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AssigneeBioNumerik Pharmaceuticals, Inc.
InventorsFrederick H. Hausheer, Kochat Haridas
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The novel compounds 11-hydroxy-7-ethyl camptothecin and 11-hydroxy-7-methoxy camptothecin (11,7-HECPT and 11,7-HMCPT) are active anticancer compounds which are poorly soluble in water. Because of their novelty, 11,7-HECPT and 11,7-HMCPT derivatives have not been directly administered by parenteral or oral routes to human subjects as an antitumor composition for the purpose of inhibiting the growth of cancer cells. The claimed compositions are useful as compared to the water soluble camptothecin derivatives, such as CPT-11, in clinical trials. The unpredictable interpatient variability in the metabolic production of an active metabolite from CPT-11 limits the utility of CPT-11. This invention overcomes these limitations by claiming novel pharmaceutically acceptable lactone stable formulations of 11,7-HECPT or 11,7-HMCPT, to directly administer to patients. The present invention also claims 11,7-HECPT and 11,7-HMCPT compositions, the synthesis of 11,7-HECPT or 11,7-HMCPT, the methods of formulation of 11,7-HECPT or 11,7 -HMCPT, and the methods of use of 11,7-HECPT or 11,7-HMCPT. Additionally, the claimed invention is directed to novel dosages, schedules, and routes of administration for both the 11,7-HECPT or 11,7-HMCPT formulations to humans with various forms of cancer. Other embodiments of this invention include isolation methods and methods of synthesis of certain camptothecin derivatives.
An 11-hydroxy-7-ethyl camptothecin solution consisting essentially of 11-hydroxy-7-ethyl camptothecin dissolved in dimethylisosorbide and a pharmaceutically acceptable acid wherein said acid is an organic carboxylic acid selected from the group consisting of citric acid and taurocholic acid in an admixture with citric acid.
An antitumor composition consisting essentially of a solution of 11-hydroxy-7-ethyl camptothecin dissolved in dimethylisosorbide having from 0.1 mg to 15.0 mg 11-hydroxy-7-ethyl camptothecin activity per ml and from 0.01 to 0.9 part by weight of a pharmaceutically acceptable organic carboxylic acid per part by weight of 11-hydroxy-7-ethyl camptothecin, wherein said organic carboxylic acid is selected from the group consisting of citric acid and taurocholic acid in an admixture with citric acid.
An antitumor composition consisting essentially of a solution of 11-hydroxy-7-methoxy camptothecin dissolved in dimethylisosorbide having from 0.1 mg to 15.0 mg 11-hydroxy-7-methoxy camptothecin activity per ml and from 0.01 to 0.9 part by weight of a pharmaceutically acceptable organic carboxylic acid per part by weight of 11-hydroxy-7-methoxy camptothecin wherein said organic carboxylic acid is selected from the group consisting of citric acid and taurocholic acid in an admixture with citric acid.
An antitumor composition consisting essentially of a solution of 11-hydroxy-7-ethyl camptothecin dissolved in dimethylisosorbide, a pharmaceutically acceptable acid selected from the group consisting of citric acid and taurocholic acid in an admixture with citric acid or a pharmaceutically acceptable salt thereof, polyethylene glycol, glycerin and a lower alcohol selected from the group consisting of ethyl alcohol and ethyl alcohol in an admixture with benzyl alcohol.
An antitumor composition consisting essentially of a solution of 11-hydroxy-7-methoxy camptothecin dissolved in dimethylisosorbide, a pharmaceutically acceptable acid selected from the group consisting of citric acid and taurocholic acid in an admixture with citric acid or a pharmaceutically acceptable salt thereof, polyethylene glycol, glycerin and a lower alcohol selected from the group consisting of ethyl alcohol and ethyl alcohol in an admixture with benzyl alcohol.
An antitumor composition consisting essentially of a solution of 11-hydroxy-7-ethyl camptothecin dissolved in dimethylisosorbide, a pharmaceutically acceptable acid selected from the group consisting of citric acid, and taurocholic acid in an admixture with citric acid, or a pharmaceutically acceptable salt thereof, polyethylene glycol, ethanol, glycerin, and a buffer.
