Self-emulsifying systems containing anticancer medicament

Abstract

The present invention relates to a stabilized self-emulsifying system, comprising a therapeutically effective amount of o-(chloroacetylcarbamoyl)fumigillol, a pharmaceutically acceptable carrier and a stabilizing component, wherein the pharmaceutically acceptable carrier comprises an oily constituent and at least one surfactant. The stabilizing component comprises from about 1% to about 15% water relative to the weight of the self-emulsifying system, an acid, an adsorbent, or a complex-forming agent.

What is claimed is:  
     
         1 . A stabilized self-emulsifying system, comprising a therapeutically effective amount of o-(chloroacetylcarbamoyl)fumigillol, a pharmaceutically acceptable carrier and a stabilizing component, wherein the pharmaceutically acceptable carrier comprises an oily constituent and at least one surfactant and the stabilizing component comprises from about 1% to about 15% water relative to the weight of the stabilized self-emulsifying system.  
     
     
         2 . The stabilized self-emulsifying system according to    claim 1   , wherein the stabilizing component comprises from about 2% to about 10% water.  
     
     
         3 . The stabilized self-emulsifying system according to    claim 2   , wherein the stabilizing component comprises from about 7.0% to about 7.5% water.  
     
     
         4 . A stabilized self-emulsifying system, comprising a therapeutically effective amount of o-(chloroacetylcarbamoyl)fumigillol, a pharmaceutically acceptable carrier and a stabilizing component, wherein the pharmaceutically acceptable carrier comprises an oily constituent and at least one surfactant and the stabilizing component comprises an acid.  
     
     
         5 . The stabilized self-emulsifying system according to    claim 4   , wherein the acid is an organic or an inorganic acid.  
     
     
         6 . The stabilized self-emulsifying system according to    claim 5   , wherein the organic acid is selected from the group consisting of aliphatic carboxylic acids, aromatic carboxylic acids, and sulfonic acids.  
     
     
         7 . The stabilized self-emulsifying system according to    claim 6   , wherein the organic acid is selected from the group consisting of aminobenzoic acid, benzoic acid, acetylsalicylic acid, salicylic acid, formic acid, acetic acid, propionic acid, butyric acid, valeric acid, caproic acid, enanthic acid, caprylic acid, pelargonic acid, capric acid, lauric acid, myristic acid, palmitic acid, stearic acid, glycolic acid, lactic acid, malic acid, citric acid, methanesulfonic acid, 2-propanesulfonic acid, trifluoromethanesulfonic acid, benzenesulfonic acid, and p-toluenesulfonic acid.  
     
     
         8 . The stabilized self-emulsifying system according to    claim 7   , wherein the acid is citric acid.  
     
     
         9 . The stabilized self-emulsifying system according to    claim 5   , wherein the inorganic acid is selected from the group consisting of orthophosphoric acid, polyphosphoric acid, pyrophosphoric acid, and hydrochloric acid.  
     
     
         10 . The stabilized self-emulsifying system according to    claim 4   , wherein the stabilizing component comprises from about 0.005% to about 5.0% acid.  
     
     
         11 . The stabilized self-emulsifying system according to    claim 10   , wherein the stabilizing component comprises from about 0.05% to about 1.0% acid.  
     
     
         12 . A stable drug system comprising a therapeutically effective amount of o-(chloroacetylcarbamoyl)fumigillol, a pharmaceutically acceptable carrier and a stabilizing component, wherein the pharmaceutically acceptable carrier comprises an oily constituent and at least one surfactant and the stabilizing component is an adsorbent or complex-forming agent.  
     
     
         13 . The stabilized self-emulsifying system according to    claim 12   , wherein the stabilizing component is selected from the group consisting of gelatin, active charcoal, and silica gel.  
     
     
         14 . The stabilized self-emulsifying system according to    claim 12   , wherein the stabilizing component is a chelate or salt of ethylenediaminetetraacetic acid.  
     
     
         15 . The stabilized self-emulsifying system according to    claim 13   , wherein the stabilizing component is gelatin.  
     
     
         16 . The stabilized self-emulsifying system according to    claim 12   , wherein the stabilizing component comprises from about 0.01% to about 15% of the adsorbent or complex-forming agent.  
     
     
         17 . The stabilized self-emulsifying system according to    claim 16   , wherein the stabilizing component comprises from about 0.05% to about 10% of the adsorbent or complex-forming agent.  
     
     
         18 . The stabilized self-emulsifying system according to    claim 1   , wherein the oily component is a non-surface active oil.  
     
     
         19 . The stabilized self-emulsifying system according to    claim 1   , wherein the oily component is selected from Captex 100, Captex 300, Captex 355, Miglyol 810, Miglyol 812, Miglyol 818, Miglyol 829, and Dynacerin 660.  
     
     
         20 . The stabilized self-emulsifying system according to    claim 1   , wherein the self-emulsifying system is suitable for oral, enteral, parenteral, and intravenous administration.  
     
     
         21 . The stabilized self-emulsifying system according to    claim 4   , wherein the self-emulsifying system is suitable for oral, enteral, parenteral, and intravenous administration.  
     
     
         22 . The stabilized self-emulsifying system according to    claim 12   , wherein the self-emulsifying system is suitable for oral, enteral, parenteral, and intravenous administration.  
     
     
         23 . A pharmaceutical composition comprising a therapeutically active amount of o-(chloroacetylcarbamoyl)fumigillol, an oily constituent, at least one surfactant, and stabilizing component, wherein the stabilizing component is selected from about 1 to about 15 weight percent water; from about 0.005 to about 5.0 weight percent acid; and 0.05 to about 15 weight percent of an adsorbent or complex-forming agent.  
     
     
         24 . The composition according to    claim 23   , comprising from 40 to 60 weight percent of the oily component; from 20 to 40 weight percent surfactant; from 4 to 20 weight percent co-surfactant, and from 2 to about 12 weight percent water.  
     
     
         25 . The composition according to    claim 24   , wherein the composition comprises from about 7.0 to about 7.5 weight percent water.  
     
     
         26 . The composition according to    claim 23   , comprising from 40 to 60 weight percent of the oily component; from 20 to 40 weight percent surfactant; from 4 to 20 weight percent co-surfactant; and from 0.005 to about 5.0 weight percent acid.  
     
     
         27 . The composition according to    claim 26   , wherein the composition comprises from about 0.05 to about 1.0 weight percent acid.  
     
     
         28 . The composition according to    claim 23   , comprising from 40 to 60 weight percent of the oily component; from 20 to 40 weight percent surfactant; from 4 to 20 weight percent co-surfactant; and from 0.05 to about 15 weight percent.  
     
     
         29 . The composition according to    claim 28   , wherein the composition comprises from about 0.05 to about 10 weight percent of the adsorbent or complex-forming agent.  
     
     
         30 . A method of suppressing cell proliferation and neovascularization comprising administering the self-emulsifying system of    claim 1   .  
     
     
         31 . A method of suppressing cell proliferation and neovascularization comprising administering the stabilized self-emulsifying system of    claim 4   .  
     
     
         32 . A method of suppressing cell proliferation and neovascularization comprising administering the stabilized self-emulsifying system of    claim 10   .