Water soluble paclitaxel derivatives

Abstract

Disclosed are water soluble compositions of paclitaxel and docetaxel formed by conjugating the paclitaxel or docetaxel to a water soluble polymer such as poly-glutamic acid, poly-aspartic acid or poly-lysine. Also disclosed are methods of using the compositions for treatment of tumors, auto-immune disorders such as rheumatoid arthritis. Other embodiments include the coating of implantable stents for prevention of restenosis.

1 - 14 . (canceled)  
     
     
         15 . A method for treating cancer in a subject, comprising administering to a subject having cancer (i) a composition of a taxoid molecule conjugated to a water soluble polymer and (ii) radiation.  
     
     
         16 . The method of  claim 15 , wherein said taxoid is paclitaxel and said water soluble polymer is polyglutamic acid.  
     
     
         17 . The method of  claim 15 , wherein said taxoid is docetaxel and said water soluble polymer is polyglutamic acid.  
     
     
         18 . The method of  claim 16 , wherein said polyglutamic acid has a molecular weight of about 5000 to about 100,000 daltons.  
     
     
         19 . The method of  claim 18 , wherein said polyglutamic acid has a molecular weight of about 20,000 to about 80,000 daltons.  
     
     
         20 . The method of  claim 19 , wherein said polyglutamic acid has a molecular weight of about 25,000 to about 50,000 daltons.  
     
     
         21 . The method of  claim 20 , wherein said polyglutamic acid has a molecular weight of about 35,000 daltons.  
     
     
         22 . The method of  claim 20 , wherein said composition comprises about 37% by weight paclitaxel.  
     
     
         23 . The method of  claim 20 , wherein said composition comprises from about 2% to about 35% by weight of paclitaxel.  
     
     
         24 . The method of  claim 20 , wherein said radiation is gamma radiation.  
     
     
         25 . The method of  claim 22 , wherein said composition is administered prior to said radiation.  
     
     
         26 . The method of  claim 22 , wherein said composition is administered following said radiation.  
     
     
         27 . The method of  claim 22 , wherein 14 GY radiation is administered.  
     
     
         28 . The method of  claim 22 , wherein 7 GY radiation is administered.  
     
     
         29 . The method of  claim 22  wherein 10 GY radiation is adminstered.  
     
     
         30 . The method of  claim 29 , wherein said 10 GY radiation is administered weekly.  
     
     
         31 . The method of  claim 30 , wherein 50 to 70 Gray is administered over 5 to 7 weeks.  
     
     
         32 . The method of  claim 20 , wherein said cancer is breast cancer, ovarian cancer, malignant melanoma, lung cancer, gastric cancer, prostate cancer, colon cancer, head and neck cancer, leukemia or Kaposi's sarcoma.  
     
     
         33 . The method of  claim 25 , wherein said cancer is breast cancer, ovarian cancer, malignant melanoma, lung cancer, gastric cancer, prostate cancer, colon cancer, head and neck cancer, leukemia or Kaposi's sarcoma.  
     
     
         34 . The method of  claim 26 , wherein said cancer is breast cancer, ovarian cancer, malignant melanoma, lung cancer, gastric cancer, prostate cancer, colon cancer, head and neck cancer, leukemia or Kaposi's sarcoma.  
     
     
         35 . The method of  claim 15 , wherein said polymer has a molecular weight of about 20000 to 80000 daltons.  
     
     
         36 . The method of  claim 15 , wherein said polymer has a molecular weight of about 25000 to 50000 daltons.  
     
     
         37 . A method of enhancing the response of a tumor to irradiation, comprising: 
 a) administering to a patient in need of such therapy a radiosensitizing amount of a pharmaceutical composition comprising paclitaxel, docetaxel, etoposide, teniposide, camptothecin or epothilone conjugated to a water soluble polyamino acid polymer and a pharmaceutically acceptable carrier;    b) irradiating said tumor;    wherein said polymer has a molecular weight of about 5000 to 100000 daltons conjugated paclitaxel or docetaxel have increased water solubility, efficacy and accumulation within a tumor compared with the corresponding unconjugated drugs.    
     
     
         38 . The method of  claim 37 , wherein said polymer is polyglutamic acid having a molecular weight of about 20000 to about 80000 and said conjugate comprises about 2% to about 35% by weight of paclitaxel.  
     
     
         39 . The method of  claim 37 , wherein said polymer is polyglutamic acid having a molecular weight of about 20000 to about 80000 and said conjugate comprises about 2% to about 35% by weight of docetaxel.