Treatment of Solid Cancerous Tumors by Oral Administration of a Halogenated Xanthene

Abstract

The present invention contemplates a method of treating a solid cancerous tumor in a mammalian subject by the oral administration of a solid cancerous tumor-effective amount of a halogenated xanthene (HX), the lactone thereof, a pharmaceutically acceptable salt, or a C1-C4 alkyl or aromatic ester thereof (collectively an HX compound) to that mammalian subject, and liquid and solid pharmaceutical compositions for administering the HX compound. In addition, a method of inhibiting the growth of a GI tract carcinoma of a mammalian subject by the oral administration of a solid cancerous tumor-effective amount of an HX compound, as well as solid and liquid pharmaceutical compositions therefor.

What is claimed: 
     
         1 . A pharmaceutical composition for oral delivery that comprises a solid tumor treating-effective amount of a halogenated xanthene (HX), the lactone thereof, a pharmaceutically acceptable salt, or a C 1 -C 4  alkyl or aromatic ester thereof (HX compound) contained within an enterically-coated solid diluent matrix, said enteric coating dissolving or disintegrating at a physiological pH value of 5 or greater. 
     
     
         2 . The pharmaceutical composition according to  claim 1 , wherein said enterically-coated solid diluent matrix is in the form of a tablet, lozenge, or a plurality of generally spherical sugar prills. 
     
     
         3 . The pharmaceutical composition according to  claim 1 , wherein said HX compound is dissolved in or dispersed in or on a solid diluent matrix. 
     
     
         4 . The pharmaceutical composition according to  claim 3 , wherein solid diluent matrix is comprised of sugar spheres coated with one or a plurality of layers of said HX compound. 
     
     
         5 . The pharmaceutical composition according to  claim 1 , wherein said aromatic ester is formed by a reaction between the halogenated xanthene and an aromatic alcohol having a 5- or 6-membered aromatic ring, or a 5,6- or 6,6-fused aromatic ring system that contains 0, 1 or 2 hetero ring atoms that are independently nitrogen, oxygen or sulfur. 
     
     
         6 . The pharmaceutical composition according to  claim 5 , wherein said aromatic alcohol is selected from the group consisting of one or more of benzyl, phenyl, pyridyl, thienyl, furyl, oxazolyl, thiazolyl, naphthyl, quinolyl, quioxalinyl, benzofuranyl, benzo[b]thienyl and benzoxazinyl alcohols. 
     
     
         7 . The pharmaceutical composition according to  claim 1 , wherein said HX compound is rose bengal disodium or rose bengal lactone. 
     
     
         8 . The pharmaceutical composition according to  claim 1 , wherein said enteric coating dissolves or disintegrates at a published pH value of 5.5 to 7.0. 
     
     
         9 . A method of treating a solid cancerous tumor in a mammalian subject that comprises orally administering an effective amount of a halogenated xanthene (HX), a pharmaceutically acceptable salt, or a C 1 -C 4  alkyl or aromatic ester thereof (HX compound) to that mammalian subject. 
     
     
         10 . The method according to  claim 9 , wherein said administration is repeated a plurality of times at least until the solid cancerous tumor has been reduced in volume by at least 30 percent. 
     
     
         11 . The method according to  claim 9 , wherein said aromatic ester is formed by a reaction between said HX and an aromatic alcohol that is selected from the group consisting of one or more of benzyl, phenyl, pyridyl, thienyl, furyl, oxazolyl, thiazolyl, naphthyl, quinolyl, quioxalinyl, benzofuranyl, benzo[b]thienyl, and benzoxazinyl alcohols. 
     
     
         12 . The method according to  claim 9 , wherein said HX compound is administered as part of an aqueous pharmaceutical composition. 
     
     
         13 . The method according to  claim 9 , wherein said HX compound is administered as part of a solid pharmaceutical composition. 
     
     
         14 . The method according to  claim 13 , wherein said solid pharmaceutical composition is in the form of a tablet or a plurality of generally spherical prills. 
     
