Anticancer formulation

Abstract

This invention relates to a pharmaceutical formulation containing z-butylidenephthalide and a polymer, e.g., a polyanhydride. Also disclosed is use of this formulation to treat tumor.

1 . A pharmaceutical formulation comprising z-butylidenephthalide, and a polymer admixed with the z-butylidenephthalide. 
     
     
         2 . The pharmaceutical formulation of  claim 1 , wherein the polymer is selected from the group consisting of poly(lactic-co-glycolic acid), a chitosan, a collagen, a hydrogel, a polyanhydride, and a mixture thereof 
     
     
         3 . The pharmaceutical formulation of  claim 2 , wherein the polyanhydride is prepared from bis(p-carboxyphenozy)propane, bis(p-carboxyphenoxy)butane, bis(p-carboxyphenoxy) pentane, bis(p-carboxyphenoxy)heptane, bis(p-carboxyphenoxy)hexane, bis(p-carboxyphenoxy)octane, isophthalic acid, 1,4-phenylene dipropionic acid, dodecanedioic acid, oxalic acid, malonic acid, succinic acid, glutaric acid, adipic acid, pimelic acid, suberic acid, azelaic acid, sebacic acid, phthalic acid, isophthalic acid, terephthalic acid, or a mixture thereof. 
     
     
         4 . The pharmaceutical formulation of  claim 3 , wherein the polyanhydride is prepared from bis(p-carbodyphenozy)propane, bis(p-carboxyphenoxy)hexane, isophthalic acid, 1,4-phenylene dipropionic acid, dodecanedioic acid, sebacic acid, or a mixture thereof 
     
     
         5 . The pharmaceutical formulation of  claim 4 , wherein the polyanhydride is prepared from a mixture of bis(p-carboxyphenoxy)propane and sebacic acid. 
     
     
         6 . The pharmaceutical formulation of  claim 5 , wherein the ratio between the bis(p-carboxyphenoxy)propane and the sebacic acid is 1:2 to 1:10. 
     
     
         7 . The pharmaceutical formulation of  claim 6 , wherein the ratio between the bis(p-carboxyphenoxy)propane and the sebacic acid is about 1:4 to 1:5. 
     
     
         8 . The pharmaceutical formulation of  claim 7 , wherein the weight percentage of the z-butylidenephthalide is 3%-20% of the formulation 
     
     
         9 . The pharmaceutical formulation of  claim 8 , wherein the weight percentage of the z-butylidenephthalide is about 10% of the formulation. 
     
     
         10 . The pharmaceutical formulation of  claim 1 , wherein the formulation is in form of powders, wafers, sheets, rods, microspheres, nanospheres, paste, or glue. 
     
     
         11 . The pharmaceutical formulation of  claim 1 , wherein the weight percentage of the z-butylidenephthalide is 3%-20% of the formulation. 
     
     
         12 . A method of treating tumor comprising administering to a subject in need thereof an effective amount of a pharmaceutical formulation containing z-butylidenephthalide and a polymer admixed with the z-butylidenephthalide. 
     
     
         13 . The method of  claim 12 , wherein the polymer is selected from the group consisting of poly(lactic-co-glycolic acid), a chitosan, a collagen, a hydrogel, a polyanhydride, and a mixture thereof 
     
     
         14 . The method of  claim 12 , wherein the tumor is glioblastoma multiforme, lung cancer, hepatocellular carcinoma, colon cancer, melanoma, breast cancer, neuroblastoma, teratoma, or human leukemia. 
     
     
         15 . The method of  claim 13 , wherein the polyanhydride is prepared from bis(p-carbodyphenozy) propane, bis(p-carboxyphenoxy)hexane, isophthalic acid, 1,4-phenylene dipropionic acid, dodecanedioic acid, sebacic acid, or a mixture thereof 
     
     
         16 . The method of  claim 15 , wherein the polyanhydride is prepared from a mixture of bis(p-carboxyphenoxy)propane and sebacic acid. 
     
     
         17 . The method of  claim 16 , wherein the ratio between the bis(p-carboxyphenoxy) propane and the sebacic acid is 1:2 to 1:10. 
     
     
         18 . The method of  claim 17 , wherein the ratio between the bis(p-carboxyphenoxy) propane and the sebacic acid is about 1:4 to 1:5. 
     
     
         19 . The method of  claim 12 , wherein the weight percentage of the z-butylidenephthalide is 3%-20% of the formulation. 
     
     
         20 . The method of  claim 19 , wherein the weight percentage of the z-butylidenephthalide is about 10% of the formulation. 
     
     
         21 . The method of  claim 12 , wherein the pharmaceutical formulation is subcutaneously implanted, interstitially implanted, or intracranially implanted in the subject. 
     
     
         22 . The method of  claim 12 , wherein the cancer is glioblastoma multiforme. 
     
     
         23 . The method of  claim 22 , wherein the z-butylidenephthalide inhibits Ax1-mediated proliferation, migration or invasion of tumor cells.