Camptothecin complexes

Abstract

Disclosed are compositions that include a camptothecin and an amorphous cyclodextrin. The camptothecin may be substituted or unsubstituted. Also disclosed are methods of treating undesirable or uncontrolled cell proliferation by administering the inventive compositions. Finally, implants including an implant structure and the inventive composition are disclosed.

What is claimed is:  
     
         1 . A composition comprising a camptothecin and an amorphous cyclodextrin.  
     
     
         2 . The composition of  claim 1 , wherein the camptothecin is a substituted camptothecin.  
     
     
         3 . The composition of  claim 2 , wherein the substituted camptothecin comprises 9-nitrocamptothecin, 9-aminocamptothecin, 10,11-methylendioxy-20(S)-camptothecin, 7-ethyl-10-hydroxy camptothecin, or another substituted camptothecin that is substituted in at least one of the 7, 9, 10, 11, or 12 positions.  
     
     
         4 . The composition of  claim 3 , wherein the substituted camptothecin comprises 9-nitrocamptothecin, or 9-aminocamptothecin.  
     
     
         5 . The composition of  claim 1  wherein said amorphous cyclodextrin has a degree of substitution of 2 to 7.  
     
     
         6 . The composition of  claim 1 , wherein the amorphous cyclodextrin is substantially free of pyrogenic contaminants.  
     
     
         7 . The composition of  claim 1 , wherein the amorphous cyclodextrin comprises hydroxypropyl, hydroxyethyl, glucosyl, maltosyl and maltotriosyl derivatives of β-cyclodextrin, carboxyamidomethyl-β-cyclodextrin, carboxymethyl-β-cyclodextrin, sulfobutylether-β-cyclodextrin, hydroxypropyl-β-cyclodextrin or diethylamino-β-cyclodextrin.  
     
     
         8 . The composition of  claim 7 , wherein the amorphous cyclodextrin comprises hydroxypropyl β-cyclodextrin.  
     
     
         9 . The composition of  claim 1 , wherein the amorphous cyclodextrin comprises hydroxypropyl, hydroxyethyl, glucosyl, maltosyl and maltotriosyl derivatives of γ-cyclodextrin.  
     
     
         10 . The composition of  claim 1 , wherein the amorphous cyclodextrin comprises a mixture of two or more of α-, β-, or γ-cyclodextrin.  
     
     
         11 . A sterile aqueous solution comprising the composition of  claim 1  in a form suitable for parenteral administration.  
     
     
         12 . The composition of  claim 1 , wherein the ratio of the weight of camptothecin to the weight of cyclodextrin compound comprises a range between 1:1 and 1:2000.  
     
     
         13 . The composition of  claim 12 , wherein the ratio of the weight of camptothecin to the weight of cyclodextrin compound comprises a range of about 1:5 to 1:200  
     
     
         14 . The composition of  claim 13 , wherein the ratio of the weight of camptothecin to the weight of cyclodextrin compound comprises a range of about 1:5 to 1:50.  
     
     
         15 . The composition of  claim 1 , wherein the camptothecin is present in an amount effective to treat undesirable or uncontrolled cell proliferation.  
     
     
         16 . The composition of  claim 15 , wherein the undesirable or uncontrolled cell proliferation comprises restenosis, various cancers, insults to body tissue due to surgery, diseases that produce fibrosis of tissue, repetitive motion disorders, disorders of tissues that are not highly vascularized, and proliferative responses associated with organ transplants.  
     
     
         17 . The composition of  claim 16 , wherein the various cancers comprise acute myelogenous leukemia, bladder, breast, cervical, cholangiocarcinoma, chronic myelogenous leukemia, colorectal, gastric sarcoma, glioma, leukemia, lung, lymphoma, melanoma, multiple myeloma, osteosarcoma, ovarian, pancreatic, prostrate, stomach, or tumors at localized sites including inoperable tumors or in tumors where localized treatment of tumors would be beneficial, and solid tumors.  
     
     
         18 . The composition of  claim 17 , wherein the various cancers comprise pancreatic or colorectal.  
     
     
         19 . The composition of  claim 1 , wherein the composition is in a lyophilized form.  
     
     
         20 . A method of treating undesirable or uncontrolled cell proliferation comprising administering the composition of  claim 1 .  
     
     
         21 . The method of  claim 20 , wherein the camptothecin is a substituted camptothecin.  
     
     
         22 . The method of  claim 21 , wherein the substituted camptothecin comprises 9-nitrocamptothecin, 9-aminocamptothecin, 10,11-methylendioxy-20(S)-camptothecin, 7-ethyl-10-hydroxy camptothecin, or another substituted camptothecin that is substituted in at least one of the 7, 9, 10, 11, or 12 positions.  
     
     
         23 . The method of  claim 22 , wherein the substituted camptothecin comprises 9-nitrocamptothecin, or 9-aminocamptothecin.  
     
     
         24 . The method of  claim 20 , wherein said amorphous cyclodextrin has a degree of substitution of 2 to 7.  
     
     
         25 . The method of  claim 20 , wherein the amorphous cyclodextrin is substantially free of pyrogenic contaminants.  
     
     
         26 . The method of  claim 20 , wherein the undesirable or uncontrolled cell proliferation comprises restenosis, various cancers, insults to body tissue due to surgery, diseases that produce fibrosis of tissue, repetitive motion disorders, disorders of tissues that are not highly vascularized, and proliferative responses associated with organ transplants.  
     
     
         27 . The method of  claim 26 , wherein the various cancers comprise acute myelogenous leukemia, bladder, breast, cervical, cholangiocarcinoma, chronic myelogenous leukemia, colorectal, gastric sarcoma, glioma, leukemia, lung, lymphoma, melanoma, multiple myeloma, osteosarcoma, ovarian, pancreatic, prostrate, stomach, or tumors at localized sites including inoperable tumors or in tumors where localized treatment of tumors would be beneficial, and solid tumors.  
     
     
         28 . The method of  claim 26 , wherein the various cancers comprise pancreatic or colorectal.  
     
     
         29 . An implant comprising an implant structure and the composition of  claim 1 .  
     
     
         30 . The implant of  claim 29 , where the implant is a time-release implant.  
     
     
         31 . The implant of  claim 29 , where the implant is a gel or polymer implant.  
     
     
         32 . The implant of  claim 29 , where the implant is coated and the composition is contained in the coating.  
     
     
         33 . The implant of  claim 29 , where the composition is contained within the implant structure.  
     
     
         34 . The implant of  claim 29 , where the implant is biodegradable or is formed in situ.  
     
     
         35 . A method of treatment comprising inserting an implant into a body wherein the implant is the implant of  claim 29 .  
     
     
         36 . A stent comprising the composition of  claim 1 .  
     
     
         37 . The stent of  claim 36 , where the stent is coated and the composition is contained in the coating.  
     
     
         38 . The stent of  claim 36 , where the composition is contained within the stent structure.  
     
     
         39 . The stent of  claim 36 , wherein the composition is present in an amount effective to reduce undesirable or uncontrolled cell proliferation once the stent is deployed.  
     
     
         40 . A method of treatment comprising inserting a stent into a body, wherein the stent comprises the composition of  claim 1 .  
     
     
         41 . A method of treatment comprising administering the composition of  claim 1  through an intraluminal catheter.  
     
     
         42 . A method of treatment comprising administering the composition of  claim 1  in a local fashion.