryostatin-1 analog or pharmaceutically acceptable salt thereof is an amount to achieve a plasma concentration in an individual being treated for graft versus host disease about 10 −7  M. 
     
     
         4 . The method of  claim 43  wherein said effective amount of Bryostatin-1, Bryostatin-1 analog or a pharmaceutically acceptable salt thereof is held in a dosage form. 
     
     
         5 . The method of  claim 43  wherein said dosage form is an oral dosage form. 
     
     
         6 . The method of  claim 5  wherein said oral dosage form is a solid oral dosage form. 
     
     
         7 . (canceled) 
     
     
         8 . The method of  claim 43  wherein said polyalkylene glycol glyceride is a mixture of polyalkylene esters of one or more eight carbons to eighteen carbons saturated fatty acids with glycerol. 
     
     
         9 . The method of  claim 8  wherein said polyalkylene glycol is a polyethylene glycol having a molecular weight of 1000 to 2000 daltons. 
     
     
         10 . The method of  claim 9  wherein said polyalkylene glycol is a polyethylene glycol having a molecular weight of 1400 to 1600 daltons. 
     
     
         11 . The method of  claim 5  wherein said Bryostatin-1, Bryostatin-1 analog or pharmaceutically acceptable salt thereof is present in said oral dosage form in an amount of 1 to 30% by weight. 
     
     
         12 . The method of  claim 5  wherein said Bryostatin-1, Bryostatin-1 analog or pharmaceutically acceptable salt thereof is present in said oral dosage form in an amount of 10 to 20% by weight. 
     
     
         13 . The method of  claim 5  wherein said Bryostatin-1, Bryostatin-1 analog or pharmaceutically acceptable salt thereof is present in said oral dosage form in an amount of 2 to 25% by weight. 
     
     
         14 . The method of  claim 4  wherein said dosage form is a pharmaceutical parenteral formulation. 
     
     
         15 . (canceled) 
     
     
         16 . The method of  claim 43  wherein said polyalkylene glycol glyceride is a mixture of polyalkylene esters of one or more eight carbons to eighteen carbons saturated fatty acids with glycerol. 
     
     
         17 . The method of  claim 43  wherein said polyalkylene glycol is a polyethylene glycol having a molecular weight of 1000 to 2000 daltons. 
     
     
         18 . The method of  claim 17  wherein said polyalkylene glycol is a polyethylene glycol having a molecular weight of 1400 to 1600 daltons. 
     
     
         19 - 22 . (canceled) 
     
     
         23 . The method of  claim 43  wherein said graft versus host disease is in humans. 
     
     
         24 . (canceled) 
     
     
         25 . The dosage form of  claim 44  wherein said dosage form is a solid oral dosage form. 
     
     
         26 . (canceled) 
     
     
         27 . The dosage form of  claim 44  wherein said polyalkylene glycol glyceride is a mixture of polyalkylene esters of one or more eight carbons to eighteen carbons saturated fatty acids with glycerol. 
     
     
         28 . The dosage form of  claim 27  wherein said polyalkylene glycol is a polyethylene glycol having a molecular weight of 1000 to 2000 daltons. 
     
     
         29 . The dosage form of  claim 28  wherein said polyalkylene glycol is a polyethylene glycol having a molecular weight of 1400 to 1600 daltons. 
     
     
         30 . The dosage form of  claim 25  wherein said Bryostatin-1, Bryostatin-1 analog or pharmaceutically acceptable salt thereof is present in said oral dosage form in an amount of 1 to 30% by weight. 
     
     
         31 . The dosage form of  claim 25  wherein said Bryostatin-1, Bryostatin-1 analog or pharmaceutically acceptable salt thereof is present in said oral dosage form in an amount of 10 to 20% by weight. 
     
     
         32 . The dosage form of  claim 25  wherein said Bryostatin-1, Bryostatin-1 analog or pharmaceutically acceptable salt thereof is present in said oral dosage form in an amount of 2 to 25% by weight. 
     
     
         33 . The dosage form of  claim 44  wherein said dosage form is a pharmaceutical parenteral formulation. 
     
     
         34 . (canceled) 
     
     
         35 . The dosage form of  claim 33  wherein said polyalkylene glycol glyceride is a mixture of polyalkylene esters of one or more eight carbons to eighteen carbons saturated fatty acids with glycerol. 
     
     
         36 . The dosage form of  claim 35  wherein said polyalkylene glycol is a polyethylene glycol having a molecular weight of 1000 to 2000 daltons. 
     
     
         37 . The dosage form of  claim 36  wherein said polyalkylene glycol is a polyethylene glycol having a molecular weight of 1400 to 1600 daltons. 
     
     
         38 . The dosage form of  claim 33  wherein said Bryostatin-1, Bryostatin-1 analog or pharmaceutically acceptable salt thereof is present in said pharmaceutical formulation in an amount of 0.0005 to 0.5% by weight. 
     
     
         39 . The dosage form of claim  2  wherein said Bryostatin-1, Bryostatin-1 analog or pharmaceutically acceptable salt thereof is present in said pharmaceutical formulation in an amount of 0.001 to 0.1% by weight. 
     
     
         40 . The dosage form of  claim 33  wherein said Bryostatin-1, Bryostatin-1 analog or pharmaceutically acceptable salt thereof is present in said pharmaceutical parenteral formulation in an amount of 0.001 to 0.1% by weight. 
     
     
         41 . The dosage form of  claim 3  wherein said Bryostatin-1, Bryostatin-1 analog or pharmaceutically acceptable salt thereof is present in said pharmaceutical parenteral formulation as a dispersion in water having a concentration of 0.0005 to 0.1% by weight. 
     
     
         42 . (canceled) 
     
     
         43 . A method of treating graft vs. host disease (GVHD) by controlling inflammatory reactions in host cells following transplantation, comprising administering an effective amount of Bryostatin-1, Bryostatin-1 analog or a pharmaceutically acceptable salt thereof to reduce or prevent induced neutrophil trans endothelial migration, and wherein said dosage form comprises polyalkylene glycol glyceride. 
     
     
         44 . A dosage form for treating graft vs. host disease (GVHD) by controlling inflammatory reactions in host cells following transplantation, comprising administering an effective amount of Bryostatin-1, Bryostatin-1 analog or a pharmaceutically acceptable salt thereof to reduce or prevent induced neutrophil trans endothelial migration wherein said dosage form is for administration to a human or animal in need thereof, wherein said dosage form comprises saturated polyalkylene glycol glyceride, and wherein said effective amount in the organ is a plasma concentration of about 10 −7  M. 
     
     
         45 . A method of reducing GVHD-related inflammatory reactions due to migration of adaptive immune cells into surrounding tissues following bone marrow transplantation, comprising administering Bryostatin-1 in an effective amount.