     
         15 . The method according to  claim 13 , wherein said solid pharmaceutical composition is coated with a polymeric film that dissolves or disperses at a pH value above that of the stomach. 
     
     
         16 . The method according to  claim 9 , wherein said HX compound is rose bengal disodium or rose bengal lactone. 
     
     
         17 . A method of treating or inhibiting the formation of a carcinoma of the gastrointestinal tract in a mammalian subject that comprises orally administering to said mammalian subject a carcinoma formation-inhibiting or carcinoma-treating effective amount of a halogenated xanthene (HX), a pharmaceutically acceptable salt, or a C 1 -C 4  alkyl or aromatic ester thereof to said mammalian subject. 
     
     
         18 . The method according to  claim 17 , wherein said HX is rose bengal disodium. 
     
     
         19 . The method according to  claim 17 , wherein said aromatic ester is formed by a reaction between said HX and an aromatic alcohol having a 5- or 6-membered aromatic ring, or a 5,6- or 6,6-fused aromatic ring system that contains 0, 1 or 2 hetero ring atoms that are independently nitrogen, oxygen or sulfur. 
     
     
         20 . The method according to  claim 19 , wherein said aromatic alcohol is selected from the group consisting of one or more of benzyl, phenyl, pyridyl, thienyl, furyl, oxazolyl, thiazolyl, naphthyl, quinolyl, quioxalinyl, benzofuranyl, benzo[b]thienyl, and benzoxazinyl alcohols. 
     
     
         21 . The method according to  claim 17 , wherein said administration is repeated. 
     
     
         22 . The method according to  claim 17 , wherein said administration treats a carcinoma of the gastrointestinal tract of said mammalian subject. 
     
     
         23 . The method according to  claim 17 , wherein said HX, a pharmaceutically acceptable salt, or a C 1 -C 4  alkyl or aromatic ester thereof is dissolved or dispersed in an aqueous diluent when administered to said mammalian subject. 
     
     
         24 . The method according to  claim 17 , wherein said aqueous diluent is free of tonicity agents except for those sugars and/or buffering agents present as flavorants. 
     
     
         25 . The method according to  claim 17 , wherein said HX, a pharmaceutically acceptable salt, or a C 1 -C 4  alkyl ester or aromatic thereof is present as part of a solid medicament when administered to said mammalian subject. 
     
     
         26 . The method according to  claim 17 , wherein said administration treats a carcinoma of the gastrointestinal tract of said mammalian subject and said solid medicament releases said HX, a pharmaceutically acceptable salt, or a C 1 -C 4  alkyl or aromatic ester thereof at the pH value of the portion of the GI tract in which said carcinoma is located. 
     
     
         27 . The method according to  claim 26 , wherein said carcinoma is in the stomach. 
     
     
         28 . The method according to  claim 26 , wherein said carcinoma is in the small intestine. 
     
     
         29 . The method according to  claim 26 , wherein said carcinoma is in in the colon. 
     
     
         30 . The method according to  claim 26 , wherein solid medicament is a tablet. 
     
     
         31 . The method according to  claim 26 , wherein said HX compound is disodium rose bengal or rose bengal lactone. 
     
     
         32 . The method according to  claim 17 , wherein said solid medicament is a capsule that contains a plurality of coated particles that contain said HX, the lactone thereof, a pharmaceutically acceptable salt, or a C 1 -C 4  alkyl or aromatic ester thereof. 
     
     
         33 . The method according to  claim 32 , wherein the coating of said coated particles dissolves or disintegrates at a preselected pH value to release said HX, a pharmaceutically acceptable salt, or a C 1 -C 4  alkyl or aromatic ester thereof. 
     
     
         34 . The method according to  claim 33 , wherein said HX, the lactone thereof, a pharmaceutically acceptable salt, or a C 1 -C 4  alkyl or aromatic ester thereof is disodium rose bengal or rose bengal lactone.