Lyophilizate of lipid complex of water insoluble porphyrins

Abstract

The present invention relates to a pharmaceutically acceptable dosage form of water insoluble porphyrins, particularly metal containing porphyrins such as tin porphyrin, which can be complexed with a lipid, reconstituted from a lyophilizate and administrated to a patient in the treatment of cancer and other diseases.

1 . A pharmaceutical composition comprising a complex of a porphyrin and a phospholipid.  
     
     
         2 . The composition of  claim 1  wherein said composition is a lyohilizate of a complex of a porphyrin and a phospholipid and a pharmaceutically acceptable excipient.  
     
     
         3 . The composition of  claim 1  wherein said porphyrin is a water insoluble metal porphyrin.  
     
     
         4 . The composition of  claim 3  wherein said metal porphyrin is a tin porphyrin.  
     
     
         5 . The composition of  claim 4  wherein said tin porphyrin has the structure:  
       
         
           
           
               
               
           
         
       
     
     
         6 . The composition of  claim 2  wherein said composition forms a colloidal dispersion of the complex when reconstituted with a physiologically acceptable aqueous diluent.  
     
     
         7 . The composition of  claim 1  wherein said phospholipid is selected from the group consisting of dimyristoylphosphatidylcholine, dimyristoylphosphalidylglycerol, dipalmitoylphosphalidylcholine, dipalmitoylphosphalidylglycerol, distearoylphophalidyl choline, distearoylphosphalidylglycerol, and mixtures thereof.  
     
     
         8 . The composition of  claim 7  wherein said phospholipid is a mixture of dimyristoyl-phosphalidylcholine and dimyristoylphosphalidylglcerol.  
     
     
         9 . The composition of  claim 8  wherein said dimyristoylphosphatidylcholine is present in a weight ratio to said dimyristoylphosphatidylglycerol of about 7 to 3.  
     
     
         10 . The composition of  claim 1  wherein the weight ratio of said porphyrin to said phospholipid in said composition is about 1 to 30.  
     
     
         11 . The composition of  claim 2  wherein said excipient is mannitol.  
     
     
         12 . The composition of  claim 5  wherein the complex is a lipid complex of the tin porphyrin and a mixture of dimyristoylphosphalidylcholine and dimyristoylphosphatidylglycerol in a ratio of said tin porphyrin to said mixture of dimyristoylphosphatidylcholine and dimyristoylphorphalidylglycerol of about 1 to 30, said dimyristoylphophatidylcholine and said dimyristoylphosphatidylglycerol being present at a weight ratio of about 7 to 3; and a mannitol lyophyilzation excipient.  
     
     
         13 . A method for preparing a lyophilizate of a lipid complex of a porphyrin which comprises the steps of preparing a concentrated solution of a porphyrin and a phospholipid in an organic solvent, adding water to the solution to cause formation of a complex of the porphyrin and the phopholipid, removing the organic solvent to provide a dispersion of the lipid complex in water as an aqueous phase, dissolving a pharmaceutically acceptable excipient in the aqueous phase of the dispersion, and lyophilizing the dispersion of the lipid complex to form a lyophilizate.  
     
     
         14 . The method of  claim 13  wherein said porphyrin is a water insoluble metal porphyrin.  
     
     
         15 . The method of  claim 14  wherein said metal porphyrin is tin porphyrin.  
     
     
         16 . The method of  claim 15  wherein said tin porphyrin has the structure:  
       
         
           
           
               
               
           
         
       
     
     
         17 . The method of  claim 14  wherein said phospholipid is selected from the group consisting of dimyristoylphosphatidylcholine, dimyristoylphosphalidylglycerol, dipalmitoylphosphalidylcholine, dipalmitoylphosphalidylglycerol, distearoylphophalidylcholine, distearoylphosphalidylglycerol, and mixtures thereof.  
     
     
         18 . The method of  claim 17  wherein said phospholipid is a mixture of dimyristoyl-phosphalidylcholine and dimyrestoylphosphalidylglcerol.  
     
     
         19 . The method of  claim 18  wherein said dimyristoylphosphatidylcholine is present in weight ratio to said dimyristoylphosphatidylglycerol of about 7 to 3.  
     
     
         20 . The method of  claim 14  wherein said lyophilization excipient is mannitol.  
     
     
         21 . A method of photodynamic therapy comprising the steps of: 
 administering an effective amount of a lipid complex of a porphyrin and a phospholipid to a patient; and    exposing said patient to radiation at a wavelength in the absorption spectrum of said porphyrin.    
     
     
         22 . The method of  claim 21  wherein said step of administering the lipid complex to the patient includes preparing a lyophilizate of the complex and a pharmaceutically acceptable excipient and preparing a colloidal dispersion of the complex in a pharmaceutically acceptable vehicle from the lyophilizate.