An antitumor composition consisting essentially of a solution 11-hydroxy-7-methoxy camptothecin dissolved in dimethylisosorbide, a pharmaceutically acceptable acid selected from the group consisting of citric acid, and taurocholic acid in an admixture with citric acid, or a pharmaceutically acceptable salt thereof, polyethylene glycol, ethanol, glycerin, and a buffer.
An antitumor composition consisting essentially of a solution of 11-hydroxy-7-ethyl camptothecin dissolved in dimethylisosorbide, in the presence of a pharmaceutically acceptable acid selected from the group consisting of citric acid and taurocholic acid in an admixture with citric acid, a lower alcohol, polyethylene glycol, and a surfactant.
An antitumor composition consisting essentially of a solution of 0.1 mg to 15.0 mg of 11-hydroxy-7-ethyl camptothecin dissolved in 1 to 10 parts of dimethylisosorbide, in the presence of 0.1 to 0.5 parts of a pharmaceutically acceptable organic carboxylic acid selected from the group consisting of citric acid and taurocholic acid in an admixture with citric acid, wherein said solution further has 5 to 9 parts by weight of polyethylene glycol, 0.1 to 2.0 parts of a pharmaceutically acceptable alcohol, and 1 to 10 parts of a non-ionic surfactant.
An antitumor composition consisting essentially of a solution of 11-hydroxy-7-methoxy camptothecin dissolved in dimethylisosorbide in the presence of a pharmaceutically acceptable acid selected from the group consisting of citric acid and taurocholic acid in an admixture with citric acid, a lower alcohol, polyethylene glycol, and a surfactant.
An antitumor composition consisting essentially of a solution of 0.1 mg to 15.0 mg of 11-hydroxy-7-methoxy camptothecin dissolved in 1 to 10 parts of dimethylisosorbide in the presence of 0.1 to 0.5 parts of a pharmaceutically acceptable organic carboxylic acid selected from the group consisting of citric acid and taurocholic acid in an admixture with citric acid, wherein said solution further has 5 to 9 parts by weight of polyethylene glycol, 0.1 to 2.0 parts of a pharmaceutically acceptable alcohol, and 1 to 10 parts of a non-ionic surfactant.
An antitumor composition consisting essentially of a solution of 0.1 mg to 15.0 mg of 11-hydroxy-7-ethyl camptothecin dissolved in 1 to 10 parts of dimethylisosorbide in the presence of 0.1 to 0.5 parts of a pharmaceutically acceptable organic carboxylic acid selected from the group consisting of citric acid and taurocholic acid in an admixture with citric acid, wherein said solution further has 0.1 to 2.0 parts of a pharmaceutically acceptable alcohol, and 1 to 10 parts of a non-ionic surfactant.
An antitumor composition consisting essentially of a solution of 0.1 mg to 15.0 mg of 11-hydroxy-7-methoxy camptothecin dissolved in 1 to 10 parts of dimethylisosorbide in the presence of 0.1 to 0.5 parts of a pharmaceutically acceptable organic carboxylic acid selected from the group consisting of citric acid and taurocholic acid in an admixture with citric acid, wherein said solution further has 0.1 to 2.0 parts of a pharmaceutically acceptable alcohol, and 1 to 10 parts of a non-ionic surfactant.
An antitumor composition consisting essentially of a solution of 0.1 mg to 15.0 mg of 11-hydroxy-7-ethyl camptothecin dissolved in 1 to 10 parts of dimethylisosorbide, wherein said solution further has 1 to 10 parts polyoxyethylated castor oil, 0.1 to 2 parts by weight dehydrated ethyl alcohol USP, and 0.1 to 0.9 parts citric acid.
An antitumor composition consisting essentially of a solution of 0.1 mg to 15.0 mg of 11-hydroxy-7-methoxy camptothecin dissolved in 1 to 10 parts of dimethylisosorbide, wherein said solution further has 1 to 10 parts polyoxyethylated castor oil, 0.1 to 2 parts by weight dehydrated ethyl alcohol USP, and 0.1 to 0.9 parts citric acid.
An 11-hydroxy 7-methoxy camptothecin solution consisting essentially of 11-hydroxy-7-methoxy camptothecin dissolved in dimethylisosorbide and a pharmaceutically acceptable acid wherein said acid is an organic carboxylic acid selected from the group consisting of citric acid and taurocholic acid in an admixture with citric acid.
Dependencies are inferred from the claim text.