Platinum aggregates and process for producing the same

Abstract

One aspect of the disclosure relates to a new fom1 of lipid-complexed active platinum compound, which allows for high concentrations of platinum compound in the composition. For example, the concentration of cisplatin in the composition is higher at room temperature, e.g., about greater than 1.2 mg/mL, compared to 1 mg/mL in aqueous solution. In one embodiment, the present invention is directed to a composition comprising a lipid-complexed active platinum compound, wherein the complex has a lipid to drug (L/D) ratio of less than about 1 by weight, e.g. about 0.10 to 1, wherein the lipid-complexed active platinum compound comprises at least one lipid and at least one active platinum compound. In other embodiments, wherein lipid-complexed active platinum compound has an average volume-weighted diameter of about 0.5 to about 20 microns. In still other embodiments, the composition further comprises a liposome. The liposome may comprise at least one lipid, and may further comprise at least one active platinum compound. The disclosure also relates to a pharmaceutical formulation comprising a lipid complexed active platinum compound and a pharmaceutically acceptable carrier or diluent. The pharmaceutical formulation may be formulated for inhalation or injection.

1 . A composition comprising a lipid-complexed active platinum compound, wherein the complex has a lipid to drug ratio less than about 1 by weight, wherein the lipid-complexed active platinum compound comprises at least one lipid and at least one active platinum compound. 
     
     
         2 . The composition of  claim 1 , wherein the lipid to drug ratio is about 0.10 to about 1 by weight. 
     
     
         3 . The composition of  claim 2 , wherein the lipid to drug ratio is about 0.10 to about 0.50 by weight. 
     
     
         4 . The composition of  claim 3 , wherein the lipid to drug ratio is about 0.15 to about 0.45 by weight. 
     
     
         5 . The composition of  claim 4 , wherein the lipid to drug ratio is about 0.20 to about 0.40 by weight. 
     
     
         6 . The composition of  claim 5 , wherein the lipid to drug ratio is about 0.2 by weight. 
     
     
         7 . The composition of  claim 1 , wherein lipid-complexed active platinum compound has an average volume-weighted diameter of about 0.5 to about 20 microns. 
     
     
         8 . The composition of  claim 7 , wherein the average volume-weighted diameter is about 1 to about 15 microns. 
     
     
         9 . The composition of  claim 8 , wherein the average volume-weighted diameter is about 2 to 10 microns. 
     
     
         10 . The composition of  claim 1 , wherein the concentration of the active platinum compound is greater than about 1.2 mg/mL. 
     
     
         11 . The composition of  claim 10 , wherein the active platinum compound has a concentration of about 1.2 to about 20 mg/mL. 
     
     
         12 . The composition of  claim 11 , wherein the platinum compound has a concentration of about 1.5 to about 5 mg/mL. 
     
     
         13 . The composition of  claim 1 , further comprising a liposome. 
     
     
         14 . The composition of  claim 13 , wherein the liposome comprises an active platinum compound. 
     
     
         15 . The composition of  claim 14 , wherein the lipid-complexed active platinum compound contains about 70 to about 100% of the total active platinum compound in the composition. 
     
     
         16 . The composition of  claim 15 , wherein in the lipid-complexed active platinum compound contains about 75 to about 99% of the total active platinum compound. 
     
     
         17 . The composition of  claim 16 , wherein the lipid-complexed active platinum compound contains about 80 to about 90% of the total active platinum compound. 
     
     
         18 . The composition of  claim 14 , wherein the liposome contains about 0 to about 30% of the total active platinum compound in the composition. 
     
     
         19 . The composition of  claim 18 , wherein the liposome contains about 0.5 to about 25% of the total active platinum compound. 
     
     
         20 . The composition of  claim 19 , wherein the liposome contains about 1 to about 20% of the total platinum compound. 
     
     
         21 - 44 . (canceled)