Method of inhibiting side effects of pharmaceutical compositions containing amphiphilic vehicles or drug carrier molecules

Abstract

A method is provided for inhibiting or preventing toxicity and other unwanted effects (a) caused by solvents for pharmaceuticals which solvents or emulsifier which contain amphiphilic molecules such as polyethoxylated oils or a derivative thereof, or (b) caused by a drug in a vehicle containing amphiphilic molecules such as phopholipids or derivative thereof, emplying a complement inhibitor. Drug compositions containing amphiphilic molecules, or derivatives thereof and a complement inhibitor, and pharmaceutical compositions including a drug, solvent or carrier containing amphiphilic molecules or derivatives thereof, and a complement inhibitor are also provided.

1 . A method for inhibiting, treating, or reducing unwanted side effects caused by a pharmaceutical composition including a drug and a solvent containing amphiphilic molecules, said method comprising employing a complement activation inhibitor in conjunction with said composition.  
     
     
         2 . The method according to  claim 1  wherein said amphiphilic molecule is polyethoxylated oil or a derivative thereof, emulsifiers or detergent molecules thereof.  
     
     
         3 . The method according to  claim 2  wherein said solvent is selected from the group consisting of hydrophilic or hydrophobic solvents that carry said amphiphilic molecules.  
     
     
         4 . The method according to  claim 3  wherein said solvent is Cremophor or Cremophor EL.  
     
     
         5 . The method according to  claim 1  wherein said drug is poorly soluble in water-based solvents and necessitates the addition of emulsifiers to become soluble.  
     
     
         6 . The method according to  claim 5  wherein said drug is selected from the group consisting essentially of: taxol, althesin, cyclosporin, diazepam, didemnin E, echinomycin, propandid, steroids, teniposide, and multivitamin products.  
     
     
         7 . A pharmaceutical composition effective for inhibiting, treating, or reducing unwanted side effects caused by a drug composition including a drug and a solvent containing amphiphilic molecules in an individual, said pharmaceutical composition comprising a complement activation inhibitor in a pharmaceutically effective amount.  
     
     
         8 . The pharmaceutical composition of  claim 7  wherein said solvent contains polythoxylated oil.  
     
     
         9 . The pharmaceutical composition of  claim 7  wherein said complement activation inhibitor is selected from the group consisting of: sCR1, Factor H, Factor I, C1qInh, soluble forms of DAF, MCP, complestatin, and anti-C 5 a, compound K-76COOH, diamines, small polyanions, sulfonated aromatic compounds, small synthetic peptide analogues of the C terminal part of C3, CAB-2, indel-proximal peptides, serine esterase inhibitors, chimeric complement inhibitor proteins, and antibodies specific for complement proteins.  
     
     
         10 . A method for preventing a complement activation reaction in an individual resulting from administration of a drug composition containing polyethoxylated oil, said method comprising any one of the steps selected from the group consisting of 
 (i) slowly infusing said drug composition,    (ii) administering to said individual a high dose of a complement activation inhibitor prior to administration of said drug composition.    
     
     
         11 . An in vitro method for predicting hypersensitivity reactions in an individual resulting 
 from a drug composition containing polyethoxylated oil, said method comprising incubating said drug composition with a sample of said individual's serum in vitro and detecting the presence or absence of complement activation.    
     
     
         12 . A method for inhibiting, treating, or reducing unwanted side effects caused by a pharmaceutical composition including a drug or active agent and a carrier containing amphiphilic molecules, said method comprising employing a complement activation inhibitor in conjunction with said composition.  
     
     
         13 . The method according o  claim 12  wherein said amphiphilic molecule is polyethoxylated oil or a derivative thereof.  
     
     
         14 . The method according to  claim 12  wherein said carrier is selected from the group consisting of liposomes, colloidal dispersions, particulate biomaterials, radiocontrast agents and emulsifier-based drug vehicles.  
     
     
         15 . The method according to  claim 12  wherein said drug is selected from the group consisting of antifungal, and anticancer drugs.  
     
     
         16 . The method according to  claim 15  wherein said drug is doxorubicin, daunorubicin, amphotericin B.  
     
     
         17 . The method according to  claim 12  wherein said active agent is selected from the group consisting of hemoglobin, and polynucleotides.  
     
     
         18 . A pharmaceutical composition effective for inhibiting, treating, or reducing unwanted side effects caused by a drug composition including a drug and a carrier containing amphiphilic molecules in an individual, said pharmaceutical composition comprising a complement activation inhibitor in a pharmaceutically effective amount.  
     
     
         19 . The pharmaceutical composition of  claim 18  wherein said complement activation inhibitor is selected from the group consisting of: sCR1, Factor H, Factor I, C1gInh, soluble forms of DAF, MCP, complestatin, and anti-C5a, compound K-76COOH, diamines, small polyanions, sulfonated aromatic compounds, small synthetic peptide analogues of the C terminal part of C3, CAB-2, indel-proximal peptides, serine esterase inhibitors, chimeric complement inhibitor proteins, and antibodies specific for complement proteins.